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Wang S, Chen J, Wu J, Peng Z, Wang K, Zhang X, Wu F, Jie K. Based on the diamond concept, application of platelet-rich plasma in the treatment of aseptic femoral shaft nonunion: A retrospective controlled study on 66 patients. Injury 2025; 56:112325. [PMID: 40222318 DOI: 10.1016/j.injury.2025.112325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/29/2025] [Accepted: 03/31/2025] [Indexed: 04/15/2025]
Abstract
BACKGROUND Biologics, particularly platelet-rich plasma (PRP), have gained attention for promoting bone healing. This study assesses the efficacy of PRP-enhanced therapy in treating aseptic femoral shaft nonunion. METHODS This retrospective study analyzed patients who underwent femoral fracture nonunion revision surgery at a high-level trauma center between January 2021 and April 2024. Patients were divided into two groups: Group 1 (PRP-enhanced) and Group 2 (non-PRP). Group 1 received internal fixation with auxiliary plate reinforcement, PRP-enriched grafts, and bioactive center creation. The primary endpoint was bone healing rate and time to healing; secondary endpoints included lower limb function, pain scores, complications, and risk factors for nonunion at final follow-up. RESULTS Sixty-six patients were included (25 in Group 1, 41 in Group 2). At final follow-up, all patients in Group 1 healed, while 80.49 % of Group 2 healed (p = 0.049). The average healing time was shorter in Group 1 (7.61 months) compared to Group 2 (11.19 months) (p < 0.001). Group 1 had superior lower limb function and pain scores (p < 0.001). Long-term smoking (OR = 9.47, 95 % CI 1.39-64.51, P = 0.022) and inappropriate post-operative weight bearing (OR = 7.62, 95 % CI 1.12-51.57, P = 0.038) were identified as risk factors for nonunion. CONCLUSION In nonunion revision surgery, PRP-enhanced therapy significantly improves bone healing rates, reduces healing time, and carries fewer safety risks than traditional bone grafting. It offers an effective approach for nonunion treatment and provides a standardized clinical application for PRP in fracture nonunion surgeries.
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Affiliation(s)
- Shiheng Wang
- The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong Province, PR China; Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, PR China
| | - Jianrong Chen
- The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong Province, PR China; Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, Guangdong Province, PR China
| | - Jiahua Wu
- The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong Province, PR China; Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, PR China
| | - Zhihao Peng
- The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong Province, PR China; Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, Guangdong Province, PR China
| | - Kunyu Wang
- Henan University of Chinese Medicine, Zhengzhou, 450000, Henan Province, PR China
| | - Xiuling Zhang
- The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong Province, PR China
| | - Feng Wu
- The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong Province, PR China; Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, Guangdong Province, PR China.
| | - Ke Jie
- The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong Province, PR China; Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, PR China; Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, Guangdong Province, PR China.
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Bozhokin MS, Bozhkova SA, Sopova JV, Leonova EI, Shubniakov MI, Rubel AA, Simental-Mendía M. Perspectives for using platelet-rich plasma in the treatment of knee osteoarthritis: Can it be improved through modifications of the protocol? Chin J Traumatol 2025:S1008-1275(25)00055-0. [PMID: 40382203 DOI: 10.1016/j.cjtee.2024.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 05/20/2025] Open
Abstract
PURPOSE Autologous platelet-rich plasma (PRP) injections are widely used in regenerative medicine, including the knee osteoarthritis (OA) therapy. This study reviews methods to enhance PRP therapy for knee OA, aiming to boost articular cartilage recovery. METHODS The search was conducted in the eLIBRARY, PubMed (MEDLINE), Ovid, ScienceDirect, and Google Scholar databases extracting publications available by the end of 2023. Studies were included if they simultaneously met the following criteria: (1) effect of using PRP in the recovery of hyaline cartilage damage after OA; (2) at least one way to modify the PRP protocol aimed to increase its efficiency; (3) data on the molecular mechanisms underlying the increase in efficiency of the modified PRP therapy in OA. RESULTS The findings of this study highlight the significant role that the composition and modification of PRP protocols play in enhancing chondrogenesis for cartilage repair. Beyond the activation or non-activation of platelets or the inclusion or removal of leukocytes, which are factors that could somehow affect the effectiveness of PRP formulations, the elimination of growth factors such as VEGF and EGF, which negatively influence cartilage regeneration, offers a promising approach to optimize PRP therapy. While growth factors like TGF-β3, PDGF, and IGF have been shown to promote chondrogenesis, the removal of detrimental factors that could contribute to chronic inflammation or OA progression could significantly improve treatment outcomes. Practices such as combining with hyaluronic acid, pre-injection PRP activation, and multiple administrations are clinically common, while other methods like adjusting growth factors concentration are still in development. CONCLUSION Various modifications of this technology allow to use molecular mechanisms involved in the restoration of hyaline cartilage and improve the effectiveness of PRP for the treatment of OA. However, significant challenges remain in standardizing PRP preparation and administration protocols. Variability in platelet concentration, growth factor composition, and activation methods complicate the assessment of efficacy and reproducibility.
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Affiliation(s)
- Mikhail S Bozhokin
- Treatment and Prevention of Wound Infection, Vreden National Medical Research Centre of Traumatology and Orthopedics, Saint Petersburg, 195427, Russia; Сenter of Cell Technologies, Institute of Cytology Russian Academy of Science, Saint Petersburg, 194064, Russia.
| | - Svetlana A Bozhkova
- Treatment and Prevention of Wound Infection, Vreden National Medical Research Centre of Traumatology and Orthopedics, Saint Petersburg, 195427, Russia
| | - Julia V Sopova
- Center of Transgenesis and Genome Editing, Saint Petersburg State University, Saint Petersburg, 198504, Russia; Laboratory of Plant Genetics and Biotechnology, Institute of General Genetics, St Petersburg Branch, Saint Petersburg, 198504, Russia
| | - Elena I Leonova
- Center of Transgenesis and Genome Editing, Saint Petersburg State University, Saint Petersburg, 198504, Russia
| | - Maxim I Shubniakov
- Treatment and Prevention of Wound Infection, Vreden National Medical Research Centre of Traumatology and Orthopedics, Saint Petersburg, 195427, Russia
| | - Aleksandr A Rubel
- Laboratory of Amyloid Biology, Saint Petersburg State University, Saint Petersburg, 198504, Russia
| | - Mario Simental-Mendía
- Orthopedic Trauma Service, "Dr. José Eleuterio González" University Hospital, School of Medicine, Autonomous University of Nuevo Leon, Monterrey, 66455, Mexico
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Khandan-Nasab N, Torkamanzadeh B, Abbasi B, Mohajeri T, Oskuee RK, Sahebkar A. Application of Platelet-Rich Plasma-Based Scaffolds in Soft and Hard Tissue Regeneration. TISSUE ENGINEERING. PART B, REVIEWS 2025. [PMID: 40296834 DOI: 10.1089/ten.teb.2024.0285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
Platelet-rich plasma (PRP) is a blood product with higher platelet concentrations than whole blood, offering controlled delivery of growth factors (GFs) for regenerative medicine. PRP plays pivotal roles in tissue restoration mechanisms, including angiogenesis, fibroblast proliferation, and extracellular matrix development, making it applicable across various regenerative medicine treatments. Despite promising results in different tissue injuries, challenges such as short half-life and rapid deactivation by proteases persist. To address these challenges, biomaterial-based delivery scaffolds, such as sponges or hydrogels, have been investigated. Current studies exhibit that PRP-loaded scaffolds fix these issues due to the sustained release of GFs. In this regard, given the widespread application of PRP in clinical studies, the use of PRP-loaded scaffolds has drawn significant consideration in tissue engineering (TE). Therefore, this review briefly introduces PRP as a rich origin of GFs, its classification, and preparation methods and discusses PRP applications in regenerative medicine. This study also emphasizes and reviews the latest research on the using scaffolds for PRP delivery in diverse fields of TE, including skin, bone, and cartilage repair.
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Affiliation(s)
- Niloofar Khandan-Nasab
- Targeted Drug Delivery Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Behdad Torkamanzadeh
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Behnam Abbasi
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Taraneh Mohajeri
- Department of Obstetrics & Gynecology, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran
| | - Reza Kazemi Oskuee
- Targeted Drug Delivery Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Centre for Research Impact and Outcome, Chitkara University, Rajpura, Punjab, India
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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Pintarić K, Vovk A, Salapura V, Snoj Ž, Vidmar J. Quantitative MRI Assessment of Supraspinatus Tendon Remodeling Following a Single Platelet-Rich Plasma Injection Using T2 Mapping and Relaxation Time Profiling. Diagnostics (Basel) 2025; 15:1049. [PMID: 40310440 PMCID: PMC12025939 DOI: 10.3390/diagnostics15081049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/17/2025] [Accepted: 04/19/2025] [Indexed: 05/02/2025] Open
Abstract
Background: Quantitative magnetic resonance imaging (MRI) techniques such as T2 mapping may detect early tendon changes following biologic therapies. This study aimed to assess the structural remodeling of the supraspinatus tendon using mean T2 values and T2 distribution profiles after an ultrasound (US)-guided single platelet-rich plasma (PRP) injection. Methods: Twenty-six patients with symptomatic supraspinatus tendinopathy were divided into tendinosis (n = 9) and partial tear (n = 13) groups. T2 mapping and clinical evaluations (shoulder pain and disability index questionnaire (SPADI), Constant-Murley score) were conducted at baseline and 6 months post-PRP. Mean T2 values were measured in three tendon segments (lateral, middle, and medial), and T2 profiles were compared to asymptomatic controls. Results: Clinical outcomes showed significant improvement in both the tendinosis and partial tear groups at the 6-month follow-up. Although no significant changes were observed in the mean T2 relaxation times across tendon segments following PRP treatment, T2 distribution profiling revealed statistically significant alterations in both groups. In the tendinosis group, post-treatment T2 profiles approached those of the asymptomatic controls, suggesting structural remodeling consistent with tendon healing. Conclusions:T2 mapping is an effective tool for detecting tendon remodeling following PRP therapy. Structural improvements indicative of tissue healing were observed in cases of tendinosis, but not in partial tendon tears. These findings support the use of T2 mapping-particularly the T2 distribution profiling-as a quantitative biomarker for assessing treatment response to PRP.
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Affiliation(s)
- Karlo Pintarić
- Institute of Radiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Department of Radiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Andrej Vovk
- Centre of Clinical Physiology, Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Vladka Salapura
- Institute of Radiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Department of Radiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Žiga Snoj
- Institute of Radiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Department of Radiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Jernej Vidmar
- Institute of Radiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Institute of Physiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
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Nakagawa HF, Kim J, Rinaldi J, Rabinowitz J, Mautner K, DeMers A, Sherman S, Borg-Stein J, Sussman WI. Systematic Review of Randomized Controlled Trials Evaluating the Use of Platelet-Rich Plasma for Knee Osteoarthritis: Adherence to Minimum Information for Studies Evaluating Biologics in Orthopaedics. Am J Sports Med 2025; 53:1241-1253. [PMID: 39754417 DOI: 10.1177/03635465241249996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
BACKGROUND The Minimum Information for Studies Evaluating Biologics in Orthopedics (MIBO) guidelines were developed in May 2017 to encourage improved reporting standards, promote increased transparency and reproducibility, and enhance clinical evaluation capabilities. The MIBO guidelines consist of 23 checklist items considered necessary to critically appraise clinical studies evaluating platelet-rich plasma (PRP). PURPOSE To assess randomized controlled trials that evaluated PRP for the treatment of knee osteoarthritis in order to systematically review their adherence to the MIBO guidelines. STUDY DESIGN Systematic review. Level 1a. METHODS A search was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The inclusion criteria were randomized controlled trials reporting on knee osteoarthritis treated with intra-articular PRP. The studies were categorized into pre-, peri-, and post-MIBO groups based on the start date of data collection. The overall MIBO scores, defined as percentage of checklist items out of the 23 checklist items reported in 1 study, individual item scores, defined as percentage of studies reporting the checklist item within a specified group, and overall item score defined as the average of the individual item scores from all the included studies were calculated. RESULTS The review included 87 studies (7925 patients; 8118 knees). Of these, 51 studies were assigned to the pre-MIBO group, 19 studies to the peri-MIBO group, and 17 studies to the post-MIBO group. The overall MIBO score was 72%. No statistically significant differences in MIBO scores were found among the 3 MIBO groups (P = .345). The majority of the studies (62 studies; 71%) had MIBO scores <80%. MIBO items with particularly low item scores included reporting of whole-blood characteristics (20%), platelet recovery rate (22%), PRP analysis (30%), and PRP activation (47%). No significant difference among the 3 MIBO groups was found for the item scores except for the reporting of the recipient details (P = .012). CONCLUSION This study highlights the deficiencies in adherence to the MIBO guidelines, particularly in reporting key variables such as whole-blood characteristics, platelet recovery rate, PRP analysis, and PRP activation. These findings suggest that the publication of the MIBO guidelines has not resulted in improved reporting practices in studies investigating intra-articular PRP for the treatment of knee osteoarthritis.
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Affiliation(s)
- Hirotaka F Nakagawa
- Department of Orthopedics and Rehabilitation, Tufts Medical Center, Boston, Massachusetts, USA
| | - James Kim
- Chobanian & Avedisian School of Medicine, Boston University, Boston, Massachusetts, USA
| | - Joseph Rinaldi
- Department of Orthopedics and Rehabilitation, Tufts Medical Center, Boston, Massachusetts, USA
| | - Judy Rabinowitz
- Hirsch Health Sciences Library, Tufts University, Boston, Massachusetts, USA
| | - Ken Mautner
- Department of Rehabilitation Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Ariana DeMers
- Restore Orthopedics and Sports Medicine, Sonora, California, USA
| | - Seth Sherman
- Department of Orthopaedic Surgery, Stanford Medicine, Redwood City, California, USA
| | - Joanne Borg-Stein
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA
| | - Walter I Sussman
- Department of Orthopedics and Rehabilitation, Tufts Medical Center, Boston, Massachusetts, USA
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Baird HBG, Ashy CC, Kodali P, Myer GD, Murray IR, Pullen WM, Slone HS. Most Publications Regarding Platelet-Rich Plasma Use in the Knee Are From Asia, Investigate Injection for Osteoarthritis, and Show Outcome Improvement: A Scoping Review. Arthroscopy 2025; 41:1184-1194.e19. [PMID: 38537725 DOI: 10.1016/j.arthro.2024.03.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/12/2024] [Accepted: 03/17/2024] [Indexed: 04/23/2024]
Abstract
PURPOSE To evaluate and synthesize the available literature related to platelet-rich plasma (PRP) treatment of knee pathologies and to provide recommendations to inform future research in the field. METHODS PubMed, CINAHL, and Scopus databases were queried on October 6, 2023. All identified citations were collated and uploaded into Covidence for screening and data extraction. Studies were included if they were human studies published in English with adult cohorts that received PRP as a procedural injection or surgical augmentation for knee pathologies with patient-reported outcome measures (PROMs) and level of evidence Levels I-IV. RESULTS Our search yielded 2,615 studies, of which 155 studies from 2006 to 2023 met the inclusion criteria. Median follow-up was 9 months (±11.2 months). Most studies (75.5%) characterized the leukocyte content of PRP, although most studies (86%) did not use a comprehensive classification scheme. In addition, most studies were from Asia (50%) and Europe (32%) and were from a single center (96%). In terms of treatment, 74% of studies examined PRP as a procedural injection, whereas 26% examined PRP as an augmentation. Most studies (68%) examined treatment of knee osteoarthritis. Many studies (83%) documented significant improvements in PROMs, including 93% of Level III/IV evidence studies and 72% of Level I/II evidence studies, although most studies (70%) failed to include minimal clinically important difference values. The visual analog scale was the most-used PROM (58% of studies), whereas the Short Form Health Survey 36-item was the least-used PROM (5% of studies). CONCLUSIONS Most published investigations of knee PRP are performed in Asia, investigate procedural injection for osteoarthritis, and show significant outcome improvements. In addition, this review highlights the need for better classification of PRP formulations. LEVEL OF EVIDENCE Level IV, scoping review of Level I-IV studies.
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Affiliation(s)
- Henry B G Baird
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina, U.S.A..
| | - Cody C Ashy
- Department of Orthopedic Surgery and Physical Medicine, Medical University of South Carolina, Charleston, South Carolina, U.S.A
| | - Prudhvi Kodali
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina, U.S.A
| | - Gregory D Myer
- Emory Sports Performance and Research Center (SPARC), Flowery Branch, Georgia, U.S.A.; Emory Sports Medicine Center, Atlanta, Georgia, U.S.A.; Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, U.S.A.; The Micheli Center for Sports Injury Prevention, Waltham, Massachusetts, U.S.A.; Youth Physical Development Centre, Cardiff Metropolitan University, Wales, United Kingdom
| | - Iain R Murray
- The University of Edinburgh, Edinburgh, United Kingdom
| | - W Michael Pullen
- Department of Orthopedic Surgery and Physical Medicine, Medical University of South Carolina, Charleston, South Carolina, U.S.A
| | - Harris S Slone
- Department of Orthopedic Surgery and Physical Medicine, Medical University of South Carolina, Charleston, South Carolina, U.S.A
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Alonso-Frías P, Francés-Herrero E, Bueno-Fernandez C, Gómez-Álvarez M, Agustina-Hernández M, Cervelló I, Cozzolino M. Beneficial Effects of Infiltration of Platelet-Rich Plasma in the Endometrium. BIOLOGY 2025; 14:319. [PMID: 40282184 PMCID: PMC12024569 DOI: 10.3390/biology14040319] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 03/14/2025] [Accepted: 03/15/2025] [Indexed: 04/29/2025]
Abstract
Platelet-rich plasma (PRP) is a concentrated product of autologous plasma platelets. It promotes the repair of tissues with low healing potential by providing supraphysiological amounts of essential growth factors and has recently become more popular in endometrial repair, achieving exciting clinical results. PRP treatment has proven to improve fertility outcomes in patients with a poor endometrial environment. However, the mechanism is not yet clear. Previous preclinical models also showed that PRP treatment decreased the expression of inflammatory markers and fibrosis, increased the endometrial proliferation rate and gene expression, and enhanced the pregnancy rate. The modulation of the endometrial immune environment and endometrial microbial community by PRP treatment appeared to be the key mechanism by which it improved endometrial receptivity. This review summarized the potential of adult PRP based on its composition and applications and the biological mechanisms and biological modifications in the endometrium after PRP instillation in preclinical models.
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Affiliation(s)
- Paula Alonso-Frías
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (P.A.-F.); (E.F.-H.); (M.G.-Á.); (M.A.-H.); (I.C.); (M.C.)
- Department of Pediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
| | - Emilio Francés-Herrero
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (P.A.-F.); (E.F.-H.); (M.G.-Á.); (M.A.-H.); (I.C.); (M.C.)
- Department of Pediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
| | - Clara Bueno-Fernandez
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (P.A.-F.); (E.F.-H.); (M.G.-Á.); (M.A.-H.); (I.C.); (M.C.)
| | - María Gómez-Álvarez
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (P.A.-F.); (E.F.-H.); (M.G.-Á.); (M.A.-H.); (I.C.); (M.C.)
| | - Marcos Agustina-Hernández
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (P.A.-F.); (E.F.-H.); (M.G.-Á.); (M.A.-H.); (I.C.); (M.C.)
| | - Irene Cervelló
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (P.A.-F.); (E.F.-H.); (M.G.-Á.); (M.A.-H.); (I.C.); (M.C.)
| | - Mauro Cozzolino
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (P.A.-F.); (E.F.-H.); (M.G.-Á.); (M.A.-H.); (I.C.); (M.C.)
- IVIRMA Global Research Alliance, IVI Roma, 00197 Rome, Italy
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Everts PA, Podesta L, Lana JF, Shapiro G, Domingues RB, van Zundert A, Alexander RW. The Regenerative Marriage Between High-Density Platelet-Rich Plasma and Adipose Tissue. Int J Mol Sci 2025; 26:2154. [PMID: 40076775 PMCID: PMC11900530 DOI: 10.3390/ijms26052154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 02/23/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
The use of autologous biological preparations (ABPs) and their combinations fills the void in healthcare treatment options that exists between surgical procedures, like plastic reconstructive, cosmetic, and orthopedic surgeries; non-surgical musculoskeletal biological procedures; and current pharmaceutical treatments. ABPs, including high-density platelet-rich plasma (HD-PRP), bone marrow aspirate concentrates (BMACs), and adipose tissue preparations, with their unique stromal vascular fractions (SVFs), can play important roles in tissue regeneration and repair processes. They can be easily and safely prepared at the point of care. Healthcare professionals can employ ABPs to mimic the classical wound healing cascade, initiate the angiogenesis cascade, and induce tissue regenerative pathways, aiming to restore the integrity and function of damaged tissues. In this review, we will address combining autologous HD-PRP with adipose tissue, in particular the tissue stromal vascular fraction (t-SVF), as we believe that this biocellular combination demonstrates a synergistic effect, where the HD-PRP constituents enhance the regenerative potential of t-SVF and its adipose-derived mesenchymal stem cells (AD-MSCs) and pericytes, leading to improved functional tissue repair, tissue regeneration, and wound healing in variety of clinical applications. We will address some relevant platelet bio-physiological aspects, since these properties contribute to the synergistic effects of combining HD-PRP with t-SVF, promoting overall better outcomes in chronic inflammatory conditions, soft tissue repair, and tissue rejuvenation.
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Affiliation(s)
- Peter A. Everts
- Medical School (GBCS), The University of Queensland, Brisbane, QLD 4006, Australia;
- Center for Collaborative Research, Zeo Scientifix, Inc., NOVA Southeastern University, Fort Lauderdale, FL 33328, USA;
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (R.B.D.)
- Regenerative Medicine Group, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil
| | - Luga Podesta
- Bluetail Medical Group and Podesta Orthopedic Sports Medicine, Naples, FL 34109, USA;
- Orlando College of Osteopathic Medicine, Orlando, FL 34787, USA
| | - José Fabio Lana
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (R.B.D.)
- Regenerative Medicine Group, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil
- Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, SP, Brazil
| | - George Shapiro
- Center for Collaborative Research, Zeo Scientifix, Inc., NOVA Southeastern University, Fort Lauderdale, FL 33328, USA;
| | - Rafael Barnabé Domingues
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (R.B.D.)
- Regenerative Medicine Group, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil
- Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, SP, Brazil
| | - Andre van Zundert
- Medical School (GBCS), The University of Queensland, Brisbane, QLD 4006, Australia;
- Royal Brisbane Clinical Unit, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Robert W. Alexander
- Regenevita Biocellular Aesthetic and Reconstructive Surgery, Cranio-Maxillofacial Surgery, Regenerative Medicine and Wound Healing, Hamilton, MT 5998840, USA;
- Department of Surgery and Maxillofacial Surgery, University of Washington, Seattle, WA 988104, USA
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Muthu S, Viswanathan VK, Gangadaran P. Is platelet-rich plasma better than steroids as epidural drug of choice in lumbar disc disease with radiculopathy? Meta-analysis of randomized controlled trials. Exp Biol Med (Maywood) 2025; 250:10390. [PMID: 39968415 PMCID: PMC11832311 DOI: 10.3389/ebm.2025.10390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 01/16/2025] [Indexed: 02/20/2025] Open
Abstract
The current meta-analysis was performed to analyze the efficacy and safety of platelet-rich plasma (PRP) as an epidural injectate, in comparison with steroids in the management of radiculopathy due to lumbar disc disease (LDD). We conducted independent and duplicate searches of the electronic databases (PubMed, Embase and Cochrane Library) in March 2024 to identify randomized controlled trials (RCTs) analyzing the efficacy of epidural PRP for pain relief in the management of LDD. Animal or in vitro studies, clinical studies without a comparator group, and retrospective or non-randomised clinical studies were excluded. Diverse post-intervention pain scores [visual analog score (VAS)] and functional scores [Oswestry Disability Index (ODI), SF-36], as reported in the reviewed studies, were evaluated. Statistical analysis was performed using STATA 17 software. 5 RCTs including 310 patients (PRP/Steroids = 153/157) were included in the analysis. The included studies compared the efficacy and safety of epidural PRP and steroids at various time-points including 1, 3, 6, 12, 24, and 48 weeks. Epidural PRP injection was found to offer comparable pain relief (VAS; WMD = -0.09, 95% CI [-0.66, 0.47], p = 0.641; I2 = 96.72%, p < 0.001), functional improvement (ODI; WMD = 0.72, 95% CI [-6.81, 8.25], p = 0.524; I2 = 98.73%, p < 0.001), and overall health improvement (SF-36; WMD = 1.01, 95% CI [-1.14, 3.17], p = 0.224; I2 = 0.0%, p = 0.36) as epidural steroid injection (ESI) at all the observed time points in the included studies without any increase in adverse events or complications. Epidural administration of PRP offers comparable benefit as epidural steroid injection (ESI) in the management of radiculopathy due to LDD. The safety profile of the epidural PRP is also similar to ESI.
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Affiliation(s)
- Sathish Muthu
- Department of Spine Surgery, Orthopaedic Research Group, Coimbatore, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore, India
- Department of Orthopaedics, Government Medical College, Karur, India
| | - Vibhu Krishnan Viswanathan
- Department of Spine Surgery, Orthopaedic Research Group, Coimbatore, India
- Department of Orthopaedics, Devadoss Hospital, Madurai, India
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- Cardiovascular Research Institute, Kyungpook National University, Daegu, Republic of Korea
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10
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Alahmadi RA, Lajdam GB, Aghashami A, Hamdan D, Almalki AH, Altalhi AA, Amoodi HA. Platelet Concentrates Impact on Myringoplasty Outcomes in Chronic Otitis Media Patients: Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg 2025; 172:25-35. [PMID: 39342500 DOI: 10.1002/ohn.988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 07/19/2024] [Accepted: 08/10/2024] [Indexed: 10/01/2024]
Abstract
OBJECTIVE We aimed to perform a systematic review and meta-analysis of myringoplasty outcomes following platelet concentrates application in patients with chronic otitis media (COM). DATA SOURCES We searched MEDLINE, Embase, and Cochrane Central register of Controlled Clinical Trials (CENTRAL). We also performed a manual search in Google Scholar and reference lists. REVIEW METHODS Eligible for inclusion were randomized controlled trials on COM patients undergoing myringoplasty with platelet concentrates (platelet-rich plasma or platelet-rich fibrin) compared to myringoplasty alone. The primary outcomes were graft uptake and air-bone gap (ABG) gain, while the secondary outcome was complication rate. We used odds ratio (OR) and standardized mean difference (SMD) to represent dichotomous and continuous outcomes, respectively. RESULTS Thirteen trials (n = 1179) were deemed eligible. Platelet concentrates significantly improved graft uptake after 6 months (OR: 2.45, 95% confidence interval [CI]: 1.34-4.47, P = .004, I2 = 0%, high certainty), ABG gain (SMD: 0.36, 95% CI: 0.17-0.55, P = .0002, I2 = 0%, moderate certainty), and complication rate (OR: 0.38, 95% CI: 0.18-0.82, P = .01, I2 = 0%, low certainty). CONCLUSION Our results showed that platelet concentrates may improve graft uptake and ABG gain and reduce complications in COM patients undergoing myringoplasty. Caution is warranted given to the relatively small sample size, as well as inconsistent reporting across included trials.
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Affiliation(s)
- Rana A Alahmadi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Ghassan Bin Lajdam
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Afnan Aghashami
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Dalia Hamdan
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Abdulaziz H Almalki
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Atheer A Altalhi
- Otolaryngology-Head and Neck Surgery Department, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia
| | - Hosam A Amoodi
- Department of Surgery, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia
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11
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Ding Q, Wang X, Liu Y, Li Y, Zhang D, Wang H, Ma S, Han Q, Zhuang W. The efficacy of platelet-rich plasma in ankle disease: a systematic review and meta-analysis. J Orthop Surg Res 2024; 19:895. [PMID: 39741342 DOI: 10.1186/s13018-024-05420-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 12/25/2024] [Indexed: 01/02/2025] Open
Abstract
OBJECTIVE Ankle osteoarthritis is a debilitating condition that significantly impairs patients' quality of life. Platelet-rich plasma has emerged as a novel cellular therapy in clinical practice. This study evaluates the clinical efficacy of platelet-rich plasma (PRP) after intervention in ankle disorders, so as to provide strong evidence in support of clinical treatment. METHODS A comprehensive and systematic search of PubMed, the Cochrane Library, Embase and web of science databases was performed, and studies that met the requirements according to the inclusion criteria were analyzed using Review Manager and STATA version 14.0. Quality assessment was performed using the Cochrane Collaboration Risk of Bias 2.0 tool. The outcome indicators were the American Orthopaedic Foot and Ankle Society Rating Scale (AOFAS) and Visual Analog Scale (VAS) scores used to evaluate the efficacy of platelet-rich plasma. RESULTS A total of 10 studies met the inclusion criteria. Regarding the AOFAS score, a meta-analysis that included five randomized controlled trials (each study extracted the score results at the last follow-up time) showed no statistically significant differences between the platelet-rich plasma intervention group and the control group, and there was a great deal of heterogeneity in the results, with subgroup analyses based on disease type. (Mean Difference = 4.14, 95% CI=-0.60-8.87, p = 0.09, I2 = 86%). Subgroup analysis showed a more significant effect in patients with talar cartilage injuries (Mean Difference = 8.66, 95%CI = 6.61-10.71, p < 0.00001, I2 = 0%). And the treatment effect of PRP remained effective in long-term follow-up (Mean Difference = 7.83, 95% CI = 5.57-10.09, p = 0.46, I2 = 0%). For VAS scores, PRP relieved patients' pain (Standardized Mean Difference=-0.62, 95%CI=-1.13-0.10, p = 0.02, I2 = 77%) but showed a greater advantage in patients with cartilage injuries of the talus (Standardized Mean Difference=-1.24, 95%CI=-1.68-0.81, p < 0.00001, I2 = 0%). Subgroup analyses according to different disease types and different follow-up times showed that PRP had significant efficacy in talar cartilage injuries in both the short and long term. A meta-analysis of single-arm studies showed that PRP was helpful in improving patients' pain before and after the intervention (Standardized Mean Difference = -1.76, 95% CI = -2.85 to -0.67, p = 0.002, I^2 = 87%).However, the high level of heterogeneity may be due to the large differences between the inclusion criteria of the single-arm studies. CONCLUSION More clinical studies are needed to further confirm the efficacy of platelet-rich plasma in ankle disorders, and the current study only suggests that platelet-rich plasma may be more effective in talus cartilage injuries than in other types of ankle disorders.
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Affiliation(s)
- Qixin Ding
- School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Xu Wang
- School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yurong Liu
- Hunan Normal University, Changshao, China
| | - Yuefang Li
- School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Di Zhang
- School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Heling Wang
- School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Shenhong Ma
- School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Qiaohua Han
- School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Weisheng Zhuang
- School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China.
- Department of Rehabilitation, Henan Provincial People's Hospital, Zhengzhou, China.
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12
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Mackay G, Allen J. Platelet-rich plasma applications in the larynx: snake oil or stupendous? Curr Opin Otolaryngol Head Neck Surg 2024; 32:374-382. [PMID: 39436958 DOI: 10.1097/moo.0000000000001019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
PURPOSE OF REVIEW To explore and summarize recent work examining the use of platelet-rich plasma (PRP) applications for vocal fold disorder. RECENT FINDINGS Intrachordal PRP injections have recently emerged as a treatment option for patients with damage to the lamina propria of the vocal fold (scar, atrophy, sulcus and inflammatory lesions). Studies support significant improvements in patient-reported and clinician-reported outcomes, and objective phonatory parameters. PRP demonstrates a good safety profile, absence of immune reactions, affordable cost model and improvement in mucosal wave features with resultant improved voice quality up to 12 months following treatment. SUMMARY PRP injection of the vocal folds is a novel repurposing of a previously validated technique, and emerging data shows consistent results across multiple centres, increasing confidence in use of this freely available material. Current published studies confirm improved voice outcomes compared with pretreatment measures and high patient satisfaction. Further research is required to properly assign the role of and ideal candidate for PRP applications, and to delineate durability of treatment.
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Affiliation(s)
| | - Jacqui Allen
- Department of Surgery, University of Auckland
- Department of Otolaryngology, Te Whatu Ora Waitemata, Auckland, New Zealand
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13
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Anitua E, Tierno R, Martínez de Lagrán Z, Alkhraisat MH. Impact of inflammatory skin conditions on the biological profile of plasma rich in growth factor. Tissue Cell 2024; 91:102560. [PMID: 39299031 DOI: 10.1016/j.tice.2024.102560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/29/2024] [Accepted: 09/10/2024] [Indexed: 09/22/2024]
Abstract
Plasma rich in growth factors (PRGF) can be used over patients suffering from dermatoses due to its anti-inflammatory effect. However, this population group might present soluble autoimmune components and there is limited information about the effect of chronic skin inflammation on PRGF bioactive properties. With the aim of characterizing PRGF composition, PRGF from healthy (H) donors and patients with atopic dermatitis (AD), psoriasis (PS), or lichen sclerosus (LS) was obtained. In order to reduce the inflammatory component, leukocyte exclusion and heat-inactivation (Immunosafe) were tested. Haematological-serological parameters, platelet functionality, clot microstructure, protein content and bioactivity were determined. Mean values and 95 % confidence intervals (mean[95 % CI]) were computed for key haematological parameters, such as platelet (410×103/mm3[371-449]) and leukocyte content (205×103/mm3[148-262]), platelet activation (resting: 4.3 %[3.1-5.5] and activated: 97.4 %[96.7-98.0]), the concentration of plasma proteins and morphogens, including immunoglobulins A (210.7 mg/dL[191.8-229.6]), G (933.1 mg/dL[887.2-978.9]), E (783.5 mg/dL[54.4-1512.6]), and M (115.0 mg/dL[97.1-133.0]), Complement Protein (31.6 mg/mL[26.6-36.6]), C-Reactive protein (3.1 mg/L[2.0-4.1]), TGF-β1 (35975.6 pg/mL[34221.3-37729.8]), fibronectin (146410.0 ng/mL[136518.3-156301.7]), PDGF-AB (13308.5 pg/mL[12401.0-14216.0]), CD40L (2389.3 pg/mL[1887.7-2890.8]), IL-4 (0.12 pg/mL[0.07-0.18]), IL-13 (35.4 pg/mL[21.0-49.7]), IL-1β (0.09 pg/mL[0.06-0.11]) and TNF-α (0.31 pg/mL[0.24-0.38]), and also for cell proliferation (332.9ngDNA/mL[317.4-348.3]), viability (135.6 %[132.0-139.2]) and migration (103.8cells/mm2[98.3-109.3]). Plasma from AD donors presented increased Immunoglobulin E (IgE) that was significantly reduced after Immunosafe along with the complement system and autoantibodies. Platelet functionality was altered for AD, but no microstructure differences were identified. Pathological groups presented reduced concentration of fibronectin (AD/LS) and Platelet-Derived Growth Factor (PDGF-AB) (P). Immunosafe treatment reduced Cluster of Differentiation 40 Protein (CD40L), interleukin 1β (IL-1β), and Tumor Necrosis Factor α (TNF-α) concentrations. Fibroblasts supplemented with PRGF obtained from pathological patients (PS/AD) showed reduced viability but Immunosafe increased cell proliferation and migration in SP (LS) and L-SP samples (PS/AD). In conclusion, PRGF derived from pathological patients present autoimmune components, but heat-inactivation or leukocyte exclusion could minimize local side effects.
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Affiliation(s)
- Eduardo Anitua
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain; BTI Biotechnology Institute, Vitoria, Spain.
| | - Roberto Tierno
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain; BTI Biotechnology Institute, Vitoria, Spain
| | | | - Mohammad H Alkhraisat
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain; BTI Biotechnology Institute, Vitoria, Spain
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14
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Eymard F, Oubaya N, Ornetti P, Sellam J, Richette P, Chevalier X. Protocol for a multicentre randomised triple-blind controlled trial assessing the clinical efficacy of intra-articular platelet-rich plasma injections versus placebo in symptomatic knee osteoarthritis (PIKOA). BMJ Open 2024; 14:e085025. [PMID: 39615889 PMCID: PMC11624835 DOI: 10.1136/bmjopen-2024-085025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 11/14/2024] [Indexed: 12/09/2024] Open
Abstract
INTRODUCTION Despite their exponential use, intra-articular (IA) injections of platelet-rich plasma (PRP) are not part of the recommended treatments for knee osteoarthritis (OA) by most international scientific societies. The most recent clinical trials have shown conflicting results, and some did not find any clinical benefit of PRP injections. The PRP In Knee OsteoArthritis (PIKOA) trial was designed to assess the clinical efficacy and structural benefit of IA injections of PRP vs saline solution (placebo) in symptomatic knee OA. METHODS AND ANALYSIS PIKOA is an academic phase 3, superiority, triple-blind (patients, investigators and injectors), multicentre, randomised placebo-controlled trial (1:1 ratio). It compares the efficacy of 1 weekly IA injection of 5 mL PRP or placebo (saline solution) for 3 weeks with a 6-month follow-up. The trial will enrol 210 participants ≥40 years old with symptomatic and moderate radiographic knee OA (Kellgren and Lawrence grade 2 or 3). PRP is prepared with the A-CP-Kit-T (20 mL) kit and its cellular composition is characterised for each patient. The main objective is to compare change in pain on a 0 mm to 100 mm visual analogue scale (VAS) between W0 and W14. The secondary objectives are to compare the two groups in terms of decrease in VAS pain, Western Ontario and McMaster Universities Osteoarthritis Index total score and subscores, analgesics consumption, OMERACT-Osteoarthritis Research Society International responder rate and improvement in quality of life measured by the EQ-5D-5L score. All these criteria are assessed at W8, W14 and W26. The decrease in serum Coll2-1 and Coll2-1 NO₂ levels (catabolic markers, reflecting cartilage destruction or joint inflammation) and increase in N-propeptide of cartilage IIA level (reflecting cartilage formation) are assessed at W8 and W14. Adverse events and study withdrawals are collected during the study. ETHICS AND DISSEMINATION Ethics approval was obtained from the Nord Ouest ethical committee (2021-A00742-39). All participants need to provide written informed consent. The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT05378815 (ClinicalTrials.gov); pre-results.Protocol version and number: V.3 of 17 July 2023.
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Affiliation(s)
- Florent Eymard
- Department of Rheumatology, Henri Mondor Hospital Rheumatology Service, Creteil, France
| | - Nadia Oubaya
- Department of Public Health, AP-HP, Henri Mondor Hospital, Creteil, France
| | - Paul Ornetti
- Department of Rheumatology, Dijon University Hospital, Dijon, France
- Plateforme d’investigations technologiques, INSERM 1093 CAPS, Dijon, France
| | - Jeremie Sellam
- CRSA Inserm UMRS_938, Sorbonne Université, Paris, France
- Department of Rheumatology, AP-HP, Saint Antoine Hospital, Paris, France
| | | | - Xavier Chevalier
- Department of Rheumatology, AP-HP Henri Mondor Hospital, Créteil, France
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15
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Anitua E, Tierno R, Martínez de Lagrán Z, Alkhraisat MH. Bioactive Effect of Plasma-Rich in Growth Factors (PRGFs) on Cell-Based In Vitro Models of Skin Inflammation in Relation to Inflammatory Skin Disorders. Cureus 2024; 16:e74252. [PMID: 39712761 PMCID: PMC11663451 DOI: 10.7759/cureus.74252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/21/2024] [Indexed: 12/24/2024] Open
Abstract
Plasma rich in growth factors (PRGFs) has proven potentially beneficial as a bioregenerator in patients with chronic skin disorders due to its anti-inflammatory effect. However, its therapeutic potential may be limited by soluble autoimmune components associated with inflammatory dermatoses in blood plasma. To evaluate the impact of skin health status on cell bioactivity, PRGF was prepared from healthy (H) donors as well as from individuals with atopic dermatitis (AD), psoriasis (PS), or lichen sclerosus (LS). Leukocyte exclusion and heat inactivation (Immunosafe treatment) were evaluated as potential methods to reduce the inflammatory components of the samples under study. The biological effect of PRGF-derived formulations was investigated using cell-based in vitro skin inflammation models, including human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) exposed to a pro-inflammatory environment. The data confirmed that viability, proliferation, and migration rates were enhanced in inflamed cell cultures supplemented with PRGF formulations compared to those maintained in standard culture media. Nevertheless, significant differences have been identified. About the healthy control, inflamed epidermal keratinocytes supplemented with most PRGF-based formulations obtained from pathological donors (PS/LS) showed lower viability. Heat inactivation significantly promoted cell proliferation in epidermal keratinocytes supplemented with SP (PS/LS) and L-PRP supernatant (LSP) samples (AD), and also cell migration in inflamed HDF (AD/H/LS) and HEK (AD/LS) models supplemented with LSP. Leukocyte exclusion improved cell behavior in terms of migration with the only exception of LSP from individuals with AD added to inflamed HEK cultures. In conclusion, PRGF derived from pathological patients contains autoimmune components that could compromise its effectiveness as a therapy for treating individuals with chronic inflammatory disorders. However, heat inactivation (Immunosafe treatment) or leukocyte exclusion could minimize local adverse effects.
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Affiliation(s)
- Eduardo Anitua
- Medicine, University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, ESP
- Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, ESP
| | - Roberto Tierno
- Medicine, University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, ESP
- Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, ESP
| | | | - Mohammad H Alkhraisat
- Medicine, University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, ESP
- Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, ESP
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Bahari Golamkaboudi A, Vojoudi E, Babaeian Roshani K, Porouhan P, Houshangi D, Barabadi Z. Current Non-Surgical Curative Regenerative Therapies for Knee Osteoarthritis. Stem Cell Rev Rep 2024; 20:2104-2123. [PMID: 39145857 DOI: 10.1007/s12015-024-10768-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2024] [Indexed: 08/16/2024]
Abstract
Osteoarthritis (OA) is a prevalent musculoskeletal disease affecting middle-aged and elderly individuals, with knee pain as a common complaint. Standard therapy approaches generally attempt to alleviate pain and inflammation, using various pharmacological and non-pharmacological options. However, the efficacy of these therapies in long-term tissue repair remains debated. As an alternative, regenerative medicine offers a promising strategy, with decreased adverse event rates and increasing evidence of safety and efficacy. This review will outline current advances in regenerative medicine for knee OA, emphasizing outpatient clinic-based therapies that use orthobiological and non-biological products. Different strategies based on orthobiologics are discussed as potential regenerative options for the management of knee OA. Cell-free therapies including platelet-rich plasma, autologous anti-inflammatories, exosomes, human placenta extract, and mitochondrial transplantation are discussed, focusing on their potential for cartilage regeneration. Additionally, cell-based therapies with regenerative properties including bone marrow aspirate concentrate, adipose stromal vascular fraction, microfat, nanofat, stem cell therapy, and genetically modified cells as part of orthobiologics, are being investigated. Also, this study is looking into non-biological approaches such as using gold-induced cytokines, extracorporeal shockwave therapy, and ozone therapy. The mechanisms of action, effectiveness, and clinical applications of each therapy are being explored, providing insights into their role in the management of knee OA.
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Affiliation(s)
- Ali Bahari Golamkaboudi
- School of Medicine, Regenerative Medicine, Organ Procurement and Transplantation Multi- Disciplinary Center, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Elham Vojoudi
- School of Medicine, Regenerative Medicine, Organ Procurement and Transplantation Multi- Disciplinary Center, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Pejman Porouhan
- Department of Radiation Oncology, Vasee Hospital, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - David Houshangi
- Department of Biomedical Engineering, University of Houston, Houston, United States
| | - Zahra Barabadi
- Department of Tissue Engineering and Biomaterials, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran.
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Tollance A, Prola A, Michel D, Bouche A, Turzi A, Hannouche D, Berndt S, Laumonier T. Platelet-Rich Plasma Promotes the Expansion of Human Myoblasts and Favors the In Vitro Generation of Human Muscle Reserve Cells in a Deeper State of Quiescence. Stem Cell Rev Rep 2024; 20:1981-1994. [PMID: 39001964 PMCID: PMC11445347 DOI: 10.1007/s12015-024-10760-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2024] [Indexed: 07/15/2024]
Abstract
Stem cell therapy holds significant potential for skeletal muscle repair, with in vitro-generated human muscle reserve cells (MuRCs) emerging as a source of quiescent myogenic stem cells that can be injected to enhance muscle regeneration. However, the clinical translation of such therapies is hampered by the need for fetal bovine serum (FBS) during the in vitro generation of human MuRCs. This study aimed to determine whether fresh allogeneic human platelet-rich plasma (PRP) combined or not with hyaluronic acid (PRP-HA) could effectively replace xenogeneic FBS for the ex vivo expansion and differentiation of human primary myoblasts. Cells were cultured in media supplemented with either PRP or PRP-HA and their proliferation rate, cytotoxicity and myogenic differentiation potential were compared with those cultured in media supplemented with FBS. The results showed similar proliferation rates among human myoblasts cultured in PRP, PRP-HA or FBS supplemented media, with no cytotoxic effects. Human myoblasts cultured in PRP or PRP-HA showed reduced fusion ability upon differentiation. Nevertheless, we also observed that human MuRCs generated from PRP or PRP-HA myogenic cultures, exhibited increased Pax7 expression and delayed re-entry into the cell cycle upon reactivation, indicating a deeper quiescent state of human MuRCs. These results suggest that allogeneic human PRP effectively replaces FBS for the ex vivo expansion and differentiation of human myoblasts and favors the in vitro generation of Pax7High human MuRCs, with important implications for the advancement of stem cell-based muscle repair strategies.
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Affiliation(s)
- Axel Tollance
- Department of Orthopedic Surgery, Geneva University Hospitals & Faculty of Medicine, Geneva, Switzerland
- Regen Lab SA, 1052, Le Mont-Sur-Lausanne, Switzerland
| | - Alexandre Prola
- Department of Cell Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland
| | - Diego Michel
- Department of Orthopedic Surgery, Geneva University Hospitals & Faculty of Medicine, Geneva, Switzerland
| | - Axelle Bouche
- Department of Orthopedic Surgery, Geneva University Hospitals & Faculty of Medicine, Geneva, Switzerland
- Department of Cell Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland
| | - Antoine Turzi
- Regen Lab SA, 1052, Le Mont-Sur-Lausanne, Switzerland
| | - Didier Hannouche
- Department of Orthopedic Surgery, Geneva University Hospitals & Faculty of Medicine, Geneva, Switzerland
- Department of Cell Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland
| | - Sarah Berndt
- Regen Lab SA, 1052, Le Mont-Sur-Lausanne, Switzerland
| | - Thomas Laumonier
- Department of Orthopedic Surgery, Geneva University Hospitals & Faculty of Medicine, Geneva, Switzerland.
- Department of Cell Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland.
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18
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Mackay G, Allen J. Platelet Rich plasma injection of the vocal folds in benign vocal pathologies. Eur Arch Otorhinolaryngol 2024; 281:5419-5428. [PMID: 39014252 PMCID: PMC11416420 DOI: 10.1007/s00405-024-08824-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 07/01/2024] [Indexed: 07/18/2024]
Abstract
PURPOSE There are few options for treatment of dysphonia secondary to vocal pathology related to lamina propria scar, atrophy, sulcus, or inflammatory disorders. Platelet rich plasma (PRP) may provide anti-inflammatory and regenerative properties seen with other tissue engineering therapies without the risks associated with these treatments. We evaluated vocal fold (VF) injection of PRP for feasibility, phonatory effects, patient satisfaction and durability. METHODS Patients with dysphonia secondary to vocal fold scar, atrophy, sulcus and inflammatory lesions were included. PRP injections were administered in office, to bilateral vocal folds. Patients were followed up at 1 week, 1 month, 3 months and 6 months to assess outcomes (GRBAS scale, maximum phonation time, vocal fatigue index (VFI), voice handicap index (VHI-10) and stroboscopy). RESULTS 75 intracordal PRP injections were administered to 48 patients. All injections were completed, and no adverse reactions were experienced. Improvements in VHI-10 scores at 1,3,6 months were seen (mean VHI 21.73 at baseline, 15.62 at six months, p < 0.001). 72.3% rated improvement at 7 or above on Likert scale. 95.7% of patients would consider a future PRP injection. Secondary outcomes VFI, MPT, and GRBAS also demonstrated significant improvements over time. Patients receiving a single PRP injection (n = 26) still demonstrated significant VHI-10 improvements at 1,3 and 6 months. CONCLUSIONS VF office PRP injections are feasible and safe and can provide phonatory benefit and reduce vocal effort in benign VF disorders. A single PRP injection is sufficient to provide sustained benefit in some cases. LEVEL OF EVIDENCE Level III: prospective cohort study.
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Affiliation(s)
- Georgia Mackay
- Department of Surgery, University of Auckland, Private Bag 91019, Grafton Auckland, New Zealand
| | - Jacqui Allen
- Department of Surgery, University of Auckland, Private Bag 91019, Grafton Auckland, New Zealand.
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Kamada K, Matsushita T, Yamashita T, Matsumoto T, Iwaguro H, Kuroda R, Sobajima S. Factors affecting the therapeutic effects of multiple intra-articular injections of platelet-rich-plasma for knee osteoarthritis. Asia Pac J Sports Med Arthrosc Rehabil Technol 2024; 38:43-48. [PMID: 39391554 PMCID: PMC11464242 DOI: 10.1016/j.asmart.2024.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 08/16/2024] [Accepted: 09/01/2024] [Indexed: 10/12/2024] Open
Abstract
Background Platelet-rich-plasma (PRP) is rapidly spreading as a conservative treatment option for knee osteoarthritis (KOA), however, its therapeutic efficacy is controversial. This study aimed to investigate the factors affecting the therapeutic effect of intra-articular PRP therapy for KOA in patients who received multiple PRP injections (PRP-I). Methods This is a historical cohort study included 1057 knees of 701 patients who received PRP-I during KOA treatment from 2018 to 2020. The difference in visual analog scale (VAS) scores before and after PRP-I was defined as the amount of change in VAS (ΔVAS). A linear mixed-effects model was employed with ΔVAS as a random effect and age, sex, BMI, KL classification, pre-treatment VAS, treatment duration, and the number of PRP injections as fixed effects. Evaluations using the Kellgren-Lawrence (KL) classification were added. Results Age, KL grade, and VAS score before treatment and after three, four, and five PRP-I were significantly associated with ΔVAS score. According to KL grade, age was significantly associated with ΔVAS score in the KL grade 4 group. VAS score before treatment was significantly associated with ΔVAS score, regardless of KL grade. Three-time PRP-I were significantly associated with ΔVAS in the KL-grade 1 and 2 groups. For KL grade 4, two or more PRP-I were significantly associated with the high efficacy. Conclusions Age, pain before treatment, KL grade and number of injections were associated with pain reduction after intra-articular PRP-I for KOA treatment. Pain reduction can be expected after PRP-I when patients are younger or experience severe pain before treatment. Three-time PRP-I are recommended to reduce pain in early-stage KOA and more than three times in advanced-stage KOA. Trial registration Retrospectively registration.
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Affiliation(s)
- Kohei Kamada
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takahiro Yamashita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
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Zhang JY, Xiang XN, Yu X, Liu Y, Jiang HY, Peng JL, He CQ, He HC. Mechanisms and applications of the regenerative capacity of platelets-based therapy in knee osteoarthritis. Biomed Pharmacother 2024; 178:117226. [PMID: 39079262 DOI: 10.1016/j.biopha.2024.117226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 08/25/2024] Open
Abstract
Osteoarthritis (OA) is the most prevalent joint disease in the elderly population and its substantial morbidity and disability impose a heavy economic burden on patients and society. Knee osteoarthritis (KOA) is the most common subtype of OA, which is characterized by damage to progressive articular cartilage, synovitis, and subchondral bone sclerosis. Most current treatments for OA are palliative, primarily aim at symptom management, and do not prevent the progression of the disease or restore degraded cartilage. The activation of α-granules in platelets releases various growth factors that are involved in multiple stages of tissue repair, suggesting potential for disease modification. In recent years, platelet-based therapies, such as platelet-rich plasma, platelet-rich fibrin, and platelet lysates, have emerged as promising regenerative treatments for KOA, but their related effects and mechanisms are still unclear. Therefore, this review aims to summarize the biological characteristics and functions of platelets, classify the products of platelet-based therapy and related preparation methods. Moreover, we summarize the basic research of platelet-based regeneration strategies for KOA and discuss the cellular effects and molecular mechanisms. Further, we describe the general clinical application of platelet-based therapy in the treatment of KOA and the results of the meta-analysis of randomized controlled trials.
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Affiliation(s)
- Jiang-Yin Zhang
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xiao-Na Xiang
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xi Yu
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Yan Liu
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Hong-Ying Jiang
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Jia-Lei Peng
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Cheng-Qi He
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Hong-Chen He
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China.
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Peng C, Yang L, Labens R, Gao Y, Zhu Y, Li J. A systematic review and meta-analysis of the efficacy of platelet-rich plasma products for treatment of equine joint disease. Equine Vet J 2024; 56:858-869. [PMID: 38185481 DOI: 10.1111/evj.14042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 11/25/2023] [Indexed: 01/09/2024]
Abstract
BACKGROUND Equine joint disease including septic arthritis (SA) and osteoarthritis (OA) is a critical cause of equine lameness. Platelet-rich plasma (PRP) is one of the most popular regenerative therapies to treat equine OA, even SA, but the evidence in support of the treatment is conflicting. OBJECTIVES The aim of the study was to systematically review the current evidence on PRP products used for SA and OA, as well as the efficacy of PRP products as treatment for OA on the basis of a meta-analysis of the available literature. STUDY DESIGN Systematic review and meta-analysis. METHODS A systematic search of relevant databases (PubMed, Web of Science, Scopus) was performed to identify studies published from 2013 to 2023, in accordance with the PRISMA guidelines. Randomised controlled trials, non-randomised trials and controlled laboratory studies that used at least one type of PRP products were included. Dichotomous outcomes were presented using odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS A total of 21 publications were identified in the systematic review and 5 of them in the meta-analysis. These publications involved various types of PRP products and reported different outcomes. Although most of the studies were associated with a high risk of bias, the overall estimated effect was consistent with a significant improvement in the PRP products treatment group compared with the control group (OR: 15.32; 95% CI: 3.00-78.15; p < 0.05). There was a significant improvement in clinical performance outcomes between the groups (OR: 36.64; 95% CI: 3.69-364.30; p < 0.05). CONCLUSION PRP products as intra-articular treatment are likely efficacious for treatment of equine OA and have potential for treating SA. These conclusions might be affected by the limited number of randomised controlled studies and high variability of different types of PRP products. To better evaluate the efficacy of PRP, a widely recognised classification system and the utilisation of randomised, blinded, equivalency or non-inferiority trials are required.
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Affiliation(s)
- Cong Peng
- Equine Clinical Diagnostic Center, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Luo Yang
- Equine Clinical Diagnostic Center, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Raphael Labens
- School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Bathurst, New South Wales, Australia
| | - Yu Gao
- University of Veterinary Medicine Hannover, Hanover, Lower Saxony, Germany
| | - Yiping Zhu
- Equine Clinical Diagnostic Center, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Jing Li
- Equine Clinical Diagnostic Center, College of Veterinary Medicine, China Agricultural University, Beijing, China
- China Agricultural University Veterinary Teaching Hospital, Beijing, China
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De Matthaeis A, Bianchi M, Putzulu R, Maccauro G. High-Dose Neutrophil-Depleted Platelet-Rich Plasma Therapy for Knee Osteoarthritis: A Retrospective Study. J Clin Med 2024; 13:4816. [PMID: 39200958 PMCID: PMC11355213 DOI: 10.3390/jcm13164816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/05/2024] [Accepted: 08/07/2024] [Indexed: 09/02/2024] Open
Abstract
Background/Objectives: Encouraging results have been reported for Platelet-Rich Plasma (PRP) treatment for knee osteoarthritis (KOA). This study reports the efficacy and safety of a high dose of neutrophile and red-blood-cell-depleted PRP to treat patients with KOA. Methods: A total of 212 consecutive patients diagnosed with Kellgren-Lawrence (KL) grading 1-3 KOA chronic knee pain for at least 1 year were treated with three injections at 15-day intervals with a high dose of neutrophil-depleted PRP (4 billion platelets). Clinical outcomes were retrospectively recorded as the percentage of responders at 3-, 6-, and 12-month follow-up, following the OMERACT-OARSI criteria. Pain, through the VAS score and WOMAC score, was also been recorded. Results: A total of 4 mL of PRP containing 4 × 109 platelets was obtained by single-spin centrifugation and injected intra-articularly into each patient with no preactivation. The overall responder rate of patients responding to the OMERACT-OARSI criteria at 3, 6, and 12 months was 68.9%, 72.7%, and 70.6%, respectively. A significant improvement in VAS and WOMAC scores at 3-, 6-, and 12-month follow-up compared to the pretreatment value (p < 0.01) was observed. The lowest VAS score was observed at 6 months overall and in all three KL-graded groups. The KL2 groups showed the best results regarding pain reduction and their WOMAC score at 6 months (p < 0.01). Conclusions: For KL1-3 KOA, a high dosage of neutrophil-depleted PRP is a successful treatment. It has long-lasting effects that last up to one year, relieves symptoms, and may slow the advancement of the disease.
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Affiliation(s)
- Andrea De Matthaeis
- Department of Orthopedics and Traumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Maria Bianchi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy (R.P.)
| | - Rossana Putzulu
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy (R.P.)
| | - Giulio Maccauro
- Department of Orthopedics and Traumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
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Mercader-Ruiz J, Beitia M, Delgado D, Sánchez P, Porras B, Gimeno I, González S, Benito-Lopez F, Basabe-Desmonts L, Sánchez M. Current Challenges in the Development of Platelet-Rich Plasma-Based Therapies. BIOMED RESEARCH INTERNATIONAL 2024; 2024:6444120. [PMID: 39157212 PMCID: PMC11329313 DOI: 10.1155/2024/6444120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 05/15/2024] [Accepted: 06/21/2024] [Indexed: 08/20/2024]
Abstract
Nowadays, biological therapies are booming and more of these formulations are coming to the market. Platelet-rich plasma, or PRP, is one of the most widely used biological therapies due to its ease of obtention and autologous character. Most of the techniques to obtain PRP are focusing on new processes and methods of optimization. However, not enough consideration is being given to modify the molecular components of PRP to generate more effective formulations with the aim of improving PRP treatments. Therefore, this review covers different novel PRP-obtaining methods that attempt to modify the molecular composition of the plasma.
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Affiliation(s)
- Jon Mercader-Ruiz
- Microfluidics Cluster UPV/EHUBIOMICs Microfluidics GroupLascaray Research CenterUniversity of the Basque Country UPV/EHU 01006, Vitoria-Gasteiz, Spain
- Advance Biological Therapy UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
| | - Maider Beitia
- Advance Biological Therapy UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
| | - Diego Delgado
- Advance Biological Therapy UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
| | - Pello Sánchez
- Advance Biological Therapy UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
- Arthroscopic Surgery UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
| | - Begoña Porras
- Arthroscopic Surgery UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
| | - Irene Gimeno
- Advance Biological Therapy UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
| | - Sergio González
- Arthroscopic Surgery UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
| | - Fernando Benito-Lopez
- Microfluidics Cluster UPV/EHUAnalytical Microsystems & Materials for Lab-on-a-Chip (AMMa-LOAC) GroupAnalytical Chemistry DepartmentUniversity of the Basque Country UPV/EHU 48940, Leioa, Spain
| | - Lourdes Basabe-Desmonts
- Microfluidics Cluster UPV/EHUBIOMICs Microfluidics GroupLascaray Research CenterUniversity of the Basque Country UPV/EHU 01006, Vitoria-Gasteiz, Spain
- Basque Foundation of ScienceIKERBASQUE 48009, Bilbao, Spain
| | - Mikel Sánchez
- Advance Biological Therapy UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
- Arthroscopic Surgery UnitHospital Vithas Vitoria 01008, Vitoria-Gasteiz, Spain
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Yoshioka T, Arai N, Sugaya H, Taniguchi Y, Kanamori A, Gosho M, Okuno K, Kikuchi N, Hyodo K, Aoto K, Yamazaki M. The Effectiveness of Leukocyte-Poor Platelet-Rich Plasma Injections for Symptomatic Mild to Moderate Osteoarthritis of the Knee With Joint Effusion or Bone Marrow Lesions in a Japanese Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Am J Sports Med 2024; 52:2493-2502. [PMID: 39097760 DOI: 10.1177/03635465241263073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/05/2024]
Abstract
BACKGROUND Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear. PURPOSE To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks. RESULTS Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, -9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group (P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups (P = .017), with no significant differences in other secondary endpoints. CONCLUSION In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks.
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Affiliation(s)
- Tomokazu Yoshioka
- Division of Regenerative Medicine, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Norihito Arai
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Hisashi Sugaya
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yu Taniguchi
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Akihiro Kanamori
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Masahiko Gosho
- Department of Biostatistics, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kosuke Okuno
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Naoya Kikuchi
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kojiro Hyodo
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Katsuya Aoto
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Masashi Yamazaki
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
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Rai S, Patel S, Chouhan DK, Jain A, Thami T, Dadra A, Dhillon MS. Is There a Need for an Exogenous Activator Along with PRP for Early Knee Osteoarthritis? A Triple-Blinded Randomized Control Trial. Indian J Orthop 2024; 58:905-913. [PMID: 38948365 PMCID: PMC11208341 DOI: 10.1007/s43465-024-01159-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 04/16/2024] [Indexed: 07/02/2024]
Abstract
Background In addition to other variables associated with PRP injections for Knee Osteoarthritis (OA), some confusion exists about the role of exogenous activators. The current study looks at matched groups getting PRP injections with or without activator (Calcium gluconate) in early knee OA patients. Methods Patients of early OA knee meeting inclusion criteria were randomly divided into 2 groups; Group A (43 patients) received 8 ml PRP injection alone, and Group B (48 patients) received 8 ml PRP along with 2 ml Calcium gluconate as activator. The patients were evaluated at baseline, 6 weeks, 3 months and 6 months for WOMAC Pain and Total WOMAC scores; secondary variables assessed were VAS score and patient satisfaction. Results The baseline characteristics of both groups were comparable. Leucocyte-depleted PRP with 5 times concentration and average absolute platelet numbers of 7.144 billion per knee was injected. Mean Pain WOMAC scores decreased in both groups from baseline (group A-8.68, group B-9.09) to final follow-up (group A-4.67, group B-5.11). Similarly, Mean Total WOMAC scores decreased from baseline (group A-37.81, group B-37.41) to (group A-21, group B-21.36) at the final follow-up in both groups. There was no significant difference between both groups, and both showed similar trends. Similar findings were noted for VAS scores. Patient satisfaction was also not different (group A, 90.69%, group B, 89.58%) at the end of 6 months. Conclusion Our study concluded doubtful role of adding exogenous activator to PRP preparation. Supplementary Information The online version contains supplementary material available at 10.1007/s43465-024-01159-7.
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Affiliation(s)
- Shivam Rai
- Department of Orthopaedics, PGIMER, Chandigarh, India
| | - Sandeep Patel
- Department of Orthopaedics, PGIMER, Chandigarh, India
| | | | - Ashish Jain
- Department of Orthopaedics, PGIMER, Chandigarh, India
| | - Tarkik Thami
- Department of Orthopaedics, PGIMER, Chandigarh, India
| | - Ankit Dadra
- Department of Orthopaedics, PGIMER, Chandigarh, India
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Anitua E, Troya M, Alkhraisat MH. Immunoregulatory role of platelet derivatives in the macrophage-mediated immune response. Front Immunol 2024; 15:1399130. [PMID: 38983851 PMCID: PMC11231193 DOI: 10.3389/fimmu.2024.1399130] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 06/07/2024] [Indexed: 07/11/2024] Open
Abstract
Background Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications. Methods A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases. Results A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies. Conclusion Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response.
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Affiliation(s)
- Eduardo Anitua
- Regenerative Medicine Laboratory, BTI-Biotechnology Institute, Vitoria, Spain
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
| | - María Troya
- Regenerative Medicine Laboratory, BTI-Biotechnology Institute, Vitoria, Spain
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
| | - Mohammad H. Alkhraisat
- Regenerative Medicine Laboratory, BTI-Biotechnology Institute, Vitoria, Spain
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
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García JR, Acuña AJ, Villareal JB, Berreta RS, Ayala SG, del Baño-Barragán L, Allende F, Chahla J. New horizons in cartilage repair: update on treatment trends and outcomes. JOURNAL OF CARTILAGE & JOINT PRESERVATION 2024; 4:100179. [DOI: 10.1016/j.jcjp.2024.100179] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Jiang Z, Huang C, Guo E, Zhu X, Li N, Huang Y, Wang P, Shan H, Yin Y, Wang H, Huang L, Han Z, Ouyang K, Sun L. Platelet-Rich Plasma in Young and Elderly Humans Exhibits a Different Proteomic Profile. J Proteome Res 2024; 23:1788-1800. [PMID: 38619924 DOI: 10.1021/acs.jproteome.4c00030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2024]
Abstract
As people age, their ability to resist injury and repair damage decreases significantly. Platelet-rich plasma (PRP) has demonstrated diverse therapeutic effects on tissue repair. However, the inconsistency of patient outcomes poses a challenge to the practical application of PRP in clinical practice. Furthermore, a comprehensive understanding of the specific impact of aging on PRP requires a systematic investigation. We derived PRP from 6 young volunteers and 6 elderly volunteers, respectively. Subsequently, 95% of high-abundance proteins were removed, followed by mass spectrometry analysis. Data are available via ProteomeXchange with the identifier PXD050061. We detected a total of 739 proteins and selected 311 proteins that showed significant differences, including 76 upregulated proteins in the young group and 235 upregulated proteins in the elderly group. Functional annotation and enrichment analysis unveiled upregulation of proteins associated with cell apoptosis, angiogenesis, and complement and coagulation cascades in the elderly. Conversely, IGF1 was found to be upregulated in the young group, potentially serving as the central source of enhanced cell proliferation ability. Our investigation not only provides insights into standardizing PRP preparation but also offers novel strategies for augmenting the functionality of aging cells or tissues.
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Affiliation(s)
- Zhitong Jiang
- Department of Cardiovascular Surgery, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Can Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Erliang Guo
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - Xiangbin Zhu
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Na Li
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Yu Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Peihe Wang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Hui Shan
- Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Yuxin Yin
- Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Hong Wang
- Central Laboratory, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Lei Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Zhen Han
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Kunfu Ouyang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Lu Sun
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
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Rossi LA, Gorodischer TD, Camino P, Brandariz RN, Tanoira I, Piuzzi NS, Ranalletta M. Leukocyte-Poor Platelet-Rich Plasma as an Adjuvant to Arthroscopic Rotator Cuff Repair Reduces the Retear Rate But Does Not Improve Functional Outcomes: A Double-Blind Randomized Controlled Trial. Am J Sports Med 2024; 52:1403-1410. [PMID: 38587033 DOI: 10.1177/03635465241239062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
BACKGROUND Whether the use of PRP as an adjuvant of rotator cuff repairs leads to improved tendon healing and better functional outcomes remains unclear in clinical evidence. PURPOSE The main purpose of this study was to assess whether the use of leukocyte-poor platelet-rich plasma (LP-PRP) as an adjuvant to arthroscopic rotator cuff repair (ARCR) decreases the rate of retears compared with a control group. The secondary objective was to analyze whether LP-PRP improves patient-reported outcomes. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS This was a double-blind randomized controlled trial at a single center. A consecutive series of 96 patients with rotator cuff tears <3 cm were enrolled and randomly allocated to the control group (double-row suture-bridge ARCR alone [n = 48]) and the PRP group (double-row suture-bridge repair, followed by 1 LP-PRP injection during surgery [n = 48]). The visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the Single Assessment Numeric Evaluation (SANE), and the Pittsburgh Sleep Quality Index (PSQI) were administered preoperatively and at 6- and 12-month follow-up. Magnetic resonance imaging (MRI) was performed to evaluate tendon integrity at 6-month follow-up. Both patients and assessors were blinded to the intervention received during surgery. RESULTS The mean patient age was 56.1 ± 2.98 years. Of the 96 patients, 90 had MRI performed at 6 months after surgery (94% radiological follow-up). The retear rate in the PRP group was 15.2% (7/46 [95% CI, 6%-28%]), which was lower than that in the control group of 34.1% (15/44 [95% CI, 20%-49%]) (P = .037). Therefore, the risk ratio of ruptures in patients exposed to LP-PRP was 0.44 (95% CI, 0.2-0.9; P = .037). Overall, the ASES, VAS, SANE, and PSQI scores showed a statistical improvement after surgery (P < .001). There were no significant differences in functional scores between the groups. Most of the patients exceeded the minimal clinically important difference for the ASES, SANE, and VAS without significant differences between the groups. CONCLUSION In patients with rotator cuff tears <3 cm undergoing double-row suture-bridge repair, a 5-mL dose of LP-PRP injected at the tendon-bone interface significantly reduced the retear rate. However, the use of LP-PRP in terms of postoperative pain and patient-reported outcomes failed to show clinically meaningful effects. REGISTRATION NCT04703998 (ClinicalTrials.gov identifier).
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Affiliation(s)
- Luciano Andres Rossi
- "Carlos E. Ottolenghi" Instituto de Ortopedia y Traumatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Tomás David Gorodischer
- "Carlos E. Ottolenghi" Instituto de Ortopedia y Traumatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Pablo Camino
- Department of Hemotherapy, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Rodrigo Nicolás Brandariz
- "Carlos E. Ottolenghi" Instituto de Ortopedia y Traumatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Ignacio Tanoira
- "Carlos E. Ottolenghi" Instituto de Ortopedia y Traumatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Nicolás Santiago Piuzzi
- Department of Hemotherapy, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
- Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Maximiliano Ranalletta
- "Carlos E. Ottolenghi" Instituto de Ortopedia y Traumatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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Vale D, Pereira A, Andrade JP, Castro JP. The Role of Platelet-Rich Plasma Injection for Muscle Strains in Athletes. Cureus 2024; 16:e60585. [PMID: 38894806 PMCID: PMC11184543 DOI: 10.7759/cureus.60585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
Muscle tears/strains are among the most common musculoskeletal injuries, posing a serious challenge for sports medicine. Aiming to reduce the time to return to play and the rate of reinjuries, apart from the traditional conservative treatments and rehabilitation protocols, new and innovative therapeutic options have emerged, particularly platelet-rich plasma (PRP). This study aims to present the available evidence regarding PRP injection for the treatment of muscle strains in athletes. Two databases were searched for articles published between January 2012 and December 2022 in Portuguese or English. The query used for the PubMed database was ("Muscles/injuries"[Mesh]) AND ("Athletes"[Mesh] OR "Athletic Injuries"[Mesh]) AND "Platelet-Rich Plasma"[Mesh], while for the Web of Science database the search was performed for "Platelet-rich plasma" AND "Muscle injuries" AND ("Athletes" OR "Athletic injuries"). Eleven studies involving athletes diagnosed with muscle injuries who received treatment with PRP injection alone, or in combination with traditional conservative treatment, compared to a control group, were included. Four randomized controlled trials, four systematic reviews/meta-analyses, two retrospective studies, and one comparative study were included. Current evidence from the highest-quality studies does not support the hypothesis of reduction of time to return to play and the rate of reinjuries after PRP injection, even though some studies reported positive results. However, the available evidence suggests that PRP might have a beneficial effect on the pain perceived by athletes following an acute muscle strain. It is challenging to arrive at definitive conclusions and translate these findings into a clinical context for treating muscle strains in athletes. The existing trials present several inconsistencies and limitations, with a heterogeneous set of patients and injuries, as well as the use of different and inconsistent methods for preparing, administering, and measuring the effects of PRP. To achieve consistent outcomes, standardizing PRP administration procedures is essential.
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Affiliation(s)
- David Vale
- Medical School, Faculty of Medicine, University of Porto, Porto, PRT
| | - Adriana Pereira
- Physical Medicine and Rehabilitation, Centro de Medicina de Reabilitação de Alcoitão, Alcoitão, PRT
| | - José Paulo Andrade
- Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, PRT
| | - João Paulo Castro
- Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, PRT
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Medina-Porqueres I, Martin-Garcia P, Sanz-De-Diego S, Reyes-Eldblom M, Moya-Torrecilla F, Mondragon-Cortes R, Rosado-Velazquez D, Gomez-Caceres A. Platelet-Rich Plasma Injections in Chronic Lateral Ankle Instability: A Case Series. Biomedicines 2024; 12:963. [PMID: 38790925 PMCID: PMC11118008 DOI: 10.3390/biomedicines12050963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/16/2024] [Accepted: 04/23/2024] [Indexed: 05/26/2024] Open
Abstract
The platelet-rich plasma (PRP) approach may be an effective treatment for joint and cartilage pathologies. However, the rationale for its effectiveness on joint instability is limited. This study aimed to assess the safety and effectiveness of PRP injections in patients with chronic lateral ankle instability (CLAI). This retrospective study was performed at a single-center outpatient clinic between January 2015 and February 2023 and included pre-intervention assessment and short-term follow-up. Patients were excluded if they had received previous surgical treatment or had constitutional hyperlaxity, systemic diseases, or grade II or III osteoarthritis. The clinical and functional evaluation consisted of the Karlsson score, the Cumberland Ankle Instability Tool (CAIT), Good's grading system, the patient's subjective satisfaction level, and the time required to return to exercise. The entire PRP therapy regime consisted of three PRP administrations at 7-day intervals and follow-up appointments. PRP was administered both intraarticularly and into talofibular ligaments. A total of 47 consecutive patients with CLAI were included, 11 were female (23.4%), with a mean age at intervention of 31.19 ± 9.74 years. A statistically significant improvement was found in the CAIT and Karlsson scores at 3 months (27.74 ± 1.68 and 96.45 ± 4.28, respectively) relative to the pre-intervention status (10.26 ± 4.33 and 42.26 ± 14.9, respectively, p < 0.000). The mean follow-up of patients with CLAI was 17.94 ± 3.25 weeks. This study represents successful short-term functional and clinical outcomes in patients with CLAI after PRP treatment, with no adverse effects. It demonstrates the feasibility of a randomized controlled trial to further assess this therapy.
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Affiliation(s)
- Ivan Medina-Porqueres
- Department of Physical Therapy, Faculty of Health Sciences, University of Malaga, 29071 Malaga, Spain;
- Medical Services, Malaga Football Club, 29011 Malaga, Spain;
| | - Pablo Martin-Garcia
- Onco-Hematology Unit, University Hospital Virgen de la Victoria, 29010 Malaga, Spain;
| | | | | | - Francisco Moya-Torrecilla
- Department of Physical Therapy, Faculty of Health Sciences, University of Malaga, 29071 Malaga, Spain;
- Vithas Xanit International Hospital, 29630 Benalmadena, Spain;
| | | | | | - Abel Gomez-Caceres
- Department of Physical Therapy, Faculty of Health Sciences, University of Malaga, 29071 Malaga, Spain;
- Medical Services, Malaga Football Club, 29011 Malaga, Spain;
- HM Hospitals, 29010 Malaga, Spain;
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32
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Marín Fermín T, Calcei JG, Della Vedova F, Martinez Cano JP, Arias Calderon C, Imam MA, Khoury M, Laupheimer MW, D'Hooghe P. Review of Dohan Eherenfest et al. (2009) on "Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)". J ISAKOS 2024; 9:215-220. [PMID: 37562572 DOI: 10.1016/j.jisako.2023.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 06/28/2023] [Accepted: 07/27/2023] [Indexed: 08/12/2023]
Abstract
This classic discusses the original publication of Dohan Eherenfest et al. on "Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)", in which the authors propose four categories of platelet concentrates depending on their leucocyte and fibrin content (P-PRP, leucocyte- and platelet-rich plasma (L-PRP), pure platelet-rich fibrin (P-PRF), and L-PRF) to group a "jungle" of products in which the term platelet-rich plasma (PRP) was used indistinctly. They were able to identify common factors such as: (1) the use of anticoagulants and immediate centrifugation of the blood after its collection; (2) most preparation techniques allowed platelet concentrate preparation within an hour; (3) the centrifugation aimed to separate the blood in layers that would allow the extraction of specific fractions; and (4) the product was activated with thrombin or calcium chloride. The reviewed manuscript has been listed among the most cited PRP articles in regenerative medicine, with more than 800 citations, driving current scientific research and clinical practise by categorising L-PRP and P-PRP (now, leucocyte-poor PRP). The classification has also opened the door to understanding intrinsic biological mechanisms between platelets, leukocytes, fibrin, and growth factors, which will later be considered for studying the proliferation and differentiation of cells in different tissues affected by PRP. Since the initial classification of platelet concentrates, several other classification systems have been proposed and published in the current literature such as platelet, activation, white blood cell (PAW), Mishra, platelet, leucocyte, red blood cells, and activation (PLRA), dose of platelet, efficiency, purity, and activation (DEPA), method, activation, red blood cells, spin, platelets, image guidance, leukocytes, and light activation (MARSPILL), etc. These classifications have identified important aspects of PRP that affect the biological composition and, ultimately, the indications and outcomes. To date, there is still a lack of standardisation in sample preparation, cohort heterogeneity, and incomplete reporting of sample preparation utilised, leading to a lack of clarity and challenging researchers and clinicians.
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Affiliation(s)
- Theodorakys Marín Fermín
- Centro Médico Profesional Las Mercedes, Las Mercedes 1060, Caracas, Venezuela; Aspetar Orthopaedic and Sports Medicine Hospital, Sports City Street, Inside Aspire Zone, Al Buwairda St, 29222, Doha, Qatar.
| | - Jacob G Calcei
- University Hospitals Drusinsky Sports Medicine Institute, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA
| | | | | | - Claudia Arias Calderon
- Department of Trauma and Orthopedic Surgery, Hospital Nacional Edgardo Rebagliati Martins, Jesús María 15072, Peru
| | - Mohamed A Imam
- Smart Health Centre, University of East London, London E16 2RD, UK; Rowley Bristow Orthopaedic Unit, Ashford and St Peter's Hospital, Ashford TW15 3AA, UK
| | - Miguel Khoury
- Aspetar Orthopaedic and Sports Medicine Hospital, Sports City Street, Inside Aspire Zone, Al Buwairda St, 29222, Doha, Qatar
| | - Markus W Laupheimer
- Aspetar Orthopaedic and Sports Medicine Hospital, Sports City Street, Inside Aspire Zone, Al Buwairda St, 29222, Doha, Qatar
| | - Pieter D'Hooghe
- Aspetar Orthopaedic and Sports Medicine Hospital, Sports City Street, Inside Aspire Zone, Al Buwairda St, 29222, Doha, Qatar
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Zugail AS, Alshuaibi M, Lombion S, Beley S. Safety and feasibility of percutaneous needle tunneling with platelet-rich plasma injections for Peyronie's disease in the outpatient setting: a pilot study. Int J Impot Res 2024; 36:140-145. [PMID: 37550385 DOI: 10.1038/s41443-023-00744-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 08/09/2023]
Abstract
The objective of this study is to evaluate the safety and feasibility of the combined simultaneous percutaneous needle tunneling coupled with injection of platelet-rich plasma in the outpatient department for the treatment of Peyronie's disease. This prospective, non-randomized, cohort and preliminary study included patients who underwent this procedure from November 2020 to July 2022. The main outcome was an improvement in penile curvature. Fifty-four patients were enrolled and underwent 6 sessions under local anesthesia followed by vacuum therapy for the treatment of Peyronie's disease in our outpatient unit. The amendment of the curvature angle was significant with a median correction percentage of -44.40% interquartile range (-66.70 to (-39.70)), [p-value = 0.001, 95% CI (-29.76 to (-18.02)), paired Student's t-test]. The median pre-treatment curvature angle was 45° (40-75), and the median post-treatment was 30° (20-40). The median score for pain during the procedure was 3 (0-4.25) according to a 10-point visual analogic scale. After two hours, 20.37% of patients still had pain but none required any pain medication. 50% of patients had a minor hematoma and 75.93% patients reported penile ecchymosis. A single patient reported an injection site skin infection. In our experience percutaneous needle tunneling with platelet-rich plasma injections for Peyronie's disease in the outpatient setting is a safe, effective, and feasible treatment of penile deformity for PD.
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Affiliation(s)
- Ahmed S Zugail
- Department of Urology, Clinique Turin, Groupe Almaviva Santé, Paris, France.
- Urology Division, Department of Surgery, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
| | - Muaath Alshuaibi
- Department of Urology, Clinique Turin, Groupe Almaviva Santé, Paris, France
- Department of Urology, Faculty of Medicine, University of Ha'il, Ha'il, Saudi Arabia
| | | | - Sébastien Beley
- Department of Urology, Clinique Turin, Groupe Almaviva Santé, Paris, France
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Anitua E, Pino A, Prado R, Muruzabal F, Alkhraisat MH. Biochemical and biomechanical characterization of an autologous protein-based fibrin sealant for regenerative medicine. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2024; 35:15. [PMID: 38456966 PMCID: PMC10923958 DOI: 10.1007/s10856-024-06780-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 01/10/2024] [Indexed: 03/09/2024]
Abstract
Accidental events or surgical procedures usually lead to tissue injury. Fibrin sealants have proven to optimize the healing process but have some drawbacks due to their allogeneic nature. Autologous fibrin sealants present several advantages. The aim of this study is to evaluate the performance of a new autologous fibrin sealant based on Endoret®PRGF® technology (E-sealant). One of the most widely used commercial fibrin sealants (Tisseel®) was included as comparative Control. E-sealant´s hematological and biological properties were characterized. The coagulation kinetics and the microstructure were compared. Their rheological profile and biomechanical behavior were also recorded. Finally, the swelling/shrinkage capacity and the enzymatic degradation of adhesives were determined. E-sealant presented a moderate platelet concentration and physiological levels of fibrinogen and thrombin. It clotted 30 s after activation. The microstructure of E-sealant showed a homogeneous fibrillar scaffold with numerous and scattered platelet aggregates. In contrast, Control presented absence of blood cells and amorphous protein deposits. Although in different order of magnitude, both adhesives had similar rheological profiles and viscoelasticity. Control showed a higher hardness but both adhesives presented a pseudoplastic hydrogel nature with a shear thinning behavior. Regarding their adhesiveness, E-sealant presented a higher tensile strength before cohesive failure but their elastic stretching capacity and maximum elongation was similar. While E-sealant presented a significant shrinkage process, Control showed a slight swelling over time. In addition, E-sealant presented a high enzymatic resorption rate, while Control showed to withstand the biodegradation process in a significant way. E-sealant presents optimal biochemical and biomechanical properties suitable for its use as a fibrin sealant with regenerative purposes.
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Affiliation(s)
- Eduardo Anitua
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain.
- BTI-Biotechnology Institute, Vitoria, Spain.
| | - Ander Pino
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain
- BTI-Biotechnology Institute, Vitoria, Spain
| | - Roberto Prado
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain
- BTI-Biotechnology Institute, Vitoria, Spain
| | - Francisco Muruzabal
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain
- BTI-Biotechnology Institute, Vitoria, Spain
| | - Mohammad Hamdan Alkhraisat
- University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain
- BTI-Biotechnology Institute, Vitoria, Spain
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Homma Y, Uchino S, Nagao M, Wakayama T, Fukusato S, Baba T, Watari T, Hayashi K, Saita Y, Ishijima M. Safety and feasibility of locoregional platelet-rich plasma injection for iliopsoas impingement after total hip arthroplasty: A phase 1 prospective observational study. Regen Ther 2024; 25:61-67. [PMID: 38077288 PMCID: PMC10697848 DOI: 10.1016/j.reth.2023.11.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/30/2023] [Accepted: 11/22/2023] [Indexed: 01/27/2025] Open
Abstract
INTRODUCTION Although numerous studies have reported outcomes with various conservative approaches for the iliopsoas impingement after total hip arthroplasty (THA), reports on the use of locoregional autologous platelet rich plasma (PRP) injections for the iliopsoas impingement after THA are lacking. This phase 1 study therefore aimed to investigate the safety and feasibility of locoregional PRP injection for iliopsoas impingement after THA. MATERIALS AND METHODS Patients diagnosed with iliopsoas impingement after THA who met the criteria for participation (symptoms persisting for more than 3 months, aged 20 years or older, and unable to receive non-steroidal analgesic or anti-inflammatory drugs) were eligible to participate in this clinical study. The primary endpoint was observed adverse events including procedure-related pain, and the secondary endpoints included pain and functionality of the hip joint, that were assessed using the Western Ontario and McMaster Universities Arthritis Index, Japanese Hip Disease Evaluation Questionnaire, and Forgotten Joint Score-12. RESULTS Three patients were screened for eligibility, and 3 patients were finally included in this study. Two participants (patients 1 and 2; aged 66 and 65 years, respectively) were female. The third participant (patient 3; age 73 years) was male. All patients experienced adverse events; however, none were found to be serious. None of the patients experienced any infections, or intra- or post-operative symptoms of nerve damage, or subcutaneous haemorrhage owing to the administration of locoregional PRP. Although patient 2 showed almost complete resolution of the symptom, patient 1 and 3 demonstrated persistent groin pain after the injection. CONCLUSION We demonstrated the results of preliminary phase 1 prospective observational clinical study that administration of locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.
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Affiliation(s)
- Yasuhiro Homma
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
- Medical Technology Innovation Center, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Sayuri Uchino
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Masashi Nagao
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
- Medical Technology Innovation Center, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Takanori Wakayama
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Shin Fukusato
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Tomonori Baba
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Taiji Watari
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Koju Hayashi
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Yoshitomo Saita
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Muneaki Ishijima
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopaedic, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
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Shivaramu S, Maiti SK, Banu SA, Kalaiselvan E, Sharun K, Mishra M, Mohan D, Palakkara S, Kumar S, Sahoo M, Hescheler J. Synergistic Hepatoprotective Effects of Mesenchymal Stem Cells and Platelet-Rich Plasma in a Rat Model of Bile Duct Ligation-Induced Liver Cirrhosis. Cells 2024; 13:404. [PMID: 38474368 PMCID: PMC10931218 DOI: 10.3390/cells13050404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/10/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open
Abstract
Liver cirrhosis poses a global health challenge marked by significant prevalence and mortality. Current therapeutic options are limited by high costs and immune-mediated rejection, necessitating the exploration of innovative strategies to enhance hepatic self-rehabilitation, and counteract the underlying pathological mechanisms. We evaluated the hepatoprotective activity of rat adipose-derived mesenchymal stem cells (ADMSCs) in combination with platelet-rich plasma (PRP) and recombinant human hepatocyte growth factor (rh-HGF) on a rat model of liver fibrosis/cirrhosis induced by bile duct ligation (BDL). Treatment with PRP or rh-HGF alone did not yield significant hepatoprotection in the BDL-induced liver cirrhosis model. However, ADMSC transplantation alone exhibited the potential to alleviate impaired liver conditions. The combination of PRP and rh-HGF demonstrated superior ameliorative effects compared to either treatment alone. Notably, the combination of ADMSC + PRP or ADMSC + rh-HGF significantly enhanced hepatoprotective capacity compared to individual or combined PRP and rh-HGF therapies. Injection of ADMSC via the tail vein reduced inflammation, hepatocyte damage, and collagen deposition, improving overall liver function. This improvement was more pronounced when ADMSC was administered with PRP and rh-HGF versus monotherapy. Our study concludes that ADMSCs exert antifibrotic effects by inhibiting hepatic stellate cell proliferation, collagen synthesis, and inducing apoptosis. ADMSCs also demonstrate immune-modulatory effects and transdifferentiate into hepatic progenitor cells, secreting trophic factors, cytokines, and chemokines that promote impaired liver regeneration. The observed arrest in liver fibrosis progression highlights the potential therapeutic impact of these interventions.
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Affiliation(s)
- Shivaraju Shivaramu
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Swapan Kumar Maiti
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Shajahan Amitha Banu
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Elangovan Kalaiselvan
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Khan Sharun
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
- Graduate Institute of Medicine, Yuan Ze University, Taoyuan 32003, Taiwan
| | - Mamta Mishra
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Divya Mohan
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Sangeetha Palakkara
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Sunil Kumar
- Division of Extension Education, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India;
| | - Monalisa Sahoo
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India;
| | - Jürgen Hescheler
- Institute of Neurophysiology, University of Cologne, 50931 Cologne, Germany;
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Grzelak A, Hnydka A, Higuchi J, Michalak A, Tarczynska M, Gaweda K, Klimek K. Recent Achievements in the Development of Biomaterials Improved with Platelet Concentrates for Soft and Hard Tissue Engineering Applications. Int J Mol Sci 2024; 25:1525. [PMID: 38338805 PMCID: PMC10855389 DOI: 10.3390/ijms25031525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/19/2024] [Accepted: 01/23/2024] [Indexed: 02/12/2024] Open
Abstract
Platelet concentrates such as platelet-rich plasma, platelet-rich fibrin or concentrated growth factors are cost-effective autologous preparations containing various growth factors, including platelet-derived growth factor, transforming growth factor β, insulin-like growth factor 1 and vascular endothelial growth factor. For this reason, they are often used in regenerative medicine to treat wounds, nerve damage as well as cartilage and bone defects. Unfortunately, after administration, these preparations release growth factors very quickly, which lose their activity rapidly. As a consequence, this results in the need to repeat the therapy, which is associated with additional pain and discomfort for the patient. Recent research shows that combining platelet concentrates with biomaterials overcomes this problem because growth factors are released in a more sustainable manner. Moreover, this concept fits into the latest trends in tissue engineering, which include biomaterials, bioactive factors and cells. Therefore, this review presents the latest literature reports on the properties of biomaterials enriched with platelet concentrates for applications in skin, nerve, cartilage and bone tissue engineering.
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Affiliation(s)
- Agnieszka Grzelak
- Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki Street 1, 20-093 Lublin, Poland; (A.G.); (A.H.)
| | - Aleksandra Hnydka
- Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki Street 1, 20-093 Lublin, Poland; (A.G.); (A.H.)
| | - Julia Higuchi
- Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Prymasa Tysiaclecia Avenue 98, 01-142 Warsaw, Poland;
| | - Agnieszka Michalak
- Independent Laboratory of Behavioral Studies, Medical University of Lublin, Chodzki 4 a Street, 20-093 Lublin, Poland;
| | - Marta Tarczynska
- Department and Clinic of Orthopaedics and Traumatology, Medical University of Lublin, Jaczewskiego 8 Street, 20-090 Lublin, Poland; (M.T.); (K.G.)
- Arthros Medical Centre, Chodzki 31 Street, 20-093 Lublin, Poland
| | - Krzysztof Gaweda
- Department and Clinic of Orthopaedics and Traumatology, Medical University of Lublin, Jaczewskiego 8 Street, 20-090 Lublin, Poland; (M.T.); (K.G.)
- Arthros Medical Centre, Chodzki 31 Street, 20-093 Lublin, Poland
| | - Katarzyna Klimek
- Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki Street 1, 20-093 Lublin, Poland; (A.G.); (A.H.)
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Bacevich BM, Smith RDJ, Reihl AM, Mazzocca AD, Hutchinson ID. Advances with Platelet-Rich Plasma for Bone Healing. Biologics 2024; 18:29-59. [PMID: 38299120 PMCID: PMC10827634 DOI: 10.2147/btt.s290341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 01/17/2024] [Indexed: 02/02/2024]
Abstract
Despite significant advances in the understanding and delivery of osteosynthesis, fracture non-union remains a challenging clinical problem in orthopaedic surgery. To bridge the gap, basic science characterization of fracture healing provides a platform to identify and target biological strategies to enhance fracture healing. Of immense interest, Platelet-rich plasma (PRP) is a point of care orthobiologic that has been extensively studied in bone and soft tissue healing given its relative ease of translation from the benchtop to the clinic. The aim of this narrative review is to describe and relate pre-clinical in-vitro and in-vivo findings to clinical observations investigating the efficacy of PRP to enhance bone healing for primary fracture management and non-union treatment. A particular emphasis is placed on the heterogeneity of PRP preparation techniques, composition, activation strategies, and delivery. In the context of existing data, the routine use of PRP to enhance primary fracture healing and non-union management cannot be supported. However, it is acknowledged that extensive heterogeneity of PRP treatments in clinical studies adds obscurity; ultimately, refinement (and consensus) of PRP treatments for specific clinical indications, including repetition studies are warranted.
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Affiliation(s)
- Blake M Bacevich
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
| | - Richard David James Smith
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
| | - Alec M Reihl
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
| | - Augustus D Mazzocca
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
- Medical Director, Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Brigham, Boston, MA, USA
| | - Ian D Hutchinson
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
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Nelson PA, George T, Bowen E, Sheean AJ, Bedi A. An Update on Orthobiologics: Cautious Optimism. Am J Sports Med 2024; 52:242-257. [PMID: 38164688 DOI: 10.1177/03635465231192473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
Orthobiologics are rapidly growing in use given their potential to augment healing for multiple musculoskeletal conditions. Orthobiologics consist of a variety of treatments including platelet-rich plasma and stem cells that provide conceptual appeal in providing local delivery of growth factors and inflammation modulation. The lack of standardization in nomenclature and applications within the literature has led to a paucity of high-quality evidence to support their frequent use. The purpose of this review was to describe the current landscape of orthobiologics and the most recent evidence regarding their use.
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Affiliation(s)
- Patrick A Nelson
- University of Chicago Department of Orthopedic Surgery, Chicago, Illinois, USA
| | - Tom George
- Northshore University Healthcare System, Evanston, Illinois, USA
| | - Edward Bowen
- Weill Cornell Medicine, New York City, New York, USA
| | - Andrew J Sheean
- San Antonio Military Medical Center, Department of Orthopedic Surgery, San Antonio, Texas, USA
| | - Asheesh Bedi
- Northshore University Healthcare System, Evanston, Illinois, USA
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Morris SC, Haselman WT, Banffy MB. Patient Outcomes Are Not Improved by Platelet-Rich Plasma Injection Onto the Capsule at the Time of Closure During Hip Arthroscopy for Femoroacetabular Impingement Syndrome. Arthrosc Sports Med Rehabil 2023; 5:100816. [PMID: 38034028 PMCID: PMC10685153 DOI: 10.1016/j.asmr.2023.100816] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 09/28/2023] [Indexed: 12/02/2023] Open
Abstract
Purpose To determine the effect of platelet-rich plasma (PRP) injection onto the capsule at time of closure on outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement syndrome. Methods Patients who underwent hip arthroscopy between January 2014 and December 2021 were retrospectively identified. The first cohort included patients who received PRP injection onto the capsule following capsular closure at the conclusion of the case. The second cohort did not receive PRP. Pain scores on a visual analog scale, Modified Harris Hip Scores, Single Assessment Numeric Evaluation (SANE), as well as Patient-Reported Outcomes Measurement Information System Physical Function scores were obtained preoperatively as well as at multiple time points postoperatively up to 2 years. Results In total, 345 patients were included in the study, with 293 in the PRP cohort and 52 in the non-PRP cohort. There was no significance difference in age (P = .69), sex, or preoperative pain (P = .92) and patient-reported outcome scores between the 2 groups (modified Harris Hip Score, P = .38; Patient-Reported Outcomes Measurement Information System Physical Function, P = .48), except for preoperative SANE scores, which had a greater baseline in the PRP group (P < .001). Using both observed data as well as repeated measure analysis of variance model to estimate for missing data after baseline, we found there were no differences in visual analog scale pain scores nor patient-reported outcome scores at any time point. There was similarly no difference in change from baseline for SANE scores. There was no difference in rate of revision surgery between the 2 cohorts (P = .66). Conclusions Based on the results of this study, intraoperative PRP injection onto the capsule at the time of capsular closure does not improve outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement syndrome. Level of Evidence Level III, retrospective comparative study.
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Affiliation(s)
- S. Craig Morris
- Cedars-Sinai Kerlan-Jobe Institute, Los Angeles, California, U.S.A
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George T, Curley AJ, Saeed SK, Kuhns BD, Parsa A, Domb BG. Orthobiologics as an adjunct in treatment of femoroacetabular impingement syndrome: cell-based therapies facilitate improved postoperative outcomes in the setting of acetabular chondral lesions-a systematic review. Knee Surg Sports Traumatol Arthrosc 2023; 31:6020-6038. [PMID: 37906291 DOI: 10.1007/s00167-023-07624-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 10/09/2023] [Indexed: 11/02/2023]
Abstract
PURPOSE To evaluate studies utilizing orthobiologics in the management of femoroacetabular impingement syndrome (FAIS) to (1) assess the indications for usage, and (2) analyze patient-reported outcome measures (PROM) following treatment. It was hypothesized that orthobiologics would (1) be utilized for symptomatic FAIS in the setting of labral or chondral pathology, and (2) improve PROM at most recent follow-up. METHODS The Pubmed, Ovid Medline, Cochrane, and Web of Science databases were searched for clinical studies evaluating orthobiologics [hyaluronic acid (HA), platelet-rich plasma (PRP), or cell-based therapy (CBT) for treatment of FAIS. Exclusion criteria included orthobiologics used in conjunction with cartilage transfer or scaffolding procedures and a primary indication other than FAIS. Data collection included patient demographics, indications, and baseline and most recent PROM. RESULTS Eleven studies (one level I, four level II, four level III, and two level IV evidence) met inclusion criteria, consisting of 440 patients with mean ages ranging from 32.8 to 47 years. All 11 studies demonstrated an improvement in PROM from baseline to most-recent follow-up. Four studies administered PRP either intraoperatively or the day after surgery as an adjunct to labral repair. CBT was used intraoperatively in the setting of acetabular chondral lesions (three studies) and labral repair (one study). When comparing to a control group at most recent follow-up, three PRP cohorts demonstrated similar PROM (n.s.), while one PRP group exhibited worse visual analog pain scores (2.5 vs. 3.4, p = 0.005) and modified Harris Hip Scores (mHHS) (82.6 vs. 78.7, p = 0.049). The four CBT studies reported favorable results compared to a control group, with a significantly higher mHHS at most recent follow-up or mean improvement from baseline in Hip Outcome Score-Activities of Daily Living (p < 0.05). Three studies reported on HA, which was utilized exclusively in the nonoperative setting. CONCLUSIONS Intraoperative PRP and CBT have been commonly reported in the setting of hip arthroscopy for labral repairs and acetabular chondral lesions, respectively. The CBT cohorts demonstrated more favorable PROM at most recent follow-up when compared to a control group, though these results should be interpreted with caution due to heterogeneity of orthobiologic preparations. LEVEL OF EVIDENCE IV.
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Affiliation(s)
- Tracy George
- American Hip Institute Research Foundation, Chicago, IL, 60018, USA
| | - Andrew J Curley
- American Hip Institute Research Foundation, Chicago, IL, 60018, USA
| | - Sheema K Saeed
- American Hip Institute Research Foundation, Chicago, IL, 60018, USA
| | - Benjamin D Kuhns
- American Hip Institute Research Foundation, Chicago, IL, 60018, USA
| | - Ali Parsa
- American Hip Institute Research Foundation, Chicago, IL, 60018, USA
| | - Benjamin G Domb
- American Hip Institute Research Foundation, Chicago, IL, 60018, USA.
- American Hip Institute, Chicago, IL, 60018, USA.
- , 999 E Touhy Ave, Suite 450, Des Plaines, IL, 60018, USA.
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Mamarelis G, Lo I. In RC Tendinopathy, Intratendinous Injections of PRGF Versus Corticosteroids Improved Shoulder Pain and Function at 6 and 12 Months. J Bone Joint Surg Am 2023; 105:1814. [PMID: 37683052 DOI: 10.2106/jbjs.23.00887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/10/2023]
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Harrison TE, Bowler J, Cheng CI, Reeves KD. Optimizing Platelet-Rich Plasma: Spin Time and Sample Source. Bioengineering (Basel) 2023; 10:1270. [PMID: 38002394 PMCID: PMC10669393 DOI: 10.3390/bioengineering10111270] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 10/25/2023] [Accepted: 10/28/2023] [Indexed: 11/26/2023] Open
Abstract
The buff-colored layer separating the plasma from red blood cells (RBCs) in centrifuged blood was named the "buffy coat" in the late 19th century. The division of platelets (PLTs) and leukocytes (WBCs) between the buffy coat, plasma, and RBC layers in centrifuged blood has not been described before. In this study, we centrifuged 8.5 mL anticoagulated blood samples at 1000× g for 1, 2, 3, 5, 10, and 20 min. We then divided each sample into ten layers and analyzed each layer for cellular composition and mean platelet volume (MPV). Our results show that even after 20 min of centrifugation, about 15% of platelets remain in the plasma layers and 65% in the RBC layers. We found that the platelet count achieved from aspiration of 1 mL volume was optimal, with aspiration beginning 1/2 mL below the buffy coat and extending 1/2 mL above the buffy coat rather than beginning at the buffy coat itself and aspirating only plasma. Using this method of aspiration, we found that the total platelet count means reached a maximum in the 1 mL around the buffy coat after only 5 min of centrifugation.
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Affiliation(s)
| | | | - Chin-I Cheng
- Department of Statistics, Actuarial and Data Science, Central Michigan University, Mt. Pleasant, MI 48859, USA;
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Rossi LA, Piuzzi N, Tanoira I, Brandariz R, Huespe I, Ranalletta M. Subacromial Platelet-Rich Plasma Injections Produce Significantly Worse Improvement in Functional Outcomes in Patients With Partial Supraspinatus Tears Than in Patients With Isolated Tendinopathy. Arthroscopy 2023; 39:2000-2008. [PMID: 37001744 DOI: 10.1016/j.arthro.2023.03.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 03/05/2023] [Accepted: 03/09/2023] [Indexed: 04/23/2023]
Abstract
PURPOSE To compare the effect of subacromial leukocyte-rich platelet-rich plasma (PRP) injections in patients with isolated rotator cuff tendinopathy (RCT) and those with partial-thickness rotator cuff tears (PTRCTs) based on functional outcomes, pain improvement, sleep disturbances, and return to sports. METHODS Between November 2019 and March 2021, 150 patients underwent PRP injections at our institution for refractory rotator cuff tendinopathy and partial rotator cuff tears (105 RCTs and 45 PTRCTs). The American Shoulder and Elbow Surgeons (ASES) score, the visual analog scale (VAS) for pain, the Single Assessment Numeric Evaluation (SANE) and The Pittsburgh Sleep Quality Index were evaluated at 2-, 6-, and 12-month follow-up. Return to sports was also evaluated. An ultrasound examination was performed to evaluate structural outcomes 12 months after the injection. RESULTS The mean age was 36.6 years (±9.08). Overall, the ASES, VAS, SANE, and Pittsburgh scores showed statistical improvement after the injection (P < .01). Specifically, the improvement in the ASES score, which was the primary outcome measure was significantly greater in the group without tears than in the group with PTRCTs at all follow-up times. Moreover, 94% of the patients in the isolated RCT group and 49% in the PTRCTs group achieved a substantial clinical benefit at 12 months follow-up. Ten out of the 50 patients (20%) who received PRP injections due to a partial RC tear underwent surgery due to the lack of clinical improvement. CONCLUSIONS Subacromial PRP injections produced a significant improvement in shoulder function, pain, and sleep disturbances in most patients with RCT refractory to conservative treatment that was maintained at the 12-month follow-up. Moreover, most patients returned to sports at the same level prior to injury. However, improvement in symptoms and functional outcomes was significantly worse in patients who had a PTRCT compared with patients who had an isolated tendinopathy. LEVEL OF EVIDENCE Level II, prospective cohort study.
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Affiliation(s)
- Luciano A Rossi
- Department of Orthopedics and Traumatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
| | - Nicolás Piuzzi
- Department of Orthopedics and Traumatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Ignacio Tanoira
- Department of Orthopedics and Traumatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Rodrigo Brandariz
- Department of Orthopedics and Traumatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Ivan Huespe
- Department of Internal Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Maximiliano Ranalletta
- Department of Orthopedics and Traumatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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Tognoloni A, Bartolini D, Pepe M, Di Meo A, Porcellato I, Guidoni K, Galli F, Chiaradia E. Platelets Rich Plasma Increases Antioxidant Defenses of Tenocytes via Nrf2 Signal Pathway. Int J Mol Sci 2023; 24:13299. [PMID: 37686103 PMCID: PMC10488198 DOI: 10.3390/ijms241713299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/21/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Tendinopathies are common disabling conditions in equine and human athletes. The etiology is still unclear, although reactive oxygen species (ROS) and oxidative stress (OS) seem to play a crucial role. In addition, OS has been implicated in the failure of tendon lesion repair. Platelet-rich plasma (PRP) is rich in growth factors that promote tissue regeneration. This is a promising therapeutic approach in tendon injury. Moreover, growing evidence has been attributed to PRP antioxidant effects that can sustain tissue healing. In this study, the potential antioxidant effects of PRP in tenocytes exposed to oxidative stress were investigated. The results demonstrated that PRP reduces protein and lipid oxidative damage and protects tenocytes from OS-induced cell death. The results also showed that PRP was able to increase nuclear levels of redox-dependent transcription factor Nrf2 and to induce some antioxidant/phase II detoxifying enzymes (superoxide dismutase 2, catalase, heme oxygenase 1, NAD(P)H oxidoreductase quinone-1, glutamate cysteine ligase catalytic subunit and glutathione, S-transferase). Moreover, PRP also increased the enzymatic activity of catalase and glutathione S-transferase. In conclusion, this study suggests that PRP could activate various cellular signaling pathways, including the Nrf2 pathway, for the restoration of tenocyte homeostasis and to promote tendon regeneration and repair following tendon injuries.
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Affiliation(s)
- Alessia Tognoloni
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.T.); (M.P.); (A.D.M.); (I.P.); (K.G.)
| | - Desiree Bartolini
- Department of Pharmaceutical Sciences, University of Perugia, 06122 Perugia, Italy; (D.B.); (F.G.)
| | - Marco Pepe
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.T.); (M.P.); (A.D.M.); (I.P.); (K.G.)
| | - Antonio Di Meo
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.T.); (M.P.); (A.D.M.); (I.P.); (K.G.)
| | - Ilaria Porcellato
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.T.); (M.P.); (A.D.M.); (I.P.); (K.G.)
| | - Kubra Guidoni
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.T.); (M.P.); (A.D.M.); (I.P.); (K.G.)
| | - Francesco Galli
- Department of Pharmaceutical Sciences, University of Perugia, 06122 Perugia, Italy; (D.B.); (F.G.)
| | - Elisabetta Chiaradia
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.T.); (M.P.); (A.D.M.); (I.P.); (K.G.)
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Anitua E, Troya M, Falcon-Pérez JM, López-Sarrio S, González E, Alkhraisat MH. Advances in Platelet Rich Plasma-Derived Extracellular Vesicles for Regenerative Medicine: A Systematic-Narrative Review. Int J Mol Sci 2023; 24:13043. [PMID: 37685849 PMCID: PMC10488108 DOI: 10.3390/ijms241713043] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 08/17/2023] [Accepted: 08/18/2023] [Indexed: 09/10/2023] Open
Abstract
The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines, chemokines, and other biological biomolecules. In recent years, developments in the field of platelets have led to new insights, and attention has been focused on the platelets' released extracellular vesicles (EVs) and their role in intercellular communication. In this context, the aim of this review was to compile the current evidence on PRP-derived extracellular vesicles to identify the advantages and limitations fortheir use in the upcoming clinical applications. A total of 172 articles were identified during the systematic literature search through two databases (PubMed and Web of Science). Twenty publications met the inclusion criteria and were included in this review. According to the results, the use of PRP-EVs in the clinic is an emerging field of great interest that represents a promising therapeutic option, as their efficacy has been demonstrated in the majority of fields of applications included in this review. However, the lack of standardization along the procedures in both the field of PRP and the EVs makes it extremely challenging to compare results among studies. Establishing standardized conditions to ensure optimized and detailed protocols and define parameters such as the dose or the EV origin is therefore urgent. Further studies to elucidate the real contribution of EVs to PRP in terms of composition and functionality should also be performed. Nevertheless, research on the field provides promising results and a novel basis to deal with the regenerative medicine and drug delivery fields in the future.
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Affiliation(s)
- Eduardo Anitua
- BTI-Biotechnology Institute, 01007 Vitoria-Gasteiz, Spain; (M.T.); (M.H.A.)
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), 01007 Vitoria-Gasteiz, Spain
| | - María Troya
- BTI-Biotechnology Institute, 01007 Vitoria-Gasteiz, Spain; (M.T.); (M.H.A.)
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), 01007 Vitoria-Gasteiz, Spain
| | - Juan Manuel Falcon-Pérez
- Exosomes Laboratory, Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, 48160 Derio, Spain; (J.M.F.-P.); (S.L.-S.); (E.G.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas, 28029 Madrid, Spain
- Metabolomics Platform, Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, 48160 Derio, Spain
- IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain
| | - Silvia López-Sarrio
- Exosomes Laboratory, Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, 48160 Derio, Spain; (J.M.F.-P.); (S.L.-S.); (E.G.)
| | - Esperanza González
- Exosomes Laboratory, Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, 48160 Derio, Spain; (J.M.F.-P.); (S.L.-S.); (E.G.)
| | - Mohammad H. Alkhraisat
- BTI-Biotechnology Institute, 01007 Vitoria-Gasteiz, Spain; (M.T.); (M.H.A.)
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), 01007 Vitoria-Gasteiz, Spain
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Vun J, Iqbal N, Jones E, Ganguly P. Anti-Aging Potential of Platelet Rich Plasma (PRP): Evidence from Osteoarthritis (OA) and Applications in Senescence and Inflammaging. Bioengineering (Basel) 2023; 10:987. [PMID: 37627872 PMCID: PMC10451843 DOI: 10.3390/bioengineering10080987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/21/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Aging and age-related changes impact the quality of life (QOL) in elderly with a decline in movement, cognitive abilities and increased vulnerability towards age-related diseases (ARDs). One of the key contributing factors is cellular senescence, which is triggered majorly by DNA damage response (DDR). Accumulated senescent cells (SCs) release senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines, matrix metalloproteinases (MMPs), lipids and chemokines that are detrimental to the surrounding tissues. Chronic low-grade inflammation in the elderly or inflammaging is also associated with cellular senescence and contributes to ARDs. The literature from the last decade has recorded the use of platelet rich plasma (PRP) to combat senescence and inflammation, alleviate pain as an analgesic, promote tissue regeneration and repair via angiogenesis-all of which are essential in anti-aging and tissue regeneration strategies. In the last few decades, platelet-rich plasma (PRP) has been used as an anti-aging treatment option for dermatological applications and with great interest in tissue regeneration for orthopaedic applications, especially in osteoarthritis (OA). In this exploration, we connect the intricate relationship between aging, ARDs, senescence and inflammation and delve into PRP's properties and potential benefits. We conduct a comparative review of the current literature on PRP treatment strategies, paying particular attention to the instances strongly linked to ARDs. Finally, upon careful consideration of this interconnected information in the context of aging, we suggest a prospective role for PRP in developing anti-aging therapeutic strategies.
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Affiliation(s)
- James Vun
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS9 7TF, UK; (J.V.); (E.J.)
- Leeds Orthopaedic & Trauma Sciences, Leeds General Infirmary, University of Leeds, Leeds LS97TF, UK
| | - Neelam Iqbal
- School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK;
| | - Elena Jones
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS9 7TF, UK; (J.V.); (E.J.)
| | - Payal Ganguly
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS9 7TF, UK; (J.V.); (E.J.)
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Palagiano P, Graziano L, Scarabello W, Berni P, Andreoli V, Grolli S. Platelet- Rich Plasma Treatment Supported by Ultrasound Detection of Septa in Recurrent Canine Aural Hematoma: A Case Series. Animals (Basel) 2023; 13:2456. [PMID: 37570265 PMCID: PMC10417061 DOI: 10.3390/ani13152456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Aural hematoma is a common pathological condition in veterinary practice with a high incidence rate in dogs. Drainage, corticosteroid injections, and surgical approaches represent the common treatments in these clinical cases. However, surgery leaves visible signs and is usually correlated with recurrence, scars, and deformation of the treated pinna. For this reason, more effective and less invasive methods have been proposed over the years. Platelet-Rich Plasma (PRP) is one of the most promising options due to its pro-regenerative properties and capability to modulate the inflammatory state. The present work reports 12 cases of canine aural hematoma treated with PRP. The PRP treatment was combined with an ultrasound evaluation of the pinna to detect and treat all involved septa. The results show that relatively large volumes (2 mL) of PRP associated with an ultrasound guide are safe and efficacious in the treatment of canine aural hematoma requiring a maximum of two infiltrations, both in acute and chronic conditions. All the patients recovered their normal ear thickness (compared with the controlateral one) without relapses, averaging 38.5 days from their first treatment (10-90 days; SD: 24.7). The key role of PRP combined with a tailored diagnosis process carried out by the veterinarian, which included using an ultrasound system and the proper bandage, suggests that this approach may represent a valid alternative to surgery and corticosteroids.
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Affiliation(s)
| | - Lisa Graziano
- Clinica Veterinaria Meda, 20821 Meda, Italy; (P.P.); (L.G.)
| | | | - Priscilla Berni
- Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma, 43126 Parma, Italy; (P.B.); (S.G.)
| | - Valentina Andreoli
- Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma, 43126 Parma, Italy; (P.B.); (S.G.)
| | - Stefano Grolli
- Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma, 43126 Parma, Italy; (P.B.); (S.G.)
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Lu J, Li H, Zhang Z, Xu R, Wang J, Jin H. Platelet-rich plasma in the pathologic processes of tendinopathy: a review of basic science studies. Front Bioeng Biotechnol 2023; 11:1187974. [PMID: 37545895 PMCID: PMC10401606 DOI: 10.3389/fbioe.2023.1187974] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/10/2023] [Indexed: 08/08/2023] Open
Abstract
Tendinopathy is a medical condition that includes a spectrum of inflammatory and degenerative tendon changes caused by traumatic or overuse injuries. The pathological mechanism of tendinopathy has not been well defined, and no ideal treatment is currently available. Platelet-rich plasma (PRP) is an autologous whole blood derivative containing a variety of cytokines and other protein components. Various basic studies have found that PRP has the therapeutic potential to promote cell proliferation and differentiation, regulate angiogenesis, increase extracellular matrix synthesis, and modulate inflammation in degenerative tendons. Therefore, PRP has been widely used as a promising therapeutic agent for tendinopathy. However, controversies exist over the optimal treatment regimen and efficacy of PRP for tendinopathy. This review focuses on the specific molecular and cellular mechanisms by which PRP manipulates tendon healing to better understand how PRP affects tendinopathy and explore the reason for the differences in clinical trial outcomes. This article has also pointed out the future direction of basic research and clinical application of PRP in the treatment of tendinopathy, which will play a guiding role in the design of PRP treatment protocols for tendinopathy.
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Affiliation(s)
- Jialin Lu
- Department of Pain, The Second Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center of Jilin University, Changchun, China
| | - Han Li
- Norman Bethune Health Science Center of Jilin University, Changchun, China
| | - Ziyu Zhang
- Norman Bethune Health Science Center of Jilin University, Changchun, China
| | - Rui Xu
- Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jincheng Wang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China
| | - Hui Jin
- Department of Pain, The Second Hospital of Jilin University, Changchun, China
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China
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García A, Navarro MR, Ramirez A, Pino A, Navarro A, Moles I, Gallego E, Anitua E. Plasma Rich in Growth Factors as an Adjuvant Treatment for the Management of Frontal Fibrosing Alopecia: A Retrospective Observational Clinical Study. J Cutan Med Surg 2023; 27:340-349. [PMID: 37233603 DOI: 10.1177/12034754231177599] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
BACKGROUND Frontal fibrosing alopecia (FFA) is a scarring alopecia in which the exact etiopathogenesis has not been completely elucidated and the available treatments are not very effective. Plasma rich in growth factors (PRGF) has shown to induce folliculogenesis in hair loss related disorders. However, the scientific evidence when facing FFA is scarce. OBJECTIVES The aim of this study was to retrospectively analyze the adjuvant use of PRGF compared to the conventional treatment in the management of FFA. METHODS Participants with clinically diagnosed FFA who had been treated with either conventional therapy (Control Group) or conventional therapy combined with PRGF (PRGF Group) were identified from the center's medical records. The clinical assessment was based on the "Frontal Fibrosing Alopecia Severity Score" (FFASS), which was fulfilled during a period of two and 4 years. RESULTS This study included 118 patients with clinically diagnosed FFA (Control Group: 57 and PRGF Group: 61). No adverse effects related to the treatments were observed. Both treatments showed to halt the steady progression of hair loss compared to baseline. PRGF treatment also induced significant hair regrowth compared to the Control Group. The scalp inflammation was reduced in response to treatments. The FFASS score indicated that PRGF Group improved the symptoms and severity of FFA in a significant manner. CONCLUSIONS The adjuvant use of PRGF may exert long-term beneficial effects on hair loss reduction and might reduce the symptoms and severity of FFA.
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Affiliation(s)
| | - M R Navarro
- Centro Dermatológico Estético, Alicante, Spain
| | - Ana Ramirez
- Centro Dermatológico Estético, Alicante, Spain
| | - Ander Pino
- BTI Biotechnology Institute, Vitoria, Spain
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