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García‐Bordes L, Álvarez‐Díaz P, Alentorn‐Geli E, Ferré‐Aniorte A, Laiz‐Boada P, Seijas‐Vázquez R, Cugat‐Bertomeu R. Demographic, anthropometric and intrasubject variations affect platelet-rich plasma formulation. J Exp Orthop 2025; 12:e70024. [PMID: 39867676 PMCID: PMC11764439 DOI: 10.1002/jeo2.70024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/07/2024] [Accepted: 08/13/2024] [Indexed: 01/28/2025] Open
Abstract
Purpose The purpose of this study is to describe the inter- and intra-individual differences in the platelet concentration between blood and platelet-rich plasma (PRP) preparation, assess intersubject differences considering demographic and anthropometric variables, describe PRP code distribution and analyse intrasubject variability. Methods A retrospective analysis was conducted using a single-centre patient database from November 2021 to November 2023. It included patients with musculoskeletal pathologies treated with PRP injections. Primary variables were demographic characteristics (sex, age, body mass index [BMI]) and platelet concentrations in blood and PRP during treatments. Secondary analysis focused on PRP code frequency distribution and intrasubject variability according to different coding systems. Results Here, 686 patients met the inclusion criteria. PRP exhibited significantly higher platelet concentrations compared to blood (378.01 ± 136.25 × 103 platelets/µL vs. 221.97 ± 58.21 × 103 platelets/µL, p < 0.001). Younger patients had higher platelet concentrations in both blood (p = 0.004) and PRP (p = 0.003), whereas female patients showed higher platelet concentrations only in blood (p < 0.001). The platelet concentration ratio was higher in males (p < 0.001) and those with higher BMI (p = 0.023). Significant differences were found between the existing and modified PRP coding systems (p < 0.001). Intrasubject variability was higher in PRP than in blood (coefficient of variance: 21.32 ± 17.36 in blood vs. 27.85 ± 19.10 in PRP, p < 0.001). Conclusion Age, gender, BMI and intrasubject variations significantly affect PRP formulation, emphasizing the importance of addressing these variables for a more predictable, personalized and effective therapeutic approach. Level of Evidence This is a retrospective study. Level IV.
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Affiliation(s)
- Luis García‐Bordes
- Instituto Cugat, Hospital Quironsalud BarcelonaBarcelonaSpain
- Fundación García CugatBarcelonaSpain
- Universitat Internacional de Catalunya, Sant Cugat del VallèsBarcelonaSpain
| | - Pedro Álvarez‐Díaz
- Instituto Cugat, Hospital Quironsalud BarcelonaBarcelonaSpain
- Fundación García CugatBarcelonaSpain
- Universitat Internacional de Catalunya, Sant Cugat del VallèsBarcelonaSpain
- Mutualidad de Futbolistas – Delegación Cataluña, Federación Española de FútbolBarcelonaSpain
| | - Eduard Alentorn‐Geli
- Instituto Cugat, Hospital Quironsalud BarcelonaBarcelonaSpain
- Fundación García CugatBarcelonaSpain
- Mutualidad de Futbolistas – Delegación Cataluña, Federación Española de FútbolBarcelonaSpain
| | - Alfred Ferré‐Aniorte
- Instituto Cugat, Hospital Quironsalud BarcelonaBarcelonaSpain
- Fundación García CugatBarcelonaSpain
| | - Patricia Laiz‐Boada
- Instituto Cugat, Hospital Quironsalud BarcelonaBarcelonaSpain
- Fundación García CugatBarcelonaSpain
| | - Roberto Seijas‐Vázquez
- Instituto Cugat, Hospital Quironsalud BarcelonaBarcelonaSpain
- Fundación García CugatBarcelonaSpain
| | - Ramon Cugat‐Bertomeu
- Instituto Cugat, Hospital Quironsalud BarcelonaBarcelonaSpain
- Fundación García CugatBarcelonaSpain
- Mutualidad de Futbolistas – Delegación Cataluña, Federación Española de FútbolBarcelonaSpain
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Thayaparan A, Kantharuban S. Anterior Cruciate Ligament Rupture: Evidence-Based Concepts on Reconstruction, Repair and Future Developments. Cureus 2024; 16:e67956. [PMID: 39328699 PMCID: PMC11426957 DOI: 10.7759/cureus.67956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2024] [Indexed: 09/28/2024] Open
Abstract
The anterior cruciate ligament (ACL) is a vital but frequently injured structure. An ACL injury can result in dysfunction, meniscal injuries, and the early onset of osteoarthritis. This article aims to discuss favourable reconstruction techniques through a literature review with consideration for novel methods in order to identify superior methods that provide a patient's return to function. Current surgical options include reconstruction using different types of autografts and allografts.
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Chalidis B, Givissis P, Papadopoulos P, Pitsilos C. Molecular and Biologic Effects of Platelet-Rich Plasma (PRP) in Ligament and Tendon Healing and Regeneration: A Systematic Review. Int J Mol Sci 2023; 24:2744. [PMID: 36769065 PMCID: PMC9917492 DOI: 10.3390/ijms24032744] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/27/2023] [Accepted: 01/27/2023] [Indexed: 02/04/2023] Open
Abstract
Platelet-rich plasma (PRP) has been introduced and applied to a wide spectrum of acute and chronic ligament and tendon pathologic conditions. Although the biological effect of PRP has been studied thoroughly in both animal and human studies, there is no consensus so far on the exact mechanism of its action as well as the optimal timing and dosage of its application. Therefore, we conducted a systematic review aiming to evaluate the molecular effect of the administration of PRP in tendoligamentous injuries and degenerative diseases. The literature search revealed 36 in vitro and in vivo studies examining the healing and remodeling response of animal and human ligament or tendon tissues to PRP. Platelet-rich plasma added in the culture media was highly associated with increased cell proliferation, migration, viability and total collagen production of both ligament- and tendon-derived cells in in vitro studies, which was further confirmed by the upregulation of collagen gene expression. In vivo studies correlated the PRP with higher fibroblastic anabolic activity, including increased cellularity, collagen production and vascularity of ligament tissue. Similarly, greater metabolic response of tenocytes along with the acceleration of the healing process in the setting of a tendon tear were noticed after PRP application, particularly between the third and fourth week after treatment. However, some studies demonstrated that PRP had no or even negative effect on tendon and ligament regeneration. This controversy is mainly related to the variable processes and methodologies of preparation of PRP, necessitating standardized protocols for both investigation and ap-plication.
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Affiliation(s)
- Byron Chalidis
- 1st Orthopaedic Department, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece
| | - Panagiotis Givissis
- 1st Orthopaedic Department, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece
| | - Pericles Papadopoulos
- 2nd Orthopaedic Department, Aristotle University of Thessaloniki, 54635 Thessaloniki, Greece
| | - Charalampos Pitsilos
- 2nd Orthopaedic Department, Aristotle University of Thessaloniki, 54635 Thessaloniki, Greece
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4
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Amini M, Venkatesan JK, Liu W, Leroux A, Nguyen TN, Madry H, Migonney V, Cucchiarini M. Advanced Gene Therapy Strategies for the Repair of ACL Injuries. Int J Mol Sci 2022; 23:ijms232214467. [PMID: 36430947 PMCID: PMC9695211 DOI: 10.3390/ijms232214467] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/07/2022] [Accepted: 11/19/2022] [Indexed: 11/23/2022] Open
Abstract
The anterior cruciate ligament (ACL), the principal ligament for stabilization of the knee, is highly predisposed to injury in the human population. As a result of its poor intrinsic healing capacities, surgical intervention is generally necessary to repair ACL lesions, yet the outcomes are never fully satisfactory in terms of long-lasting, complete, and safe repair. Gene therapy, based on the transfer of therapeutic genetic sequences via a gene vector, is a potent tool to durably and adeptly enhance the processes of ACL repair and has been reported for its workability in various experimental models relevant to ACL injuries in vitro, in situ, and in vivo. As critical hurdles to the effective and safe translation of gene therapy for clinical applications still remain, including physiological barriers and host immune responses, biomaterial-guided gene therapy inspired by drug delivery systems has been further developed to protect and improve the classical procedures of gene transfer in the future treatment of ACL injuries in patients, as critically presented here.
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Affiliation(s)
- Mahnaz Amini
- Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421 Homburg, Germany
| | - Jagadeesh K. Venkatesan
- Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421 Homburg, Germany
| | - Wei Liu
- Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421 Homburg, Germany
| | - Amélie Leroux
- Laboratoire CSPBAT UMR CNRS 7244, Université Sorbonne Paris Nord, Avenue JB Clément, 93430 Villetaneuse, France
| | - Tuan Ngoc Nguyen
- Laboratoire CSPBAT UMR CNRS 7244, Université Sorbonne Paris Nord, Avenue JB Clément, 93430 Villetaneuse, France
| | - Henning Madry
- Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421 Homburg, Germany
| | - Véronique Migonney
- Laboratoire CSPBAT UMR CNRS 7244, Université Sorbonne Paris Nord, Avenue JB Clément, 93430 Villetaneuse, France
| | - Magali Cucchiarini
- Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr. Bldg 37, D-66421 Homburg, Germany
- Correspondence: or
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5
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Cao Y, Wan Y. Effectiveness of Platelet-Rich Plasma in Anterior Cruciate Ligament Reconstruction: A Systematic Review of Randomized Controlled Trials. Orthop Surg 2022; 14:2406-2417. [PMID: 36056588 PMCID: PMC9531067 DOI: 10.1111/os.13279] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 03/05/2022] [Accepted: 03/21/2022] [Indexed: 11/29/2022] Open
Abstract
This study aimed to identify the effectiveness of platelet-rich plasma (PRP) for patients operated with anterior cruciate ligament reconstruction (ACLR). Databases of PubMed, Embase, and CENTRAL were independently retrieved by two authors, for identifying the eligible randomized controlled trials (RCTs) comparing the clinical and imaging outcomes of ACL reconstructed patients augmented with or without PRP. The Cochrane Collaboration tool was utilized to assess the risk of bias of the included trials. We qualitatively synthesized the outcomes include the image evaluations on the healing of bone tunnels, graft remodeling, donor site healing and tunnel widening, and clinical evaluations on knee stability and function, pain symptom by visual analogue scale (VAS), inflammatory parameters and so on. A total of 16 RCTs, including 1025 patients, were included for eligibility. Generally, the included studies were of low risk of bias, but the conducting of allocation concealment was not clearly described in many studies. Three imaging techniques, including MRI, CT and ultrasound, were selected in these trials. Significant improvement on graft remodeling, bone tunnel healing, harvest site healing and bone tunnel diameters were demonstrated in one of five (20.0%), three of five (60.0%), two of four (50.0%) and one of five (20.0%) studies respectively, for PRP group. Various clinical outcomes, such as IKDC score, Lysholm score, Tegner score, knee anteroposterior and rotational laxity, range of motion and VAS, could not be improved with PRP application. The PRP is associated with very limited role in improving knee outcomes following ACLR, and there is no indication for PRP procedures in ACLR at this stage.
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Affiliation(s)
- Yi Cao
- Radiology DepartmentTianjin HospitalTianjin CityChina
| | - Ye‐da Wan
- Radiology DepartmentTianjin HospitalTianjin CityChina
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Campón Chekroun A, Velázquez-Saornil J, Guillén Vicente I, Sánchez Milá Z, Rodríguez-Sanz D, Romero-Morales C, Fernandez-Jaén T, Garrido González JI, Sánchez-Garrido MÁ, Guillén García P. Consensus Delphi study on guidelines for the assessment of anterior cruciate ligament injuries in children. World J Orthop 2022; 13:777-790. [PMID: 36189335 PMCID: PMC9516626 DOI: 10.5312/wjo.v13.i9.777] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/16/2022] [Accepted: 08/17/2022] [Indexed: 02/06/2023] Open
Abstract
Background: Knee examination guidelines in minors are intended to aid decision-making in the management of knee instability. Clinical question: A Delphi study was conducted with a formal consensus process using a validated methodology with sufficient scientific evidence. A group consensus meeting was held to develop recommendations and practical guidelines for use in the assessment of instability injuries in children. Key findings: there is a lack of evidence to analyse anterior cruciate ligament injuries in children and their subsequent surgical management if necessary. Diagnostic guidelines and clinical assessment of the patient based on a thorough examination of the knee are performed and a guide to anterior cruciate ligament exploration in children is developed. Clinical application: In the absence of a strong evidence base, these established guidelines are intended to assist in that decision-making process to help the clinician decide on the most optimal treatment with the aim of benefiting the patient as much as possible. Following this expert consensus, surgical treatment is advised when the patient has a subjective sensation of instability accompanied by a pivot shift test ++, and may include an anterior drawer test + and a Lachman test +. If these conditions are not present, the conservative approach should be chosen, as the anatomical and functional development of children, together with a physiotherapy programme, may improve the evolution of the injury.
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Affiliation(s)
| | | | - Isabel Guillén Vicente
- Department of Orthopaedic and Trauma Surgery, Clínica Cemtro, Madrid 28035, Madrid, Spain
| | - Zacarías Sánchez Milá
- Department of Physiotherapy, Universidad Católica de Ávila, Ávila 05005, Ávila, Spain
| | - David Rodríguez-Sanz
- Nursing, Physiotherapy and Podiatry, Universidad Complutense de Madrid, Madrid 28040, Madrid, Spain
| | - Carlos Romero-Morales
- Department of Physical Therapy, Universidad Europea de Madrid, Madrid 28023, Madrid, Spain
| | - Tomas Fernandez-Jaén
- Department of Orthopaedic and Trauma Surgery, Clínica Cemtro, Madrid 28035, Madrid, Spain
| | | | | | - Pedro Guillén García
- Department of Orthopaedic and Trauma Surgery, Clínica Cemtro, Madrid 28035, Madrid, Spain
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7
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Kunze KN, Pakanati JJ, Vadhera AS, Polce EM, Williams BT, Parvaresh KC, Chahla J. The Efficacy of Platelet-Rich Plasma for Ligament Injuries: A Systematic Review of Basic Science Literature With Protocol Quality Assessment. Orthop J Sports Med 2022; 10:23259671211066504. [PMID: 35155701 PMCID: PMC8832618 DOI: 10.1177/23259671211066504] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 09/27/2021] [Indexed: 02/01/2023] Open
Abstract
Background: Despite the existence of many clinical studies on platelet-rich plasma (PRP) interventions for ligamentous pathology, basic science consensus regarding the indications, mechanisms, and optimal composition of PRP for treating ligament injuries is lacking. Purpose: To (1) compare the efficacy of PRP in animal models of ligament injury with placebo and (2) describe the potential variability in PRP preparation using accepted classification systems. Study Design: Systematic review. Methods: The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, PubMed, Embase, and Ovid MEDLINE were queried in April 2020 for in vivo and in vitro basic science studies regarding PRP use for ligament injury. Study design, results, PRP composition, and analyzed cellular and molecular markers were extracted, and outcomes relative to control models were documented. Bias was assessed using the SYRCLE risk-of-bias tool. Results: Included were 43 articles (31 in vivo and 12 in vitro studies) investigating the anterior cruciate ligament/cranial cruciate ligament (n = 32), medial collateral ligament (n = 6), suspensory ligament (n = 3), patellar ligament (n = 1), and Hock ligament (n = 1). Platelet concentration was reported in 34 studies (77.3%); leukocyte composition, in 12 (27.3%); and red blood cell counts, in 7 (15.9%). With PRP treatment, 5 of 12 in vitro studies demonstrated significant increases in cell viability, 6 of 12 in gene expression, 14 of 32 in vivo studies reported superior ligament repair via histological evaluation, and 13 in vivo studies reported superior mechanical properties. Variability in PRP preparation methods was observed across all articles, and only 1 study reported all necessary information to be classified by the 4 schemes we used to evaluate reporting. Among the in vivo studies, detection and performance bias were consistently high, whereas selection, attrition, reporting, and other biases were consistently low. Conclusion: Conflicting data on the cellular and molecular effects of PRP for ligament injuries were observed secondary to the finding that included studies were heterogeneous, limiting interpretation across studies and the ability to draw meaningful conclusions. Clinical trials and any causal relationship between PRP use in ligament injuries and its potential for regeneration and healing should be pursued with caution if based solely on basic science data.
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Affiliation(s)
- Kyle N. Kunze
- Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, USA
| | - Jeevana J. Pakanati
- Rosalind Franklin University, Chicago Medical School, Chicago, Illinois, USA
| | - Amar S. Vadhera
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Evan M. Polce
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Brady T. Williams
- Department of Orthopaedic Surgery, University of Colorado, Aurora, Colorado, USA
| | - Kevin C. Parvaresh
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Jorge Chahla
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, Illinois, USA
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Kon E, Di Matteo B, Altomare D, Iacono F, Kurpyakov A, Lychagin A, Timashev P, Kalinsky E, Lipina M. Biologic agents to optimize outcomes following ACL repair and reconstruction: A systematic review of clinical evidence. J Orthop Res 2022; 40:10-28. [PMID: 33586785 DOI: 10.1002/jor.25011] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/03/2021] [Accepted: 02/10/2021] [Indexed: 02/04/2023]
Abstract
Treatment options for anterior cruciate ligament (ACL) injuries have greatly developed over the past decades. Although reconstruction surgery is a concrete reality, stimulation of ACL healing through biological techniques could represent a revolutionary conservative approach. The use of biologic products, such as platelet-rich plasma (PRP) or mesenchymal stem cells (MSCs), to treat partial ruptures or to enhance ligamentization after reconstruction, could thoroughly improve clinical outcomes. The aim of the present paper is to systematically review the available literature on this topic, to (i) describe the current state of the art in available biologic techniques; (ii) clarify the outcomes of their application; (iii) identify areas needing further investigation and possible future development. A systematic review of the literature on the use of biologically active agents (PRP and MSCs) to enhance outcomes of ACL surgery was performed: 31 studies were included. Based on the ACL injury pattern, 6 papers investigated biologic agents in ACL partial tears whereas 25 papers in ACL reconstruction. Sixteen of twenty-five studies dealing with ACL reconstruction were randomized controlled trials, whereas only case series are available for partial ACL tears. Current evidence is still lacking sound data to support the use of biological agents: no clinical superiority has been described when using PRP in ACL reconstruction. Concerning ACL healing in partial tears, the application of PRP has led to encouraging outcomes, but these findings should be confirmed by appropriately designed RCTs.
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Affiliation(s)
- Elizaveta Kon
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.,Department of Traumatology, Orthopaedics and Disaster Surgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Berardo Di Matteo
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Daniele Altomare
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Francesco Iacono
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Anton Kurpyakov
- Department of Traumatology, Orthopaedics and Disaster Surgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Aleksey Lychagin
- Department of Traumatology, Orthopaedics and Disaster Surgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Peter Timashev
- Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.,Department of Polymers and Composites, N.N. Semenov Institute of Chemical Physics, Moscow, Russia.,Chemistry Department, Lomonosov Moscow State University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare," Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Eugene Kalinsky
- Department of Traumatology, Orthopaedics and Disaster Surgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Marina Lipina
- Department of Traumatology, Orthopaedics and Disaster Surgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
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Second Generation of Tissue-Engineered Ligament Substitutes for Torn ACL Replacement: Adaptations for Clinical Applications. Bioengineering (Basel) 2021; 8:bioengineering8120206. [PMID: 34940359 PMCID: PMC8698634 DOI: 10.3390/bioengineering8120206] [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: 10/30/2021] [Revised: 12/03/2021] [Accepted: 12/08/2021] [Indexed: 11/16/2022] Open
Abstract
The anterior cruciate ligament (ACL) of the knee joint is one of the strongest ligaments of the body and is often the target of traumatic injuries. Unfortunately, its healing potential is limited, and the surgical options for its replacement are frequently associated with clinical issues. A bioengineered ACL (bACL) was developed using a collagen matrix, seeded with autologous cells and successfully grafted and integrated into goat knee joints. We hypothesize that, in order to reduce the cost and simplify the model, an acellular bACL can be used as a substitute for a torn ACL, and bone plugs can be replaced by endobuttons to fix the bACL in situ. First, acellular bACLs were successfully grafted in the goat model with 18% recovery of ultimate tensile strength 6 months after implantation (94 N/mm2 vs. 520). Second, a bACL with endobuttons was produced and tested in an exvivo bovine knee model. The natural collagen scaffold of the bACL contributes to supporting host cell migration, growth and differentiation in situ post-implantation. Bone plugs were replaced by endobuttons to design a second generation of bACLs that offer more versatility as biocompatible grafts for torn ACL replacement in humans. A robust collagen bACL will allow solving therapeutic issues currently encountered by orthopedic surgeons such as donor-site morbidity, graft failure and post-traumatic osteoarthritis.
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10
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Murray MM. Optimizing outcomes of ACL surgery-Is autograft reconstruction the only reasonable option? J Orthop Res 2021; 39:1843-1850. [PMID: 34191344 PMCID: PMC8387392 DOI: 10.1002/jor.25128] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/25/2021] [Indexed: 02/04/2023]
Abstract
Anterior cruciate ligament (ACL) injuries occur at a high frequency in the United States with approximately 400,000 ACL reconstructions being performed each year. While ACL reconstruction is our current gold standard of treatment, it does not restore joint motion, or prevent the premature development of posttraumatic osteoarthritis (PTOA) in many patients. Thus, new treatments for an ACL injury, which are less invasive and minimize patient morbidity, including cartilage damage, are highly desirable. We have used a tissue-engineered approach to stimulate ligament healing, to improve upon current treatment options. In this review, we describe and discuss our work moving a tissue engineering strategy from the concept to bench, preclinical, clinical trials and ultimately FDA 510(k) de Novo approval, providing clinicians and patients with a viable alternative to ACL reconstruction.
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Affiliation(s)
- Martha M. Murray
- Department of Orthopaedic Surgery, Division of Sports Medicine, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA
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11
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Research trends of platelet-rich plasma application in orthopaedics from 2002 to 2020: a bibliometric analysis. INTERNATIONAL ORTHOPAEDICS 2021; 45:2773-2790. [PMID: 34337692 DOI: 10.1007/s00264-021-05163-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 07/17/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Platelet-rich plasma (PRP) has been widely used to treat various orthopaedic diseases, and there are a large number of studies on the matter. However, there have been no bibliometric reports on the publications in this field. Bibliometrics is an excellent method to systematically evaluate the current research status of a specific field. In this study, CiteSpace 5.7.R2 software was used to analyse the status, hotspots, and frontiers of PRP in the treatment of orthopaedic diseases in the past 19 years. METHODS All articles about the application of PRP in orthopaedics from 2002 to 2020 were searched from the Web of Science Core Collection. The author, country, institution, journal, cited journal, and keywords were retrieved, and the bibliometric analysis was done in CiteSpace 5.7.R2. RESULTS A total of 321 articles were retrieved. The analysis showed that the number of publications increased in the past 19 years, and the most productive author in this field was Brian J. Cole. The most productive country and the most productive institution were the US and the Hospital for Special Surgery in New York, respectively. The journals with the highest output and the highest citation frequency were the Journal of Orthopaedic Research and the American Journal of Sports Medicine, respectively. From the keyword analysis, we observed that the primary research hotspots were the study of the PRP composition, growth factors, and the combination of PRP and mesenchymal stem cells. The frontiers of PRP were in vivo experiments, the treatment of rotator cuff and cartilage injury, and the comparison of clinical efficacy between PRP and hyaluronic acid. CONCLUSION The efficacy of PRP in treating orthopaedic diseases remains controversial. There are still some problems with the experimental methods, such as insufficient sample size, low level of evidence, confusion of system naming, lack of standardisation of preparation methods and application programs, and lack of in-depth basic scientific research. The research status shown by co-occurrence and cluster maps and the analysis of hotspots and frontiers may help solve present problems and explore new directions.
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12
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Kobayashi EF, Tang K, Grant JA. Is ACL Repair Really Back? A Review of Modern Techniques. OPER TECHN SPORT MED 2021. [DOI: 10.1016/j.otsm.2021.150828] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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13
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Bascuñán A, Soula M, Millar KK, Biedrzycki A, Banks SA, Lewis DD, Kim SE. In vivo three-dimensional knee kinematics in goats with unilateral anterior cruciate ligament transection. J Orthop Res 2021; 39:1052-1063. [PMID: 32633844 DOI: 10.1002/jor.24795] [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: 06/09/2019] [Revised: 04/10/2020] [Accepted: 06/25/2020] [Indexed: 02/04/2023]
Abstract
Although the goat is an established animal model in anterior cruciate ligament (ACL) research, in vivo kinematics associated with ACL deficiency have not been previously described in this species. Three-dimensional knee kinematics were determined before and after unilateral ACL transection in eight goats. Fluoroscopic imaging of the knees during treadmill walking and force-platform gait analysis during over-ground walking were performed prior to ACL transection, and 2 weeks, 3 months, and 6 months after ACL transection. Transient lameness of the ACL-transected limb was noted in all goats but resolved by 3 months post-ACL transection. Increased extension of 8.7° to 17.0° was noted throughout the gait cycle in both the ACL-transected and the contralateral unaffected knees by 3 months post-ACL transection, in a bilaterally symmetric pattern. Peak anterior tibial translation increased by 3 to 6 mm after ACL transection and persisted over the 6-month study period. No changes in axial rotation or abduction angle were observed after ACL transection. Unilateral ACL deficiency in goats resulted in persistent kinematic alterations, despite the resolution of lameness by 3 months post-ACL transection.
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Affiliation(s)
- Ana Bascuñán
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida
| | - Mariajesus Soula
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida
| | - Kristina K Millar
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida
| | - Adam Biedrzycki
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida
| | - Scott A Banks
- Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, Florida
| | - Daniel D Lewis
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida
| | - Stanley E Kim
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida
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King W, Cawood K, Bookmiller M. The Use of Autologous Protein Solution (Pro-Stride ®) and Leukocyte-Rich Platelet-Rich Plasma (Restigen ®) in Canine Medicine. VETERINARY MEDICINE-RESEARCH AND REPORTS 2021; 12:53-65. [PMID: 33777723 PMCID: PMC7989049 DOI: 10.2147/vmrr.s286913] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/01/2021] [Indexed: 12/01/2022]
Abstract
The use of autologous orthobiologics is an emerging area of interest in veterinary medicine. In this retrospective study, we reviewed the clinical results achieved using two orthobiologics devices to address orthopedic injuries and tissue repair. Leukocyte (White blood cell)-rich platelet-rich plasma (L-PRP) devices produce outputs containing high concentrations of growth factors from venous blood. The Autologous Protein Solution (APS) device produces an orthobiologic containing high concentrations of growth factors and anti-inflammatory cytokines. L-PRP has commonly been used to address soft tissue injuries. APS has been injected into the joint to address osteoarthritis. In the last five years, our practice has treated 35 dogs (38 treatments) with L-PRP and 98 dogs (108 treatments) with APS. Our group has used L-PRP and APS to address orthopedic conditions including osteoarthritis, bursitis, tendinitis, tendon/ligament rupture/repair procedures, post-surgical femoral head osteotomy/tibial-plateau-leveling osteotomy tissue repair, lumbosacral stenosis, patellar luxation, joint laxity, and osteochondral dissecans. The results achieved with L-PRP and APS have been favorable (observed pain improvement and minimal adverse reactions), but sometimes have not achieved complete pain relief or tissue repair. The most common application for L-PRP was patellar luxation and the most common application for APS was injection post-ACL surgery. Canine OA has been successfully managed in several patients with repeat injections of APS over the course of several years. Future studies on specific conditions are ongoing and including efforts to further characterize these products in canine medicine.
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Affiliation(s)
| | - Kevin Cawood
- Indian Creek Veterinary Hospital, Fort Wayne, IN, USA
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15
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Scull G, Fisher MB, Brown AC. Fibrin-Based Biomaterial Systems to Enhance Anterior Cruciate Ligament Healing. MEDICAL DEVICES & SENSORS 2021; 4:e10147. [PMID: 34458685 PMCID: PMC8386506 DOI: 10.1002/mds3.10147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Anterior cruciate ligament (ACL) tears are a common and potentially career-ending injury, particularly for athletes and soldiers. Partial and complete ruptures of this ligament cause instability in the knee, and the ACL does not have the capacity for healing due, in part, to its position within the highly thrombolytic synovial fluid environment of the knee joint. Traditional methods of ACL reconstruction, such as graft replacement with attached bone anchors for bone integration, restore stability, but do not prevent the development of post-traumatic osteoarthritis. To enhance therapeutic treatment options, novel fibrin-based technologies and repair techniques have been recently explored and show promise for improved patient outcomes. Through modification of existing surgical methods, such as the use of fibrin glues incorporating growth factors and cells and the implementation of scaffolds containing platelet-rich plasma, platelet-rich fibrin, and other blood derivatives, surgeons are attempting to overcome the shortcomings of traditional treatments. This mini-review will detail current efforts using fibrin-based treatments and discuss opportunities to further enhance ACL healing.
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Affiliation(s)
- Grant Scull
- Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, NC 27695
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27695
| | - Matthew B. Fisher
- Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, NC 27695
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27695
| | - Ashley C. Brown
- Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, NC 27695
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27695
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16
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Anderson FL, Wright ML, Anderson MJ, Alexander FJ, Popa G, Ahmad CS. Inter- and Intraobserver Reliability Between Orthopaedic Surgeons for Reparability of the Anterior Cruciate Ligament Using MRI. Orthop J Sports Med 2020; 8:2325967120964608. [PMID: 33283010 PMCID: PMC7686628 DOI: 10.1177/2325967120964608] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 06/15/2020] [Indexed: 11/15/2022] Open
Abstract
Background Anterior cruciate ligament (ACL) reconstruction is the standard of care for patients after an ACL tear, as poor historical outcomes were observed after primary ACL repair. Certain subgroups of patients, however, have been shown to have outcomes equivalent to reconstruction after undergoing ACL repair and therefore may benefit from the potential advantages offered by avoiding reconstruction. It is important to accurately and consistently identify and indicate these candidates for ACL repair. Purpose/Hypothesis The purpose of this study was to determine the inter- and intraobserver reliability of magnetic resonance imaging (MRI) evaluation for the reparability of ACL tears and to identify imaging factors that may lead to surgeon uncertainty or disagreement in decision making. Our hypothesis was that the orthopaedic surgeons surveyed would not be able to reliably agree on the reparability of an ACL using MRI scans alone. Study Design Cohort study (diagnosis); Level of evidence, 3. Methods We administered 2 surveys to 6 fellowship-trained orthopaedic sports medicine surgeons. Each surgeon reviewed preoperative MRI scans for 20 patients and answered a series of questions, ultimately determining whether they would choose an ACL reconstruction or repair for the patient based on the imaging alone. The same survey was repeated 6 weeks later. Kappa values for inter- and intraobserver reliability of their decision making were then calculated. Results The average kappa for interobserver reliability in the 2 surveys was 0.22, and the average kappa for intraobserver reliability was 0.34. Interobserver reliability among the surgeons in this group was poor to moderate; intraobserver reliability was slightly better. The choice for ACL repair was significantly correlated with proximal tear locations (r = 0.854; P < .001), good-quality ACL tissue remnant (r = 0.929; P < .001), and how many surgeons believed that the tear only involved a single bundle (r = 0.590; P = .006). Conclusion The surgeons surveyed in this study did not consistently agree on candidates for ACL repair using MRI alone.
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Affiliation(s)
- Forrest L. Anderson
- Department of Orthopedic Surgery, Columbia University Irving Medical
Center, New York, New York, USA
| | - Margaret L. Wright
- Department of Orthopedic Surgery, Columbia University Irving Medical
Center, New York, New York, USA
| | - Matthew J. Anderson
- Department of Orthopedic Surgery, Columbia University Irving Medical
Center, New York, New York, USA
| | - Frank J. Alexander
- Department of Orthopedic Surgery, Columbia University Irving Medical
Center, New York, New York, USA
| | - George Popa
- Department of Orthopedic Surgery, Columbia University Irving Medical
Center, New York, New York, USA
| | - Christopher S. Ahmad
- Department of Orthopedic Surgery, Columbia University Irving Medical
Center, New York, New York, USA
- Christopher S. Ahmad, MD, Columbia University Irving Medical
Center, 622 W 168th Street, PH-11, New York, NY 10032, USA (
) (Twitter:
@drchrisahmad)
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17
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Hughes JD, Lawton CD, Nawabi DH, Pearle AD, Musahl V. Anterior Cruciate Ligament Repair: The Current Status. J Bone Joint Surg Am 2020; 102:1900-1915. [PMID: 32932291 DOI: 10.2106/jbjs.20.00509] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Jonathan D Hughes
- UPMC Freddie Fu Sports Medicine Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Cort D Lawton
- Sports Medicine Institute, Hospital for Special Surgery, New York, NY
| | - Danyal H Nawabi
- Sports Medicine Institute, Hospital for Special Surgery, New York, NY
| | - Andrew D Pearle
- Sports Medicine Institute, Hospital for Special Surgery, New York, NY
| | - Volker Musahl
- UPMC Freddie Fu Sports Medicine Center, University of Pittsburgh, Pittsburgh, Pennsylvania
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Biological Augmentation of ACL Repair and Reconstruction: Current Status and Future Perspective. Sports Med Arthrosc Rev 2020; 28:49-55. [PMID: 32345926 DOI: 10.1097/jsa.0000000000000266] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Historically, anterior cruciate ligament (ACL) suture repair mostly resulted in failure because of intra-articular hypovascularity and poor intrinsic healing capacity of ACL. ACL reconstruction was therefore deemed the gold standard with a high success rate because of more evolved surgical technique. There are, however, clinical and subclinical disadvantages of reconstruction; low rate in full recovery to sports, donor harvest morbidity, tunnel enlargement, and incomplete microscopic healing of the graft. Recent experimental and clinical studies on biological augmentation of mesenchymal stem cells, platelet-rich plasma, or the other biologic agents with scaffold suggested potential feasibility of positive effects by such bio-therapies for both ACL repair and reconstruction. Biological augmentation of ACL surgery is still in the exploratory stages and more evidence from preclinical and clinical studies is required for implementation in clinical practice.
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19
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Synovialization and Revascularization Enhancement in Repaired and Reconstructed ACL: PCL Fat Pad Transfer Technique. Arthrosc Tech 2020; 9:e1559-e1563. [PMID: 33134060 PMCID: PMC7587456 DOI: 10.1016/j.eats.2020.06.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 06/11/2020] [Indexed: 02/03/2023] Open
Abstract
The rapid development of anterior cruciate ligament (ACL) reconstruction and repair techniques has significantly improved the outcomes of these procedures. However, there is still some place for how to improve surgical techniques to limit the amount of revision surgeries. Over the past decade, biological solutions and methods of ligament remodeling enhancement have been proposed. The use of the native ACL remnants has been the most thoroughly analyzed technique. However, despite its benefits, this technique may not to be sufficient to improve outcomes and may cause some technical difficulties. On the other hand, the posterior cruciate ligament (PCL) fat pad contains an abundant synovial vascular network and is located in close proximity to the ACL, which makes it a potential biological donor place of cells and tissue that could enhance the ligamentization of the repaired or reconstructed ACL. To optimize the use of this donor site, we propose the technique of ACL synovialization and revascularization enhancement with a PCL fat pad transfer.
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20
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Kumar A, Palit P, Thomas S, Gupta G, Ghosh P, Goswami RP, Kumar Maity T, Dutta Choudhury M. Osteoarthritis: Prognosis and emerging therapeutic approach for disease management. Drug Dev Res 2020; 82:49-58. [PMID: 32931079 DOI: 10.1002/ddr.21741] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 08/24/2020] [Accepted: 08/25/2020] [Indexed: 12/21/2022]
Abstract
Osteoarthritis (OA), a disorder of joints, is prevalent in older age. The contemporary cure for OA is aimed to confer symptomatic relief, consisting of temporary pain and swelling relief. In this paper, we discuss various modalities responsible for the onset of OA and associated with its severity. Inhibition of chondrocytes receptors such as DDR2, SDF-1, Asporin, and CXCR4 by specific pharmacological inhibitors attenuates OA, a critical step for finding potential disease modifying drugs. We critically analyzed recent OA studies with an emphasis on intermediate target molecules for OA intervention. We also explored some novel and safe treatments for OA by considering disease prognosis crosstalk with cellular signaling pathways.
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Affiliation(s)
- Amresh Kumar
- Department of Life Sciences and Bioinformatics, Assam University, Silchar, India
| | - Partha Palit
- Department of Pharmaceutical Sciences, Assam University, Silchar, India
| | - Sabu Thomas
- Department of Chemical Sciences, Mahatma Gandhi University, Kottayam, India
| | - Gaurav Gupta
- Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.,Area of Biotechnology and Bioinformatics, NIIT University, Neemrana, Rajasthan, India
| | - Parasar Ghosh
- Department of Rheumatology, Institute of Post Graduate Medical Education &Research, Kolkata, India
| | | | - Tapan Kumar Maity
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
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Desai S, Jayasuriya CT. Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair. Bioengineering (Basel) 2020; 7:E86. [PMID: 32759659 PMCID: PMC7552784 DOI: 10.3390/bioengineering7030086] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 07/25/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be categorized into two main approaches: (1) Facilitating the recruitment of endogenous host cells to the injury site; and (2) physically administering into the injury site cells themselves, exogenously, either by autologous or allogeneic implantation. The aim of this paper is to comprehensively review recent key literature on the use of these two approaches in stimulating healing and repair of different skeletal tissues. As expected, each of the two strategies have their own advantages and limitations (which we describe), especially when considering the diverse microenvironments of different skeletal tissues like bone, tendon/ligament, and cartilage/fibrocartilage. This paper also discusses stem/progenitor cells commonly used for repairing different skeletal tissues, and it lists ongoing clinical trials that have risen from the implementation of these cells and strategies. Lastly, we discuss our own thoughts on where the field is headed in the near future.
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Affiliation(s)
| | - Chathuraka T. Jayasuriya
- Department of Orthopaedics, Warren Alpert Medical School of Brown University and the Rhode Island Hospital, Providence, RI 02903, USA;
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22
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Isolated Meniscus Tears in Adolescent Patients Treated with Platelet-Rich Plasma Intra-articular Injections: 3-Month Clinical Outcome. BIOMED RESEARCH INTERNATIONAL 2020; 2020:8282460. [PMID: 32596381 PMCID: PMC7273443 DOI: 10.1155/2020/8282460] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 05/03/2020] [Accepted: 05/05/2020] [Indexed: 01/19/2023]
Abstract
Objectives Meniscus repair is a challenge for a practitioner, as an injured meniscus can lead to osteoarthritic joint changes with a greatly disabling outcome. Platelet-rich plasma has been regarded as a promising therapy to help induce healing. The purpose of the study is to clinically assess the effectiveness of PRP treatment in adolescents with meniscal lesions. Methods This retrospective study analyzed 30 patients with meniscal tears, aged 12 to 17 years, who had documented MRI meniscal lesion and persistent knee pain. In order to evaluate the outcome, the Lysholm knee scoring scale and numerical rating scale were used before injection and 3 months after treatment. Results Patients had a mean age of 13.93 years, 70% girls and 30% boys. The most affected was the medial meniscus. The mean value before injection on the numerical rating scale (NRS) of pain was 7.73, after the treatment being of 2.0. After treatment, 76.7% of the patients had “excellent” and “good” outcomes, while before injection, just 3% of the patients had a “good” score. Conclusions Platelet-rich plasma treatment can be effective in improving the clinical outcomes of adolescent patients with meniscus tears, for whom conservative management and physical therapy have failed to achieve pain relief.
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Looney AM, Leider JD, Horn AR, Bodendorfer BM. Bioaugmentation in the surgical treatment of anterior cruciate ligament injuries: A review of current concepts and emerging techniques. SAGE Open Med 2020; 8:2050312120921057. [PMID: 32435488 PMCID: PMC7222656 DOI: 10.1177/2050312120921057] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 03/22/2020] [Indexed: 12/27/2022] Open
Abstract
Injuries involving the anterior cruciate ligament are among the most common athletic injuries, and are the most common involving the knee. The anterior cruciate ligament is a key translational and rotational stabilizer of the knee joint during pivoting and cutting activities. Traditionally, surgical intervention in the form of anterior cruciate ligament reconstruction has been recommended for those who sustain an anterior cruciate ligament rupture and wish to remain active and return to sport. The intra-articular environment of the anterior cruciate ligament makes achieving successful healing following repair challenging. Historically, results following repair were poor, and anterior cruciate ligament reconstruction emerged as the gold-standard for treatment. While earlier literature reported high rates of return to play, the results of more recent studies with longer follow-up have suggested that anterior cruciate ligament reconstruction may not be as successful as once thought: fewer athletes are able to return to sport at their preinjury level, and many still go on to develop osteoarthritis of the knee at a relatively younger age. The four principles of tissue engineering (cells, growth factors, scaffolds, and mechanical stimuli) combined in various methods of bioaugmentation have been increasingly explored in an effort to improve outcomes following surgical treatment of anterior cruciate ligament injuries. Newer technologies have also led to the re-emergence of anterior cruciate ligament repair as an option for select patients. The different biological challenges associated with anterior cruciate ligament repair and reconstruction each present unique opportunities for targeted bioaugmentation strategies that may eventually lead to better outcomes with better return-to-play rates and fewer revisions.
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Affiliation(s)
| | - Joseph Daniel Leider
- Department of Orthopaedic Surgery, Georgetown University Medical Center, Washington, DC, USA
| | - Andrew Ryan Horn
- Department of Orthopaedic Surgery, Georgetown University Medical Center, Washington, DC, USA
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Murray MM, Fleming BC, Badger GJ, Freiberger C, Henderson R, Barnett S, Kiapour A, Ecklund K, Proffen B, Sant N, Kramer DE, Micheli LJ, Yen YM. Bridge-Enhanced Anterior Cruciate Ligament Repair Is Not Inferior to Autograft Anterior Cruciate Ligament Reconstruction at 2 Years: Results of a Prospective Randomized Clinical Trial. Am J Sports Med 2020; 48:1305-1315. [PMID: 32298131 PMCID: PMC7227128 DOI: 10.1177/0363546520913532] [Citation(s) in RCA: 135] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Preclinical studies suggest that for complete midsubstance anterior cruciate ligament (ACL) injuries, a suture repair of the ACL augmented with a protein implant placed in the gap between the torn ends (bridge-enhanced ACL repair [BEAR]) may be a viable alternative to ACL reconstruction (ACLR). HYPOTHESIS We hypothesized that patients treated with BEAR would have a noninferior patient-reported outcomes (International Knee Documentation Committee [IKDC] Subjective Score; prespecified noninferiority margin, -11.5 points) and instrumented anteroposterior (AP) knee laxity (prespecified noninferiority margin, +2-mm side-to-side difference) and superior muscle strength at 2 years after surgery when compared with patients who underwent ACLR with autograft. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS One hundred patients (median age, 17 years; median preoperative Marx activity score, 16) with complete midsubstance ACL injuries were enrolled and underwent surgery within 45 days of injury. Patients were randomly assigned to receive either BEAR (n = 65) or autograft ACLR (n = 35 [33 with quadrupled semitendinosus-gracilis and 2 with bone-patellar tendon-bone]). Outcomes-including the IKDC Subjective Score, the side-to-side difference in instrumented AP knee laxity, and muscle strength-were assessed at 2 years by an independent examiner blinded to the procedure. Patients were unblinded after their 2-year visit. RESULTS In total, 96% of the patients returned for 2-year follow-up. Noninferiority criteria were met for both the IKDC Subjective Score (BEAR, 88.9 points; ACLR, 84.8 points; mean difference, 4.1 points [95% CI, -1.5 to 9.7]) and the side-to-side difference in AP knee laxity (BEAR, 1.61 mm; ACLR, 1.77 mm; mean difference, -0.15 mm [95% CI, -1.48 to 1.17]). The BEAR group had a significantly higher mean hamstring muscle strength index than the ACLR group at 2 years (98.2% vs 63.2%; P < .001). In addition, 14% of the BEAR group and 6% of the ACLR group had a reinjury that required a second ipsilateral ACL surgical procedure (P = .32). Furthermore, the 8 patients who converted from BEAR to ACLR in the study period and returned for the 2-year postoperative visit had similar primary outcomes to patients who had a single ipsilateral ACL procedure. CONCLUSION BEAR resulted in noninferior patient-reported outcomes and AP knee laxity and superior hamstring muscle strength when compared with autograft ACLR at 2-year follow-up in a young and active cohort. These promising results suggest that longer-term studies of this technique are justified. REGISTRATION NCT02664545 (ClinicalTrials.gov identifier).
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Affiliation(s)
- Martha M. Murray
- Martha M. Murray, MD, Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children’s Hospital, 300 Longwood Ave, Hunnewell 2, Boston, MA 02115, USA ()
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25
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Berdis AS, Veale K, Fleissner PR. Outcomes of Anterior Cruciate Ligament Reconstruction Using Biologic Augmentation in Patients 21 Years of Age and Younger. Arthroscopy 2019; 35:3107-3113. [PMID: 31439458 DOI: 10.1016/j.arthro.2019.05.047] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 05/21/2019] [Accepted: 05/23/2019] [Indexed: 02/02/2023]
Abstract
PURPOSE To report on the outcomes of a subset of patients ≤21 years of age after anterior cruciate ligament (ACL) reconstruction coupled with biologic augmentation using platelet-rich plasma (PRP) and a porous collagen carrier. METHODS A cohort of patients was retrospectively reviewed after ACL reconstruction with hamstring autograft tendon. All reconstructive surgeries combined biologic augmentation in which the ACL graft was coupled with PRP contained within porous collagen membrane. Patients were included if they maintained a minimum follow-up period of 24 months. Outcomes were assessed through patient-reported questionnaires and physical examination in the clinical setting. Patient-reported outcomes including International Knee Documentation Committee (IKDC), Lysholm, Tegner, and Single Assessment Numeric Evaluation (SANE) scores were collected. ACL stability was evaluated using Lachman and KT-1000 testing. Patients were also evaluated for return to play at the same level of competition, family history of ACL injury, and time to complete rehabilitation. RESULTS A total of 194 patients were initially eligible; 143 (74%) patients with 151 knees were ultimately evaluated. The average patient age was 16 years; 79 patients were female and 64 were male. Follow-up duration averaged 52 months. IKDC and Lysholm scores averaged 91 and 91; the average SANE score was 94. The KT-1000 side-to-side difference averaged 1.2 mm. The average time to complete physical therapy was 22 weeks, and 132 patients (92%) returned to their preinjury level of competition. There were 23 cases of contralateral ACL injury (15%) and 7 cases of ACL reinjury necessitating revision surgery (5%). CONCLUSIONS Biologic augmentation with hamstring autograft in ACL reconstruction shows a decreased rate of second ACL injury, specifically with regard to ACL revision surgery. The patients in this study also show higher return to preinjury level of competition at a faster rate than other studies have shown. LEVEL OF EVIDENCE Level IV, Therapeutic Case Series.
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Affiliation(s)
- Anthony S Berdis
- Department of Graduate Medical Education, Aultman Hospital, Canton, Ohio, U.S.A..
| | - Kodi Veale
- Crystal Clinic Orthopaedic Center, Bell Chapter of the Hawkins Foundation, Akron, Ohio, U.S.A
| | - Paul R Fleissner
- Crystal Clinic Orthopaedic Center, Bell Chapter of the Hawkins Foundation, Akron, Ohio, U.S.A
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26
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Schulz KS, Ash KJ, Cook JL. Clinical outcomes after common calcanean tendon rupture repair in dogs with a loop-suture tenorrhaphy technique and autogenous leukoreduced platelet-rich plasma. Vet Surg 2019; 48:1262-1270. [PMID: 30950083 DOI: 10.1111/vsu.13208] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 02/22/2019] [Accepted: 03/16/2019] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To report outcomes of dogs with common calcanean tendon (CCT) ruptures treated with a platelet-rich plasma (PRP) enhanced nonabsorbable loop-suture technique. STUDY DESIGN Retrospective case series. ANIMALS Client-owned dogs (n = 12). METHODS Medical records (2015-2017) of dogs with CCT ruptures repaired with a loop-suture tenorrhaphy and autogenous leukoreduced PRP were reviewed for signalment, history, type of injury, treatment, and clinical follow-up. Outcomes were assessed by functional anatomic measurements and Canine Orthopedic Index (COI) scores transformed to percentages, with 100% representing no problems. RESULTS Twelve tendons were treated. Two dogs had major complications that were successfully revised. Follow-up was available in 11 of 12 dogs, with a median time of 12 months (range, 4-36), including COI for 11 dogs and anatomic measurements for 6 dogs. Anatomic measurements did not differ between treated and normal contralateral limbs (midthigh muscle mass P > .99, cranial tibial muscle mass P = .37, CCT diameter P = .08, tibiotarsal joint angle P > .99). Owners scored function (COI) as 96.4% (range, 93.3%-97.8%) and quality of life as 94.6% (range, 92%-98.2%). CONCLUSION Loop-suture tenorrhaphy with application of autogenous leukoreduced PRP at the repair site resulted in restoration of functional anatomic measurements, high COI, and client satisfaction. CLINICAL SIGNIFICANCE Loop-suture tenorrhaphy with local application of autogenous leukoreduced PRP appears to offer an acceptable option to treat CCT injuries in dogs.
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Affiliation(s)
- Kurt S Schulz
- Department of Surgery, Peak Veterinary Referral Center at Ethos, Williston, Vermont
| | - Krisitan J Ash
- Department of Surgery, Peak Veterinary Referral Center at Ethos, Williston, Vermont
| | - James L Cook
- Thompson Laboratory for Regenerative Orthopaedics & Mizzou BioJoint® Center, Missouri Orthopedic Institute, Columbia, Missouri
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Christensen K, Cox B, Anz A. Emerging Orthobiologic Techniques and the Future. Clin Sports Med 2018; 38:143-161. [PMID: 30466719 DOI: 10.1016/j.csm.2018.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The future of orthopedic surgery appears to be intimately associated with the development of orthobiologics to facilitate healing and the treatment of multiple disease processes. The orthopedic community should understand developmental processes to ensure that products are adequately studied and the effects are fully known before widespread implementation in the clinical setting. Technologies that embrace this paradigm will impact the field the most.
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Affiliation(s)
- Kevin Christensen
- Andrews Institute, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA
| | - Benjamin Cox
- PLLC, 2890 Health Parkway, Mount Pleasant, MI 48858, USA
| | - Adam Anz
- Andrews Institute, Andrews Research and Education Foundation, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA.
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Abstract
In the last few decades, several techniques have been used to optimize tendon, ligament, and musculoskeletal healing. The evidence in favor of these techniques is still not proven, and level I studies are lacking. We performed an analysis of the therapeutic strategies and tissue engineering projects recently published in this field. Here, we try to give an insight into the current status of cell therapies and the latest techniques of bioengineering applied to the field of orthopedic surgery. The future areas for research in the management of musculoskeletal injuries are outlined. There are emerging technologies developing into substantial clinical treatment options that need to be critically evaluated. Mechanical stimulation of the constructs reproduces a more propitious environment for effective healing.
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Malahias MA, Chytas D, Nakamura K, Raoulis V, Yokota M, Nikolaou VS. A Narrative Review of Four Different New Techniques in Primary Anterior Cruciate Ligament Repair: "Back to the Future" or Another Trend? SPORTS MEDICINE - OPEN 2018; 4:37. [PMID: 30094753 PMCID: PMC6085215 DOI: 10.1186/s40798-018-0145-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 07/02/2018] [Indexed: 01/28/2023]
Abstract
Recently, four different operative techniques, referring to the primary anterior cruciate ligament (ACL) repair, were described. These are the dynamic intraligamentary stabilization (DIS) with Ligamys™, the Bridge-enhanced repair (BEAR), the use of internal brace, and the refixation with suture anchors. The purpose of this study was to assess the already-published, clinical, and pre-clinical results of those techniques. A literature review was conducted and implemented by three independent researchers. Inclusion criteria were clinical or cadaveric or animal studies about patients suffering from ACL rupture, who were treated with one of those four different arthroscopic techniques of primary ACL repair. There were 10 clinical trials dealing with the different techniques of primary ACL repair and 12 cadaveric or animal studies. The majority of the published clinical trials investigated the dynamic intraligamentary stabilization (DIS), while only four studies referred to the three other surgical techniques. Most of the clinical trials suggested that primary ACL repair should be done during the first 14-21 days after a proximal ACL rupture and not later. Further clinical evidence is needed for the techniques of bridge-enhanced ACL repair, internal brace, and suture anchors ACL refixation in order to support the animal and cadaveric biomechanical studies. Till now, the existing clinical trials were not enough to establish the use of those techniques in the ACL-ruptured patients. On the contrary, the Dynamic intraligamentary stabilization with Ligamys™ device demonstrated very promising results in different types of clinical studies.
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Affiliation(s)
- Michael-Alexander Malahias
- 2nd Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- ATOS Hospital, Heidelberg, Germany
- Orthopaedic Surgeon, ATOS Klinik, Schlossberg 21, 69117 Heidelberg, Germany
| | - Dimitrios Chytas
- 2nd Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Kaori Nakamura
- Department of Joint Surgery and Sports Medicine, Graduate School of Medical Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510 Japan
- ATOS Hospital, Heidelberg, Germany
| | - Vasileios Raoulis
- Department of Orthopaedic Surgery, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
- ATOS Hospital, Heidelberg, Germany
| | - Masashi Yokota
- Department of Sports Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Vasileios S. Nikolaou
- 2nd Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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van Eck CF, Limpisvasti O, ElAttrache NS. Is There a Role for Internal Bracing and Repair of the Anterior Cruciate Ligament? A Systematic Literature Review. Am J Sports Med 2018; 46:2291-2298. [PMID: 28783472 DOI: 10.1177/0363546517717956] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Renewed interest has arisen in arthroscopic anterior cruciate ligament (ACL) repair techniques. HYPOTHESIS ACL repair with or without some form of internal bracing could lead to good outcomes in a carefully selected subset of patients. STUDY DESIGN Systematic review. METHODS An electronic database search was performed to identify 89 papers describing preclinical and clinical studies on the outcome of ACL repair. RESULTS Proximal ACL tear patterns showed a better healing potential with primary repair than distal or midsubstance tears. Some form of internal bracing increased the success rate of ACL repair. Improvement in the biological characteristics of the repair was obtained by bone marrow access by drilling tunnels or microfracture. Augmentation with platelet-rich plasma was beneficial only in combination with a structural scaffold. Skeletally immature patients had the best outcomes. Acute repair offered improved outcomes with regard to load, stiffness, laxity, and rerupture. CONCLUSION ACL repair may be a viable option in young patients with acute, proximal ACL tears. The use of internal bracing, biological augmentation, and scaffold tissue may increase the success rate of repair.
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Affiliation(s)
| | - Orr Limpisvasti
- Kerlan Jobe Orthopaedic Clinic, Los Angeles, California, USA
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Chen X, Jones IA, Park C, Vangsness CT. The Efficacy of Platelet-Rich Plasma on Tendon and Ligament Healing: A Systematic Review and Meta-analysis With Bias Assessment. Am J Sports Med 2018; 46:2020-2032. [PMID: 29268037 PMCID: PMC6339617 DOI: 10.1177/0363546517743746] [Citation(s) in RCA: 147] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND There has been a surge in high-level studies investigating platelet-rich plasma (PRP) for tendon and ligament injuries. A number of meta-analyses have been published, but few studies have focused exclusively on tendon and ligament injuries. PURPOSE To perform a meta-analysis assessing the ability of PRP to reduce pain in patients with tendon and ligament injuries. STUDY DESIGN Systematic review and meta-analysis. METHODS This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in April 2017 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Only level 1 studies were included. Platelet and leukocyte count, injection volume, kit used, participant age/sex, comparator, and activating agent used were recorded. The short-term and long-term efficacy of PRP was assessed using the visual analog scale (VAS) to measure pain intensity. Injury subgroups (rotator cuff, tendinopathy, anterior cruciate ligament, and lateral epicondylitis) were evaluated. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers by removing studies one at a time. RESULTS Thirty-seven articles were included in this review, 21 (1031 participants) of which could be included in the quantitative analysis. The majority of studies published investigated rotator cuff injuries (38.1%) or lateral epicondylitis (38.1%). Seventeen studies (844 participants) reported short-term VAS data, and 14 studies (771 participants) reported long-term VAS data. Overall, long-term follow-up results showed significantly less pain in the PRP group compared with the control group (weighted mean difference [WMD], -0.84; 95% CI, -1.23 to -0.44; P < .01). Patients treated with PRP for rotator cuff injuries (WMD, -0.53; 95% CI, -0.98 to -0.09; P = .02) and lateral epicondylitis (WMD, -1.39; 95% CI, -2.49 to -0.29; P = .01) reported significantly less pain in the long term. Substantial heterogeneity was reported at baseline ( I2 = 72.0%; P < .01), short-term follow-up ( I2 = 72.5%; P < .01), long-term follow-up ( I2 = 76.1%; P < .01), and overall ( I2 = 75.8%; P < .01). The funnel plot appeared to be asymmetric, with some missingness at the lower right portion of the plot suggesting possible publication bias. CONCLUSION This review shows that PRP may reduce pain associated with lateral epicondylitis and rotator cuff injuries.
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Affiliation(s)
- X Chen
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - IA Jones
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - C Park
- Southern California Clinical and Translational Science Institute, Los Angeles, California, USA
| | - CT Vangsness
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Sample SJ, Racette MA, Hans EC, Volstad NJ, Schaefer SL, Bleedorn JA, Little JP, Waller KR, Hao Z, Block WF, Muir P. Use of a platelet-rich plasma-collagen scaffold as a bioenhanced repair treatment for management of partial cruciate ligament rupture in dogs. PLoS One 2018; 13:e0197204. [PMID: 29920524 PMCID: PMC6008044 DOI: 10.1371/journal.pone.0197204] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 04/27/2018] [Indexed: 01/14/2023] Open
Abstract
Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. All dogs were treated with tibial plateau leveling osteotomy (TPLO) on the unstable stifle and a single intra-articular application of PRP-collagen in the stable partial CR stifle. Dogs were evaluated at the time of diagnosis, and at 10-weeks and 12-months after treatment. We evaluated correlation between both development of complete CR and time to complete CR with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla magnetic resonance (MR) imaging, and bilateral stifle arthroscopy. Additionally, histologic evaluation of synovial biopsies, C-reactive protein (CRP) concentrations in serum and synovial fluid, and synovial total nucleated cell count, were determined. Results indicated that a single application of PRP-collagen in partial CR stifles of client owned dogs is not an effective disease-modifying therapy for the prevention of progression to complete CR. Radiographic effusion, arthroscopic evaluation of cranial cruciate ligament (CrCL) damage, and MR assessment of ligament fiber tearing in partial CR stifles correlated with progression to complete CR over the 12-month follow-up period. We determined that the best predictive model for development of complete CR in PRP-collagen treated partial CR stifles included variables from multiple diagnostic modalities.
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Affiliation(s)
- Susannah J. Sample
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Molly A. Racette
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Eric C. Hans
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Nicola J. Volstad
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Susan L. Schaefer
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Jason A. Bleedorn
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Jeffrey P. Little
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Kenneth R. Waller
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Zhengling Hao
- Comparative Orthopaedic Research Laboratory, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Walter F. Block
- Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Peter Muir
- Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
- * E-mail:
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Mahapatra P, Horriat S, Anand BS. Anterior cruciate ligament repair - past, present and future. J Exp Orthop 2018; 5:20. [PMID: 29904897 PMCID: PMC6002325 DOI: 10.1186/s40634-018-0136-6] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/31/2018] [Indexed: 12/14/2022] Open
Abstract
Background This article provides a detailed narrative review on the history and current concepts surrounding ligamentous repair techniques in athletic patients. In particular, we will focus on the anterior cruciate ligament (ACL) as a case study in ligament injury and ligamentous repair techniques. PubMed (MEDLINE), EMBASE and Cochrane Library databases for papers relating to primary anterior cruciate ligament reconstruction were searched by all participating authors. All relevant historical papers were included for analysis. Additional searches of the same databases were made for papers relating to biological enhancement of ligament healing. Current standard The poor capacity of the ACL to heal is one of the main reasons why the current gold standard surgical treatment for an ACL injury in an athletic patient is ACL reconstruction with autograft from either the hamstrings or patella tendon. It is hypothesised that by preserving and repairing native tissues and negating the need for autograft that primary ACL repair may represent a key step change in the treatment of ACL injuries. History of primary ACL repair The history of primary ACL repair will be discussed and the circumstances that led to the near-abandonment of primary ACL repair techniques will be reviewed. New primary repair techniques There has been a recent resurgence in interest with regards to primary ACL repair. Improvements in imaging now allow for identification of tear location, with femoral-sided injuries, being more suitable for repair. We will discuss in details strategies for improving the mechanical and biological environment in order to allow primary healing to occur. In particular, we will explain mechanical supplementation such as Internal Brace Ligament Augmentation and Dynamic Intraligamentary Stabilisation techniques. These are novel techniques that aim to protect the primary repair by providing a stabilising construct that connects the femur and the tibia, thus bridging the repair. Bio enhanced repair In addition, biological supplementation is being investigated as an adjunct and we will review the current literature with regards to bio-enhancement in the form platelet rich plasma, bio-scaffolds and stem cells. On the basis of current evidence, there appears to be a role for bio-enhancement, however, this is not yet translated into clinical practice. Conclusions Several promising avenues of further research now exist in the form of mechanical and biological augmentation techniques. Further work is clearly needed but there is renewed interest and focus for primary ACL repair that may yet prove the new frontier in ligament repair.
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Affiliation(s)
- Piyush Mahapatra
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK.
| | - Saman Horriat
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK
| | - Bobby S Anand
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK
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Xiong G, Lingampalli N, Koltsov JC, Leung LL, Bhutani N, Robinson WH, Chu CR. Men and Women Differ in the Biochemical Composition of Platelet-Rich Plasma. Am J Sports Med 2018; 46:409-419. [PMID: 29211968 PMCID: PMC8487642 DOI: 10.1177/0363546517740845] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Autologous platelet-rich plasma (PRP) is widely used for a variety of clinical applications. However, clinical outcome studies have not consistently shown positive effects. The composition of PRP differs based on many factors. An improved understanding of factors influencing the composition of PRP is important for the optimization of PRP use. HYPOTHESIS Age and sex influence the PRP composition in healthy patients. STUDY DESIGN Controlled laboratory study. METHODS Blood from 39 healthy patients was collected at a standardized time and processed into leukocyte-poor PRP within 1 hour of collection using the same laboratory centrifuge protocol and frozen for later analysis. Eleven female and 10 male patients were "young" (aged 18-30 years), while 8 male and 10 female patients were "older" (aged 45-60 years). Thawed PRP samples were assessed for cytokine and growth factor levels using a multiplex assay and enzyme-linked immunosorbent assay. The platelet count and high-sensitivity C-reactive protein levels were measured. Two-way analysis of variance determined age- and sex-based differences. RESULTS Platelet and high-sensitivity C-reactive protein concentrations were similar in PRP between the groups ( P = .234). Male patients had higher cytokine and growth factor levels in PRP compared with female patients for inflammatory cytokines such as interleukin-1 beta (IL-1β) (9.83 vs 7.71 pg/mL, respectively; P = .008) and tumor necrosis factor-alpha (TNF-α) (131.6 vs 110.5 pg/mL, respectively; P = .048); the anti-inflammatory IL-1 receptor antagonist protein (IRAP) (298.0 vs 218.0 pg/mL, respectively; P < .001); and growth factors such as fibroblast growth factor-basic (FGF-basic) (237.9 vs 194.0 pg/mL, respectively; P = .01), platelet-derived growth factor (PDGF-BB) (3296.2 vs 2579.3 pg/mL, respectively; P = .087), and transforming growth factor-beta 1 (TGF-β1) (118.8 vs 92.8 ng/mL, respectively; P = .002). Age- but not sex-related differences were observed for insulin-like growth factor-1 (IGF-1) ( P < .001). Age and sex interaction terms were not significant. While mean differences were significant, there was also substantial intragroup variability. CONCLUSION This study in healthy patients shows differences in the composition of PRP between men and women, with sex being a greater factor than age. There was also proteomic variability within the groups. These data support a personalized approach to PRP treatment and highlight the need for a greater understanding of the relationships between proteomic factors in PRP and clinical outcomes. CLINICAL RELEVANCE Variability in the proteomic profile of PRP may affect tissue and clinical responses to treatment. These data suggest that clinical studies should account for the composition of PRP used.
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Affiliation(s)
- Grace Xiong
- Department of Orthopaedic Surgery, Stanford University
School of Medicine, Stanford, California, USA
- Veterans Affairs Palo Alto Health Care System, Palo
Alto, California, USA
| | - Nithya Lingampalli
- Veterans Affairs Palo Alto Health Care System, Palo
Alto, California, USA
- Division of Immunology and Rheumatology, Department
of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Jayme C.B. Koltsov
- Department of Orthopaedic Surgery, Stanford University
School of Medicine, Stanford, California, USA
| | - Lawrence L. Leung
- Veterans Affairs Palo Alto Health Care System, Palo
Alto, California, USA
- Division of Hematology, Department of Medicine,
Stanford University School of Medicine, Stanford, California, USA
| | - Nidhi Bhutani
- Department of Orthopaedic Surgery, Stanford University
School of Medicine, Stanford, California, USA
| | - William H. Robinson
- Veterans Affairs Palo Alto Health Care System, Palo
Alto, California, USA
- Division of Immunology and Rheumatology, Department
of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Constance R. Chu
- Department of Orthopaedic Surgery, Stanford University
School of Medicine, Stanford, California, USA
- Veterans Affairs Palo Alto Health Care System, Palo
Alto, California, USA
- Address correspondence to Constance R. Chu, MD,
Department of Orthopaedic Surgery, Stanford University School of Medicine, 450
Broadway Street, MC 6342, Redwood City, CA 94063, USA
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Costa ELD, Teixeira LEM, Pádua BJ, Araújo IDD, Vasconcellos LDS, Dias LSB. Biomechanical study of the effect of platelet rich plasma on the treatment of medial collateral ligament lesion in rabbits. Acta Cir Bras 2018; 32:827-835. [PMID: 29160369 DOI: 10.1590/s0102-865020170100000004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 09/21/2017] [Indexed: 12/30/2022] Open
Abstract
PURPOSE To evaluate the use of platelet-rich plasma in the early stages of healing of traumatic injury of the medial collateral ligament in the knee of rabbits. METHODS Thirty rabbits were subjected to surgical lesion of the medial collateral ligament. Of these, 16 were treated with platelet-rich plasma and 14 with saline (control). After 3 and 6 weeks of treatment, 50% of the animals from each group were sacrificed, and biomechanical tests were performed on the injured ligament to compare the tensile strength between the two groups. RESULTS Platelet-rich plasma significantly increased the tensile strength of the ligament in the groups treated after3 and 6 weeks. In the group treated with platelet-rich plasma vs. saline, the tensile strength values were 3192.5 ± 189.7 g/f vs. 2851.1 ± 193.1 g/f at3 weeks (p = 0.005) and 5915.6 ± 832.0 g/f vs. 4187.6 ± 512.9 g/f at 6 weeks (p = 0.0001). CONCLUSION The use of platelet-rich plasma at the injury site accelerated ligament healing in an animal model, demonstrated by an increase in the tensile strength of the medial collateral ligament.
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Affiliation(s)
- Eduardo Louzada da Costa
- MSc, Department of Orthopedics, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte-MG, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; manuscript writing; critical revision
| | - Luiz Eduardo Moreira Teixeira
- PhD, Assistant Professor, Department of Locomotive Apparatus, UFMG, Belo Horizonte-MG, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; manuscript writing; critical revision
| | - Bruno Jannotti Pádua
- MD, Department of Orthopedics, UFMG, Belo Horizonte-MG, Brazil. Acquisition, analysis and interpretation of data
| | - Ivana Duval de Araújo
- PhD, Assistant Professor, Department of Surgery, UFMG, Belo Horizonte-MG, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; manuscript writing; critical revision
| | - Leonardo de Souza Vasconcellos
- PhD, Assistant Professor, Pharmacy Department, UFMG, Belo Horizonte-MG, Brazil. Acquisition, analysis and interpretation of data; manuscript writing; critical revision
| | - Luide Scalioni Borges Dias
- Graduate student, School of Medicine, UFMG, Belo Horizonte-MG, Brazil. Acquisition, analysis and interpretation of data
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Krismer AM, Cabra RS, May RD, Frauchiger DA, Kohl S, Ahmad SS, Gantenbein B. Biologic response of human anterior cruciate ligamentocytes on collagen-patches to platelet-rich plasma formulations with and without leucocytes. J Orthop Res 2017; 35:2733-2739. [PMID: 28485509 DOI: 10.1002/jor.23599] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2017] [Accepted: 05/01/2017] [Indexed: 02/04/2023]
Abstract
Due to the poor self-healing capacities of the anterior cruciate ligament, previous primary repair attempts have failed. To enhance biologic healing, platelet rich plasma and collagen scaffold have shown promise in animal models. Platelet rich plasma (PRP) is already used in several clinical applications although outcomes are quite debated. The purpose of this study was to examine the effects of different PRP formulations during 21 days: With leucocytes and pure PRP on human anterior cruciate ligament-derived ligamentocytes grown on collagen patches in 3D cell cultures in vitro. Three experimental groups were formed: 2.5% leucocyte rich PRP, 2.5% pure PRP, 20% leucocyte rich PRP, a negative control, and a positive control. Cell proliferation, cell phenotype on mRNA transcript level, and extracellular matrix production (total collagen and glycosaminoglycan content) were evaluated. DNA content and metabolic cell activity increased significantly in all groups on day 21 compared to day 7, except in the negative control. No changes in extracellular matrix production were detected. Different catabolic genes were induced depending on the concentration of leucocyte rich PRP. PRP with and without leucocytes treated anterior cruciate ligamentocytes significantly increased cell proliferation but not extracellular matrix production. However, the specific activation of different catabolic genes was dependent on the relative content of leucocytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2733-2739, 2017.
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Affiliation(s)
- Anna M Krismer
- Tissue and Organ Mechanobiology, Institute for Surgical Technology and Biomechanics, University of Bern, Stauffacherstrasse 78, CH-3014 Bern, Switzerland.,Department of Orthopaedic Surgery & Traumatology, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland
| | - Romina S Cabra
- Tissue and Organ Mechanobiology, Institute for Surgical Technology and Biomechanics, University of Bern, Stauffacherstrasse 78, CH-3014 Bern, Switzerland
| | - Rahel D May
- Tissue and Organ Mechanobiology, Institute for Surgical Technology and Biomechanics, University of Bern, Stauffacherstrasse 78, CH-3014 Bern, Switzerland
| | - Daniela A Frauchiger
- Tissue and Organ Mechanobiology, Institute for Surgical Technology and Biomechanics, University of Bern, Stauffacherstrasse 78, CH-3014 Bern, Switzerland
| | - Sandro Kohl
- Department of Orthopaedic Surgery & Traumatology, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland
| | - Sufian S Ahmad
- Department of Orthopaedic Surgery & Traumatology, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland
| | - Benjamin Gantenbein
- Tissue and Organ Mechanobiology, Institute for Surgical Technology and Biomechanics, University of Bern, Stauffacherstrasse 78, CH-3014 Bern, Switzerland
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Raeissadat SA, Babaee M, Rayegani SM, Hashemi Z, Hamidieh AA, Mojgani P, Fouladi Vanda H. An overview of platelet products (PRP, PRGF, PRF, etc.) in the Iranian studies. Future Sci OA 2017; 3:FSO231. [PMID: 29134118 PMCID: PMC5674219 DOI: 10.4155/fsoa-2017-0045] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 06/16/2017] [Indexed: 02/06/2023] Open
Abstract
Aim The aim of the study was to carry out a review of published studies on various platelet products in Iranian studies. Materials & methods Electronic databases were searched for relevant articles. Two review authors independently extracted data via a tested extraction sheet, and disagreements were resolved by a meeting with a third review author. Results Bone disorders (25%), wound and fistula (16%), dental and gingival disorders (14%) and osteoarthritis (11%) have more relative frequency based on different fields. Conclusion The necessity of pursuing standard protocols in the preparation of platelet products, stating the precise content of platelets and growth factors, and long-term follow-up of study subjects were the most important points in Iranian studies.
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Affiliation(s)
- Seyed Ahmad Raeissadat
- Clinical Research Development Center of Shahid Modarres Hospital & Physical Medicine & Rehabilitation Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marzieh Babaee
- Clinical Research Development Center of Shahid Modarres Hospital & Physical Medicine & Rehabilitation Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Mansour Rayegani
- Clinical Research Development Center of Shahid Modarres Hospital & Physical Medicine & Rehabilitation Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Hashemi
- Clinical Research Development Center of Shahid Modarres Hospital & Physical Medicine & Rehabilitation Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ali Hamidieh
- Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Parviz Mojgani
- Rehabilitation and Medical Education Department, Iran Helal institute of Applied Sciences and Technology, affiliated to the Red Crescent Society of Iran, Tehran, Iran
| | - Hossein Fouladi Vanda
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
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Pancreatic Cancer-Induced Neutrophil Extracellular Traps: A Potential Contributor to Cancer-Associated Thrombosis. Int J Mol Sci 2017; 18:ijms18030487. [PMID: 28245569 PMCID: PMC5372503 DOI: 10.3390/ijms18030487] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 01/30/2017] [Accepted: 02/13/2017] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer (PaCa) is a highly metastatic cancer, and patients are at high risk of developing venous thromboembolism (VTE). Neutrophil extracellular traps (NETs) have been associated with cancer metastasis and cancer-associated thrombosis, but the ability of cancer to stimulate NET release is not known. The release of NETs has been shown to be a slow process and requires reactive oxygen species (ROS) production. Studies suggest that activated platelets are important mediators in the release. Here, we show that PaCa cells can stimulate the rapid release of NETs, independently of ROS production. We further assessed the role of platelets in PaCa-induced NETs and observed a trend of increased the NET release by PaCa-primed platelets. Additionally, NETs promoted thrombus formation under venous shear stress ex vivo. Taken together, our results suggest that PaCa-induced NETs can contribute to the high risk of venous thromboembolism development in PaCa patients, and reveal NETs as a potential therapeutic target.
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Biomaterials as Tendon and Ligament Substitutes: Current Developments. REGENERATIVE STRATEGIES FOR THE TREATMENT OF KNEE JOINT DISABILITIES 2017. [DOI: 10.1007/978-3-319-44785-8_17] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Mengsteab PY, Nair LS, Laurencin CT. The past, present and future of ligament regenerative engineering. Regen Med 2016; 11:871-881. [PMID: 27879170 DOI: 10.2217/rme-2016-0125] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes.
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Affiliation(s)
- Paulos Y Mengsteab
- Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.,Raymond & Beverly Sackler Center for Biomedical, Biological, Physical & Engineering Sciences, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030, USA
| | - Lakshmi S Nair
- Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.,Raymond & Beverly Sackler Center for Biomedical, Biological, Physical & Engineering Sciences, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Materials Science & Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Chemical & Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA
| | - Cato T Laurencin
- Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.,Raymond & Beverly Sackler Center for Biomedical, Biological, Physical & Engineering Sciences, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030, USA.,Department of Materials Science & Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Chemical & Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT 06030, USA
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Häberli J, Henle P, Acklin YP, Zderic I, Gueorguiev B. Knee joint kinematics with dynamic augmentation of primary anterior cruciate ligament repair - a biomechanical study. J Exp Orthop 2016; 3:29. [PMID: 27783350 PMCID: PMC5080274 DOI: 10.1186/s40634-016-0064-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 10/04/2016] [Indexed: 01/28/2023] Open
Abstract
Background Dynamic augmentation of anterior cruciate ligament tears seems to reduce anteroposterior knee translation close to the pre-injury level. The aim of the present study is to biomechanically investigate the course of translation during a simulated early post-operative phase. It is hypothesized that anteroposterior translation is maintained at the immediate post-operative level over a simulated rehabilitation period of 50’000 gait cycles. Methods Eight fresh-frozen human cadaveric knee joints from donors with a mean age of 35.5 (range 25–40) years were subjected to 50’000 cycles of 0°-70°-0° flexion-extension movements in a custom-made test setup. Anteroposterior translation was assessed with simulated Lachman/KT-1000 testing in 0°, 15°, 30°, 60° and 90° of flexion in knee joints treated with the novel technique initially and after 50’000 cycles testing. Statistical analysis was performed using the Wilcoxon Signed-Rank Test. The level of significance was set at p = 0.05. Results Anteroposterior translation changed non-significantly for all flexion angles between cycle 0 and 50’000 (p = 0.39 to p = 0.89), except for 30° flexion, where a significant increase by 1.4 mm was found (p = 0.03). Conclusion Increase in anteroposterior translation of knees treated with this dynamic augmentation procedure is low. The procedure maintains translation close to the immediate post-operative level over a simulated rehabilitation period of 50’000 gait cycles and therefore supports anterior cruciate ligament repair during biological healing.
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Affiliation(s)
- Janosch Häberli
- Sonnenhof Orthopaedic Centre, Buchserstrasse 30, 3006, Bern, Switzerland.
| | - Philipp Henle
- Sonnenhof Orthopaedic Centre, Buchserstrasse 30, 3006, Bern, Switzerland
| | - Yves P Acklin
- AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland
| | - Ivan Zderic
- AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland
| | - Boyko Gueorguiev
- AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland
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Redler LH, Degen RM, McDonald LS, Altchek DW, Dines JS. Elbow ulnar collateral ligament injuries in athletes: Can we improve our outcomes? World J Orthop 2016; 7:229-243. [PMID: 27114930 PMCID: PMC4832224 DOI: 10.5312/wjo.v7.i4.229] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 11/18/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
Injury to the ulnar collateral ligament (UCL) most commonly occurs in the overhead throwing athlete. Knowledge surrounding UCL injury pathomechanics continues to improve, leading to better preventative treatment strategies and rehabilitation programs. Conservative treatment strategies for partial injuries, improved operative techniques for reconstruction in complete tears, adjunctive treatments, as well as structured sport specific rehabilitation programs including resistive exercises for the entire upper extremity kinetic chain are all important factors in allowing for a return to throwing in competitive environments. In this review, we explore each of these factors and provide recommendations based on the available literature to improve outcomes in UCL injuries in athletes.
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Negahi Shirazi A, Chrzanowski W, Khademhosseini A, Dehghani F. Anterior Cruciate Ligament: Structure, Injuries and Regenerative Treatments. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 881:161-86. [PMID: 26545750 DOI: 10.1007/978-3-319-22345-2_10] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Anterior cruciate ligament (ACL) is one of the most vulnerable ligaments of the knee. ACL impairment results in episodic instability, chondral and meniscal injury and early osteoarthritis. The poor self-healing capacity of ACL makes surgical treatment inevitable. Current ACL reconstructions include a substitution of torn ACL via biological grafts such as autograft, allograft. This review provides an insight of ACL structure, orientation and properties followed by comparing the performance of various constructs that have been used for ACL replacement. New approaches, undertaken to induce ACL regeneration and fabricate biomimetic scaffolds, are also discussed.
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Affiliation(s)
- Ali Negahi Shirazi
- School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, NSW, 2006, Australia
| | | | - Ali Khademhosseini
- Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.,Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Fariba Dehghani
- School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, NSW, 2006, Australia. .,Department of Bioengineering, University of Sydney, Sydney, NSW, Australia.
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Assessment of canine autologous platelet-rich plasma produced with a commercial centrifugation and platelet recovery kit. Vet Comp Orthop Traumatol 2015; 29:14-9. [PMID: 26603823 DOI: 10.3415/vcot-15-03-0046] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 07/24/2015] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To characterize the cellular composition (platelets, erythrocytes, and leukocytes) and confirm reproducibility of platelet enrichment, as well as determine the platelet activation status in the final product of a commercial platelet-rich plasma kit using canine blood. METHODS Venous blood from 20 sedated client-owned dogs was used to prepare platelet-rich plasma (PRP) from a commercial kit. Complete blood counts were performed to determine erythrocyte, leukocyte, and platelet numbers in both whole blood (WB) and resultant PRP. The WB and PRP samples from jugular (fast collection) and cephalic (slow collection) venipuncture were also compared. P-selectin externalization was measured in WB and PRP samples from 15 of 20 dogs. RESULTS This commercial kit produced an average percent recovery in platelets of 64.7 ± 17.4; erythrocytes of 3.7 ± 0.8, and leukocytes of 31.6 ± 10.0. Neutrophil, monocyte, and lymphocyte percent recovery was 19.6 ± 7.2, 44.89 ± 19.8, and 57.5 ± 10.6, respectively. The recovery of platelets from jugular venipuncture (59.7 ± 13.6%) was lower than from cephalic recovery (68.8 ± 19.1%). The mean percent P-Selectin externalization for WB, PRP, and PRP with thrombin was 25.5 ± 30.9, 4.5 ± 6.4, and 90.6 ± 4.4 respectively. CLINICAL SIGNIFICANCE Cellular reproducibility of this kit was confirmed and platelets were concentrated within autologous serum. Additionally, measurements of P-selectin externalization showed that platelets are inactive in PRP unless stimulated to degranulate.
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Taylor SA, Khair MM, Roberts TR, DiFelice GS. Primary Repair of the Anterior Cruciate Ligament: A Systematic Review. Arthroscopy 2015; 31:2233-47. [PMID: 26165465 DOI: 10.1016/j.arthro.2015.05.007] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 04/13/2015] [Accepted: 05/13/2015] [Indexed: 02/02/2023]
Abstract
PURPOSE To describe the clinical and preclinical research conducted on primary repair of the anterior cruciate ligament (ACL) during the past 10 years. METHODS A systematic search of PubMed, the Cochrane Central Register of Controlled Trials, and Embase was performed for all English-language studies published between 2003 and April 2014 on primary repair of the ACL. RESULTS Twenty-six studies met the inclusion and exclusion criteria. In the clinical research group, 8 studies (166 patients; age range, 10 to 71 years) met the inclusion and exclusion criteria and were largely long-term clinical outcome studies, based on the original cohorts from the 1970s and 1980s, and suggested high failure rates, additional surgery, and revision for instability. A subset of patients, however, achieved good to excellent subjective and objective long-term outcomes. In the preclinical research group, 18 studies met the inclusion and exclusion criteria and were based on an ACL transection model; they suggested that (1) stabilization of the knee with an internal suture strut improved the healing and biomechanical properties of the repaired ACL, (2) "enhancing" the repair with biological collagen-platelet composite augmentation improved healing and mechanical strength, (3) younger age and skeletal immaturity seem to correlate with improved histologic healing and biomechanical properties, (4) enhanced primary repair of the ACL may reduce post-traumatic osteoarthritis, and (5) the native ACL biomechanically outperformed the repaired ACL. CONCLUSIONS Although long-term human studies suggest collectively unacceptable outcomes for open primary repair of the ACL, a subset of patients achieved acceptable long-term results. ACL transection model animal studies showed improved healing and biomechanics with primary suture repair stabilization, early intervention, biological augmentation techniques, and younger age. Primary repair of the ACL may be an effective treatment modality for an appropriately selected subset of patients. LEVEL OF EVIDENCE Level IV, systematic review of preclinical and clinical Level IV studies.
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Affiliation(s)
- Samuel A Taylor
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - M Michael Khair
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - Timothy R Roberts
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - Gregory S DiFelice
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A..
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Zhou Y, Zhang J, Wu H, Hogan MV, Wang JHC. The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries. Stem Cell Res Ther 2015; 6:173. [PMID: 26373929 PMCID: PMC4572462 DOI: 10.1186/s13287-015-0172-4] [Citation(s) in RCA: 121] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 08/25/2015] [Accepted: 08/27/2015] [Indexed: 12/21/2022] Open
Abstract
Introduction Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair. Methods TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively. Results Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III. Conclusions These findings indicate that, while both L-PRP and P-PRP appear to be “safe” in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects.
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Affiliation(s)
- Yiqin Zhou
- MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA. .,Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu, Shanghai, 200003, China.
| | - Jianying Zhang
- MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA.
| | - Haishan Wu
- Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu, Shanghai, 200003, China.
| | - MaCalus V Hogan
- MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA.
| | - James H-C Wang
- MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA.
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Central defect type partial ACL injury model on goat knees: the effect of infrapatellar fat pad excision. J Orthop Surg Res 2015; 10:137. [PMID: 26338041 PMCID: PMC4558767 DOI: 10.1186/s13018-015-0281-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 08/25/2015] [Indexed: 01/12/2023] Open
Abstract
Background The mid-substance central defect injury has been used to investigate the primary healing capacity of the anterior cruciate ligament (ACL) in a goat model. The sagittal plane stability on this model has not been confirmed, and possible effects of fat pad excision on healing have not been evaluated. We hypothesize that excising the fat pad tissue results in poorer ligament healing as assessed histologically and decreased tensile strength of the healing ligament. We further hypothesize that the creation of a central defect does not affect sagittal plane knee stability. Methods A mid-substance central defect was created with a 4-mm arthroscopic punch in the ACLs of right knees of all the subjects through a medial mini-arthrotomy. Goats were assigned to groups based on whether the fat pad was preserved (group 1, n = 5) or excised completely (group 2, n = 5). The left knees served as controls in each goat. Histopathology of the defect area along with measurement of type I collagen in one goat from each group were performed at 10th week postoperatively. The remaining knees were evaluated biomechanically at the 12th week, by measuring anterior tibial translation (ATT) of the knee joints at 90° of flexion and testing tensile properties (ultimate tensile load (UTL), ultimate elongation (UE), stiffness (S), failure mode (FM)) of the femur-ACL-tibia complex. Results and discussion Histopathology analysis revealed that the central defect area was fully filled macroscopically and microscopically. However, myxoid degeneration and fibrosis were observed in group 2 and increased collagen type I content was noted in group 2. There were no significant differences within and between groups in terms of ATT values (p = 0.715 and p = 0.149, respectively). There were no significance between or within groups in terms of ultimate tensile load and ultimate elongation; however, group 2 demonstrated greater stiffness than group 1 that was correlated with the fibrotic changes detected microscopically (p = 0.043). Conclusions The central defect type injury model was confirmed to be biomechanically stable in a goat model. Resection of the fat pad was noted to negatively affect defect healing and increase ligament stiffness in the central defect injury model.
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PRP Augmentation for ACL Reconstruction. BIOMED RESEARCH INTERNATIONAL 2015; 2015:371746. [PMID: 26064903 PMCID: PMC4430629 DOI: 10.1155/2015/371746] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Accepted: 08/15/2014] [Indexed: 12/19/2022]
Abstract
Current research is investigating new methods to enhance tissue healing to speed up recovery time and decrease the risk of failure in Anterior Cruciate Ligament (ACL) reconstructive surgery. Biological augmentation is one of the most exploited strategies, in particular the application of Platelet Rich Plasma (PRP). Aim of the present paper is to systematically review all the preclinical and clinical papers dealing with the application of PRP as a biological enhancer during ACL reconstructive surgery. Thirty-two studies were included in the present review. The analysis of the preclinical evidence revealed that PRP was able to improve the healing potential of the tendinous graft both in terms of histological and biomechanical performance. Looking at the available clinical evidence, results were not univocal. PRP administration proved to be a safe procedure and there were some evidences that it could favor the donor site healing in case of ACL reconstruction with patellar tendon graft and positively contribute to graft maturation over time, whereas the majority of the papers did not show beneficial effects in terms of bony tunnels/graft area integration. Furthermore, PRP augmentation did not provide superior functional results at short term evaluation.
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Henle P, Röder C, Perler G, Heitkemper S, Eggli S. Dynamic Intraligamentary Stabilization (DIS) for treatment of acute anterior cruciate ligament ruptures: case series experience of the first three years. BMC Musculoskelet Disord 2015; 16:27. [PMID: 25813910 PMCID: PMC4341869 DOI: 10.1186/s12891-015-0484-7] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Accepted: 01/29/2015] [Indexed: 01/26/2023] Open
Abstract
Background In recent years, the scientific discussion has focused on new strategies to enable a torn anterior cruciate ligament (ACL) to heal into mechanically stable scar tissue. Dynamic intraligamentary stabilization (DIS) was first performed in a pilot study of 10 patients. The purpose of the current study was to evaluate whether DIS would lead to similarly sufficient stability and good clinical function in a larger case series. Methods Acute ACL ruptures were treated by using an internal stabilizer, combined with anatomical repositioning of torn bundles and microfracturing to promote self-healing. Clinical assessment (Tegner, Lysholm, IKDC, and visual analogue scale [VAS] for patient satisfaction scores) and assessment of knee laxity was performed at 3, 6, 12, and 24 months. A one-sample design with a non-inferiority margin was chosen to compare the preoperative and postoperative IKDS and Lysholm scores. Results 278 patients with a 6:4 male to female ratio were included. Average patient age was 31 years. Preoperative mean IKDC, Lysholm, and Tegner scores were 98.8, 99.3, and 5.1 points, respectively. The mean anteroposterior (AP) translation difference from the healthy contralateral knee was 4.7 mm preoperatively. After DIS treatment, the mean 12-month IKDC, Lysholm, and Tegner scores were 93.6, 96.2, and 4.9 points, respectively, and the mean AP translation difference was 2.3 mm. All these outcomes were significantly non-inferior to the preoperative or healthy contralateral values (p < 0.0001). Mean patient satisfaction was 8.8 (VAS 0–10). Eight ACL reruptures occurred and 3 patients reported insufficient subjective stability of the knee at the end of the study period. Conclusions Anatomical repositioning, along with DIS and microfracturing, leads to clinically stable healing of the torn ACL in the large majority of patients. Most patients exhibited almost normal knee function, reported excellent satisfaction, and were able to return to their previous levels of sporting activity. Moreover, this strategy resulted in stable healing of all sutured menisci, which could lower the rate of osteoarthritic changes in future. The present findings support the discussion of a new paradigm in ACL treatment based on preservation and self-healing of the torn ligament.
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Affiliation(s)
- Philipp Henle
- Sonnenhof Orthopaedic Center, Department of Knee Surgery and Sports Traumatology, Buchserstrasse 30, CH-3006, Bern, Switzerland.
| | - Christoph Röder
- Institute for Evaluative Research in Medicine, University of Bern, Stauffacherstrasse 78, CH-3014, Bern, Switzerland.
| | - Gosia Perler
- Institute for Evaluative Research in Medicine, University of Bern, Stauffacherstrasse 78, CH-3014, Bern, Switzerland.
| | - Sven Heitkemper
- Sonnenhof Orthopaedic Center, Department of Knee Surgery and Sports Traumatology, Buchserstrasse 30, CH-3006, Bern, Switzerland.
| | - Stefan Eggli
- Sonnenhof Orthopaedic Center, Department of Knee Surgery and Sports Traumatology, Buchserstrasse 30, CH-3006, Bern, Switzerland.
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Proffen BL, Vavken P, Haslauer CM, Fleming BC, Harris CE, Machan JT, Murray MM. Addition of autologous mesenchymal stem cells to whole blood for bioenhanced ACL repair has no benefit in the porcine model. Am J Sports Med 2015; 43:320-30. [PMID: 25549633 PMCID: PMC4511104 DOI: 10.1177/0363546514559826] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Coculture of mesenchymal stem cells (MSCs) from the retropatellar fat pad and peripheral blood has been shown to stimulate anterior cruciate ligament (ACL) fibroblast proliferation and collagen production in vitro. Current techniques of bioenhanced ACL repair in animal studies involve adding a biologic scaffold, in this case an extracellular matrix-based scaffold saturated with autologous whole blood, to a simple suture repair of the ligament. Whether the enrichment of whole blood with MSCs would further improve the in vivo results of bioenhanced ACL repair was investigated. HYPOTHESIS The addition of MSCs derived from adipose tissue or peripheral blood to the blood-extracellular matrix composite, which is used in bioenhanced ACL repair to stimulate healing, would improve the biomechanical properties of a bioenhanced ACL repair after 15 weeks of healing. STUDY DESIGN Controlled laboratory study. METHODS Twenty-four adolescent Yucatan mini-pigs underwent ACL transection followed by (1) bioenhanced ACL repair, (2) bioenhanced ACL repair with the addition of autologous adipose-derived MSCs, and (3) bioenhanced ACL repair with the addition of autologous peripheral blood derived MSCs. After 15 weeks of healing, the structural properties of the ACL (yield load, failure load, and linear stiffness) were measured. Cell and vascular density were measured in the repaired ACL via histology, and its tissue structure was qualitatively evaluated using the advanced Ligament Maturity Index. RESULTS After 15 weeks of healing, there were no significant improvements in the biomechanical or histological properties with the addition of adipose-derived MSCs. The only significant change with the addition of peripheral blood MSCs was an increase in knee anteroposterior laxity when measured at 30° of flexion. CONCLUSION These findings suggest that the addition of adipose or peripheral blood MSCs to whole blood before saturation of an extracellular matrix carrier with the blood did not improve the functional results of bioenhanced ACL repair after 15 weeks of healing in the pig model. CLINICAL RELEVANCE Whole blood represents a practical biologic additive to ligament repair, and any other additive (including stem cells) should be demonstrated to be superior to this baseline before clinical use is considered.
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Affiliation(s)
- Benedikt L. Proffen
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Patrick Vavken
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
- Department of Orthopaedic Surgery, University Hospital Basel, Switzerland
| | - Carla M. Haslauer
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Braden C. Fleming
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Chad E. Harris
- Department of Hematology/Oncology, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Jason T. Machan
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
- Biostatistics, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Martha M. Murray
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
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