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Annicchiarico A, Barile B, Buccoliero C, Nicchia GP, Brunetti G. Alternative therapeutic strategies in diabetes management. World J Diabetes 2024; 15:1142-1161. [PMID: 38983831 PMCID: PMC11229975 DOI: 10.4239/wjd.v15.i6.1142] [Citation(s) in RCA: 2] [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: 01/29/2024] [Revised: 02/17/2024] [Accepted: 04/12/2024] [Indexed: 06/11/2024] Open
Abstract
Diabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreatic β cells, insulin resistance in peripheral tissues, or both, and results in a non-sufficient production of insulin. To adjust blood glucose levels, diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity. With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities, different strategies have been investigated. The first approaches included enhancing endogenous β cell activity or transplanting new islets. The protocol for this kind of intervention has recently been optimized, leading to standardized procedures. It is indicated for diabetic patients with severe hypoglycemia, complicated by impaired hypoglycemia awareness or exacerbated glycemic lability. Transplantation has been associated with improvement in all comorbidities associated with diabetes, quality of life, and survival. However, different trials are ongoing to further improve the beneficial effects of transplantation. Furthermore, to overcome some limitations associated with the availability of islets/pancreas, alternative therapeutic strategies are under evaluation, such as the use of mesenchymal stem cells (MSCs) or induced pluripotent stem cells for transplantation. The cotransplantation of MSCs with islets has been successful, thus providing protection against proinflammatory cytokines and hypoxia through different mechanisms, including exosome release. The use of induced pluripotent stem cells is recent and requires further investigation. The advantages of MSC implantation have also included the improvement of diabetes-related comorbidities, such as wound healing. Despite the number of advantages of the direct injection of MSCs, new strategies involving biomaterials and scaffolds have been developed to improve the efficacy of mesenchymal cell delivery with promising results. In conclusion, this paper offered an overview of new alternative strategies for diabetes management while highlighting some limitations that will need to be overcome by future approaches.
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Affiliation(s)
- Alessia Annicchiarico
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Barbara Barile
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Cinzia Buccoliero
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Grazia Paola Nicchia
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Giacomina Brunetti
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
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Gholijani A, Tavanafar S, Zareifard N, Vojdani Z, Namavar MR, Emami A, Talaei-Khozani T. In Situ Casting of Platelet Rich Plasma/SiO2/Alginate for Bone Tissue Engineering Application in Rabbit Mandible Defect Model. JOURNAL OF DENTISTRY (SHIRAZ, IRAN) 2022; 23:349-360. [PMID: 36588966 PMCID: PMC9789338 DOI: 10.30476/dentjods.2021.90677.1513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Revised: 05/08/2021] [Accepted: 07/31/2021] [Indexed: 01/03/2023]
Abstract
Statement of the Problem The administration of both platelet rich plasma (PRP) and silicon dioxide (SiO2) to the bone defects accelerates bone repair and regeneration. Appli-cation of both of them may show synergistic regenerative effects. Purpose Our objective was to evaluate the possible synergistic osteogenic effects of PRP and SiO2 by injecting them using an ad hoc device. Materials and Method In this experimental study, PRP/SiO2 scaffolds were fabricated by in situ casting method with the help of CaCl2 as the gelation factor and alginate as the stroma; and then, the biodegradability and spatial arrangement were assessed. The injecta-ble scaffold was introduced into the 40 rabbit mandibular defects by an ad hoc two-channel injecting device. Five defects received PRP/SiO2/alginate as the treatment; the other sets of defects were treated by PRP/alginate, SiO2/alginate, and the last five defects served as the control groups by getting only alginate injections. The osteogenicity of the scaffolds was evaluated by radiological and histological procedures; they were then compared with each other. Analysis of variance and least significant difference tests were used to analyze the data. Results The SiO2-treated group showed a significant higher bone area compared to PRP/ SiO2-treated groups on day 40 (p= 0.013). The number of osteocytes was higher in SiO2-treated than the control groups on both 20 and 40 days (p= 0.032 and 0.022, respectively). The number of osteoclast was also higher in SiO2-treated than PRP-treated group (p= 0.028). In addition, the cells of this group had just started to create Haversian systems in newly formed bone tissues. Conclusion Silica demonstrated a superior osteogenic activity over PRP in both short and long term periods. Evidently, they showed no synergistic regenerative effects. Our ad hoc device was efficiently capable of inserting the scaffolds into the injured sites with no diffi-culties or complications.
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Affiliation(s)
- Amin Gholijani
- Student, Tissue Engineering Lab, Dept. of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saeid Tavanafar
- Dept. of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nehleh Zareifard
- Morphometry and Stereology Research Center, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Vojdani
- Student, Tissue Engineering Lab, Dept. of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Reza Namavar
- Morphometry and Stereology Research Center, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran,
Dept. of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Asrin Emami
- Student, Tissue Engineering Lab, Dept. of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Tahere Talaei-Khozani
- Student, Tissue Engineering Lab, Dept. of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran,
Morphometry and Stereology Research Center, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
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Xiang Z, Guan X, Ma Z, Shi Q, Panteleev M, Ataullakhanov FI. Bioactive engineered scaffolds based on PCL-PEG-PCL and tumor cell-derived exosomes to minimize the foreign body reaction. BIOMATERIALS AND BIOSYSTEMS 2022; 7:100055. [PMID: 36824486 PMCID: PMC9934494 DOI: 10.1016/j.bbiosy.2022.100055] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 05/31/2022] [Accepted: 06/08/2022] [Indexed: 11/16/2022] Open
Abstract
Long-term presence of M1 macrophages causes serious foreign body reaction (FBR), which is the main reason for the failure of biological scaffold integration. Inducing M2 polarization of macrophages near scaffolds to reduce foreign body response has been widely researched. In this work, inspired by the special capability of tumor exosomes in macrophages M2 polarization, we integrate tumor-derived exosomes into biological scaffolds to minimize the FBR. In brief, breast cancer cell-derived exosomes are loaded into polycaprolactone-b-polyethylene glycol-b-polycaprolactone (PCL-PEG-PCL) fiber scaffold through physical adsorption and entrapment to constructed bioactive engineered scaffold. In cellular experiments, we demonstrate bioactive engineered scaffold based on PCL-PEG-PCL and exosomes can promote the transformation of macrophages from M1 to M2 through the PI3K/Akt signaling pathway. In addition, the exosomes release gradually from scaffolds and act on the macrophages around the scaffolds to reduce FBR in a subcutaneous implant mouse model. Compared with PCL-PEG-PCL scaffolds without exosomes, bioactive engineered scaffolds reduce significantly inflammation and fibrosis of tissues around the scaffolds. Therefore, cancer cell-derived exosomes show the potential for constructing engineered scaffolds in inhibiting the excessive inflammation and facilitating tissue formation.
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Affiliation(s)
- Zehong Xiang
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China
- University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Xinghua Guan
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China
- University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Zhifang Ma
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China
| | - Qiang Shi
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China
- University of Science and Technology of China, Hefei, Anhui 230026, China
- Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function, Soochow University, Suzhou 215123, China
| | - Mikhail Panteleev
- Dmitry Rogachev Natl Res Ctr Pediat Hematol Oncol, 1 Samory Mashela St, Moscow, 117198, Russia
- Faculty of Physics, Lomonosov Moscow State University, Leninskie Gory, 1, build. 2, GSP-1, Moscow 119991, Russia
| | - Fazly I Ataullakhanov
- Dmitry Rogachev Natl Res Ctr Pediat Hematol Oncol, 1 Samory Mashela St, Moscow, 117198, Russia
- Faculty of Physics, Lomonosov Moscow State University, Leninskie Gory, 1, build. 2, GSP-1, Moscow 119991, Russia
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Araujo-Gutierrez R, Van Eps JL, Scherba JC, Anastasio AT, Cabrera F, Vatsaas CJ, Youker K, Fernandez Moure JS. Platelet rich plasma concentration improves biologic mesh incorporation and decreases multinucleated giant cells in a dose dependent fashion. J Tissue Eng Regen Med 2021; 15:1037-1046. [PMID: 34551456 DOI: 10.1002/term.3247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 08/19/2021] [Accepted: 08/31/2021] [Indexed: 11/09/2022]
Abstract
Platelet rich plasma (PRP) has been shown to improve incorporation and reduce inflammation in ventral hernia repair (VHR) with acellular dermal matrix (ADM). The concentration of platelets in PRP varies in clinical studies and an ideal concentration has yet to be defined. The effects of varied concentrations of PRP on ADM incorporation and inflammatory cell infiltration in a rat model of VHR. We hypothesized that increasing concentration of PRP would lead to improved incorporation, decreased CD8+ and multinucleated giant cell (MNGC) infiltrate. Lewis rats underwent ventral hernia creation and repair 30 days later with porcine non-crosslinked ADM. PRP was applied to the mesh prior to skin closure at concentrations of 1 × 104 plt/μL (PRP-LOW), 1 × 106 plt/μL (PRP-MID), or 1 × 107 plt/μL (PRP-HIGH) and tissue harvested at 2 and 4 weeks. Cellularization, tissue deposition, and mesh thickness using hematoxylin and eosin and Masson's trichrome, and neovascularization was assessed with VVG staining, to establish the relationship of PRP concentration to metrics of incorporation. MNGC and CD8+ T-cell infiltration were quantified to establish the relationship of inflammatory cell infiltration in response to PRP concentration. Lymphocyte infiltration was assessed using immunohistochemical staining for CD8. PRP-HIGH treated had significantly greater tissue deposition at 4 weeks. PRP-MID showed increasing mesh thickness at 2 weeks. Cell infiltration was significantly higher with PRP-HIGH at both 2 and 4 weeks while PRP-LOW showed increased cell infiltration only at 4 weeks. At both time points there was a trend towards a dose dependent response in cell infiltration to PRP concentration. Neovascularization was highest with MID-plt at 2 weeks, yet no significant differences were noted compared to controls. CD8+ cell infiltrate was significantly decreased at 2 and 4 weeks in PRP-LOW and PRP-MID treated groups. PRP at all concentrations significantly decreased MNGC infiltration at 2 weeks while only PRP-HIGH and PRP-MID had significant reductions in MNGC at 4 weeks. Both MNGC and CD8+ cell infiltration demonstrated dose dependent reduction in relation to PRP concentration. Increasing platelet concentrations of PRP correlated with improved incorporation, tissue deposition, and decreased scaffold degradation. These findings were associated with a blunted foreign body response. These findings suggest PRP reduces inflammation which may be beneficial for ADM incorporation in VHR.
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Affiliation(s)
| | - Jeffrey L Van Eps
- Department of Surgery, Section of Colon & Rectal Surgery, UTHealth at McGovern Medical School, Houston, Texas, USA
| | - Jacob C Scherba
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
| | - Albert Thomas Anastasio
- Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, North Carolina, USA
| | - Fernando Cabrera
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA
| | - Cory J Vatsaas
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA
| | - Keith Youker
- Department of Cardiovascular Science, Houston Methodist Hospital, Houston, Texas, USA
| | - Joseph S Fernandez Moure
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA
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Zhang S, Li Q, Liu P, Lin C, Tang Z, Wang HL. Three-Dimensional Cell Printed Lock-Key Structure for Oral Soft and Hard Tissue Regeneration. Tissue Eng Part A 2021; 28:13-26. [PMID: 33957771 DOI: 10.1089/ten.tea.2021.0022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Alveolar ridge absorbs rapidly following tooth extraction. To promote implant rehabilitation, an adequate bone and soft tissue volume are required. Three-dimensional (3D) cell printing technique provides the advantages of precise spatial distribution and personalization. In this study, 3D cell printing was used to establish a soft-hard construct that is composed of alginate/gelatin (AG)/gingival fibroblast cells (GFs) and alginate/gelatin/nano-hydroxyapatite (AGH)/bone marrow-derived mesenchymal stem cells (BMSCs). Physicochemical results showed that nano-hydroxyapatite (nHA) added in the bioink maintained its crystalline phase. In addition, an increase of viscosity, the improvement of compressive modulus (p < 0.01), and slow degradation rate (p < 0.01) were found after adding nHA. SEM showed cell stretched and attached well on the surface of the 3D printed construct. At day 7 after printing, the viability of GFs in AG was 94.80% ± 1.14%, while BMSC viability in AGH was 86.59% ± 0.75%. Polymerase chain reaction results indicated that the expression levels of ALP, RUNX-2, and OCN in BMSCs were higher in AGH than AG bioink (p < 0.01). After 8-week implantation into the dorsum of 6- to 8-week-old male athymic and inbred (BALB/c) nude mice, the cellular printed construct displayed a more integrated structure and better healing of subcutaneous tissue compared with the acellular printed construct. In conclusion, this 3D cell printed soft-hard construct exhibits favorable biocompatibility and has potential for alveolar ridge preservation. Impact statement Alveolar ridge resorption after tooth extraction has posed great difficulty in the subsequent restorative procedure. Clinically, to preserve the dimension of alveolar ridge, covering soft tissue healing and underlying bone formation is necessary after tooth extraction. Three-dimensional (3D) cell printing, which can distribute different biomaterials and cells with spatial control, provides a novel approach to develop a customized plug to put in the fresh socket to minimize bone resorption and improve gingiva growth. In this study, an integrated and heterogeneous soft-hard construct with lock-key structure was successfully developed using 3D cell printing. The physicochemical and biological properties were tested in vitro and in vivo. This 3D cell printed soft-hard construct will be a customized plug in alveolar ridge preservation in the future.
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Affiliation(s)
- Shihan Zhang
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
| | - Qing Li
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China.,Center of Digital Dentistry, Peking University School and Hospital of Stomatology, Beijing, China
| | - Peng Liu
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
| | - Chunping Lin
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China
| | - Zhihui Tang
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China
| | - Hom-Lay Wang
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
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Biomaterials for human space exploration: A review of their untapped potential. Acta Biomater 2021; 128:77-99. [PMID: 33962071 DOI: 10.1016/j.actbio.2021.04.033] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 04/01/2021] [Accepted: 04/15/2021] [Indexed: 02/08/2023]
Abstract
As biomaterial advances make headway into lightweight radiation protection, wound healing dressings, and microbe resistant surfaces, a relevance to human space exploration manifests itself. To address the needs of the human in space, a knowledge of the space environment becomes necessary. Both an understanding of the environment itself and an understanding of the physiological adaptations to that environment must inform design parameters. The space environment permits the fabrication of novel biomaterials that cannot be produced on Earth, but benefit Earth. Similarly, designing a biomaterial to address a space-based challenge may lead to novel biomaterials that will ultimately benefit Earth. This review describes several persistent challenges to human space exploration, a variety of biomaterials that might mitigate those challenges, and considers a special category of space biomaterial. STATEMENT OF SIGNIFICANCE: This work is a review of the major human and environmental challenges facing human spaceflight, and where biomaterials may mitigate some of those challenges. The work is significant because a broad range of biomaterials are applicable to the human space program, but the overlap is not widely known amongst biomaterials researchers who are unfamiliar with the challenges to human spaceflight. Additionaly, there are adaptations to microgravity that mimic the pathology of certain disease states ("terrestrial analogs") where treatments that help the overwhelmingly healthy astronauts can be applied to help those with the desease. Advances in space technology have furthered the technology in that field on Earth. By outlining ways that biomaterials can promote human space exploration, space-driven advances in biomaterials will further biomaterials technology.
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7
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Najdanović JG, Cvetković VJ, Stojanović ST, Vukelić-Nikolić MĐ, Živković JM, Najman SJ. Vascularization and osteogenesis in ectopically implanted bone tissue-engineered constructs with endothelial and osteogenic differentiated adipose-derived stem cells. World J Stem Cells 2021; 13:91-114. [PMID: 33584982 PMCID: PMC7859989 DOI: 10.4252/wjsc.v13.i1.91] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 11/01/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A major problem in the healing of bone defects is insufficient or absent blood supply within the defect. To overcome this challenging problem, a plethora of approaches within bone tissue engineering have been developed recently. Bearing in mind that the interplay of various diffusible factors released by endothelial cells (ECs) and osteoblasts (OBs) have a pivotal role in bone growth and regeneration and that adjacent ECs and OBs also communicate directly through gap junctions, we set the focus on the simultaneous application of these cell types together with platelet-rich plasma (PRP) as a growth factor reservoir within ectopic bone tissue engineering constructs.
AIM To vascularize and examine osteogenesis in bone tissue engineering constructs enriched with PRP and adipose-derived stem cells (ASCs) induced into ECs and OBs.
METHODS ASCs isolated from adipose tissue, induced in vitro into ECs, OBs or just expanded were used for implant construction as followed: BPEO, endothelial and osteogenic differentiated ASCs with PRP and bone mineral matrix; BPUI, uninduced ASCs with PRP and bone mineral matrix; BC (control), only bone mineral matrix. At 1, 2, 4 and 8 wk after subcutaneous implantation in mice, implants were extracted and endothelial-related and bone-related gene expression were analyzed, while histological analyses were performed after 2 and 8 wk.
RESULTS The percentage of vascularization was significantly higher in BC compared to BPUI and BPEO constructs 2 and 8 wk after implantation. BC had the lowest endothelial-related gene expression, weaker osteocalcin immunoexpression and Spp1 expression compared to BPUI and BPEO. Endothelial-related gene expression and osteocalcin immunoexpression were higher in BPUI compared to BC and BPEO. BPEO had a higher percentage of vascularization compared to BPUI and the highest CD31 immunoexpression among examined constructs. Except Vwf, endothelial-related gene expression in BPEO had a later onset and was upregulated and well-balanced during in vivo incubation that induced late onset of Spp1 expression and pronounced osteocalcin immunoexpression at 2 and 8 wk. Tissue regression was noticed in BPEO constructs after 8 wk.
CONCLUSION Ectopically implanted BPEO constructs had a favorable impact on vascularization and osteogenesis, but tissue regression imposed the need for discovering a more optimal EC/OB ratio prior to considerations for clinical applications.
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Affiliation(s)
- Jelena G Najdanović
- Department of Biology and Human Genetics; Department for Cell and Tissue Engineering, Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Vladimir J Cvetković
- Department of Biology and Ecology, Faculty of Sciences and Mathematics, University of Niš, Niš 18106, Serbia
| | - Sanja T Stojanović
- Department of Biology and Human Genetics; Department for Cell and Tissue Engineering, Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Marija Đ Vukelić-Nikolić
- Department of Biology and Human Genetics; Scientific Research Center for Biomedicine; Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Jelena M Živković
- Department of Biology and Human Genetics; Scientific Research Center for Biomedicine; Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Stevo J Najman
- Department of Biology and Human Genetics; Department for Cell and Tissue Engineering, Faculty of Medicine, University of Niš, Niš 18108, Serbia
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Anastasio A, Gergues M, Lebhar MS, Rameshwar P, Fernandez-Moure J. Isolation and characterization of mesenchymal stem cells in orthopaedics and the emergence of compact bone mesenchymal stem cells as a promising surgical adjunct. World J Stem Cells 2020; 12:1341-1353. [PMID: 33312402 PMCID: PMC7705465 DOI: 10.4252/wjsc.v12.i11.1341] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 09/26/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
The potential clinical and economic impact of mesenchymal stem cell (MSC) therapy is immense. MSCs act through multiple pathways: (1) as “trophic” cells, secreting various factors that are immunomodulatory, anti-inflammatory, anti-apoptotic, proangiogenic, proliferative, and chemoattractive; (2) in conjunction with cells native to the tissue they reside in to enhance differentiation of surrounding cells to facilitate tissue regrowth. Researchers have developed methods for the extraction and expansion of MSCs from animal and human tissues. While many sources of MSCs exist, including adipose tissue and iliac crest bone graft, compact bone (CB) MSCs have shown great potential for use in orthopaedic surgery. CB MSCs exert powerful immunomodulatory effects in addition to demonstrating excellent regenerative capacity for use in filling boney defects. CB MSCs have been shown to have enhanced response to hypoxic conditions when compared with other forms of MSCs. More work is needed to continue to characterize the potential applications for CB MSCs in orthopaedic trauma.
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Affiliation(s)
- Albert Anastasio
- Department of Orthopedic Surgery, Duke University Health System, Durham, NC 27710, United States
| | - Marina Gergues
- Department of Medicine, Hematology/Oncology, Rutgers University, New Jersey Medical School, Newark, NJ 07103, United States
| | - Michael S Lebhar
- School of Medicine, Duke University School of Medicine, Durham, NC 27710, United States
| | - Pranela Rameshwar
- Department of Medicine-Hematology/Oncology, Rutgers School of Biomedical Health Science, Newark, NJ 07103, United States
| | - Joseph Fernandez-Moure
- Department of Surgery, Division of Trauma, Acute, and Critical Care Surgery, Duke University School of Medicine, Durham, NC 27710, United States
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Cipollaro L, Ciardulli MC, Della Porta G, Peretti GM, Maffulli N. Biomechanical issues of tissue-engineered constructs for articular cartilage regeneration: in vitro and in vivo approaches. Br Med Bull 2019; 132:53-80. [PMID: 31854445 DOI: 10.1093/bmb/ldz034] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/17/2019] [Indexed: 01/04/2023]
Abstract
BACKGROUND Given the limited regenerative capacity of injured articular cartilage, the absence of suitable therapeutic options has encouraged tissue-engineering approaches for its regeneration or replacement. SOURCES OF DATA Published articles in any language identified in PubMed and Scopus electronic databases up to August 2019 about the in vitro and in vivo properties of cartilage engineered constructs. A total of 64 articles were included following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. AREAS OF AGREEMENT Regenerated cartilage lacks the biomechanical and biological properties of native articular cartilage. AREAS OF CONTROVERSY There are many different approaches about the development of the architecture and the composition of the scaffolds. GROWING POINTS Novel tissue engineering strategies focus on the development of cartilaginous biomimetic materials able to repair cartilage lesions in association to cell, trophic factors and gene therapies. AREAS TIMELY FOR DEVELOPING RESEARCH A multi-layer design and a zonal organization of the constructs may lead to achieve cartilage regeneration.
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Affiliation(s)
- Lucio Cipollaro
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Via San Leonardo 1, 84131 Salerno, Italy
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy
| | - Maria Camilla Ciardulli
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy
| | - Giovanna Della Porta
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy
| | - Giuseppe M Peretti
- IRCCS Istituto Ortopedico Galeazzi, Via Riccardo Galeazzi 4, 20161 Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, via Mangiagalli 31, 20133, Milan, Italy
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Via San Leonardo 1, 84131 Salerno, Italy
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy
- Centre for Sports and Exercise Medicine, Barts and The London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, Queen Mary University of London, London, UK
- Institute of Science and Technology in Medicine, Keele University School of Medicine, Thornburrow Drive, Stoke on Trent, UK
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10
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Rosenberg M, Shilo D, Galperin L, Capucha T, Tarabieh K, Rachmiel A, Segal E. Bone Morphogenic Protein 2-Loaded Porous Silicon Carriers for Osteoinductive Implants. Pharmaceutics 2019; 11:E602. [PMID: 31726775 PMCID: PMC6920899 DOI: 10.3390/pharmaceutics11110602] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 11/07/2019] [Accepted: 11/08/2019] [Indexed: 12/19/2022] Open
Abstract
Bone morphogenetic proteins (BMPs) are probably the most important growth factors in bone formation and healing. However, the utilization of BMPs in clinical applications is mainly limited due to the protein poor solubility at physiological pH, rapid clearance and relatively short biological half-life. Herein, we develop degradable porous silicon (PSi)-based carriers for sustained delivery of BMP-2. Two different loading approaches are examined, physical adsorption and covalent conjugation, and their effect on the protein loading and release rate is thoroughly studied. The entrapment of the protein within the PSi nanostructures preserved its bioactivity for inducing osteogenic differentiation of rabbit bone marrow mesenchymal stems cells (BM-MSCs). BM-MSCs cultured with the BMP-2 loaded PSi carriers exhibit a relatively high alkaline phosphatase (ALP) activity. We also demonstrate that exposure of MSCs to empty PSi (no protein) carriers generates some extent of differentiation due to the ability of the carrier's degradation products to induce osteoblast differentiation. Finally, we demonstrate the integration of these promising BMP-2 carriers within a 3D-printed patient-specific implant, constructed of poly(caprolactone) (PCL), as a potential bone graft for critical size bone defects.
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Affiliation(s)
- Michal Rosenberg
- Department of Biotechnology and Food Engineering, Technion—Israel Institute of Technology, Haifa 3200003, Israel; (M.R.); (L.G.)
| | - Dekel Shilo
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
- Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 3109601, Israel
| | - Leonid Galperin
- Department of Biotechnology and Food Engineering, Technion—Israel Institute of Technology, Haifa 3200003, Israel; (M.R.); (L.G.)
| | - Tal Capucha
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
| | - Karim Tarabieh
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
| | - Adi Rachmiel
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
- Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 3109601, Israel
| | - Ester Segal
- Department of Biotechnology and Food Engineering, Technion—Israel Institute of Technology, Haifa 3200003, Israel; (M.R.); (L.G.)
- Russell Berrie Nanotechnology Institute, Technion—Israel Institute of Technology, Haifa 3200003, Israel
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11
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Ultrasound shear wave elastography effectively predicts integrity of ventral hernia repair using acellular dermal matrix augmented with platelet-rich plasma (PRP). Surg Endosc 2018; 33:2802-2811. [DOI: 10.1007/s00464-018-6571-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 11/01/2018] [Indexed: 10/27/2022]
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12
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Taraballi F, Sushnitha M, Tsao C, Bauza G, Liverani C, Shi A, Tasciotti E. Biomimetic Tissue Engineering: Tuning the Immune and Inflammatory Response to Implantable Biomaterials. Adv Healthc Mater 2018; 7:e1800490. [PMID: 29995315 DOI: 10.1002/adhm.201800490] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 05/31/2018] [Indexed: 12/31/2022]
Abstract
Regenerative medicine technologies rely heavily on the use of well-designed biomaterials for therapeutic applications. The success of implantable biomaterials hinges upon the ability of the chosen biomaterial to negotiate with the biological barriers in vivo. The most significant of these barriers is the immune system, which is composed of a highly coordinated organization of cells that induce an inflammatory response to the implanted biomaterial. Biomimetic platforms have emerged as novel strategies that aim to use the principle of biomimicry as a means of immunomodulation. This principle has manifested itself in the form of biomimetic scaffolds that imitate the composition and structure of biological cells and tissues. Recent work in this area has demonstrated the promising potential these technologies hold in overcoming the barrier of the immune system and, thereby, improve their overall therapeutic efficacy. In this review, a broad overview of the use of these strategies across several diseases and future avenues of research utilizing these platforms is provided.
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Affiliation(s)
- Francesca Taraballi
- Center for Biomimetic Medicine Houston Methodist Research Institute Houston TX 77030 USA
- Department of Orthopedic & Sports Medicine The Houston Methodist Hospital Houston TX 77030 USA
| | - Manuela Sushnitha
- Center for Biomimetic Medicine Houston Methodist Research Institute Houston TX 77030 USA
- Department of Bioengineering Rice University Houston TX 77005 USA
| | - Christopher Tsao
- Center for Biomimetic Medicine Houston Methodist Research Institute Houston TX 77030 USA
| | - Guillermo Bauza
- Center for Biomimetic Medicine Houston Methodist Research Institute Houston TX 77030 USA
- Center for NanoHealth Swansea University Medical School Swansea University Bay Singleton Park Wales Swansea SA2 8PP UK
| | - Chiara Liverani
- Center for Biomimetic Medicine Houston Methodist Research Institute Houston TX 77030 USA
- Biosciences Laboratory Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Via Piero Maroncelli 40 47014 Meldola FC Italy
| | - Aaron Shi
- Center for Biomimetic Medicine Houston Methodist Research Institute Houston TX 77030 USA
- Wiess School of Natural Sciences Rice University Houston TX 77251‐1892 USA
| | - Ennio Tasciotti
- Center for Biomimetic Medicine Houston Methodist Research Institute Houston TX 77030 USA
- Department of Orthopedic & Sports Medicine The Houston Methodist Hospital Houston TX 77030 USA
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13
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Increased Internal Porosity and Surface Area of Hydroxyapatite Accelerates Healing and Compensates for Low Bone Marrow Mesenchymal Stem Cell Concentrations in Critically-Sized Bone Defects. APPLIED SCIENCES-BASEL 2018. [DOI: 10.3390/app8081366] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
For clinical treatment of skeletal defects, osteoinductive scaffolds must have the ability to conform to the unique geometry of the injury site without sacrificing biologically favorable properties, including porosity. This investigation seeks to combine the osteoinductive properties of porous hydroxyapatite (HA) scaffolds with the beneficial handling characteristics of granules or putties, while evaluating the effects of mesenchymal stem cell (MSC) concentration on the composite grafts’ ability to regenerate bone in vivo. The results demonstrate that porous HA granules regenerate significantly larger volumes of bone compared to non-porous HA. Increased MSC concentrations in autologous bone marrow aspirate (BMA) contributed to greater bone regeneration. This effect was most predominant with non-porous HA. While the extent of bone regeneration using non-porous HA was strongly correlated with MSC concentration of the marrow, porous HA microparticles combined with autologous BMA were successful in faster treatment of critically-sized bone defects and with less dependence on the MSC concentration than non-porous HA.
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14
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Yajima Y, Yamada M, Utoh R, Seki M. Collagen Microparticle-Mediated 3D Cell Organization: A Facile Route to Bottom-up Engineering of Thick and Porous Tissues. ACS Biomater Sci Eng 2017; 3:2144-2154. [DOI: 10.1021/acsbiomaterials.7b00131] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- Yuya Yajima
- Department of Applied Chemistry
and Biotechnology, Graduate School of Engineering, Chiba University, 1-33
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
| | - Masumi Yamada
- Department of Applied Chemistry
and Biotechnology, Graduate School of Engineering, Chiba University, 1-33
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
| | - Rie Utoh
- Department of Applied Chemistry
and Biotechnology, Graduate School of Engineering, Chiba University, 1-33
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
| | - Minoru Seki
- Department of Applied Chemistry
and Biotechnology, Graduate School of Engineering, Chiba University, 1-33
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
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15
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Pettine KA, Suzuki RK, Sand TT, Murphy MB. Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. INTERNATIONAL ORTHOPAEDICS 2017; 41:2097-2103. [PMID: 28748380 DOI: 10.1007/s00264-017-3560-9] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/26/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE The purpose of this study is to assess safety and feasibility of intradiscal bone marrow concentrate (BMC) injections to treat low back discogenic pain as an alternative to surgery with three year minimum follow-up. METHODS A total of 26 patients suffering from degenerative disc disease and candidates for spinal fusion or total disc replacement surgery were injected with 2 ml autologous BMC into the nucleus pulposus of treated lumbar discs. A sample aliquot of BMC was characterized by flow cytometry and CFU-F assay to determine progenitor cell content. Improvement in pain and disability scores and 12 month post-injection MRI were compared to patient demographics and BMC cellularity. RESULTS After 36 months, only six patients progressed to surgery. The remaining 20 patients reported average ODI and VAS improvements from 56.7 ± 3.6 and 82.1 ± 2.6 at baseline to 17.5 ± 3.2 and 21.9 ± 4.4 after 36 months, respectively. One year MRI indicated 40% of patients improved one modified Pfirrmann grade and no patient worsened radiographically. Cellular analysis showed an average of 121 million total nucleated cells per ml, average CFU-F of 2713 per ml, and average CD34+ of 1.82 million per ml in the BMC. Patients with greater concentrations of CFU-F (>2000 per ml) and CD34+ cells (>2 million per ml) in BMC tended to have significantly better clinical improvement. CONCLUSIONS There were no adverse events related to marrow aspiration or injection, and this study provides evidence of safety and feasibility of intradiscal BMC therapy. Patient improvement and satisfaction with this surgical alternative supports further study of the therapy.
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Affiliation(s)
- Kenneth A Pettine
- Elite Regenerative Stem Cell Specialists, 4795 Larimer Pkwy, Johnstown, CO, 80534, USA
| | - Richard K Suzuki
- Celling Biosciences, 93 Red River Street, Austin, TX, 78701, USA
| | - Theodore T Sand
- Celling Biosciences, 93 Red River Street, Austin, TX, 78701, USA
| | - Matthew B Murphy
- Celling Biosciences, 93 Red River Street, Austin, TX, 78701, USA. .,Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78705, USA.
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16
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Fernandez-Moure JS, Van Eps JL, Peterson LE, Shirkey BA, Menn ZK, Cabrera FJ, Karim A, Tasciotti E, Weiner BK, Ellsworth WA. Cross-linking of porcine acellular dermal matrices negatively affects induced neovessel formation using platelet-rich plasma in a rat model of hernia repair. Wound Repair Regen 2017; 25:98-108. [DOI: 10.1111/wrr.12508] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 12/15/2016] [Indexed: 01/10/2023]
Affiliation(s)
- Joseph S. Fernandez-Moure
- Department of Surgery; Houston Methodist Hospital
- Surgical Advanced Technologies Lab; Center for Biomimetic Medicine
| | - Jeffrey L. Van Eps
- Department of Surgery; Houston Methodist Hospital
- Surgical Advanced Technologies Lab; Center for Biomimetic Medicine
| | - Leif E. Peterson
- Biostatistics Core; Institute of Academic Medicine, Houston Methodist Research Institute; Houston Texas
- Weill Cornell Medical College; New York New York
| | - Beverly A. Shirkey
- Department of Surgery; Houston Methodist Hospital
- Center for Outcomes Research, Department of Surgery
| | | | | | - Azim Karim
- Surgical Advanced Technologies Lab; Center for Biomimetic Medicine
| | - Ennio Tasciotti
- Surgical Advanced Technologies Lab; Center for Biomimetic Medicine
| | - Bradley K. Weiner
- Surgical Advanced Technologies Lab; Center for Biomimetic Medicine
- Department of Orthopedic Surgery
- Weill Cornell Medical College; New York New York
| | - Warren A. Ellsworth
- Department of Plastic & Reconstructive Surgery; Institute of Reconstructive Surgery, Houston Methodist Hospital; Houston Texas
- Weill Cornell Medical College; New York New York
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17
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Sartori M, Pagani S, Ferrari A, Costa V, Carina V, Figallo E, Maltarello M, Martini L, Fini M, Giavaresi G. A new bi-layered scaffold for osteochondral tissue regeneration: In vitro and in vivo preclinical investigations. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017; 70:101-111. [DOI: 10.1016/j.msec.2016.08.027] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 08/03/2016] [Accepted: 08/12/2016] [Indexed: 01/31/2023]
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18
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Ectopic osteogenic capacity of freshly isolated adipose-derived stromal vascular fraction cells supported with platelet-rich plasma: A simulation of intraoperative procedure. J Craniomaxillofac Surg 2016; 44:1750-1760. [PMID: 27624644 DOI: 10.1016/j.jcms.2016.08.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 07/02/2016] [Accepted: 08/15/2016] [Indexed: 01/13/2023] Open
Abstract
Bone defects represent a serious problem in cranio-maxillofacial surgery. Autologous adipose-derived stromal vascular fraction (SVF) cells in combination with biological factors and bone substitutes were previously proposed as alternative to bone grafting. By simulating an intraoperative procedure we examined osteogenic capacity of the combination of two autologous components, freshly isolated adipose-derived SVF cells, and platelet-rich plasma (PRP), delivered on bone mineral matrix (BMM) carrier (SPB group) in mice ectopic bone forming model. Implantation of BMM only (B group) was a control. The presence of adipose-derived stem cells (ADSCs) in SVF was detected by immunocytochemical analysis. Expression of bone- and endothelial-related genes was compared between freshly isolated SVF and ADSCs obtained from SVF after in vitro cultivation. The implants were analyzed using expression analysis of bone-related genes at one, two, four and eight weeks and histochemical, immunohistochemical and histomorphometrical analyses at two and eight weeks after implantation. Freshly isolated adipose-derived SVF contained ADSCs and exhibited promising osteogenic and vasculogenic capacity. At two and four weeks, significantly higher expression of bone-related genes was detected in SPB group compared to B group. The signs of osteogenic process were more pronounced in SPB than in B implants. By the end of experiment, percentage of infiltrated tissue and vascularization was significantly higher in SPB than in B implants. Adipose-derived SVF cells, PRP and BMM rapidly initiated osteogenesis what makes this combination promising candidate for treatment of bone defects.
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19
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Blashki D, Murphy MB, Ferrari M, Simmons PJ, Tasciotti E. Mesenchymal stem cells from cortical bone demonstrate increased clonal incidence, potency, and developmental capacity compared to their bone marrow-derived counterparts. J Tissue Eng 2016; 7:2041731416661196. [PMID: 27579159 PMCID: PMC4989583 DOI: 10.1177/2041731416661196] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 07/03/2016] [Indexed: 12/19/2022] Open
Abstract
In this study, we show that matrix dense cortical bone is the more potent compartment of bone than bone marrow as a stromal source for mesenchymal stem cells as isolated from adult rats. Lineage-depleted cortical bone-mesenchymal stem cells demonstrated >150-fold enrichment of colony forming unit-fibroblasts per cell incidence. compared to lineage-depleted bone marrow-mesenchymal stem cells, corresponding to a 70-fold increase in absolute recovered colony forming unit-fibroblasts. The composite phenotype Lin(-)/CD45(-)/CD31(-)/VLA-1(+)/Thy-1(+) enriched for clonogenic mesenchymal stem cells solely from cortical bone-derived cells from which 70% of clones spontaneously differentiated into all lineages of bone, cartilage, and adipose. Both populations generated vascularized bone tissue within subcutaneous implanted collagen scaffolds; however, cortical bone-derived cells formed significantly more osteoid than bone marrow counterparts, quantified by histology. The data demonstrate that our isolation protocol identifies and validates mesenchymal stem cells with superior clonal, proliferative, and developmental potential from cortical bone compared to the bone marrow niche although marrow persists as the typical source for mesenchymal stem cells both in the literature and current pre-clinical therapies.
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Affiliation(s)
- Daniel Blashki
- Center for Stem Cell Research, The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Immunology, The University of Melbourne, Parkville, VIC, Australia
| | - Matthew B Murphy
- Center for Stem Cell Research, The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA
| | - Mauro Ferrari
- Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA
| | - Paul J Simmons
- Center for Stem Cell Research, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Ennio Tasciotti
- Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA
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20
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Pountos I, Panteli M, Lampropoulos A, Jones E, Calori GM, Giannoudis PV. The role of peptides in bone healing and regeneration: a systematic review. BMC Med 2016; 14:103. [PMID: 27400961 PMCID: PMC4940902 DOI: 10.1186/s12916-016-0646-y] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. METHODS A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. RESULTS Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. CONCLUSION Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge.
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Affiliation(s)
- Ippokratis Pountos
- Department of Trauma & Orthopaedics, School of Medicine, University of Leeds, Leeds, UK
| | - Michalis Panteli
- Department of Trauma & Orthopaedics, School of Medicine, University of Leeds, Leeds, UK
| | | | - Elena Jones
- Unit of Musculoskeletal Disease, Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James University Hospital, University of Leeds, LS9 7TF, Leeds, UK
| | - Giorgio Maria Calori
- Department of Trauma & Orthopaedics, School of Medicine, ISTITUTO ORTOPEDICO GAETANO PINI, Milan, Italy
| | - Peter V Giannoudis
- Department of Trauma & Orthopaedics, School of Medicine, University of Leeds, Leeds, UK. .,NIHR Leeds Biomedical Research Unit, Chapel Allerton Hospital, LS7 4SA Leeds, West Yorkshire, Leeds, UK.
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21
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Uzunalli G, Mammadov R, Yesildal F, Alhan D, Ozturk S, Ozgurtas T, Guler MO, Tekinay AB. Angiogenic Heparin-Mimetic Peptide Nanofiber Gel Improves Regenerative Healing of Acute Wounds. ACS Biomater Sci Eng 2016; 3:1296-1303. [DOI: 10.1021/acsbiomaterials.6b00165] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Gozde Uzunalli
- Institute
of Materials Science and Nanotechnology, National Nanotechnology Research
Center (UNAM), Bilkent University, Ankara, Turkey 06800
| | - Rashad Mammadov
- Institute
of Materials Science and Nanotechnology, National Nanotechnology Research
Center (UNAM), Bilkent University, Ankara, Turkey 06800
| | - Fatih Yesildal
- Department
of Medical Biochemistry, Diyarbakir Military Hospital, Diyarbakir, Turkey
| | - Dogan Alhan
- Gulhane Military Medical Academy, Ankara, Turkey
| | | | | | - Mustafa O. Guler
- Institute
of Materials Science and Nanotechnology, National Nanotechnology Research
Center (UNAM), Bilkent University, Ankara, Turkey 06800
| | - Ayse B. Tekinay
- Institute
of Materials Science and Nanotechnology, National Nanotechnology Research
Center (UNAM), Bilkent University, Ankara, Turkey 06800
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22
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Decreased hernia recurrence using autologous platelet-rich plasma (PRP) with Strattice™ mesh in a rodent ventral hernia model. Surg Endosc 2015; 30:3239-49. [PMID: 26578432 PMCID: PMC4956706 DOI: 10.1007/s00464-015-4645-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 10/24/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Recurrence after ventral hernia repair (VHR) remains a multifactorial problem still plaguing surgeons today. Some of the many contributing factors include mechanical strain, poor tissue-mesh integration, and degradation of matrices. The high recurrence rate witnessed with the use of acellular dermal matrices (ADM) for definitive hernia repair has reduced their use largely to bridging repair and breast reconstruction. Modalities that improve classic cellular metrics of successful VHR could theoretically result in improved rates of hernia recurrence; autologous platelet-rich plasma (PRP) may represent one such tool, but has been underinvestigated for this purpose. METHODS Lewis rats (32) had chronic ventral hernias created surgically and then repaired with Strattice™ mesh alone (control) or mesh + autologous PRP. Samples were harvested at 3 and 6 months postoperatively and compared for gross, histologic, and molecular outcomes of: neovascularization, tissue incorporation, peritoneal adhesions, hernia recurrence, and residual mesh thickness. RESULTS Compared to control at 3 months postoperatively, PRP-treated rats displayed significantly more neovascularization of implanted mesh and considerable upregulation of both angiogenic genes (vEGF 2.73-fold, vWF 2.21-fold) and myofibroblastic genes (αSMA 9.68-fold, FSP-1 3.61-fold, Col1a1 3.32-fold, Col31a1 3.29-fold). Histologically, they also showed enhanced tissue deposition/ingrowth and diminished chronic immune cell infiltration. Peritoneal adhesions were less severe at both 3 (1.88 vs. 2.94) and 6 months (1.63 vs. 2.75) by Modified Hopkins Adhesion Scoring. PRP-treated rats experienced decreased hernia recurrence at 6 months (0/10 vs. 7/10) and had significantly improved ADM preservation as evidenced by quantification of residual mesh thickness. CONCLUSIONS PRP is an autologous source of pro-regenerative growth factors and chemokines uniquely suited to soft tissue wound healing. When applied to a model of chronic VHR, it incites enhanced angiogenesis, myofibroblast recruitment and tissue ingrowth, ADM preservation, less severe peritoneal adhesions, and diminished hernia recurrence. We advocate further investigation regarding PRP augmentation of human VHR.
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23
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Uzunalli G, Tumtas Y, Delibasi T, Yasa O, Mercan S, Guler MO, Tekinay AB. Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels. Acta Biomater 2015; 22:8-18. [PMID: 25931015 DOI: 10.1016/j.actbio.2015.04.032] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 04/17/2015] [Accepted: 04/21/2015] [Indexed: 11/29/2022]
Abstract
Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.
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Affiliation(s)
- Gozde Uzunalli
- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey
| | - Yasin Tumtas
- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey
| | - Tuncay Delibasi
- Pancreas Islet Cell Research Center, Ankara Diskapi Yildirim Beyazit Training and Research Hospital Etlik Polyclinic, Department of Endocrinology and Metabolism, Ankara 06800, Turkey; Hacettepe University, School of Medicine, Department of Endocrinology, Ankara 06100, Turkey.
| | - Oncay Yasa
- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey
| | - Sercan Mercan
- Pancreas Islet Cell Research Center, Ankara Diskapi Yildirim Beyazit Training and Research Hospital Etlik Polyclinic, Department of Endocrinology and Metabolism, Ankara 06800, Turkey; Gazi University, Faculty of Science, Department of Chemistry, Ankara 06560, Turkey
| | - Mustafa O Guler
- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
| | - Ayse B Tekinay
- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
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Najdanović JG, Cvetković VJ, Stojanović S, Vukelić-Nikolić MĐ, Stanisavljević MN, Živković JM, Najman SJ. The Influence of Adipose-Derived Stem Cells Induced into Endothelial Cells on Ectopic Vasculogenesis and Osteogenesis. Cell Mol Bioeng 2015. [DOI: 10.1007/s12195-015-0403-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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25
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Liu L, Liu X, Deng H, Wu Z, Zhang J, Cen B, Xu Q, Ji A. Something between the amazing functions and various morphologies of self-assembling peptides materials in the medical field. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2014; 25:1331-45. [DOI: 10.1080/09205063.2014.943536] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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26
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Yazdi IK, Murphy MB, Loo C, Liu X, Ferrari M, Weiner BK, Tasciotti E. Cefazolin-loaded mesoporous silicon microparticles show sustained bactericidal effect against Staphylococcus aureus. J Tissue Eng 2014; 5:2041731414536573. [PMID: 24904728 PMCID: PMC4046808 DOI: 10.1177/2041731414536573] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Accepted: 04/28/2014] [Indexed: 12/19/2022] Open
Abstract
Cefazolin is an antibiotic frequently used in preoperative prophylaxis of orthopedic surgery and to fight secondary infections post-operatively. Although its systemic delivery in a bulk or bolus dose is usually effective, the local and controlled release can increase its effectiveness by lowering dosages, minimizing total drug exposure, abating the development of antibiotic resistance and avoiding the cytotoxic effect. A delivery system based on mesoporous silicon microparticles was developed that is capable of efficiently loading and continuously releasing cefazolin over several days. The in vitro release kinetics from mesoporous silicon microparticles with three different nanopore sizes was evaluated, and minimal inhibitory concentration of cefazolin necessary to eliminate a culture of Staphylococcus aureus was identified to be 250 µg/mL. A milder toxicity toward mesenchymal stem cells was observed from mesoporous silicon microparticles over a 7-day period. Medium pore size-loaded mesoporous silicon microparticles exhibited long-lasting bactericidal properties in a zone inhibition assay while they were able to kill all the bacteria growing in suspension cultures within 24 h. This study demonstrates that the sustained release of cefazolin from mesoporous silicon microparticles provides immediate and long-term control over bacterial growth both in suspension and adhesion while causing minimal toxicity to a population of mesenchymal stem cell. Mesoporous silicon microparticles offer significant advantageous properties for drug delivery applications in tissue engineering as it favorably extends drug bioavailability and stability, while reducing concomitant cytotoxicity to the surrounding tissues.
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Affiliation(s)
- Iman K Yazdi
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA ; Department of Biomedical Engineering, University of Houston, Houston, TX, USA
| | - Matthew B Murphy
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA
| | - Christopher Loo
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA
| | - Xuewu Liu
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA
| | - Mauro Ferrari
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA
| | - Bradley K Weiner
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA ; Department of Orthopedic Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ennio Tasciotti
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA
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Lozano RM, Pérez-Maceda BT, Carboneras M, Onofre-Bustamante E, García-Alonso MC, Escudero ML. Response of MC3T3-E1 osteoblasts, L929 fibroblasts, and J774 macrophages to fluoride surface-modified AZ31 magnesium alloy. J Biomed Mater Res A 2013; 101:2753-62. [DOI: 10.1002/jbm.a.34579] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Revised: 11/11/2012] [Accepted: 12/12/2012] [Indexed: 11/06/2022]
Affiliation(s)
- Rosa María Lozano
- Cell-Biomaterial Recognition Laboratory; Department of Cellular and Molecular Biology; Centro de Investigaciones Biológicas (CIB-CSIC); c/Ramiro de Maeztu 9; 28040 Madrid; Spain
| | - Blanca Teresa Pérez-Maceda
- Cell-Biomaterial Recognition Laboratory; Department of Cellular and Molecular Biology; Centro de Investigaciones Biológicas (CIB-CSIC); c/Ramiro de Maeztu 9; 28040 Madrid; Spain
| | - Mónica Carboneras
- Department of Surface Engineering; Corrosion and Durability; Centro Nacional de Investigaciones Metalúrgicas (CENIM-CSIC). Avda Gregorio del Amo 8; 28040 Madrid; Spain
| | - Edgar Onofre-Bustamante
- Department of Surface Engineering; Corrosion and Durability; Centro Nacional de Investigaciones Metalúrgicas (CENIM-CSIC). Avda Gregorio del Amo 8; 28040 Madrid; Spain
| | - María Cristina García-Alonso
- Department of Surface Engineering; Corrosion and Durability; Centro Nacional de Investigaciones Metalúrgicas (CENIM-CSIC). Avda Gregorio del Amo 8; 28040 Madrid; Spain
| | - María Lorenza Escudero
- Department of Surface Engineering; Corrosion and Durability; Centro Nacional de Investigaciones Metalúrgicas (CENIM-CSIC). Avda Gregorio del Amo 8; 28040 Madrid; Spain
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Murphy MB, Blashki D, Buchanan RM, Yazdi IK, Ferrari M, Simmons PJ, Tasciotti E. Adult and umbilical cord blood-derived platelet-rich plasma for mesenchymal stem cell proliferation, chemotaxis, and cryo-preservation. Biomaterials 2012; 33:5308-16. [PMID: 22542609 DOI: 10.1016/j.biomaterials.2012.04.007] [Citation(s) in RCA: 109] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 04/01/2012] [Indexed: 02/07/2023]
Abstract
Platelet-rich plasma (PRP) was prepared from human adult peripheral blood and from human umbilical cord (uc) blood and the properties were compared in a series of in vitro bioassays. Quantification of growth factors in PRP and platelet-poor plasma (PPP) fractions revealed increased levels of mitogenic growth factors PDGF-AB, PDGF-BB, and FGF-2, the angiogenic agent VEGF and the chemokine RANTES in ucPRP compared to adult PRP (aPRP) and PPP. To compare the ability of the various PRP products to stimulate proliferation of human bone marrow (BM), rat BM and compact bone (CB)-derived mesenchymal stem cells (MSC), cells were cultured in serum-free media for 4 and 7 days with varying concentrations of PRP, PPP, or combinations of recombinant mitogens. It was found that while all forms of PRP and PPP were more mitogenic than fetal bovine serum, ucPRP resulted in significantly higher proliferation by 7 days than adult PRP and PPP. We observed that addition of as little as 0.1% ucPRP caused greater proliferation of MSC effects than the most potent combination of recombinant growth factors tested, namely PDGF-AB + PDGF-BB + FGF-2, each at 10 ng/mL. Similarly, in chemotaxis assays, ucPRP showed greater potency than adult PRP, PPP from either source, or indeed than combinations of either recombinant growth factors (PDGF, FGF, and TGF-β1) or chemokines previously shown to stimulate chemotactic migration of MSC. Lastly, we successfully demonstrated that PRP and PPP represented a viable alternative to FBS containing media for the cryo-preservation of MSC from human and rat BM.
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Affiliation(s)
- Matthew B Murphy
- Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX 77025, USA
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Murphy MB, Khaled S, Fan D, Yazdi IK, Sprintz M, Buchanan RM, Smid CA, Weiner BK, Ferrari M, Tasciotti E. A multifunctional nanostructured platform for localized sustained release of analgesics and antibiotics. ACTA ACUST UNITED AC 2012. [DOI: 10.1016/j.eujps.2011.08.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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