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Khalili MR, Molafilabi A, Mousazadeh S, Mehrabi A, Kiani J, Brouki Milan P, Ghasemi F. Development of in situ forming autologous fibrin scaffold incorporating synthetic teriparatide peptide for bone tissue engineering. Int J Artif Organs 2024; 47:707-718. [PMID: 39370606 DOI: 10.1177/03913988241262907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/08/2024]
Abstract
INTRODUCTION This study investigates the potential of an in-situ forming scaffold using a fibrin-based scaffold derived from autologous plasma combined with Synthetic Teriparatide (TP) for bone regeneration application. TP is known for its bone formation stimulation but has limited clinical use due to side effects. This autologous delivery system aims to provide precise, controlled, localized, and long-term release of TP for accelerating bone regeneration. METHODS Fibrinogen from autologous plasma was extracted using ethanol, and thrombin was precipitated with ammonium sulfate to create the fibrin scaffold. Characterization of fibrinogen was done through FTIR, SDS-Page, porosity, SEM, degradation, and rheology tests. Viability was assessed by MTT in five groups with different concentrations of TP in fibrin scaffold (50, 100, and 150 µl/ml), fibrin alone, and a control group against HEK and Wharton's jelly cells. The release profile of different concentrations of TP in the fibrin scaffold was also examined. RESULTS The formation time of the fibrin scaffold was 4 ± 0.2 s. The highest Infrared absorption for fibrinogen was confirmed. Rheology assessment revealed a higher elastic modulus than the viscous modulus. The created fibrin scaffold displayed a consistent three-dimensional microstructure with an interconnected porous network. Cytotoxicity assays demonstrated good biocompatibility and enhanced cell growth with different concentrations of TP in the fibrin scaffold. The TP release increased with higher concentrations, peaking at an average of 61% over 54 h. CONCLUSION Autologous plasma-derived fibrin scaffolds incorporating TP exhibit satisfactory release within the scaffold and hold promise as a versatile bone filler for clinical use, facilitating osteoregeneration.
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Affiliation(s)
- Mohammad Reza Khalili
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Azam Molafilabi
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Sepideh Mousazadeh
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Arezou Mehrabi
- School of Medicine, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - Jafar Kiani
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Peiman Brouki Milan
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Faezeh Ghasemi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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Kunnasegaran R, Ng JW, Kwek E. Use of Fibrin Glue as a Surgical Adjunct in Bone Grafting of Fracture Non-unions. Malays Orthop J 2024; 18:49-54. [PMID: 39130505 PMCID: PMC11315943 DOI: 10.5704/moj.2407.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 11/20/2023] [Indexed: 08/13/2024] Open
Abstract
Introduction Non-union of long bones is a common challenge in the treatment of fractures. Bone grafting is commonly used to treat atrophic non-union, but mechanical displacement of the graft may occur, resulting in delay or failure of treatment. Fibrin glue has demonstrated positive results in management of bone defects in neurosurgery and oromaxillary facial surgery, however, there has yet to be any study on its use in long bone fractures. Materials and Methods We conducted a prospective randomised controlled trial at a single tertiary centre involving adult patients with long bone fractures that had undergone non-union and requiring bone grafting only. Autologous iliac crest bone graft was applied to the debrided non-union site, with additional fibrin glue applied for the intervention arm. Patients were followed-up with serial radiographs until clinical and radiographical union. Results Ten patients (3 male, 7 female), of mean age 41.7 (19 - 63) were recruited over five years, with one drop out. Eight out of nine fractures united after treatment. One patient underwent hypertrophic non-union requiring re-fixation and bone grafting. There was no difference in the time to union for patients in the fibrin glue group (19.5 weeks) versus the control group (18.75 weeks) (p=0.86). There were no complications sustained from usage of fibrin glue. Conclusion Fibrin glue appears to be a safe adjunct for treatment of non-union of long bone fractures across varying fracture sites by holding the bone graft in place despite not demonstrating a faster time to union.
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Affiliation(s)
- R Kunnasegaran
- Department of Orthopaedic Surgery, Tan Tock Seng Hospital, Singapore
| | - J W Ng
- Department of Orthopaedic Surgery, Tan Tock Seng Hospital, Singapore
| | - Ebk Kwek
- Department of Orthopaedic Surgery, Woodlands Health, Singapore
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Awadeen MA, Al-Belasy FA, Ameen LE, Helal ME, Grawish ME. Early therapeutic effect of platelet-rich fibrin combined with allogeneic bone marrow-derived stem cells on rats' critical-sized mandibular defects. World J Stem Cells 2020; 12:55-69. [PMID: 32110275 PMCID: PMC7031757 DOI: 10.4252/wjsc.v12.i1.55] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 05/13/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide. These defects generally result from severe trauma or resection of a whole large tumour. Autologous bone grafts are the current gold standard for the reconstruction of such defects. However, due to increased patient morbidity and the need for a second operative site, other lines of treatment should be introduced. To find alternative unconventional therapies to manage such defects, bone tissue engineering using a combination of suitable bioactive factors, cells, and biocompatible scaffolds offers a promising new approach for bone regeneration. AIM To evaluate the healing capacity of platelet-rich fibrin (PRF) membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells (BMSCs) on critically sized mandibular defects in a rat model. METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur. Rats were allocated to three equal groups of 21 rats each. Group I bone defects were irrigated with normal saline and designed as negative controls. Defects of group II were grafted with PRF membranes and served as positive controls, while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs. Seven rats from each group were killed at 1, 2 and 4 wk. The mandibles were dissected and prepared for routine haematoxylin and eosin (HE) staining, Masson's trichrome staining and CD68 immunohistochemical staining. RESULTS Four weeks postoperatively, the percentage area of newly formed bone was significantly higher in group III (0.88 ± 0.02) than in groups I (0.02 ± 0.00) and II (0.60 ± 0.02). The amount of granulation tissue formation was lower in group III (0.12 ± 0.02) than in groups I (0.20 ± 0.02) and II (0.40 ± 0.02). The number of inflammatory cells was lower in group III (0.29 ± 0.03) than in groups I (4.82 ± 0.08) and II (3.09 ± 0.07). CONCLUSION Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.
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Affiliation(s)
- Muhammad A Awadeen
- Department of Oral Biology, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Mansoura 11152, Egypt
| | - Fouad A Al-Belasy
- Department of Oral Surgery and Anesthesia, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Mansoura 11152, Egypt
| | - Laila E Ameen
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt
| | - Mohamad E Helal
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt
| | - Mohammed E Grawish
- Department of Oral Biology, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Mansoura 11152, Egypt
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt.
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Mao SH, Chen CH, Chen CT. Osteogenic potential of induced pluripotent stem cells from human adipose-derived stem cells. Stem Cell Res Ther 2019; 10:303. [PMID: 31623672 PMCID: PMC6798413 DOI: 10.1186/s13287-019-1402-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 08/20/2019] [Accepted: 09/02/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Bone regeneration is a crucial and challenging issue in clinical practice. Bone tissue engineering (BTE) with an optimal cell source may provide an ideal strategy for the reconstruction of bone defects. This study examined whether induced pluripotent stem cells (iPSCs) derived from adipose-derived stem cells (ASCs) could act as an osteogenic substitute and whether these ASC-iPSCs yield more new bone formation than ASCs in hydrogel scaffolds. METHODS ASC-iPSCs were reprogrammed from ASCs through a retroviral system. ASCs were harvested and isolated from adipose tissue of humans. An aliquot of cell suspension (1 × 106 cells/mL) was seeded directly onto the nHAP-gelatin cryogel scaffolds. Nude mice back implantation of cell-seeded scaffolds was designed for in vivo comparison of osteogenic potentials between ASCs and ASC-iPSCs. Samples were harvested 4 and 8 weeks after implantation for further analysis based on histology and RT-PCR. RESULTS ASC-iPSCs were successfully obtained from human adipose-derived stem cells. PCR results also showed that specific genes of iPSCs with the ability to cause the differentiation of cells into the three germ layers were expressed. In our in vivo experiments, iPSCs were subcutaneously injected into nude mice to induce teratoma formation. The morphology of the three germ layers was confirmed by histological staining. ASC is an essential cell source for BTE with benefits of high volume and less-invasive acquisition. With additional transforming Yamanaka factors, ASC-iPSCs showed higher osteogenic differentiation and elevated expression of collagen type I (Col I), osteocalcin (OCN), alkaline phosphate (ALP), and runt-related transcription factor 2 (RunX-2). CONCLUSIONS This report suggests that ASC-iPSCs could be a superior cell source in BTE with better osteogenic differentiation efficacy for future clinical applications.
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Affiliation(s)
- Shih-Hsuan Mao
- Craniofacial Research Center and Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University, College of Medicine, Taoyuan, 333 Taiwan
| | - Chih-Hao Chen
- Craniofacial Research Center and Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University, College of Medicine, Taoyuan, 333 Taiwan
| | - Chien-Tzung Chen
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Keelung, Chang Gung University, College of Medicine, Keelung, 204 Taiwan
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Freitas GP, Lopes HB, Souza ATP, Oliveira PGFP, Almeida ALG, Souza LEB, Coelho PG, Beloti MM, Rosa AL. Cell Therapy: Effect of Locally Injected Mesenchymal Stromal Cells Derived from Bone Marrow or Adipose Tissue on Bone Regeneration of Rat Calvarial Defects. Sci Rep 2019; 9:13476. [PMID: 31530883 PMCID: PMC6748998 DOI: 10.1038/s41598-019-50067-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 09/05/2019] [Indexed: 02/07/2023] Open
Abstract
Treatment of large bone defects is a challenging clinical situation that may be benefited from cell therapies based on regenerative medicine. This study was conducted to evaluate the effect of local injection of bone marrow-derived mesenchymal stromal cells (BM-MSCs) or adipose tissue-derived MSCs (AT-MSCs) on the regeneration of rat calvarial defects. BM-MSCs and AT-MSCs were characterized based on their expression of specific surface markers; cell viability was evaluated after injection with a 21-G needle. Defects measuring 5 mm that were created in rat calvaria were injected with BM-MSCs, AT-MSCs, or vehicle-phosphate-buffered saline (Control) 2 weeks post-defect creation. Cells were tracked by bioluminescence, and 4 weeks post-injection, the newly formed bone was evaluated by µCT, histology, nanoindentation, and gene expression of bone markers. BM-MSCs and AT-MSCs exhibited the characteristics of MSCs and maintained their viability after passing through the 21-G needle. Injection of both BM-MSCs and AT-MSCs resulted in increased bone formation compared to that in Control and with similar mechanical properties as those of native bone. The expression of genes associated with bone formation was higher in the newly formed bone induced by BM-MSCs, whereas the expression of genes involved in bone resorption was higher in the AT-MSC group. Cell therapy based on local injection of BM-MSCs or AT-MSCs is effective in delivering cells that induced a significant improvement in bone healing. Despite differences observed in molecular cues between BM-MSCs and AT-MSCs, both cells had the ability to induce bone tissue formation at comparable amounts and properties. These results may drive new cell therapy approaches toward complete bone regeneration.
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Affiliation(s)
- Gileade P Freitas
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | - Helena B Lopes
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | - Alann T P Souza
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | - Paula G F P Oliveira
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | - Adriana L G Almeida
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | - Lucas E B Souza
- Hemotherapy Center of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | - Paulo G Coelho
- Department of Biomaterials, New York University College of Dentistry, New York, NY, USA.,Hanjorg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY, USA
| | - Marcio M Beloti
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | - Adalberto L Rosa
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil.
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Alves E, Serakides R, Rosado I, Machado F, Fukushima F, Pereira M, Góes A, Rezende C. Matriz porosa do BV60S associada a células osteoprogenitoras alógenas no tratamento de defeitos ósseos críticos em rádios de cães. ARQ BRAS MED VET ZOO 2019. [DOI: 10.1590/1678-4162-10613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
RESUMO O objetivo do estudo foi avaliar o efeito da matriz porosa do biovidro 60S (BV60S) associada a células osteoprogenitoras (CO) alógenas no tratamento de defeitos ósseos críticos de cães. Foram utilizados 20 cães, machos, sem raça definida, com dois anos de idade e massa corporal média de 25kg. Com os cães sob anestesia geral, foram criados defeitos ósseos críticos no terço médio dos ossos rádios. Procedeu-se à fixação óssea com uma placa em ponte, e os defeitos foram tratados de acordo com cada grupo experimental. Constituíram-se três grupos experimentais, em que os defeitos ósseos foram preenchidos com: BV60S associado a CO alógenas (grupo BV60S+CO), osso autógeno (grupo C+), ou não preenchidos (grupo C-). A regeneração óssea foi avaliada por meio de exames radiográficos, densitométricos e histomorfométricos ao longo de 90 dias. Os grupos C- e BV60S+CO mostraram preenchimento ósseo parcial do defeito de, no máximo, 56,68% e 35,23%, respectivamente, sem a formação de ponte óssea entre as extremidades, e o controle positivo (C+) mostrou regeneração óssea completa. Conclui-se que a matriz porosa do BV60S associada às células osteoprogenitoras não é eficiente no tratamento de defeitos ósseos críticos em rádios de cães.
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Affiliation(s)
- E.G.L. Alves
- Universidade de Uberaba, Brazil; Universidade Federal de Minas Gerais, Brazil
| | | | - I.R. Rosado
- Universidade de Uberaba, Brazil; Universidade Federal de Minas Gerais, Brazil
| | | | | | | | - A.M. Góes
- Universidade Federal de Minas Gerais, Brazil
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Donos N, Dereka X, Calciolari E. The use of bioactive factors to enhance bone regeneration: A narrative review. J Clin Periodontol 2019; 46 Suppl 21:124-161. [DOI: 10.1111/jcpe.13048] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 11/08/2018] [Accepted: 12/20/2018] [Indexed: 12/17/2022]
Affiliation(s)
- Nikos Donos
- Centre for Oral Immunobiology & Regenerative Medicine & Centre for Oral Clinical Research (COCR); Institute of Dentistry, Barts & The London School of Medicine & Dentistry; Queen Mary University of London (QMUL); London UK
| | - Xanthippi Dereka
- Centre for Oral Immunobiology & Regenerative Medicine & Centre for Oral Clinical Research (COCR); Institute of Dentistry, Barts & The London School of Medicine & Dentistry; Queen Mary University of London (QMUL); London UK
- Department of Periodontology; School of Dentistry; National and Kapodistrian University of Athens; Athens Greece
| | - Elena Calciolari
- Centre for Oral Immunobiology & Regenerative Medicine & Centre for Oral Clinical Research (COCR); Institute of Dentistry, Barts & The London School of Medicine & Dentistry; Queen Mary University of London (QMUL); London UK
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Omar O, Elgali I, Dahlin C, Thomsen P. Barrier membranes: More than the barrier effect? J Clin Periodontol 2019; 46 Suppl 21:103-123. [PMID: 30667525 PMCID: PMC6704362 DOI: 10.1111/jcpe.13068] [Citation(s) in RCA: 151] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/21/2018] [Accepted: 01/09/2019] [Indexed: 12/13/2022]
Abstract
AIM To review the knowledge on the mechanisms controlling membrane-host interactions in guided bone regeneration (GBR) and investigate the possible role of GBR membranes as bioactive compartments in addition to their established role as barriers. MATERIALS AND METHODS A narrative review was utilized based on in vitro, in vivo and available clinical studies on the cellular and molecular mechanisms underlying GBR and the possible bioactive role of membranes. RESULTS Emerging data demonstrate that the membrane contributes bioactively to the regeneration of underlying defects. The cellular and molecular activities in the membrane are intimately linked to the promoted bone regeneration in the underlying defect. Along with the native bioactivity of GBR membranes, incorporating growth factors and cells in membranes or with graft materials may augment the regenerative processes in underlying defects. CONCLUSION In parallel with its barrier function, the membrane plays an active role in hosting and modulating the molecular activities of the membrane-associated cells during GBR. The biological events in the membrane are linked to the bone regenerative and remodelling processes in the underlying defect. Furthermore, the bone-promoting environments in the two compartments can likely be boosted by strategies targeting both material aspects of the membrane and host tissue responses.
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Affiliation(s)
- Omar Omar
- Department of BiomaterialsInstitute of Clinical SciencesSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Ibrahim Elgali
- Department of BiomaterialsInstitute of Clinical SciencesSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Christer Dahlin
- Department of BiomaterialsInstitute of Clinical SciencesSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Oral Maxillofacial Surgery/ENTNU‐Hospital OrganisationTrollhättanSweden
| | - Peter Thomsen
- Department of BiomaterialsInstitute of Clinical SciencesSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
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Lin H, Sohn J, Shen H, Langhans MT, Tuan RS. Bone marrow mesenchymal stem cells: Aging and tissue engineering applications to enhance bone healing. Biomaterials 2019; 203:96-110. [PMID: 29980291 PMCID: PMC6733253 DOI: 10.1016/j.biomaterials.2018.06.026] [Citation(s) in RCA: 263] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 06/18/2018] [Accepted: 06/19/2018] [Indexed: 12/11/2022]
Abstract
Bone has well documented natural healing capacity that normally is sufficient to repair fractures and other common injuries. However, the properties of bone change throughout life, and aging is accompanied by increased incidence of bone diseases and compromised fracture healing capacity, which necessitate effective therapies capable of enhancing bone regeneration. The therapeutic potential of adult mesenchymal stem cells (MSCs) for bone repair has been long proposed and examined. Actions of MSCs may include direct differentiation to become bone cells, attraction and recruitment of other cells, or creation of a regenerative environment via production of trophic growth factors. With systemic aging, MSCs also undergo functional decline, which has been well investigated in a number of recent studies. In this review, we first describe the changes in MSCs during aging and discuss how these alterations can affect bone regeneration. We next review current research findings on bone tissue engineering, which is considered a promising and viable therapeutic solution for structural and functional restoration of bone. In particular, the importance of MSCs and bioscaffolds is highlighted. Finally, potential approaches for the prevention of MSC aging and the rejuvenation of aged MSC are discussed.
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Affiliation(s)
- Hang Lin
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Jihee Sohn
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - He Shen
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Division of Nanobiomedicine, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of Sciences, China
| | - Mark T Langhans
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Rocky S Tuan
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; The Chinese University of Hong Kong, Hong Kong SAR, China.
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Duan X, Lin Z, Lin X, Wang Z, Wu Y, Ji M, Lu W, Wang X, Zhang D. Study of platelet-rich fibrin combined with rat periodontal ligament stem cells in periodontal tissue regeneration. J Cell Mol Med 2019; 22:1047-1055. [PMID: 29368432 PMCID: PMC5783838 DOI: 10.1111/jcmm.13461] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 09/28/2017] [Indexed: 12/13/2022] Open
Abstract
The objective of this study was to investigate the advantages and feasibility of periodontal tissue regeneration using platelet‐rich fibrin (PRF) combined with rat periodontal ligament stem cells (PDLSCs) for the first time. We first determined the effect of PRF on rat PDLSCs in vitro. We next conducted an in vivo study, in which a tissue engineering technique was performed to repair periodontal defects in five groups: a blank group, collagen group (implanted collagen membrane), collagen + cells group (implanted collagen membrane and rat PDLSCs), PRF group (implanted PRF membrane) and PRF + cells group (implanted PRF membrane and rat PDLSCs). PRF greatly enhanced cell proliferation, mRNA and protein expression levels of bone sialoprotein (BSP), osteocalcin (OC), and runt‐related transcription factor 2 (RUNX2) and activity of alkaline phosphatase (ALP) in vitro. Transplantation of PRF combined with rat PDLSCs resulted in higher expression of osteopontin (Opn), collagen I (COL1A) and RUNX2 at both 12 and 24 days after surgery. Micro‐computed tomography and histological analysis showed substantially more new bone formation in the PRF + cells group at 24 days after surgery. Based on these results, we discuss the role of PRF in the proliferation and differentiation of rat PDLSCs and suggest that PRF combined with rat PDLSCs provides a valuable tool for periodontal tissue engineering.
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Affiliation(s)
- Xuejing Duan
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Zhiyong Lin
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Xiujuan Lin
- School of Stomatology, Qianfoshan Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Zhiqiang Wang
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Yihua Wu
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Mei Ji
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Wei Lu
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Xiaoyang Wang
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
| | - Dongsheng Zhang
- School of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China
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Sadeghinia A, Davaran S, Salehi R, Jamalpoor Z. Nano-hydroxy apatite/chitosan/gelatin scaffolds enriched by a combination of platelet-rich plasma and fibrin glue enhance proliferation and differentiation of seeded human dental pulp stem cells. Biomed Pharmacother 2019; 109:1924-1931. [DOI: 10.1016/j.biopha.2018.11.072] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Revised: 11/14/2018] [Accepted: 11/19/2018] [Indexed: 12/26/2022] Open
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Vácz G, Major B, Gaál D, Petrik L, Horváthy DB, Han W, Holczer T, Simon M, Muir JM, Hornyák I, Lacza Z. Hyperacute serum has markedly better regenerative efficacy than platelet-rich plasma in a human bone oxygen-glucose deprivation model. Regen Med 2018; 13:531-543. [PMID: 30132395 DOI: 10.2217/rme-2017-0141] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
AIM Platelet-rich plasma (PRP) and hyperacute serum (HAS) were compared in a novel human model of ex vivo bone damage induced by oxygen-glucose deprivation (OGD). MATERIALS & METHODS Osteoarthritic subchondral bone pieces were harvested from discarded femoral heads during hip replacement surgery and subjected to transient OGD. RESULTS Proteome profiling revealed that PRP is more angiopoietic, whereas HAS is more antiangiopoietic in composition. However, treatment of OGD-exposed bone with multiple PRP preparations had no effect on cell counts, whereas HAS restored cell proliferation capacity and rescued viable cell number following OGD. CONCLUSION A similar pro-proliferation effect was observed with recombinant growth factors, indicating that HAS may be an alternative agent for enhancing the regeneration of damaged bone cells.
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Affiliation(s)
- Gabriella Vácz
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Bálint Major
- Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Orthopaedic Department, Frankel Leo u. 54., Budapest, Hungary, 1023
| | - Dorottya Gaál
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Laura Petrik
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Dénes Balázs Horváthy
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Weiping Han
- Bioimaging Consortium, A-STAR, Singapore, Helios, Biopolis Way 11
| | - Tünde Holczer
- Department of Laboratory Medicine, Semmelweis University, Nagyvárad t. 4, Budapest, Hungary, 1089
| | - Melinda Simon
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Jeffrey M Muir
- Motion Research, 3-35 Stone Church Rd, Suite 215, Ancaster, Ontario, L9K 3S9 Canada
| | - István Hornyák
- OrthoSera GmbH, Dr. Karl-Dorrek-Straße 23-29, 3500 Krems an der Donau, Austria
| | - Zsombor Lacza
- OrthoSera GmbH, Dr. Karl-Dorrek-Straße 23-29, 3500 Krems an der Donau, Austria.,University of Physical Education, Alkotás u. 44, Budapest, Hungary 1123
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Meimandi-Parizi A, Oryan A, Gholipour H. Healing potential of nanohydroxyapatite, gelatin, and fibrin-platelet glue combination as tissue engineered scaffolds in radial bone defects of rats. Connect Tissue Res 2018; 59:332-344. [PMID: 29035127 DOI: 10.1080/03008207.2017.1387541] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Different biomaterials have been used in orthopedic surgery. Evaluation of biomaterials for bone healing promotion has been a wide area of research of the orthopedic field. Sixty critical size defects of 5 mm long were bilaterally created in the radial diaphysis of 30 rats. The animals were randomly divided into six equal groups as empty defect, autograft, nanohydroxyapatite (nHA), Gelatin (Gel)-nHA, fibrin-platelet glue (FPG)-nHA, and Gel-FPG-nHA groups (n = 10 in each group). Radiographs of each forelimb were taken postoperatively on the 1st day and then at the 28th and 56th days post injury. After 56 days, the rats were euthanized and their harvested healing bone samples were evaluated by histopathology, scanning electron microscopy, and biomechanical testing. All the treated defects demonstrated significantly superior new bone formation, remodeling, and bone tissue volume. Moreover, the defects treated with FPG-nHA showed significantly higher ultimate load, yield load, and stiffness. The Gel-FPG-nHA moderately improved bone regeneration that was not close to the autograft in some parameters, whereas FPG-nHA significantly improved bone healing closely comparable with the autograft group in most parameters. In conclusion, although all the nHA-containing scaffolds had some beneficial effects on bone regeneration, the FPG-nHA scaffold was more effective in improving the structural and functional properties of the newly formed bone and was more osteoinductive than the Gel and was comparable to the autograft. Therefore, the FPG can be regarded as a promising option to be used in conjunction with mineral scaffolds for bone tissue engineering.
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Affiliation(s)
- Abdolhamid Meimandi-Parizi
- a Division of Surgery, Department of Clinical Sciences, School of Veterinary Medicine , Shiraz University , Shiraz , Iran
| | - Ahmad Oryan
- b Department of Pathology, School of Veterinary Medicine , Shiraz University , Shiraz , Iran
| | - Hojjat Gholipour
- a Division of Surgery, Department of Clinical Sciences, School of Veterinary Medicine , Shiraz University , Shiraz , Iran
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Eshghpour M, Danaeifar N, Kermani H, Nejat AH. Does Intra-Alveolar Application of Chlorhexidine Gel in Combination With Platelet-Rich Fibrin Have an Advantage Over Application of Platelet-Rich Fibrin in Decreasing Alveolar Osteitis After Mandibular Third Molar Surgery? A Double-Blinded Randomized Clinical Trial. J Oral Maxillofac Surg 2018; 76:939.e1-939.e7. [DOI: 10.1016/j.joms.2017.12.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Revised: 12/08/2017] [Accepted: 12/08/2017] [Indexed: 01/28/2023]
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The effects of gelatin, fibrin-platelet glue and their combination on healing of the experimental critical bone defect in a rat model: radiological, histological, scanning ultrastructural and biomechanical evaluation. Cell Tissue Bank 2017; 19:341-356. [PMID: 29264693 DOI: 10.1007/s10561-017-9679-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 12/12/2017] [Indexed: 01/09/2023]
Abstract
Fibrin-platelet glue (FPG) is a blood derivative, in which platelets and fibrinogen are concentrated in a small plasma volume, by differential centrifugation and precipitation. It can form a three-dimensional and biocompatible fibrin scaffold with a myriad of growth factors and proteins that are released progressively to the local environment and contribute to the accelerated postoperative bone healing. Gelatin (Gel) is a derivative of collagen and can promote cell adhesion and proliferation due to its unique sequence of amino acids, so it is suitable for bone tissue applications. This study examined the effects of Gel, FPG and their combinations as bone scaffold on the healing of surgically created critical-size defects in rat radius. Fifty critical size defects of 5 mm long were bilaterally created in the radial diaphysis of 25 rats. The animals were randomly divided into five equal groups as empty defect, autograft, Gel, FPG and Gel-FPG groups (n = 10 in each group). Radiographs of each forelimb were taken postoperatively on the 1st day and then at the 28th and 56th days post injury to evaluate bone formation, union and remodeling of the defect. After 56 days, the rats were euthanized and their harvested healing bone samples were evaluated by histopathology, scanning electron microscopy (SEM) and biomechanical testing. The results of present study showed that the Gel alone did not significantly affect bone healing and regeneration; however, the Gel treated defects promoted healing more than those that were left untreated (negative control). Furthermore, the FPG-enhanced grafts provided a good scaffold containing numerous growth factors for proliferation of osteoinduction and was effective in improving the structural and functional properties of the newly formed bone more than that of the untreated and also the Gel treated groups. Incorporation of Gel into the FPG scaffold improved healing potential of the FPG scaffold; however, it was still inferior to the autograft (positive control). Although the Gel-FPG scaffolds had best effectiveness during bone regeneration, it still needs to be further enhanced by incorporation of the ceramic and osteoinductive biomaterials.
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Wang X, Li G, Guo J, Yang L, Liu Y, Sun Q, Li R, Yu W. Hybrid composites of mesenchymal stem cell sheets, hydroxyapatite, and platelet-rich fibrin granules for bone regeneration in a rabbit calvarial critical-size defect model. Exp Ther Med 2017; 13:1891-1899. [PMID: 28565782 PMCID: PMC5443196 DOI: 10.3892/etm.2017.4199] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 01/13/2017] [Indexed: 12/15/2022] Open
Abstract
The reconstruction of large bone defects remains a major clinical challenge, and tissue engineering is a promising technique for resolving this problem. Many attempts have been made to optimize bone tissue engineering protocols. The aim of the present study was to develop a process incorporating mesenchymal stem cell (MSC) sheets with nanoscale hydroxyapatite (nano-HA) and autologous platelet-rich fibrin (PRF) granules for enhanced bone formation within a critical-sized rabbit cranial defect. MSC sheets and PRF were prepared prior to in vivo experiments. The osteogenic differentiation ability of MSCs and the ultrastructure of PRF were also studied. A total of 15 New Zealand white rabbits were used in the current study and critical-size defects (CSDs) were surgically introduced in the cranium (diameter, 15 mm). The surgical defects were treated with MSC/PRF composites, MSC composites or left empty. Animals were euthanized at week 8 post-surgery. Iconography, histological and histomorphometric analysis were performed to assess de novo bone formation. The percentage of new bone in the MSC/PRF group (35.7±5.1%) was significantly higher than that in the MSC (18.3±3.2%; P<0.05) and empty defect groups (4.7±1.5%; P<0.05). The results of the present study suggest that combined application of an MSC sheet with nano-HA and granular PRF enhances bone regeneration in a rabbit calvarial CSD model, and provides a novel insight into bone tissue regeneration for large bone defects.
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Affiliation(s)
- Xi Wang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Guanghui Li
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Jia Guo
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Lei Yang
- Department of Orthodontics, Beijing Ruitai Dental Hospital, Beijing 100107, P.R. China
| | - Yiming Liu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Qiang Sun
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Rui Li
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Weiwei Yu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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Wang M, Li H, Si J, Dai J, Shi J, Wang X, Guo L, Shen G. Amniotic fluid-derived stem cells mixed with platelet rich plasma for restoration of rat alveolar bone defect. Acta Biochim Biophys Sin (Shanghai) 2017; 49:197-207. [PMID: 28104582 DOI: 10.1093/abbs/gmw133] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Indexed: 12/12/2022] Open
Abstract
Stem cells isolated from the amniotic fluid have been shown as a promising candidate for cell therapy and tissue engineering. However, the experimental and preclinical applications of amniotic fluid-derived stem cells (AFSCs) in the very field of maxillofacial bone tissue engineering are still limited. In this study, rat AFSCs were successfully harvested and characterized in vitro. The rat AFSCs showed typical fibroblastoid morphology, stable proliferation activity and multi-differentiation potential. Flow-cytometry analysis demonstrated that these cells were positive for CD29, CD44, and CD90, while negative for hematopoietic markers such as CD34 and CD45. The regenerative performance of AFSCs-premixed with platelet rich plasma (PRP) gel in restoration of alveolar bone defect was further investigated using a modified rat maxillary alveolar defect model. Micro-computer tomography and histological examination showed a superior regenerative capacity of AFSCs-premixed with PRP gel at both 4 and 8 weeks after operation comparing with control groups. Moreover, the implanted AFSCs can survive in the defect site and directly participate in the bone tissue regeneration. Taken together, these results indicated the feasibility of an AFSCs-based alveolar bone tissue engineering strategy for alveolar defect restoration.
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Affiliation(s)
- Minjiao Wang
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
| | - Hongliang Li
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
| | - Jiawen Si
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
| | - Jiewen Dai
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
| | - Jun Shi
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
| | - Xudong Wang
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
| | - Lihe Guo
- Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Guofang Shen
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
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Liao HT, James IB, Marra KG, Rubin JP. The Effects of Platelet-Rich Plasma on Cell Proliferation and Adipogenic Potential of Adipose-Derived Stem Cells. Tissue Eng Part A 2016; 21:2714-22. [PMID: 26416350 DOI: 10.1089/ten.tea.2015.0159] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Platelet-rich plasma (PRP) contains multiple growth factors and has been shown to enhance fat graft survival after lipotransfer. However, the molecular mechanisms mediating this effect remain unknown. Adipose-derived stem cells (ASCs) play an important role in fat graft survival and are a likely target for PRP-mediated effects. This study seeks to investigate the impact of PRP on ASC proliferation and adipogenic differentiation. METHODS Human ASCs were isolated using our laboratory protocol. The experiments were divided into four arms: (1) ASCs cultured in general culture medium alone; (2) ASCs in general culture medium + 5%, 10%, 15%, or 20% PRP; (3) ASCs cultured in adipogenic differentiation medium alone; (4) ASCs cultured in adipogenic medium + 5%, 10%, 15%, or 20% PRP. Cell proliferation was analyzed and comparative m-RNA expression of adipogenic genes was assessed by quantitative PCR. Protein expression was determined by western blot. RESULTS PRP significantly enhanced proliferation of ASCs, even in the presence of antiproliferative, proadipogenic media. In contrast, PRP inhibited adipogenic differentiation in adipogenic media, evidenced by decreased intracellular lipid accumulation and reduced adipogenic gene expression (PPAR-γ and FABP4). Inhibition appears to occur through downregulation of bone morphogenetic protein receptor IA (BMPRIA) and fibroblast growth factor receptor 1 (FGFR1). Interestingly, PRP elicited these effects across the entire range of doses studied. CONCLUSIONS PRP appears to modulate ASC function primarily by enhancing cell proliferation. The consequences of its impact on adipogenesis are less clear. Enhanced proliferation initially might set the stage for more robust regeneration and adipogenesis at later time points, providing an important target for ongoing research.
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Affiliation(s)
- Han Tsung Liao
- 1 Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania .,2 Division of Trauma Plastic Surgery, Department of Plastic and Reconstructive Surgery, Craniofacial Research Center, Chang Gung Memorial Hospital, Chang Gung University , Taiwan, Republic of China
| | - Isaac B James
- 1 Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania .,3 University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania
| | - Kacey G Marra
- 1 Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania .,4 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania .,5 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - J Peter Rubin
- 1 Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania .,4 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania .,5 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
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Brierly GI, Tredinnick S, Lynham A, Woodruff MA. Critical Sized Mandibular Defect Regeneration in Preclinical In Vivo Models. ACTA ACUST UNITED AC 2016. [DOI: 10.1007/s40610-016-0036-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Shalumon KT, Lai GJ, Chen CH, Chen JP. Modulation of Bone-Specific Tissue Regeneration by Incorporating Bone Morphogenetic Protein and Controlling the Shell Thickness of Silk Fibroin/Chitosan/Nanohydroxyapatite Core-Shell Nanofibrous Membranes. ACS APPLIED MATERIALS & INTERFACES 2015; 7:21170-21181. [PMID: 26355766 DOI: 10.1021/acsami.5b04962] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
The presence of both osteoconductive and osteoinductive factors is important in promoting stem cell differentiation toward the osteogenic lineage. In this study, we prepared silk fibroin/chitosan/nanohydroxyapatite/bone morphogenetic protein-2 (SF/CS/nHAP/BMP-2, SCHB2) nanofibrous membranes (NFMs) by incorporating BMP-2 in the core and SF/CS/nHAP as the shell layer of a nanofiber with two different shell thicknesses (SCHB2-thick and SCHB-thin). The physicochemical properties of SCHB2 membranes were characterized and compared with those of SF/CS and SF/CS/nHAP NFMs. When tested in release studies, the release rate of BMP-2 and the concentration of BMP-2 in the release medium were higher for SCHB2-thin NFMs because of reduced shell thickness. The BMP-2 released from the nanofiber retained its osteoinductive activity toward human-bone-marrow-derived mesenchymal stem cells (hMSCs). Compared with SF/CS and SF/CS/nHAP NFMs, the incorporation of BMP-2-promoted osteogenic differentiation of hMSCs and the SCHB-thin NFM is the best scaffold during in vitro cell culture. Gene expression analysis by real-time quantitative polymerase chain reaction detected the evolution of both early and late marker genes of bone formation. The relative mRNA expression is in accordance with the effect of BMP-2 incorporation and shell thickness, while the same was reconfirmed through the quantification of bone marker protein osteocalcin. In vivo experiments were carried out by subcutaneously implanting hMSC-seeded SCHB2-thin NFMs and acellular controls on the back sides of nude mice. Immunohistochemical and histological staining confirmed ectopic bone formation and osteogenesis of hMSCs in SCHB2-thin NFMs. In conclusion, the SCHB2-thin NFM could be suggested as a promising scaffold for bone tissue engineering.
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Affiliation(s)
- K T Shalumon
- Department of Chemical and Materials Engineering, Chang Gung University , Kwei-San, Taoyuan 333, Taiwan Republic of China
| | - Guo-Jyun Lai
- Department of Chemical and Materials Engineering, Chang Gung University , Kwei-San, Taoyuan 333, Taiwan Republic of China
| | - Chih-Hao Chen
- Department of Chemical and Materials Engineering, Chang Gung University , Kwei-San, Taoyuan 333, Taiwan Republic of China
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine , Kwei-San, Taoyuan 333, Taiwan Republic of China
| | - Jyh-Ping Chen
- Department of Chemical and Materials Engineering, Chang Gung University , Kwei-San, Taoyuan 333, Taiwan Republic of China
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Liao Y, Zhang XL, Li L, Shen FM, Zhong MK. Stem cell therapy for bone repair: a systematic review and meta-analysis of preclinical studies with large animal models. Br J Clin Pharmacol 2015; 78:718-26. [PMID: 24645974 DOI: 10.1111/bcp.12382] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 03/13/2014] [Indexed: 12/12/2022] Open
Abstract
AIM Injury to bone is a significant clinical challenge, due to its limited regenerative capacity. The current methods of repairing bone defect are surgical, highly invasive and not always successful. A systematic review and meta-analysis of preclinical studies involving large animals with bone defects were conducted to determine the treatment outcomes with stem cell therapies. METHODS A random effects meta-analysis of the available studies was conducted to assess the treatment outcomes including the rate of new bone formation and new bone mineral density (BMD). Stratified analyses were also conducted by separating studies based on each characteristic independently. RESULTS Pooled analysis of 20 preclinical studies showed a significant beneficial effect of stem cell therapy in increasing new bone formation (17.79%, 95% confidence interval [CI], 10.54, 25.03; P < 0.001) and BMD (276.94 mg cm(-2) , 95% CI, 62.71, 491.17; P < 0.001) for disease amelioration. Regarding new bone formation, a statistical improvement was similarly detected from randomized controlled trial groups (17.06%, 95% CI, 8.87, 25.24; P < 0.001) and cohort groups (17.43%, 95% CI, 10.79, 24.07; P < 0.001). Exploratory stratified analysis yielded significant predictors of new bone formation including cell number (<10(7) vs. ≥10(7) ; P = 0.048) and the route of cell delivery (combining with matrix scaffold showed more effect than direct cell injection, P = 0.041). The effect of stem cell therapy diminished after 12 weeks. CONCLUSION The study results suggest that stem cell therapy improves new bone formation and BMD in bone defect models. Future trials should focus on the transplantation of ≥10(7) stem cells, especially using slow release biodegradable scaffolds or repetitive cell injections.
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Affiliation(s)
- Yun Liao
- Department of Clinical Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China
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Rodella LF, Bonazza V. Platelet preparations in dentistry: How? Why? Where? When? World J Stomatol 2015; 4:39-55. [DOI: 10.5321/wjs.v4.i2.39] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 04/08/2015] [Accepted: 04/30/2015] [Indexed: 02/06/2023] Open
Abstract
The aim of this article is to review the outcomes of platelet preparations in dentistry. A structured electronic search discovered 348 articles, which described the use of autologous platelet concentrates with a relevance to clinical dentistry. Among these articles, 220 articles investigated platelet rich plasma, 99 investigated platelet rich fibrin, 22 investigated plasma rich in growth factors and 7 investigated the use of concentrated growth factors. Several studies reported beneficial treament outcomes in terms of enhanced bone and soft tissue regeneration.
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Lara FJP, Serrano AM, Moreno JU, Carmona JH, Marquez MF, Pérez LR, del Rey Moreno A, Muñoz HO. Platelet-rich fibrin sealant as a treatment for complex perianal fistulas: a multicentre study. J Gastrointest Surg 2015; 19:360-8. [PMID: 25421358 DOI: 10.1007/s11605-014-2698-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Accepted: 11/05/2014] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The incidence of perianal fistulas is high, and this condition has a profoundly negative impact on patients' quality of life. The problem is greater when the fistula tract is high because treatment is necessarily complex (limited surgery may lead to recurrence, while aggressive surgery is associated with higher rates of faecal incontinence). To achieve a balance between these two options, we suggest that complex fistulas should be treated by sealing the tract with platelet-rich fibrin. Our objective is to evaluate the medium- to long-term results obtained from the treatment of complex perianal fistulas by sealing with platelet-rich fibrin. MATERIAL AND METHODS Prospective longitudinal multicentre study involves three colorectal surgeons working at three hospitals. The study period was October 2010 to June 2013, during which a total of 60 patients were treated for complex fistulas. In all cases, the intervention consisted of curetting the fistula tract, sealing it with platelet-rich fibrin and closing the internal orifice. We evaluated the clinical outcomes (clinical examination and pelvic magnetic resonance (MRI)) and the quality of life results, both general (SF-36) and gastrointestinal (GIQLI questionnaire) in periodic reviews during consultation. RESULT The median follow-up period was 24 months (11-43 months), during which in 40 patients (66.66 %) the fistulas remained closed, with a zero rate of faecal incontinence. The results of the quality of life questionnaires are comparable (indeed, they are better in some items for the cured patients) to those of the reference population. CONCLUSION In our opinion, this procedure is safe and its results are promising in terms of clinical outcome and medium- to long-term quality of life.
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Affiliation(s)
- F J Pérez Lara
- Digestive Surgeon, Service of Surgery, Hospital de Antequera, Málaga, Spain,
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Si JW, Wang XD, Shen SGF. Perinatal stem cells: A promising cell resource for tissue engineering of craniofacial bone. World J Stem Cells 2015; 7:149-159. [PMID: 25621114 PMCID: PMC4300925 DOI: 10.4252/wjsc.v7.i1.149] [Citation(s) in RCA: 15] [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: 07/22/2014] [Revised: 08/28/2014] [Accepted: 09/17/2014] [Indexed: 02/06/2023] Open
Abstract
In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application.
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Eshghpour M, Dastmalchi P, Nekooei AH, Nejat A. Effect of Platelet-Rich Fibrin on Frequency of Alveolar Osteitis Following Mandibular Third Molar Surgery: A Double-Blinded Randomized Clinical Trial. J Oral Maxillofac Surg 2014; 72:1463-7. [DOI: 10.1016/j.joms.2014.03.029] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 03/16/2014] [Accepted: 03/26/2014] [Indexed: 01/10/2023]
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The osteogenesis of bone marrow stem cells on mPEG-PCL-mPEG/hydroxyapatite composite scaffold via solid freeform fabrication. BIOMED RESEARCH INTERNATIONAL 2014; 2014:321549. [PMID: 24868523 PMCID: PMC4020560 DOI: 10.1155/2014/321549] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Accepted: 04/08/2014] [Indexed: 11/17/2022]
Abstract
The study described a novel bone tissue scaffold fabricated by computer-aided, air pressure-aided deposition system to control the macro- and microstructure precisely. The porcine bone marrow stem cells (PBMSCs) seeded on either mPEG-PCL-mPEG (PCL) or mPEG-PCL-mPEG/hydroxyapatite (PCL/HA) composite scaffold were cultured under osteogenic medium to test the ability of osteogenesis in vitro. The experimental outcomes indicated that both scaffolds possessed adequate pore size, porosity, and hydrophilicity for the attachment and proliferation of PBMSCs and the PBMSCs expressed upregulated genes of osteogensis and angiogenesis in similar manner on both scaffolds. The major differences between these two types of the scaffolds were the addition of HA leading to higher hardness of PCL/HA scaffold, cell proliferation, and VEGF gene expression in PCL/HA scaffold. However, the in vivo bone forming efficacy between PBMSCs seeded PCL and PCL/HA scaffold was different from the in vitro results. The outcome indicated that the PCL/HA scaffold which had bone-mimetic environment due to the addition of HA resulted in better bone regeneration and mechanical strength than those of PCL scaffold. Therefore, providing a bone-mimetic scaffold is another crucial factor for bone tissue engineering in addition to the biocompatibility, 3D architecture with high porosity, and interpored connection.
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Naik B, Karunakar P, Jayadev M, Marshal VR. Role of Platelet rich fibrin in wound healing: A critical review. J Conserv Dent 2013; 16:284-93. [PMID: 23956527 PMCID: PMC3740636 DOI: 10.4103/0972-0707.114344] [Citation(s) in RCA: 139] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Revised: 03/21/2013] [Accepted: 04/22/2013] [Indexed: 02/02/2023] Open
Abstract
AIM The aim is to review and discuss the strategies available for use of platelet rich fibrin as healing aid in dentistry. BACKGROUND Platelet rich fibrin (PRF) is a fibrin matrix in which platelet cytokines, growth factors, and cells are trapped and may be released after a certain time and that can serve as a resorbable membrane. Choukroun and his associates were amongst the pioneers for using PRF protocol in oral and maxillofacial surgery to improve bone healing in implant dentistry. Autologous PRF is considered to be a healing biomaterial, and presently, studies have shown its application in various disciplines of dentistry. MATERIALS AND METHODS By using specific keywords, electronic search of scientific papers was carried out on the entire PubMed database with custom range of 5 years. The electronic search yielded 302 papers; based on inclusion and exclusion criteria which were specifically predetermined, 72 papers were identified as suitable to the inclusion criteria and the remaining 230 papers were excluded. After adding three more selected papers through hand search, full text of all the articles retrieved and review was done. By pooling the extracted data from selected papers, the reviewed data was synthesized. CONCLUSION Recently by showing good promising results with use of the PRF, it has proved to have a good prospect for its use as healing aid in various aspects of the dentistry.
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Affiliation(s)
- Balaram Naik
- Department of Conservative Dentistry and Endodontics, Sri Dharmasthala Manjunatheshwara College of Dental Sciences, Dharwad, Karnataka, India
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Tsung LH, Chang KH, Chen JP. OSTEOGENESIS OF ADIPOSE-DERIVED STEM CELLS ON THREE-DIMENSIONAL, MACROPOROUS GELATIN–HYALURONIC ACID CRYOGELS. BIOMEDICAL ENGINEERING-APPLICATIONS BASIS COMMUNICATIONS 2012. [DOI: 10.4015/s1016237211002463] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Aim. Macroporous sponge-like gelatin–hyaluronic acid (Gl–HA) scaffolds cross-linked by EDC were produced using cryogelation technology, which allows for the preparation of highly porous scaffolds without compromising their mechanical properties, and is a more cost-efficient process than freeze drying. The aim of this study is to evaluate the osteogenic potential of porcine adipose-derived stem cells (PADSCs) in GI–HA cryogel. Method. The character of the GI–HA cryogel was evaluated. The pore size and the microstructure were observed using scanning electron microscope (SEM). The swelling ratio was measured. The PADSCs were harvested and isolated from pig inguinal area. Then, the GI–HA cryogel was seeded with PADSCs. The cryogel/ASCs mixture was cultured in osteogenic medium for 0, 3, 7, 14, and 21 days. The cell proliferation was measured by MTS. The RT-PCR of specific osteogenic gene expression such as osteocalcin (OC), RUNX2 was used to assess the osteogenic ability. The SEM was used to observe the interaction between scaffold and cells. Energy dispersive spectrum (EDS) was used to analyze the mineralization around cells. Results. The pore size was variable between 200 and 369 μm. The swelling ratio was around 8.67 ± 1.669%. The cell proliferation was increasing along with the increase of induction periods. The expression of early gene of RUNX2 and late gene of OC mean that the PADSCs were differentiated well into osteoblasts within the cryogels. The SEM detailed that the PADSCs cell can proliferate well in the pore of GI–HA scaffold. The EDS also demonstrated the mineralization of PADSCs in GI–HA scaffold after induction. Conclusions. To conclude, the PADSCs can proliferate and differentiate well into osteoblasts in the three-dimensional, porous, GI–HA cryogel.
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Affiliation(s)
- Liao Han Tsung
- Department of Plastic and Reconstructive Surgery, Craniofacial Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan
- Department of Chemical and Materials Engineering, Chang Gung University, Gueishan, Taoyuan, Taiwan
| | - Kun-Hung Chang
- Department of Chemical and Materials Engineering, Chang Gung University, Gueishan, Taoyuan, Taiwan
| | - Jyh Ping Chen
- Department of Chemical and Materials Engineering, Chang Gung University, Gueishan, Taoyuan, Taiwan
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LEE MINGYIH, LIU SIWEN, CHEN JYHPING, LIAO HANTSUNG, TSAI WENWEI, WANG HSIUCHEN. IN VITRO EXPERIMENTS ON LASER SINTERED POROUS PCL SCAFFOLDS WITH POLYMER HYDROGEL FOR BONE REPAIR. J MECH MED BIOL 2012. [DOI: 10.1142/s0219519411004885] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Bone defects caused by tumors, diseased infection, trauma or abnormal bone development create a lot of serious health problems. Tissue engineering aims to fabricate tissues or organs using patients' cells for repairing the damaged tissues or organs in clinic. The aim of this study was to design and fabricate polycaprolactone (PCL) scaffolds using the inhouse-built selective laser sintering (SLS) rapid prototyping (RP) machine and combining with polymer hydrogel for in vitro study for bone repair. In this study, three configurations of scaffolds structure (0/45/0/45°, 0/90/0/90°, and 0/45/90/135° patterns) were designed and produced. The compressive modulus, porosity and pore size of porous scaffolds were first determined. In addition, polymer hydrogel was combined with PCL scaffolds with three loading methods (i.e., immersion method, injection method and titration method) to enhance scaffolds surface hydrophilicity for cell proliferation. Mesenchymal stem cells from New Zealand White rabbits were loaded on PCL scaffolds and induced to osteoblasts in vitro. Bone formation was determined by MTS assays, von Kossa stains and ALP activities. The experimental results showed the compressive moduli of scaffolds with 0/45/0/45°, 0/90/0/90°, and 0/45/90/135° patterns was 2 MPa, 3.4 MPa, and 3.75 MPa, respectively. The porosity of scaffolds was 72%, 76%, and 83%, respectively. The ranges of pore size of scaffolds were 350–400 μm, 400–500 μm, and 350–400 μm, respectively. By comparing three kinds of polymer hydrogel loading methods, titration method had the best result. The in vitro experimental results revealed that OD values of MTS tests and ALP activities increased from day 7 to day 21 and von Kossa stain revealed dark brown mineralized tissue, indicating cells could proliferate and differentiate in polymer hydrogel and scaffolds.
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Affiliation(s)
- MING-YIH LEE
- Graduate Institute of Medical Mechatronics, Chang Gung University, Tao-Yuan, Taiwan, R.O.C
| | - SI-WEN LIU
- Graduate Institute of Medical Mechatronics, Chang Gung University, Tao-Yuan, Taiwan, R.O.C
| | - JYH-PING CHEN
- Department of Chemical and Medical Engineering, Chang Gung University, Tao-Yuan, Taiwan, R.O.C
| | - HAN-TSUNG LIAO
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, R.O.C
| | - WEN-WEI TSAI
- Graduate Institute of Medical Mechatronics, Chang Gung University, Tao-Yuan, Taiwan, R.O.C
| | - HSIU-CHEN WANG
- Graduate Institute of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan, R.O.C
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Stem cell-based tissue engineering in veterinary orthopaedics. Cell Tissue Res 2012; 347:677-688. [PMID: 22287044 DOI: 10.1007/s00441-011-1316-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2011] [Accepted: 12/21/2011] [Indexed: 01/23/2023]
Abstract
Regenerative medicine is one of the most intensively researched medical branches, with enormous progress every year. When it comes to translating research from bench to bedside, many of the pioneering innovations are achieved by cooperating teams of human and veterinary medical scientists. The veterinary profession has an important role to play in this new and evolving technology, holding a great scientific potential, because animals serve widely as models for human medicine and results obtained from animals may serve as preclinical results for human medicine. Regenerative veterinary medicine utilizing mesenchymal stromal cells (MSC) for the treatment of acute injuries as well as chronic disorders is gradually turning into clinical routine. As orthopaedic disorders represent a major part of all cases in veterinary clinical practice, it is not surprising that they are currently taking a leading role in MSC therapies. Therefore, the purpose of this paper is to give an overview on past and current achievements as well as future perspectives in stem cell-based tissue engineering in veterinary orthopaedics.
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Wu X, Ren J, Li J. Fibrin glue as the cell-delivery vehicle for mesenchymal stromal cells in regenerative medicine. Cytotherapy 2011; 14:555-62. [PMID: 22175911 DOI: 10.3109/14653249.2011.638914] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The use of tissue-engineering techniques such as stem-cell therapy to renew injured tissues is a promising strategy in regenerative medicine. As a cell-delivery vehicle, fibrin glues (FG) facilitate cell attachment, growth and differentiation and, ultimately, tissue formation and organization by its three-dimensional structure. Numerous studies have provided evidence that stromal cells derived from bone marrow (bone marrow stromal cells; BMSC) and adipose tissue (adipose-derived stromal cells; ADSC) contain a population of adult multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells that can differentiate into several lineages. By combining MSC with FG, the implantation could take advantage of the mutual benefits. Researchers and physicians have pinned their hopes on stem cells for developing novel approaches in regenerative medicine. This review focuses on the therapeutic potential of MSC with FG in bone defect reconstruction, cartilage and tendon injury repair, ligament, heart and nerve regeneration, and, furthermore, wound healing.
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Affiliation(s)
- Xiuwen Wu
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
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Liao HT, Chen CT, Chen JP. Osteogenic Differentiation and Ectopic Bone Formation of Canine Bone Marrow-Derived Mesenchymal Stem Cells in Injectable Thermo-Responsive Polymer Hydrogel. Tissue Eng Part C Methods 2011; 17:1139-49. [DOI: 10.1089/ten.tec.2011.0140] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Affiliation(s)
- Han-Tsung Liao
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan, Taiwan, Republic of China
- Division of Traumatic Plastic Surgery, Department of Plastic and Reconstructive Surgery, Craniofacial Research Center, Chang Gung Memorial Hospital, Chang Gung University, Kwei-San, Taoyuan, Taiwan, Republic of China
| | - Chien-Tzung Chen
- Division of Traumatic Plastic Surgery, Department of Plastic and Reconstructive Surgery, Craniofacial Research Center, Chang Gung Memorial Hospital, Chang Gung University, Kwei-San, Taoyuan, Taiwan, Republic of China
| | - Jyh-Ping Chen
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan, Taiwan, Republic of China
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