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Pagani BT, Rosso MPDO, Moscatel MBM, Trazzi BFDM, da Cunha MR, Issa JPM, Buchaim DV, Buchaim RL. Update on synthetic biomaterials combined with fibrin derivatives for regenerative medicine: Applications in bone defect treatment: Systematic review. World J Orthop 2025; 16:106181. [DOI: 10.5312/wjo.v16.i5.106181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 04/01/2025] [Accepted: 04/21/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND Bone regeneration is a central focus of regenerative medicine, with applications in orthopedics and dentistry, particularly for treating bone defects caused by trauma, infection, or congenital anomalies. Synthetic biomaterials, often combined with fibrin derivatives, offer promising solutions for bone healing and restoration.
AIM To Explore the increasingly important role of the association of synthetic biomaterials with fibrin in bone regeneration.
METHODS Search terms included: “synthetic biomaterials AND fibrin sealant”, “hydroxyapatite AND fibrin sealant”, “tricalcium phosphate AND fibrin sealant”, and “synthetic biomaterials AND platelet-rich fibrin (PRF)”, resulting in 67 articles. After rigorous screening, 21 articles met the inclusion criteria.
RESULTS The reviewed studies assessed biomaterials like hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), and fibrin-based products. Key findings highlighted the enhanced osteoconductivity and biocompatibility of HA and β-TCP, especially when combined with fibrin sealants. These composites show significant potential for improving cellular adhesion, promoting osteogenic differentiation, and accelerating bone regeneration. The antimicrobial properties and structural support for cell growth of certain biomaterials indicate a promising potential for clinical applications.
CONCLUSION This systematic review emphasizes the growing role of fibrin-based biomaterials in bone regeneration and urges continued research to improve their clinical use for complex bone defects.
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Affiliation(s)
| | | | | | | | - Marcelo Rodrigues da Cunha
- Interunit Graduate Program in Bioengineering, University of Sao Paulo, Sao Carlos 13566-970, Brazil
- Postgraduate Program in Health Sciences, Faculty of Medicine of Jundiaí, Jundiai 13202-550, Brazil
| | - João Paulo Mardegan Issa
- Department of Basic and Oral Biology, Ribeirão Preto School of Dentistry, University of São Paulo, Ribeirao Preto 14040-904, Brazil
| | - Daniela Vieira Buchaim
- Medical School, University Center of Adamantina, Adamantina 17800-000, Brazil
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil
| | - Rogério Leone Buchaim
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru 17012-901, Brazil
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Guda T, Stukel Shah JM, Lundquist BD, Macaitis JM, Pérez ML, Pfau-Cloud MR, Beltran FO, Schmitt CW, Corbin EM, Grunlan MA, Lien W, Wang HC, Burdette AJ. An In Vivo Assessment of Different Mesenchymal Stromal Cell Tissue Types and Their Differentiation State on a Shape Memory Polymer Scaffold for Bone Regeneration. J Biomed Mater Res B Appl Biomater 2024; 112:e35516. [PMID: 39607370 DOI: 10.1002/jbm.b.35516] [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: 01/26/2024] [Revised: 10/16/2024] [Accepted: 11/16/2024] [Indexed: 11/29/2024]
Abstract
A combined biomaterial and cell-based solution to heal critical size bone defects in the craniomaxillofacial area is a promising alternative therapeutic option to improve upon autografting, the current gold standard. A shape memory polymer (SMP) scaffold, composed of biodegradable poly(ε-caprolactone) and coated with bioactive polydopamine, was evaluated with mesenchymal stromal cells (MSCs) derived from adipose (ADSC), bone marrow (BMSC), or umbilical cord (UCSC) tissue in their undifferentiated state or pre-differentiated toward osteoblasts for bone healing in a rat calvarial defect model. Pre-differentiating ADSCs and UCSCs resulted in higher new bone volume fraction (15.69% ± 1.64%) compared to empty (i.e., untreated) defects and scaffold-only (i.e., unseeded) groups (4.41% ± 1.11%). Notably, only differentiated UCSCs exhibited a significant increase in new bone volume, surpassing both undifferentiated UCSCs and unseeded scaffolds. Further, differentiated ADSCs and UCSCs had significantly higher trabecular numbers than their undifferentiated counterparts, unseeded scaffolds, and untreated defects. Although the mineral density regenerated within the unseeded scaffold surpassed that achieved with cell seeding, the connectivity of this bone was diminished, as the regenerated tissue confined itself to the spherical morphology of the scaffold pores. The SMP scaffold alone, with undifferentiated BMSCs, with undifferentiated and differentiated ADSCs, and differentiated UCSCs (29.72 ± 1.49 N) demonstrated significant osseointegration compared to empty defects (14.34 ± 2.21 N) after 12 weeks of healing when assessed by mechanical push-out testing. Based on these results and tissue availability to obtain the cells, pre-differentiated ADSCs and UCSCs emerge as particularly promising candidates when paired with the SMP scaffold for repairing critical size bone defects in the craniofacial skeleton.
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Affiliation(s)
- Teja Guda
- Department of Biomedical Engineering and Chemical Engineering, University of Texas San Antonio, San Antonio, Texas, USA
| | | | | | | | - Mística Lozano Pérez
- Department of Biomedical Engineering and Chemical Engineering, University of Texas San Antonio, San Antonio, Texas, USA
| | - Michaela R Pfau-Cloud
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
| | - Felipe O Beltran
- Department of Materials Science & Engineering, Texas A&M University, College Station, Texas, USA
| | - Connie W Schmitt
- Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioeffects Division, Veterinary Science Branch, San Antonio, Texas, USA
| | - Emily M Corbin
- Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioeffects Division, Veterinary Science Branch, San Antonio, Texas, USA
| | - Melissa A Grunlan
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
- Department of Materials Science & Engineering, Texas A&M University, College Station, Texas, USA
- Department of Chemistry, Texas A&M University, College Station, Texas, USA
| | - Wen Lien
- USAF Dental Research & Consultation Service, San Antonio, USA
| | - Heuy-Ching Wang
- Naval Medical Research Unit San Antonio, San Antonio, Texas, USA
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Maita KC, Avila FR, Torres-Guzman RA, Sarabia-Estrada R, Zubair AC, Quinones-Hinojosa A, Forte AJ. In Vitro Enhanced Osteogenic Potential of Human Mesenchymal Stem Cells Seeded in a Poly (Lactic- co-Glycolic) Acid Scaffold: A Systematic Review. Craniomaxillofac Trauma Reconstr 2024; 17:61-73. [PMID: 38371215 PMCID: PMC10874209 DOI: 10.1177/19433875231157454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2024] Open
Abstract
Study Design Human bone marrow stem cells (hBMSCs) and human adipose-derived stem cells (hADSCs) have demonstrated the capability to regenerate bone once they have differentiated into osteoblasts. Objective This systematic review aimed to evaluate the in vitro osteogenic differentiation potential of these cells when seeded in a poly (lactic-co-glycolic) acid (PLGA) scaffold. Methods A literature search of 4 databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in January 2021 for studies evaluating the osteogenic differentiation potential of hBMSCs and hADSCs seeded in a PLGA scaffold. Only in vitro models were included. Studies in languages other than English were excluded. Results A total of 257 studies were identified after the removal of duplicates. Seven articles fulfilled our inclusion and exclusion criteria. Four of these reviews used hADSCs and three used hBMSCs in the scaffold. Upregulation in osteogenic gene expression was seen in all the cells seeded in a 3-dimensional scaffold compared with 2-dimensional films. High angiogenic gene expression was found in hADSCs. Addition of inorganic material to the scaffold material affected cell performance. Conclusions Viability, proliferation, and differentiation of cells strongly depend on the environment where they grow. There are several factors that can enhance the differentiation capacity of stem cells. A PLGA scaffold proved to be a biocompatible material capable of boosting the osteogenic differentiation potential and mineralization capacity in hBMSCs and hADSCs.
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Affiliation(s)
- Karla C. Maita
- Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL, USA
| | | | | | | | - Abba C. Zubair
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA
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Alrumaih S, Alshibani N, Alssum L, Alshehri FA, AlMayrifi MA, AlMayouf M, Alrahlah A, Bautista LSJ. The impact of Resolvin E1 on bone regeneration in critical-sized calvarial defects of rat model-A gene expression and micro-CT analysis. J Periodontal Res 2024; 59:195-203. [PMID: 37947141 DOI: 10.1111/jre.13206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 10/15/2023] [Accepted: 10/30/2023] [Indexed: 11/12/2023]
Abstract
OBJECTIVE To investigate, in vivo, the effect of local application of Resolvin E1 (RvE1) on the bone regeneration of critical-size defects (CSDs) in Wistar rats utilizing gene expression and micro-computed tomographic (micro-CT) analysis. BACKGROUND The inflammation-resolving actions of RvE1 are well established. The molecular mechanism of its bone-regenerative actions has been of significant interest in recent years; however, there is limited information regarding the same. MATERIALS AND METHODS Thirty Wistar rats with a 5 mm induced critical-size calvarial defect were randomly allocated into four groups: no treatment/negative control (n = 5), treatment using bovine bone grafts/positive control (n = 5), treatment using local delivery of RvE1 (n = 11) and treatment using RvE1 mixed with bovine bone graft (n = 9). After 4 weeks, RNA isolation, complementary DNA synthesis and real-time polymerase chain reaction were used for genetic expression of alkaline phosphatase (ALP), osteocalcin (OCN) and osteopontin (OPN). The rats were sacrificed after 12 weeks and micro-CT imaging was performed to analyse the characteristics of the newly formed bone (NFB). The data were analysed using ANOVA and the least significant difference tests (α ≤ .05). RESULTS The RvE1 + bovine graft group had statistically highest mean NFB (20.75 ± 2.67 mm3 ) compared to other groups (p < .001). Similarly, RvE1 + bovine graft group also demonstrated statistically highest mean genetic expression of ALP (31.71 ± 2.97; p = .008) and OPN (34.78 ± 3.62; p < .001) compared to negative control and RvE1 groups. CONCLUSION Resolvin E1 with adjunct bovine bone graft demonstrated an enhanced bone regeneration compared to RvE1 or bovine graft alone in the calvarial defect of Wistar rats.
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Affiliation(s)
- Sara Alrumaih
- Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
- Hail Health Cluster, Ministry of Health, Hail, Saudi Arabia
| | - Nouf Alshibani
- Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Lamees Alssum
- Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Fahad A Alshehri
- Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed A AlMayrifi
- Prince Naif bin Abdulaziz Center for Health Research, Experimental Surgery and Animal Laboratory, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed AlMayouf
- General Director of Medical Services, Al Nakheel Center, Riyadh, Saudi Arabia
| | - Ali Alrahlah
- Restorative Dental Sciences Department, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
- Engineer Abdullah Bugshan Research Chair for Dental and Oral Rehabilitation, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Leonel S J Bautista
- Engineer Abdullah Bugshan Research Chair for Dental and Oral Rehabilitation, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
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Später T, Kaneda G, Chavez M, Sheyn J, Wechsler J, Yu V, Del Rio P, Huang D, Metzger M, Tawackoli W, Sheyn D. Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites. Bioengineering (Basel) 2023; 10:1049. [PMID: 37760151 PMCID: PMC10525500 DOI: 10.3390/bioengineering10091049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 08/18/2023] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.
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Affiliation(s)
- Thomas Später
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Giselle Kaneda
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Melissa Chavez
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Julia Sheyn
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Jacob Wechsler
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Victoria Yu
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Patricia Del Rio
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Dave Huang
- Orthopedics Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (D.H.); (M.M.)
- Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Melodie Metzger
- Orthopedics Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (D.H.); (M.M.)
- Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Wafa Tawackoli
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Dmitriy Sheyn
- Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (T.S.); (G.K.); (M.C.); (J.S.); (J.W.); (V.Y.); (P.D.R.); (W.T.)
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Naudot M, Le Ber J, Marcelo P. TMT-Based Quantitative Proteomics Analysis Reveals Differentially Expressed Proteins between Different Sources of hMSCs. Int J Mol Sci 2023; 24:13544. [PMID: 37686351 PMCID: PMC10488246 DOI: 10.3390/ijms241713544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/23/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and regenerative medicine owing to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs, which are currently being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have different secretion potentials and production, which may influence their therapeutic effects. To confirm this, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from three different sources: Wharton's jelly (WJ), dental pulp (DP), and bone marrow (BM). Our analysis focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 differentially expressed human proteins. WJ-MSCs showed the greatest variation compared with the other sources. WJ produced more extracellular matrix (ECM) proteins and ECM-affiliated proteins and proteins related to the inflammatory and immune response processes. BM-MSCs expressed more proteins involved in osteogenic, adipogenic, neuronal, or muscular differentiation and proteins involved in paracrine communication. Compared to the other sources, DP-MSCs overexpressed proteins involved in the exocytosis process. The results obtained confirm the existence of differences between WJ, DP, and BM-MSCs and the need to select the MSC origin according to the therapeutic objective sought.
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Affiliation(s)
- Marie Naudot
- UR7516, CHirurgie, IMagerie et REgénération Tissulaire de l’Extrémité Céphalique (CHIMERE), Université de Picardie Jules Verne, 80039 Amiens, France;
| | - Julie Le Ber
- PLATANN, Université de Picardie Jules Verne, 80039 Amiens, France;
| | - Paulo Marcelo
- Plateforme d’Ingénierie Cellulaire & Analyses des Protéines ICAP, FR CNRS 3085 ICP, Université de Picardie Jules Verne, 80039 Amiens, France
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Therapeutic Efficacy of Adipose-Derived Stem Cells Versus Bone Marrow Stromal Cells for Irradiated Mandibular Fracture Repair. Ann Plast Surg 2022; 89:459-464. [PMID: 36149985 DOI: 10.1097/sap.0000000000003301] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Mesenchymal stem cells have immense potential in applications of bone healing and regeneration. However, few studies have evaluated the therapeutic efficacy of adipose-derived stem cells (ASCs) and bone marrow stromal cells (BMSCs) in irradiated bone. The purpose of this study is to compare the ability of ASCs versus BMSCs to enhance healing outcomes in a murine model of irradiated mandibular fracture repair. METHODS Forty-eight isogenic male Lewis rats underwent radiation therapy followed by mandibular osteotomy with intraoperative placement of either ASCs or BMSCs. Animals were killed on postoperative day 40. Mandibles were analyzed for union rate, biomechanical strength, vascularity, and mineralization. Groups were compared at P < 0.05 significance. RESULTS The ASC and BMSC groups demonstrated 92% and 75% union rates. Compared with the BMSC group, the ASC group demonstrated a trending increase in maximum load ( P = 0.095) on biomechanical strength analysis and a significant increase in vessel number ( P = 0.001), vessel thickness ( P = 0.035), and vessel volume fraction ( P = 0.007) on micro-computed tomography angiography analysis. No significant differences in bone mineralization were identified on micro-computed tomography analysis. CONCLUSION This study demonstrates the superior therapeutic efficacy of ASCs over BMSCs in irradiated fracture healing as evidenced by union rate, vascular morphometry, and a trend in biomechanical strength. We posit that the robust vascular response induced by ASCs better recapitulates the sequence and synchronicity of physiologic bone healing compared with BMSCs, thereby improving the reliability of irradiated fracture repair.
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Zhu J, Xiong J, Ji W. A systematic review of bone marrow stromal cells and periosteum-derived cells for bone regeneration. TISSUE ENGINEERING PART B: REVIEWS 2022; 29:103-122. [PMID: 36066333 DOI: 10.1089/ten.teb.2022.0115] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Bone marrow stromal cells (BMSCs) and periosteum-derived cells (PDCs) represent promising skeletal stem cell sources to treat critical-size bone defects. However, the large number of preclinical tests with a variety of in vivo data complicates the selection of cells for further clinical translation. This systematic review aims to analyze the in vivo bone-forming efficacy of BMSCs- and PDCs-based approaches in all published preclinical experiments until November 2020. For this purpose, four databases (PubMed, Embase, Cochrane Central Register of Controlled Trial, and Web of Science) were searched for eligible literature, which yielded a total of 94 full-text articles for systematic review. This review generated an evidence-based list of BMSC- or PDC-based approaches, which have been evaluated for bone formation in different animal models. Among them, 74 studies were included for pairwise and network meta-analysis. The results revealed that both PDC and BMSC had beneficial bone-forming efficacy compared to bare scaffold. In addition, BMSC- and PDC-based approaches had no significant difference regarding in vivo bone-forming efficacy. However, BMSC-based approach had a higher probability to be ranked better than PDC-based approach. Furthermore, the review discusses (i) the possible risk of bias of the in vivo evaluation of cell-based approaches, (ii) the difficulty in replication of such experiments due to frequent poor reporting of the methods and results, and (iii) the clinical relevance of the currently utilized BMSC- and PDC-based approaches. Systematic review registration: The study was prospectively registered in PROSPERO, Registration No. CRD42021270922.
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Affiliation(s)
- Jingxian Zhu
- The State Key Laboratory Breeding Base of Basic Sciences of Stomatology, Key Laboratory of Oral Biomedicine, Ministry of Education (Hubei-MOST KLOS & KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China, Wuhan, Hubei Province, China,
| | - Jiabi Xiong
- The State Key Laboratory Breeding Base of Basic Sciences of Stomatology, Key Laboratory of Oral Biomedicine, Ministry of Education (Hubei-MOST KLOS & KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China, Wuhan, Hubei Province, China,
| | - Wei Ji
- The State Key Laboratory Breeding Base of Basic Sciences of Stomatology, Key Laboratory of Oral Biomedicine, Ministry of Education (Hubei-MOST KLOS & KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China, No.237 Luoyu Road, Hongshan District, Wuhan, Hubei Province, China, Wuhan, Hubei Province, China, 430079
- Department of Implantology, School and Hospital of Stomatology, Wuhan University, Wuhan, China, No.237 Luoyu Road, Hongshan District, Wuhan, Hubei Province, China, Wuhan, Hubei Province, China, 430079,
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Yu H, Xia L, Leng X, Chen Y, Zhang L, Ni X, Luo J, Leng W. Improved repair of rabbit calvarial defects with hydroxyapatite/chitosan/polycaprolactone composite scaffold-engrafted EPCs and BMSCs. Front Bioeng Biotechnol 2022; 10:928041. [PMID: 35992335 PMCID: PMC9382592 DOI: 10.3389/fbioe.2022.928041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/28/2022] [Indexed: 11/13/2022] Open
Abstract
Endothelial progenitor cells (EPCs) expressing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) and bone marrow mesenchymal stem cells (BMSCs) expressing endogenous bone morphogenetic protein-2 (BMP-2) play the important role in new bone formation. This study investigated the effects of a porous hydroxyapatite (HA)/chitosan (CS)/polycaprolactone (PCL) composite scaffold-engrafted EPCs and BMSCs on the expression of BMP-2, VEGF, and PDGF in the calvarial defect rabbit model in vivo. It showed that a three-dimensional composite scaffold was successfully constructed by physical interaction with a pore size of 250 μm. The HA/CS/PCL scaffold degraded slowly within 10 weeks and showed non-cytotoxicity. By X-ray, micro-CT examination, and H&E staining, compared with the HA/CS/PCL group, HA/CS/PCL + EPCs, HA/CS/PCL + BMSCs, and HA/CS/PCL + EPCs + BMSCs groups performed a more obvious repair effect, and the dual factor group presented particularly significant improvement on the percentages of bone volume at week 4 and week 8, with evident bone growth. Osteogenesis marker (BMP-2) and vascularization marker (VEGF and PDGF) expression in the dual factor group were much better than those of the HA/CS/PCL control group and single factor groups. Collectively, the HA/CS/PCL composite scaffold-engrafting EPCs and BMSCs is effective to repair calvarial defects by regulating endogenous expression of BMP-2, VEGF, and PDGF. Thus, this study provides important implications for the potential clinical application of biomaterial composite scaffold-engrafted engineering cells.
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Affiliation(s)
- Hedong Yu
- Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- Institute of Dental Research, School of Dentistry, Hubei University of Medicine, Shiyan, China
| | - Lingyun Xia
- Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- Institute of Dental Research, School of Dentistry, Hubei University of Medicine, Shiyan, China
| | - Xieyuan Leng
- The First Clinical College, Anhui Medical University, Hefei, China
| | - Yongji Chen
- Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- Institute of Dental Research, School of Dentistry, Hubei University of Medicine, Shiyan, China
| | - Li Zhang
- Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- Institute of Dental Research, School of Dentistry, Hubei University of Medicine, Shiyan, China
| | - Xiaobing Ni
- Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- Institute of Dental Research, School of Dentistry, Hubei University of Medicine, Shiyan, China
| | - Jie Luo
- Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- *Correspondence: Weidong Leng, ; Jie Luo,
| | - Weidong Leng
- Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- Institute of Dental Research, School of Dentistry, Hubei University of Medicine, Shiyan, China
- *Correspondence: Weidong Leng, ; Jie Luo,
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10
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Mosaddad SA, Rasoolzade B, Namanloo RA, Azarpira N, Dortaj H. Stem cells and common biomaterials in dentistry: a review study. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2022; 33:55. [PMID: 35716227 PMCID: PMC9206624 DOI: 10.1007/s10856-022-06676-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 05/16/2022] [Indexed: 05/16/2023]
Abstract
Stem cells exist as normal cells in embryonic and adult tissues. In recent years, scientists have spared efforts to determine the role of stem cells in treating many diseases. Stem cells can self-regenerate and transform into some somatic cells. They would also have a special position in the future in various clinical fields, drug discovery, and other scientific research. Accordingly, the detection of safe and low-cost methods to obtain such cells is one of the main objectives of research. Jaw, face, and mouth tissues are the rich sources of stem cells, which more accessible than other stem cells, so stem cell and tissue engineering treatments in dentistry have received much clinical attention in recent years. This review study examines three essential elements of tissue engineering in dentistry and clinical practice, including stem cells derived from the intra- and extra-oral sources, growth factors, and scaffolds.
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Affiliation(s)
- Seyed Ali Mosaddad
- Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Boshra Rasoolzade
- Student Research Committee, Department of Pediatric Dentistry, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hengameh Dortaj
- Department of Tissue Engineering, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
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11
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Olguín Y, Acuna-Mendoza S, Otero C, Acevedo CA, Covarrubias C. Osteoconductive Effect of a Nanocomposite Membrane Treated with UV Radiation. Polymers (Basel) 2022; 14:289. [PMID: 35054693 PMCID: PMC8780835 DOI: 10.3390/polym14020289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/29/2021] [Accepted: 01/07/2022] [Indexed: 12/04/2022] Open
Abstract
Modulation of the bio-regenerative characteristics of materials is an indispensable requirement in tissue engineering. Particularly, in bone tissue engineering, the promotion of the osteoconductive phenomenon determines the elemental property of a material be used therapeutically. In addition to the chemical qualities of the constituent materials, the three-dimensional surface structure plays a fundamental role that various methods are expected to modulate in a number of ways, one most promising of which is the use of different types of radiation. In the present manuscript, we demonstrate in a calvarial defect model, that treatment with ultraviolet irradiation allows modification of the osteoconductive characteristics in a biomaterial formed by gelatin and chitosan, together with the inclusion of hydroxyapatite and titanium oxide nanoparticles.
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Affiliation(s)
- Yusser Olguín
- Centro Científico Tecnológico de Valparaíso CCTVaL, Universidad Técnica Federico Santa María, Valparaíso 2390123, Chile;
| | - Soledad Acuna-Mendoza
- Department of Oral Pathology and Medicine, Faculty of Dentistry, University of Chile, Santiago 8380453, Chile;
| | - Carolina Otero
- Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago 8370149, Chile;
| | - Cristian A. Acevedo
- Centro Científico Tecnológico de Valparaíso CCTVaL, Universidad Técnica Federico Santa María, Valparaíso 2390123, Chile;
- Centro de Biotecnología, Universidad Técnica Federico Santa María, Valparaíso 2390123, Chile
- Departamento de Física, Universidad Técnica Federico Santa María, Valparaíso 2390123, Chile
| | - Cristian Covarrubias
- Laboratory of Nanobiomaterials, Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago 8380453, Chile;
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12
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Cao C, Huang P, Prasopthum A, Parsons AJ, Ai F, Yang J. Characterisation of bone regeneration in 3D printed ductile PCL/PEG/hydroxyapatite scaffolds with high ceramic microparticle concentrations. Biomater Sci 2021; 10:138-152. [PMID: 34806738 DOI: 10.1039/d1bm01645h] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
3D printed bioactive glass or bioceramic particle reinforced composite scaffolds for bone tissue engineering currently suffer from low particle concentration (<50 wt%) hence low osteoconductivity. Meanwhile, composites with very high inorganic particle concentrations are very brittle. Scaffolds combining high particle content and ductility are urgently required for bone tissue engineering. Herein, 3D printed PCL/hydroxyapatite (HA) scaffolds with high ceramic concentration (up to 90 wt%) are made ductile (>100% breaking strain) by adding poly(ethylene glycol) which is biocompatible and FDA approved. The scaffolds require no post-printing washing to remove hazardous components. More exposure of HA microparticles on strut surfaces is enabled by incorporating higher HA concentrations. Compared to scaffolds with 72 wt% HA, scaffolds with higher HA content (90 wt%) enhance matrix formation but not new bone volume after 12 weeks implantation in rat calvarial defects. Histological analyses demonstrate that bone regeneration within the 3D printed scaffolds is via intramembranous ossification and starts in the central region of pores. Fibrous tissue that resembles non-union tissue within bone fractures is formed within pores that do not have new bone. The amount of blood vessels is similar between scaffolds with mainly fibrous tissue and those with more bone tissue, suggesting vascularization is not a deciding factor for determining the type of tissues regenerated within the pores of 3D printed scaffolds. Multinucleated immune cells are commonly present in all scaffolds surrounding the struts, suggesting a role of managing inflammation in bone regeneration within 3D printed scaffolds.
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Affiliation(s)
- Chuanliang Cao
- School of Mechatronic Engineering, Nanchang University, Nanchang, Jiangxi, China 330031.
| | - Pengren Huang
- Department of Orthopedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China 330006
| | - Aruna Prasopthum
- Biodiscovery Institute, University of Nottingham, Nottingham, UK NG7 2RD.
| | - Andrew J Parsons
- Composites Research Group, Faculty of Engineering, University of Nottingham, Nottingham, UK NG7 2RD
| | - Fanrong Ai
- School of Mechatronic Engineering, Nanchang University, Nanchang, Jiangxi, China 330031.
| | - Jing Yang
- Biodiscovery Institute, University of Nottingham, Nottingham, UK NG7 2RD.
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13
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Calabrese EJ. Hormesis and bone marrow stem cells: Enhancing cell proliferation, differentiation and resilience to inflammatory stress. Chem Biol Interact 2021; 351:109730. [PMID: 34728189 DOI: 10.1016/j.cbi.2021.109730] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/13/2021] [Accepted: 10/27/2021] [Indexed: 12/21/2022]
Abstract
This paper identifies and provides the first detailed assessment of hormetic dose responses by bone marrow stem cells (BMSCs) from a broad range of animal models and humans with particular emphasis on cell renewal (proliferation), cell differentiation and enhancing resilience to inflammatory stress. Such hormetic dose responses are commonly reported, being induced by a broad range of chemicals, including pharmaceuticals (e.g., caffeine, dexamethasone, nicotine), dietary supplements (e.g., curcumin, Ginkgo biloba, green tea extracts. resveratrol, sulforaphane), endogenous agents (e.g., hydrogen sulfide, interleukin 10), environmental contaminants (e.g., arsenic, PFOS) and physical stressor agents (e.g., EMF, shockwaves). Hormetic dose responses reported here for BMSCs are similar to those induced with other stem cell types [e.g., adipose-derived stem cells (ADSCs), dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), neuro stem cells (NSCs), embryonic stem cells (ESCs)], indicating a substantial degree of generality for hormetic responses in stem cells. The paper assesses both the underlying mechanistic foundations of BMSC hormetic responses and their potential therapeutic implications.
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Affiliation(s)
- Edward J Calabrese
- Professor of Toxicology, Environmental Health Sciences, School of Public Health and Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA, 01003, USA.
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14
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Pfau MR, McKinzey KG, Roth AA, Graul LM, Maitland DJ, Grunlan MA. Shape memory polymer (SMP) scaffolds with improved self-fitting properties. J Mater Chem B 2021; 9:3826-3837. [PMID: 33979417 DOI: 10.1039/d0tb02987d] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
"Self-fitting" shape memory polymer (SMP) scaffolds prepared as semi-interpenetrating networks (semi-IPNs) with crosslinked linear-poly(ε-caprolactone)-diacrylate (PCL-DA, Mn∼10 kg mol-1) and linear-poly(l-lactic acid) (PLLA, Mn∼15 kg mol-1) [75/25 wt%] exhibited robust mechanical properties and accelerated degradation rates versus a PCL-DA scaffold control. However, their potential to treat irregular craniomaxillofacial (CMF) bone defects is limited by their relatively high fitting temperature (Tfit∼55 °C; related to the Tm of PCL) required for shape recovery (i.e. expansion) and subsequent shape fixation during press fitting of the scaffold, which can be harmful to surrounding tissue. Additionally, the viscosity of the solvent-based precursor solutions, cast over a fused salt template during fabrication, can limit scaffold size. Thus, in this work, analogous semi-IPN SMP scaffolds were formed with a 4-arm star-PCL-tetracryalate (star-PCL-TA) (Mn∼10 kg mol-1) and star-PLLA (Mn∼15 kg mol-1). To assess the impact of a star-polymer architecture, four semi-IPN compositions were prepared: linear-PCL-DA/linear-PLLA (L/L), linear-PCL-DA/star-PLLA (L/S), star-PCL-TA/linear-PLLA (S/L) and star-PCL-TA/star-PLLA (S/S). Two PCL controls were also prepared: LPCL (i.e. 100% linear-PCL-DA) and SPCL (i.e. 100% star-PCL-TA). The S/S semi-IPN scaffold exhibited particularly desirable properties. In addition to achieving a lower, tissue-safe Tfit (∼45 °C), it exhibited the fastest rate of degradation which is anticipated to more favourably permit neotissue infiltration. The radial expansion pressure exerted by the S/S semi-IPN scaffold at Tfit was greater than that of LPCL, which is expected to enhance osseointegration and mechanical stability. The intrinsic viscosity of the S/S semi-IPN macromer solution was also reduced such that larger scaffold specimens could be prepared.
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Affiliation(s)
- Michaela R Pfau
- Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.
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15
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Zhang G, Chen X, Cheng X, Ma W, Chen C. BMSC seeding in different scaffold incorporation with hyperbaric oxygen treats seawater-immersed bony defect. J Orthop Surg Res 2021; 16:249. [PMID: 33849602 PMCID: PMC8042966 DOI: 10.1186/s13018-021-02368-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 03/18/2021] [Indexed: 12/31/2022] Open
Abstract
Introduction The experiment was undertaken to estimate the effect of BMSC seeding in different scaffold incorporation with HBO on the repair of a seawater-immersed bone defect. And future compared n-HA/PLGA with β-TCP/PLGA as a scaffold in treatment effect of the seawater-immersed bone defect. Methods Sixty New Zealand White rabbits with standard seawater defect in radius were randomly divided into group A (implant with nothing), group B (implanted with autogenous bone), group C (implanted with n-HA/PLGA/BMSCs), and group D (implanted with β-TCP/PLGA/BMSCs). After the implant, each rabbit receives HBO treatment at 2.4 ATA 100% oxygen for 120 min/day for 2 weeks. Radiograph, histological, and biomechanical examinations were used to analyze osteogenesis. Result X-ray analysis shows that n-HA/PLGA/BMSCs and β-TCP/PLGA/BMSCs could accelerate the new bone formation, and the new bone formation in group C was larger than that in group D or group A and close to group B (P < 0.05). After 12 weeks, in group A, the defect without scaffold shows a loose connect tissue filled in the areas. The medullary canal in group B was recanalized. Defects in groups C and D show a larger number of woven bone formation. The new woven bone formation in defect areas in group C was larger than that in group D. The mechanical examination revealed ultimate strength at 12 weeks was group D > group C > group B > group A (P < 0.05). Conclusion Scaffolds of n-HA/PLGA and β-TCP/PLGA incorporation with HBO and BMSCs were effective to treat seawater-immersed bone defect, and n-HA/PLGA was more excellent than β-TCP/PLGA. Supplementary Information The online version contains supplementary material available at 10.1186/s13018-021-02368-8.
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Affiliation(s)
- Gan Zhang
- Department of Orthopaedics, The 901th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Hefei, 230031, China.
| | - Xiaosong Chen
- Department of Orthopaedics, The 901th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Hefei, 230031, China
| | - Xunsheng Cheng
- Department of Orthopaedics, The 901th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Hefei, 230031, China
| | - Wuxiu Ma
- Department of Orthopaedics, The 901th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Hefei, 230031, China
| | - Congcong Chen
- Department of Orthopaedics, The 901th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Hefei, 230031, China
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16
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Della Coletta BB, Jacob TB, Moreira LADC, Pomini KT, Buchaim DV, Eleutério RG, Pereira EDSBM, Roque DD, Rosso MPDO, Shindo JVTC, Duarte MAH, Alcalde MP, Júnior RSF, Barraviera B, Dias JA, Andreo JC, Buchaim RL. Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer. Molecules 2021; 26:847. [PMID: 33562825 PMCID: PMC7914843 DOI: 10.3390/molecules26040847] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/01/2021] [Accepted: 02/03/2021] [Indexed: 12/13/2022] Open
Abstract
The aim is to evaluate the effects of photobiomodulation therapy (PBMT) on the guided bone regeneration process (GBR) in defects in the calvaria of rats filled with biphasic calcium phosphate associated with fibrin biopolymer. Thirty male Wistar rats were randomly separated: BMG (n = 10), defects filled with biomaterial and covered by membrane; BFMG (n = 10), biomaterial and fibrin biopolymer covered by membrane; and BFMLG (n = 10), biomaterial and fibrin biopolymer covered by membrane and biostimulated with PBMT. The animals were euthanized at 14 and 42 days postoperatively. Microtomographically, in 42 days, there was more evident bone growth in the BFMLG, limited to the margins of the defect with permanence of the particles. Histomorphologically, an inflammatory infiltrate was observed, which regressed with the formation of mineralized bone tissue. In the quantification of bone tissue, all groups had a progressive increase in new bone tissue with a significant difference in which the BFMLG showed greater bone formation in both periods (10.12 ± 0.67 and 13.85 ± 0.54), followed by BFMG (7.35 ± 0.66 and 9.41 ± 0.84) and BMG (4.51 ± 0.44 and 7.11 ± 0.44). Picrosirius-red staining showed greater birefringence of collagen fibers in yellow-green color in the BFMLG, showing more advanced bone maturation. PBMT showed positive effects capable of improving and accelerating the guided bone regeneration process when associated with biphasic calcium phosphate and fibrin biopolymer.
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Affiliation(s)
- Bruna Botteon Della Coletta
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru 17012-901, São Paulo, Brazil; (B.B.D.C.); (K.T.P.); (M.P.d.O.R.); (J.V.T.C.S.); (J.C.A.)
| | - Thiago Borges Jacob
- Medical and Dentistry School, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil; (T.B.J.); (L.A.d.C.M.); (D.V.B.); (R.G.E.); (E.d.S.B.M.P.); (D.D.R.)
| | - Luana Aparecida de Carvalho Moreira
- Medical and Dentistry School, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil; (T.B.J.); (L.A.d.C.M.); (D.V.B.); (R.G.E.); (E.d.S.B.M.P.); (D.D.R.)
| | - Karina Torres Pomini
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru 17012-901, São Paulo, Brazil; (B.B.D.C.); (K.T.P.); (M.P.d.O.R.); (J.V.T.C.S.); (J.C.A.)
- Medical and Dentistry School, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil; (T.B.J.); (L.A.d.C.M.); (D.V.B.); (R.G.E.); (E.d.S.B.M.P.); (D.D.R.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil;
| | - Daniela Vieira Buchaim
- Medical and Dentistry School, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil; (T.B.J.); (L.A.d.C.M.); (D.V.B.); (R.G.E.); (E.d.S.B.M.P.); (D.D.R.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil;
- Medical School, University Center of Adamantina (UniFAI), Adamantina 17800-000, São Paulo, Brazil
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (Univ Estadual Paulista, UNESP), Botucatu 18610-307, São Paulo, Brazil; (R.S.F.J.); (B.B.)
| | - Rachel Gomes Eleutério
- Medical and Dentistry School, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil; (T.B.J.); (L.A.d.C.M.); (D.V.B.); (R.G.E.); (E.d.S.B.M.P.); (D.D.R.)
| | - Eliana de Souza Bastos Mazuqueli Pereira
- Medical and Dentistry School, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil; (T.B.J.); (L.A.d.C.M.); (D.V.B.); (R.G.E.); (E.d.S.B.M.P.); (D.D.R.)
| | - Domingos Donizeti Roque
- Medical and Dentistry School, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil; (T.B.J.); (L.A.d.C.M.); (D.V.B.); (R.G.E.); (E.d.S.B.M.P.); (D.D.R.)
| | - Marcelie Priscila de Oliveira Rosso
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru 17012-901, São Paulo, Brazil; (B.B.D.C.); (K.T.P.); (M.P.d.O.R.); (J.V.T.C.S.); (J.C.A.)
| | - João Vitor Tadashi Cosin Shindo
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru 17012-901, São Paulo, Brazil; (B.B.D.C.); (K.T.P.); (M.P.d.O.R.); (J.V.T.C.S.); (J.C.A.)
| | - Marco Antônio Húngaro Duarte
- Department of Dentistry, Endodontics and Dental Materials, Bauru School of Dentistry, University of São Paulo (USP), Bauru 17012-901, São Paulo, Brazil;
| | - Murilo Priori Alcalde
- Department of Health Science, Unisagrado University Center, Bauru 17011-160, São Paulo, Brazil;
| | - Rui Seabra Ferreira Júnior
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (Univ Estadual Paulista, UNESP), Botucatu 18610-307, São Paulo, Brazil; (R.S.F.J.); (B.B.)
- Graduate Program in Tropical Diseases, Botucatu Medical School (FMB), São Paulo State University (UNESP – Univ Estadual Paulista), Botucatu 18618-687, São Paulo, Brazil
- Graduate Program in Clinical Research, Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP–Univ Estadual Paulista), Botucatu 18610-307, São Paulo, Brazil
| | - Benedito Barraviera
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (Univ Estadual Paulista, UNESP), Botucatu 18610-307, São Paulo, Brazil; (R.S.F.J.); (B.B.)
- Graduate Program in Tropical Diseases, Botucatu Medical School (FMB), São Paulo State University (UNESP – Univ Estadual Paulista), Botucatu 18618-687, São Paulo, Brazil
- Graduate Program in Clinical Research, Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP–Univ Estadual Paulista), Botucatu 18610-307, São Paulo, Brazil
| | - Jefferson Aparecido Dias
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil;
- Postgraduate Program in Law, University of Marilia (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Jesus Carlos Andreo
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru 17012-901, São Paulo, Brazil; (B.B.D.C.); (K.T.P.); (M.P.d.O.R.); (J.V.T.C.S.); (J.C.A.)
| | - Rogério Leone Buchaim
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru 17012-901, São Paulo, Brazil; (B.B.D.C.); (K.T.P.); (M.P.d.O.R.); (J.V.T.C.S.); (J.C.A.)
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (Univ Estadual Paulista, UNESP), Botucatu 18610-307, São Paulo, Brazil; (R.S.F.J.); (B.B.)
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17
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Jiang L, Sheng K, Wang C, Xue D, Pan Z. The Effect of MMP-2 Inhibitor 1 on Osteogenesis and Angiogenesis During Bone Regeneration. Front Cell Dev Biol 2021; 8:596783. [PMID: 33553142 PMCID: PMC7862568 DOI: 10.3389/fcell.2020.596783] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 12/28/2020] [Indexed: 01/03/2023] Open
Abstract
Bone regeneration is a popular research focus around the world. Recent studies have suggested that the formation of a vascular network as well as intrinsic osteogenic ability is important for bone regeneration. Here, we show for the first time that matrix metalloproteinase (MMP) 2 inhibitor 1 (MMP2-I1) has a positive role in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) and angiogenesis of human vascular endothelial cells (HUVECs). MMP2-I1 activated the p38/mitogen-activated protein kinase signaling pathway to promote the osteogenesis of hBMSCs, and promoted the angiogenesis of HUVECs via the hypoxia-inducible factor-1α signaling pathway. We also found that MMP2-I1 enhanced bone formation using a rat tibial defect model and prevented bone loss using an ovariectomy-induced mouse model of osteoporosis. Data from the mouse model demonstrated that MMP2-I1 generated more type H vessels (CD31hiEmcnhi) when preventing bone loss. These results provide important insights into the regulatory effects of MMP2-I1 on bone regeneration.
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Affiliation(s)
- Liangjun Jiang
- Department of Orthopedics, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China
| | - Kunkun Sheng
- Department of Orthopedics, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Cong Wang
- Department of Orthopedics, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Deting Xue
- Department of Orthopedics, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China
| | - Zhijun Pan
- Department of Orthopedics, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China
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18
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Mohamed-Ahmed S, Yassin MA, Rashad A, Espedal H, Idris SB, Finne-Wistrand A, Mustafa K, Vindenes H, Fristad I. Comparison of bone regenerative capacity of donor-matched human adipose-derived and bone marrow mesenchymal stem cells. Cell Tissue Res 2020; 383:1061-1075. [PMID: 33242173 PMCID: PMC7960590 DOI: 10.1007/s00441-020-03315-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 09/28/2020] [Indexed: 12/22/2022]
Abstract
Adipose-derived stem cells (ASC) have been used as an alternative to bone marrow mesenchymal stem cells (BMSC) for bone tissue engineering. However, the efficacy of ASC in bone regeneration in comparison with BMSC remains debatable, since inconsistent results have been reported. Comparing ASC with BMSC obtained from different individuals might contribute to this inconsistency in results. Therefore, this study aimed to compare the bone regenerative capacity of donor-matched human ASC and BMSC seeded onto poly(l-lactide-co-ε-caprolactone) scaffolds using calvarial bone defects in nude rats. First, donor-matched ASC and BMSC were seeded onto the co-polymer scaffolds to evaluate their in vitro osteogenic differentiation. Seeded scaffolds and scaffolds without cells (control) were then implanted in calvarial defects in nude rats. The expression of osteogenesis-related genes was examined after 4 weeks. Cellular activity was investigated after 4 and 12 weeks. Bone formation was evaluated radiographically and histologically after 4, 12, and 24 weeks. In vitro, ASC and BMSC demonstrated mineralization. However, BMSC showed higher alkaline phosphatase activity than ASC. In vivo, human osteogenesis–related genes Runx2 and collagen type I were expressed in defects with scaffold/cells. Defects with scaffold/BMSC had higher cellular activity than defects with scaffold/ASC. Moreover, bone formation in defects with scaffold/BMSC was greater than in defects with scaffold/ASC, especially at the early time-point. These results suggest that although ASC have the potential to regenerate bone, the rate of bone regeneration with ASC may be slower than with BMSC. Accordingly, BMSC are more suitable for bone regenerative applications.
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Affiliation(s)
- Samih Mohamed-Ahmed
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway.
| | - Mohammed A Yassin
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Ahmad Rashad
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Heidi Espedal
- Department of Biomedicine, University of Bergen, Bergen, Norway
| | - Shaza B Idris
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Anna Finne-Wistrand
- Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Kamal Mustafa
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Hallvard Vindenes
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway.,Department for Plastic, Hand and Reconstructive Surgery, National Fire Damage Center, Bergen, Norway
| | - Inge Fristad
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
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19
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Sartawi Z, Waeber C, Schipani E, Ryan KB. Development of electrospun polymer scaffolds for the localized and controlled delivery of siponimod for the management of critical bone defects. Int J Pharm 2020; 590:119956. [DOI: 10.1016/j.ijpharm.2020.119956] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 10/01/2020] [Accepted: 10/03/2020] [Indexed: 12/20/2022]
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20
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Kampleitner C, Changi K, Felfel RM, Scotchford CA, Sottile V, Kluger R, Hoffmann O, Grant DM, Epstein MM. Preclinical biological and physicochemical evaluation of two-photon engineered 3D biomimetic copolymer scaffolds for bone healing. Biomater Sci 2020; 8:1683-1694. [PMID: 31984995 DOI: 10.1039/c9bm01827a] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A major challenge in orthopedics is the repair of large non-union bone fractures. A promising therapy for this indication is the use of biodegradable bioinspired biomaterials that stabilize the fracture site, relieve pain and initiate bone formation and healing. This study uses a multidisciplinary evaluation strategy to assess immunogenicity, allergenicity, bone responses and physicochemical properties of a novel biomaterial scaffold. Two-photon stereolithography generated personalized custom-built scaffolds with a repeating 3D structure of Schwarz Primitive minimal surface unit cell with a specific pore size of ∼400 μm from three different methacrylated poly(d,l-lactide-co-ε-caprolactone) copolymers with lactide to caprolactone monomer ratios of 16 : 4, 18 : 2 and 9 : 1. Using in vitro and in vivo assays for bone responses, immunological reactions and degradation dynamics, we found that copolymer composition influenced the scaffold physicochemical and biological properties. The scaffolds with the fastest degradation rate correlated with adverse cellular effects and mechanical stiffness correlated with in vitro osteoblast mineralization. The physicochemical properties also correlated with in vivo bone healing and immune responses. Overall these observations provide compelling support for these scaffolds for bone repair and illustrate the effectiveness of a promising multidisciplinary strategy with great potential for the preclinical evaluation of biomaterials.
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Affiliation(s)
- Carina Kampleitner
- Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
| | - Katayoon Changi
- Laboratory of Experimental Allergy, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Department of Dermatology, Vienna, Austria.
| | - Reda M Felfel
- Advanced Materials Research Group, Faculty of Engineering, University of Nottingham, UK
| | - Colin A Scotchford
- Advanced Materials Research Group, Faculty of Engineering, University of Nottingham, UK
| | | | - Rainer Kluger
- Wolfson STEM Centre, School of Medicine, University of Nottingham, UK
| | - Oskar Hoffmann
- Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
| | - David M Grant
- Advanced Materials Research Group, Faculty of Engineering, University of Nottingham, UK
| | - Michelle M Epstein
- Laboratory of Experimental Allergy, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Department of Dermatology, Vienna, Austria.
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21
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Effects of electromagnetic fields treatment on rat critical-sized calvarial defects with a 3D-printed composite scaffold. Stem Cell Res Ther 2020; 11:433. [PMID: 33023631 PMCID: PMC7542469 DOI: 10.1186/s13287-020-01954-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 09/25/2020] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Current strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough. METHODS In this study, polylactic acid/hydroxyapatite (PLA/HA) composite scaffold was fabricated. After seeding rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds, the effects of electromagnetic fields (EMF) on the proliferation and osteogenic differentiation capacity of BMSCs were investigated. Additionally, 6-mm critical-sized calvarial defect was created in rats. BMSC-laden scaffolds were implanted into the defects with or without EMF treatment. RESULTS Our results showed that PLA/HA composite scaffolds exhibited uniform porous structure, high porosity (~ 70%), suitable compression strength (31.18 ± 4.86 MPa), modulus of elasticity (10.12 ± 1.24 GPa), and excellent cyto-compatibility. The proliferation and osteogenic differentiation capacity of BMSCs cultured on the scaffolds were enhanced with EMF treatment. Mechanistically, EMF exposure functioned partly by activating mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways. In vivo, significantly higher new bone formation and vascularization were observed in groups involving scaffold, BMSCs, and EMF treatment, compared to scaffold alone. Furthermore, after 12 weeks of implanting, craniums in groups including scaffold, BMSCs, and EMF exposure showed the greatest biomechanical properties. CONCLUSION In conclusion, EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration.
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22
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Chen K, Zhou Q, Kang H, Yan Y, Qian N, Li C, Wang F, Yang K, Deng L, Qi J. High Mineralization Capacity of IDG-SW3 Cells in 3D Collagen Hydrogel for Bone Healing in Estrogen-Deficient Mice. Front Bioeng Biotechnol 2020; 8:864. [PMID: 32984264 PMCID: PMC7488085 DOI: 10.3389/fbioe.2020.00864] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 07/06/2020] [Indexed: 01/10/2023] Open
Abstract
Tissue engineering with 3D scaffold is a simple and effective method for bone healing after large-scale bone loss. So far, bone marrow-derived mesenchymal stem cells (BMSCs) are mostly used in the treatment of bone healing in animal models due to their self-renewal capability and osteogenic potential. Due to the fact that the main functional cells in promoting osteoid mineralization and bone remodeling were osteocytes, we chose an osteoblast-to-osteocyte transition cell line, IDG-SW3, which are not proliferative under physiological conditions, and compared the healing capability of these cells to that of BMSCs in bone defect. In vitro, IDG-SW3 cells revealed a stronger mineralization capacity when grown in 3D collagen gel, compared to that of BMSCs. Although both BMSC and IDG-SW3 can generate stable calcium-phosphate crystal similar to hydroxyapatite (HA), the content was much more enriched in IDG-SW3-mixed collagen gel. Moreover, the osteoclasts co-cultured with IDG-SW3-mixed collagen gel were easier to be activated, indicating that the IDG-SW3 grafting could promote the bone remodeling more efficiently in vivo. Last, in order to reduce the self-healing capability, we assessed the healing capability between the IDG-SW3 cells and BMSCs in osteoporotic mice. We found that the collagen hydrogel mixed with IDG-SW3 cells has a better healing pattern than what was seen in hydrogel mixed with BMSCs. Therefore, these results demonstrated that by promoting osteoblast-to-osteocyte transition, the therapeutic effect of BMSCs in bone defect repair could be improved.
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Affiliation(s)
- Kaizhe Chen
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qi Zhou
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Kang
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yufei Yan
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Niandong Qian
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Changwei Li
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fei Wang
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kai Yang
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lianfu Deng
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jin Qi
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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23
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Ghaffarinovin Z, Soltaninia O, Mortazavi Y, Esmaeilzadeh A, Nadri S. Repair of rat cranial bone defect by using amniotic fluid-derived mesenchymal stem cells in polycaprolactone fibrous scaffolds and platelet-rich plasma. ACTA ACUST UNITED AC 2020; 11:209-217. [PMID: 34336609 PMCID: PMC8314035 DOI: 10.34172/bi.2021.28] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 04/20/2020] [Accepted: 05/10/2020] [Indexed: 12/28/2022]
Abstract
Introduction: Tissue regenerative medicine strategies, as a promising alternative has become of major interest to the reconstruction of critical size bone defects. This study evaluated the effects of the simultaneous application of polycaprolactone (PCL), amniotic fluid mesenchymal stem cells (AF-MSCs) and platelet-rich plasma (PRP) on the repair of rat cranial bone defects. Methods: The AF-MSCs were isolated at the end of the second week of pregnancy in rats. PRP obtained from rat blood and the random PCL fibrous scaffolds were prepared using the electrospinning method. Circular full thickness (5 mm) bone defects were developed on both sides of the parietal bones (animal number=24) and the scaffolds containing AF-MSCs and PRP were implanted in the right lesions. Thereafter, after eight weeks the histological and immunohistochemistry studies were performed to evaluate the bone formation and collagen type I expression. Results: The spindle-shaped mesenchymal stem cells were isolated and the electron microscope images indicated the preparation of a random PCL scaffold. Immunohistochemical findings showed that collagen type I was expressed by AF-MSCs cultured on the scaffold. The results of hematoxylin and eosin (H&E) staining indicated the formation of blood vessels in the presence of PRP. Additionally, immunofluorescence findings suggested that PRP had a positive effect on collagen type I expression. Conclusion: The simultaneous application of fibrous scaffold + AF-MSCs + PRP has positive effects on bone regeneration. This study showed that PRP can affect the formation of new blood vessels in the scaffold transplanted in the bone defect.
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Affiliation(s)
- Zeinab Ghaffarinovin
- Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Omid Soltaninia
- Department of Oral & Maxillofacial Surgery, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Yousef Mortazavi
- Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.,Cancer Gene therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Abdolreza Esmaeilzadeh
- Cancer Gene therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.,Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Samad Nadri
- Cancer Gene therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.,Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.,Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.,Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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24
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Westhauser F, Essers C, Karadjian M, Reible B, Schmidmaier G, Hagmann S, Moghaddam A. Supplementation with 45S5 Bioactive Glass Reduces In Vivo Resorption of the β-Tricalcium-Phosphate-Based Bone Substitute Material Vitoss. Int J Mol Sci 2019; 20:ijms20174253. [PMID: 31480285 PMCID: PMC6747147 DOI: 10.3390/ijms20174253] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 08/28/2019] [Indexed: 12/18/2022] Open
Abstract
Compared to other materials such as 45S5 bioactive glass (BG), β-tricalcium phosphate (β-TCP)-based bone substitutes such as Vitoss show limited material-driven stimulation of osteogenesis and/or angiogenesis. The unfavorable degradation kinetics of β-TCP-based bone substitutes may result in an imbalance between resorption and osseous regeneration. Composite materials like Vitoss BA (Vitoss supplemented with 20 wt % 45S5-BG particles) might help to overcome these limitations. However, the influence of BG particles in Vitoss BA compared to unsupplemented Vitoss on osteogenesis, resorption behavior, and angiogenesis is not yet described. In this study, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stromal cells before subcutaneous implantation in immunodeficient mice for 10 weeks. Scaffold resorption was monitored by micro-computed tomography, while osteoid formation and vascularization were assessed by histomorphometry and gene expression analysis. Whilst slightly more osteoid and improved angiogenesis were found in Vitoss BA, maturation of the osteoid was more advanced in Vitoss scaffolds. The volume of Vitoss implants decreased significantly, combined with a significantly increased presence of resorbing cells, whilst the volume remained stable in Vitoss BA scaffolds. Future studies should evaluate the interaction of 45S5-BG with resorbing cells and bone precursor cells in greater detail to improve the understanding and application of β-TCP/45S5-BG composite bone substitute materials.
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Affiliation(s)
- Fabian Westhauser
- Center of Orthopedics, Traumatology and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany.
| | - Christopher Essers
- Center of Orthopedics, Traumatology and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany
| | - Maria Karadjian
- Center of Orthopedics, Traumatology and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany
| | - Bruno Reible
- Center of Orthopedics, Traumatology and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany
| | - Gerhard Schmidmaier
- Center of Orthopedics, Traumatology and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany
| | - Sébastien Hagmann
- Center of Orthopedics, Traumatology and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany
| | - Arash Moghaddam
- Center of Orthopedics, Traumatology and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany
- ATORG-Aschaffenburg Trauma and Orthopedic Research Group, Center for Trauma Surgery, Orthopedics and Sports Medicine, Klinikum Aschaffenburg-Alzenau, Am Hasenkopf 1, 63739 Aschaffenburg, Germany
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25
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Dihydroartemisinin Promotes the Osteogenesis of Human Mesenchymal Stem Cells via the ERK and Wnt/ β-Catenin Signaling Pathways. BIOMED RESEARCH INTERNATIONAL 2019; 2019:3456719. [PMID: 31534957 PMCID: PMC6732601 DOI: 10.1155/2019/3456719] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 03/26/2019] [Accepted: 07/25/2019] [Indexed: 12/14/2022]
Abstract
Dihydroartemisinin (DHA), which is considered to be one of the active compounds within Artemisia annua, has extensively been used in recent years as the most effective drug against malaria, having many biological functions including anticancer, antifungal, and immunomodulatory activities. However, DHA plays a role in the regulation of the proliferation and human mesenchymal stem cells (hMSCs) osteogenic differentiation that remains unknown. We explored DHA's effect on hMSCs' proliferation as well as the osteogenic differentiation, together with its underlying mechanisms of action. We showed that DHA enhanced osteogenic differentiation but had no significant effect on hMSCs' proliferation. It probably exerted its functions through the signaling pathways of ERK1/2 as well as Wnt/β. Because DHA has low toxicity and costs, it might be regarded as an important drug for fracture treatment and tissue engineering.
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26
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Caetano G, Wang W, Murashima A, Passarini JR, Bagne L, Leite M, Hyppolito M, Al-Deyab S, El-Newehy M, Bártolo P, Frade MAC. Tissue Constructs with Human Adipose-Derived Mesenchymal Stem Cells to Treat Bone Defects in Rats. MATERIALS (BASEL, SWITZERLAND) 2019; 12:E2268. [PMID: 31311087 PMCID: PMC6679084 DOI: 10.3390/ma12142268] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 07/11/2019] [Accepted: 07/11/2019] [Indexed: 12/29/2022]
Abstract
The use of porous scaffolds created by additive manufacturing is considered a viable approach for the regeneration of critical-size bone defects. This paper investigates the xenotransplantation of polycaprolactone (PCL) tissue constructs seeded with differentiated and undifferentiated human adipose-derived mesenchymal stem cells (hADSCs) to treat calvarial critical-sized defect in Wistar rats. PCL scaffolds without cells were also considered. In vitro and in vivo biological evaluations were performed to assess the feasibility of these different approaches. In the case of cell seeded scaffolds, it was possible to observe the presence of hADSCs in the rat tissue contributing directly (osteoblasts) and indirectly (stimulation by paracrine factors) to tissue formation, organization and mineralization. The presence of bone morphogenetic protein-2 (BMP-2) in the rat tissue treated with cell-seeded PCL scaffolds suggests that the paracrine factors of undifferentiated hADSC cells could stimulate BMP-2 production by surrounding cells, leading to osteogenesis. Moreover, BMP-2 acts synergistically with growth factors to induce angiogenesis, leading to higher numbers of blood vessels in the groups containing undifferentiated and differentiated hADSCs.
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Affiliation(s)
- Guilherme Caetano
- Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto 14040-900, SP, Brazil
- Graduate Program in Biomedical Sciences, University Centre of Hermínio Ometto Foundation, Araras 13607339, SP, Brazil
| | - Weiguang Wang
- School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester M13 9PL, UK
| | - Adriana Murashima
- Department of Ophthalmology, Otolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto 14040-900, SP, Brazil
| | - José Roberto Passarini
- Graduate Program in Biomedical Sciences, University Centre of Hermínio Ometto Foundation, Araras 13607339, SP, Brazil
| | - Leonardo Bagne
- Graduate Program in Biomedical Sciences, University Centre of Hermínio Ometto Foundation, Araras 13607339, SP, Brazil
| | - Marcel Leite
- Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto 14040-900, SP, Brazil
| | - Miguel Hyppolito
- Department of Ophthalmology, Otolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto 14040-900, SP, Brazil
| | - Salem Al-Deyab
- Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohamed El-Newehy
- Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
- Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Paulo Bártolo
- School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester M13 9PL, UK
| | - Marco Andrey Cipriani Frade
- Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto 14040-900, SP, Brazil.
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27
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Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects. Int J Mol Sci 2019; 20:ijms20143430. [PMID: 31336890 PMCID: PMC6678255 DOI: 10.3390/ijms20143430] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 07/08/2019] [Accepted: 07/09/2019] [Indexed: 12/21/2022] Open
Abstract
The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.
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28
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Xu F, Wu Y, Zhang Y, Yin P, Fang C, Wang J. Influence of in vitro differentiation status on the in vivo bone regeneration of cell/chitosan microspheres using a rat cranial defect model. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2019; 30:1008-1025. [PMID: 31159676 DOI: 10.1080/09205063.2019.1619959] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
The aim of this study was to investigate the influence of the in vitro osteogenic differentiation status on the in vivo bone regeneration of cell/chitosan microspheres qualitatively and quantitatively. To this end, rat bone-marrow-derived mesenchymal stromal cells (BMSCs) were seeded onto apatite-coated chitosan microspheres. The constructs were osteogenically differentiated for 0, 7, 14, and 21 days followed by calvarial defect implantation in vivo for up to 8 weeks. In vitro studies showed that BMSCs in the constructs proliferated from day 0 to day 7. The activity and gene expression of alkaline phosphatise increased from day 0 to day 14 and then decreased. The gene expression of collagen type I and osteocalcin peaked at day 21. In vivo, constructs retrieved from day 0 group were filled with fibrous tissues and capillaries, but no bone formation was observed. Constructs retrieved from day 7 and day 21 groups showed progressive bone formation, whereas those retrieved from day 14 group had the highest percentage of bone formation. These data suggested that to generate a substantial amount of bone in vivo, not only the in vitro osteogenic differentiation was necessary, but also the period of pre-differentiation was important for the cell-scaffold constructs. The period of pre-differentiation for 14 days was found to be the most suitable for chitosan microspheres.
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Affiliation(s)
- Fei Xu
- a Department of Stomatology , Xiangya Hospital, Central South University , Changsha , China.,b The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology , Wuhan University , Wuhan , China
| | - Yingfang Wu
- a Department of Stomatology , Xiangya Hospital, Central South University , Changsha , China
| | - Yiyi Zhang
- a Department of Stomatology , Xiangya Hospital, Central South University , Changsha , China
| | - Ping Yin
- a Department of Stomatology , Xiangya Hospital, Central South University , Changsha , China
| | - Changyun Fang
- a Department of Stomatology , Xiangya Hospital, Central South University , Changsha , China
| | - Jiawei Wang
- b The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology , Wuhan University , Wuhan , China
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29
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Injectable chitosan/β-glycerophosphate hydrogels with sustained release of BMP-7 and ornidazole in periodontal wound healing of class III furcation defects. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 99:919-928. [DOI: 10.1016/j.msec.2019.02.024] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 01/21/2019] [Accepted: 02/06/2019] [Indexed: 12/11/2022]
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30
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Pomini KT, Cestari TM, Santos German ÍJ, de Oliveira Rosso MP, de Oliveira Gonçalves JB, Buchaim DV, Pereira M, Andreo JC, Rosa GM, Della Coletta BB, Cosin Shindo JVT, Buchaim RL. Influence of experimental alcoholism on the repair process of bone defects filled with beta-tricalcium phosphate. Drug Alcohol Depend 2019; 197:315-325. [PMID: 30875652 DOI: 10.1016/j.drugalcdep.2018.12.031] [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] [Received: 09/12/2018] [Revised: 12/03/2018] [Accepted: 12/10/2018] [Indexed: 12/16/2022]
Abstract
This study evaluated the effect of ethanol on the repair in calvaria treated with beta-tricalcium phosphate (β-TCP). Forty rats were distributed into 2 groups: Water group (CG, n = 20) and Alcohol Group (AG, n = 20), which received 25% ethanol ad libitum after an adaptation period of 3 weeks. After 90 days of liquid diet, the rats were submitted to a 5.0 mm bilateral craniotomy in the parietal bones; the left parietal was filled with β-TCP (CG-TCP and AG-TCP) and the contralateral only with blood clot (CG-Clot and AG-Clot). The animals were killed after 10, 20, 40 and 60 days. The groups CG-Clot and AG-Clot showed similar pattern of bone formation with a gradual and significant increase in the amount of bone in CG-Clot (22.17 ± 3.18 and 34.81 ± 5.49) in relation to AG-Clot (9.35 ± 5.98 and 21.65 ± 6.70) in periods of 20-40 days, respectively. However, in the other periods there was no statistically significant difference. Alcohol ingestion had a negative influence on bone formation, even with the use of β-TCP, exhibiting slow resorption and replacement by fibrous tissue, with 16% of bone formation within 60 days in AG-TCP, exhibiting immature bone tissue with predominance of disorganized collagen fibers. Defects in CG-TCP showed bone tissue with predominance of lamellar arrangement filling 39% of the original defect. It can be concluded that chronic ethanol consumption impairs the ability to repair bone defects, even with the use of a β-TCP biomaterial.
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Affiliation(s)
- Karina Torres Pomini
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil.
| | - Tânia Mary Cestari
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil.
| | | | | | | | - Daniela Vieira Buchaim
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil; Medical School, University of Marilia (UNIMAR), Marília, Brazil; Medical School, University Center of Adamantina (UNIFAI), Adamantina, Brazil.
| | - Mizael Pereira
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil.
| | - Jesus Carlos Andreo
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil.
| | - Geraldo Marco Rosa
- University of the Sacred Heart (USC), Bauru, Brazil; University of the Ninth of July (UNINOVE), Bauru, Brazil.
| | - Bruna Botteon Della Coletta
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil.
| | | | - Rogério Leone Buchaim
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil; Medical School, University of Marilia (UNIMAR), Marília, Brazil.
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Yao Y, Bi Z, Wu R, Zhao Y, Liu Y, Liu Q, Wang Y, Wang X. METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m 6A-YTHDF2-dependent manner. FASEB J 2019; 33:7529-7544. [PMID: 30865855 DOI: 10.1096/fj.201802644r] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Bone marrow stem cells (BMSCs) are multipotent stem cells that can regenerate mesenchymal tissues, such as adipose tissue, bone, and muscle. Recent studies have shown that N6-methyladenosine (m6A) methylation, one of the most prevalent epigenetic modifications, is involved in the development process. However, whether it plays roles in BMSC differentiation is still elusive. Here, we found that the deletion of m6A "writer" protein methyltransferase-like (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expression via an m6A-dependent way. Knockdown of METTL3 decreased mRNA m6A levels of JAK1, leading to enhanced YTH m6A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) β, which could ultimately lead to a modulated adipogenic process. Collectively, our results reveal an orchestrated network linking the m6A methylation and JAK1/STAT5/C/EBPβ pathway in pBMSCs adipogenic differentiation. Our findings provide novel insights into the underlying molecular mechanisms of m6A modification in the regulation of BMSCs differentiating into adipocytes, which may pave a way to develop more effective therapeutic strategies in stem cell regenerative medicine and the treatment of obesity.-Yao, Y., Bi, Z., Wu, R., Zhao, Y., Liu, Y., Liu, Q., Wang, Y., Wang, X. METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m6A-YTHDF2-dependent manner.
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Affiliation(s)
- Yongxi Yao
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Zhen Bi
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Ruifan Wu
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Yuanling Zhao
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Youhua Liu
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Qing Liu
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Yizhen Wang
- College of Animal Sciences, Zhejiang University, Hangzhou, China.,Key Laboratory of Animal Nutrition and Feed Sciences in Eastern China, Ministry of Agriculture, Hangzhou, China
| | - Xinxia Wang
- College of Animal Sciences, Zhejiang University, Hangzhou, China.,Key Laboratory of Animal Nutrition and Feed Sciences in Eastern China, Ministry of Agriculture, Hangzhou, China
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32
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A Biomimetic Alternative to Synthetic Hydroxyapatite: "Boron-Containing Bone-Like Hydroxyapatite" Precipitated From Simulated Body Fluid. Ann Plast Surg 2018; 79:304-311. [PMID: 28430676 DOI: 10.1097/sap.0000000000001072] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Biological hydroxyapatite (HA), has several mechanical and physical advantages over the commercially available synthetic apatite (CAP-HA). The aim of this in vivo study was to investigate the effect of osteoinductive "bone-like hydroxyapatite" obtained from simulated body fluid (SBF) combined with osteoinductive "boron" (B) on bone healing. MATERIALS Bone like nanohydroxyapatite (SBF-HA) was precipitated from 10× simulated body fluid (10×SBF). Thirty Sprague-Dawley rats were randomly divided into 5 experimental groups (n = 6 each). The groups were involving blank defect, chitosan, SBF-HA, SBF-HA/B, and CAP-HA. Two biparietal round critical sized bone defect was created using a dental burr. The rats were sacrificed respectively at the end of second and fourth months after surgery and their calvarium were harvested for further macroscopic, microtomographic, and histologic evaluation. RESULTS The SBF-HA/B group demonstrated the highest mineralized matrix formation rates (30.69 ± 3.73 for the second month, 62.68 ± 7.03 for the fourth month) and was significantly higher than SBF-HA and the CAP-HA groups. The SBF-HA/B group demonstrated the highest mineralized matrix formation rates (30.69 ± 3.73 for the second month, 62.68 ± 7.03 for the fourth month) and was significantly higher than SBF-HA and the CAP-HA groups. In means of bone defect repair histologically, the highest result was observed in the SBF-HA/B group (P < 0.001). CONCLUSIONS The "bone-like hydroxapatite" obtained from simulated body fluid is worth attention when both its beneficial effects on bone healing and its biological behavior is taken in consideration for further bone tissue engineering studies. It appears to be a potential alternative to the commercially available hydroxyapatite samples.
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Chen E, Liu G, Zhou X, Zhang W, Wang C, Hu D, Xue D, Pan Z. Concentration-dependent, dual roles of IL-10 in the osteogenesis of human BMSCs via P38/MAPK and NF-κB signaling pathways. FASEB J 2018; 32:4917-4929. [PMID: 29630408 DOI: 10.1096/fj.201701256rrr] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Microenvironmental conditions can influence the differentiation and functional roles of mesenchymal stem cells (MSCs). Recent studies have suggested that an inflammatory microenvironment can significantly affect the osteogenic differentiation of MSCs. Here, we show, for the first time, that IL-10 has concentration-dependent, dual roles in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs). Low physiologic concentrations of IL-10 (0.01-1.0 ng/ml) activate the p38/MAPK signaling pathway to promote the osteogenesis of hBMSCs, but higher pathologic doses of IL-10 (10-100 ng/ml) inhibit p38/MAPK signaling by activating NF-κB, inhibiting osteogenesis. These results demonstrate that p38/MAPK and NF-κB signaling mediates the double-edged sword effect of IL-10 on hBMSCs. The osteogenic impairment was reversed at higher doses of IL-10 when cells were supplemented with the NF-κB inhibitor BAY11-7082. These data provide important insights into the regulatory effects of IL-10 on the biologic behavior of hBMSCs.-Chen, E., Liu, G., Zhou, X., Zhang, W., Wang, C., Hu, D., Xue, D., Pan, Z. Concentration-dependent, dual roles of IL-10 in the osteogenesis of human BMSCs via P38/MAPK and NF-κB signaling pathways.
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Affiliation(s)
- Erman Chen
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and.,Orthopedics Research Institute, Zhejiang University, Hangzhou, China
| | - Guanyi Liu
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and.,Orthopedics Research Institute, Zhejiang University, Hangzhou, China
| | - Xiaopeng Zhou
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and.,Orthopedics Research Institute, Zhejiang University, Hangzhou, China
| | - Wei Zhang
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and.,Orthopedics Research Institute, Zhejiang University, Hangzhou, China
| | - Cong Wang
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and
| | - Dongcai Hu
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and
| | - Deting Xue
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and.,Orthopedics Research Institute, Zhejiang University, Hangzhou, China
| | - Zhijun Pan
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and.,Orthopedics Research Institute, Zhejiang University, Hangzhou, China
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Fouad H, AlFotawi R, Alothman OY, Alshammari BA, Alfayez M, Hashem M, Mahmood A. Porous Polyethylene Coated with Functionalized Hydroxyapatite Particles as a Bone Reconstruction Material. MATERIALS 2018; 11:ma11040521. [PMID: 29596358 PMCID: PMC5951367 DOI: 10.3390/ma11040521] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 03/26/2018] [Accepted: 03/27/2018] [Indexed: 12/28/2022]
Abstract
In this study, porous polyethylene scaffolds were examined as bone substitutes in vitro and in vivo in critical-sized calvarial bone defects in transgenic Sprague-Dawley rats. A microscopic examination revealed that the pores appeared to be interconnected across the material, making them suitable for cell growth. The creep recovery behavior of porous polyethylene at different loads indicated that the creep strain had two main portions. In both portions, strain increased with increased applied load and temperature. In terms of the thermographic behavior of the material, remarkable changes in melting temperature and heat fusion were revealed with increased the heating rates. The tensile strength results showed that the material was sensitive to the strain rate and that there was adequate mechanical strength to support cell growth. The in vitro cell culture results showed that human bone marrow mesenchymal stem cells attached to the porous polyethylene scaffold. Calcium sulfate–hydroxyapatite (CS–HA) coating of the scaffold not only improved attachment but also increased the proliferation of human bone marrow mesenchymal stem cells. In vivo, histological analysis showed that the study groups had active bone remodeling at the border of the defect. Bone regeneration at the border was also evident, which confirmed that the polyethylene acted as an osteoconductive bone graft. Furthermore, bone formation inside the pores of the coated polyethylene was also noted, which would enhance the process of osteointegration.
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Affiliation(s)
- H Fouad
- Applied Medical Science Department, Community College, King Saud University, Riyadh 11437, Saudi Arabia.
- Department of Biomedical Engineering, Faculty of Engineering, Helwan University, Helwan 11792, Egypt.
| | - Randa AlFotawi
- Maxillofacial Surgery Department, Dental Faculty, King Saud University, Riyadh 11545, Saudi Arabia.
| | - Othman Y Alothman
- Chemical Engineering Department, King Saud University, Riyadh 11421, Saudi Arabia.
- Deanship of Graduate Studies, Saudi Electronic University, Riyadh 11637, Saudi Arabia.
| | - Basheer A Alshammari
- Material Science Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia.
| | - Musaad Alfayez
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
| | - Mohamed Hashem
- Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh 11437, Saudi Arabia.
| | - Amer Mahmood
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
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Bougioukli S, Sugiyama O, Pannell W, Ortega B, Tan MH, Tang AH, Yoho R, Oakes DA, Lieberman JR. Gene Therapy for Bone Repair Using Human Cells: Superior Osteogenic Potential of Bone Morphogenetic Protein 2-Transduced Mesenchymal Stem Cells Derived from Adipose Tissue Compared to Bone Marrow. Hum Gene Ther 2018; 29:507-519. [PMID: 29212377 DOI: 10.1089/hum.2017.097] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Ex vivo regional gene therapy strategies using animal mesenchymal stem cells genetically modified to overexpress osteoinductive growth factors have been successfully used in a variety of animal models to induce both heterotopic and orthotopic bone formation. However, in order to adapt regional gene therapy for clinical applications, it is essential to assess the osteogenic capacity of transduced human cells and choose the cell type that demonstrates the best clinical potential. Bone-marrow stem cells (BMSC) and adipose-derived stem cells (ASC) were selected in this study for in vitro evaluation, before and after transduction with a lentiviral two-step transcriptional amplification system (TSTA) overexpressing bone morphogenetic protein 2 (BMP-2; LV-TSTA-BMP-2) or green fluorescent protein (GFP; LV-TSTA-GFP). Cell growth, transduction efficiency, BMP-2 production, and osteogenic capacity were assessed. The study demonstrated that BMSC were characterized by a slower cell growth compared to ASC. Fluorescence-activated cell sorting analysis of GFP-transduced cells confirmed successful transduction with the vector and revealed an overall higher but not statistically significant transduction efficiency in ASC versus BMSC (90.2 ± 4.06% vs. 80.4 ± 8.51%, respectively; p = 0.146). Enzyme-linked immunosorbent assay confirmed abundant BMP-2 production by both cell types transduced with LV-TSTA-BMP-2, with BMP-2 production being significantly higher in ASC versus BMSC (239.5 ± 116.55 ng vs. 70.86 ± 24.7 ng; p = 0.001). Quantitative analysis of extracellular deposition of calcium (Alizarin red) and alkaline phosphatase activity showed that BMP-2-transduced cells had a higher osteogenic differentiation capacity compared to non-transduced cells. When comparing the two cell types, ASC/LV-TSTA-BMP-2 demonstrated a significantly higher mineralization potential compared to BMSC/LV-TSTA-BMP-2 7 days post transduction (p = 0.014). In conclusion, this study demonstrates that transduction with LV-TSTA-BMP-2 can significantly enhance the osteogenic potential of both human BMSC and ASC. BMP-2-treated ASC exhibited higher BMP-2 production and greater osteogenic differentiation capacity compared to BMP-2-treated BMSC. These results, along with the fact that liposuction is an easy procedure with lower donor-site morbidity compared to BM aspiration, indicate that adipose tissue might be a preferable source of MSCs to develop a regional gene therapy approach to treat difficult bone-repair scenarios.
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Affiliation(s)
- Sofia Bougioukli
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Osamu Sugiyama
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - William Pannell
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Brandon Ortega
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Matthew H Tan
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Amy H Tang
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Robert Yoho
- 2 Cosmetic Surgery Practice , Pasadena, California
| | - Daniel A Oakes
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Jay R Lieberman
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
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Zhang C, Li L, Jiang Y, Wang C, Geng B, Wang Y, Chen J, Liu F, Qiu P, Zhai G, Chen P, Quan R, Wang J. Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis. FASEB J 2018. [PMID: 29533735 DOI: 10.1096/fj.201700208rr] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Bone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 satellite. The satellite returned to Earth after going through space experiments in orbit for 12 d, and cell samples were harvested and analyzed for differentiation potentials. The results showed that space microgravity inhibited osteogenic differentiation and resulted in adipogenic differentiation, even under osteogenic induction conditions. Under space microgravity, the expression of 10 genes specific for osteogenesis decreased, including collagen family members, alkaline phosphatase ( ALP), and runt-related transcription factor 2 ( RUNX2), whereas the expression of 4 genes specific for adipogenesis increased, including adipsin ( CFD), leptin ( LEP), CCAAT/enhancer binding protein β ( CEBPB), and peroxisome proliferator-activated receptor-γ ( PPARG). In the analysis of signaling pathways specific for osteogenesis, we found that the expression and activity of RUNX2 was inhibited, expression of bone morphogenetic protein-2 ( BMP2) and activity of SMAD1/5/9 were decreased, and activity of focal adhesion kinase (FAK) and ERK-1/2 declined significantly under space microgravity. These data indicate that space microgravity plays a dual role by decreasing RUNX2 expression and activity through the BMP2/SMAD and integrin/FAK/ERK pathways. In addition, we found that space microgravity increased p38 MAPK and protein kinase B (AKT) activities, which are important for the promotion of adipogenic differentiation of hMSCs. Space microgravity significantly decreased the expression of Tribbles homolog 3 ( TRIB3), a repressor of adipogenic differentiation. Y15, a specific inhibitor of FAK activity, was used to inhibit the activity of FAK under normal gravity; Y15 decreased protein expression of TRIB3. Therefore, it appears that space microgravity decreased FAK activity and thereby reduced TRIB3 expression and derepressed AKT activity. Under space microgravity, the increase in p38 MAPK activity and the derepression of AKT activity seem to synchronously lead to the activation of the signaling pathway specifically promoting adipogenesis.-Zhang, C., Li, L., Jiang, Y., Wang, C., Geng, B., Wang, Y., Chen, J., Liu, F., Qiu, P., Zhai, G., Chen, P., Quan, R., Wang, J. Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis.
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Affiliation(s)
- Cui Zhang
- Institute of Cell and Development Biology, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, China
| | - Liang Li
- Institute of Cell and Development Biology, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, China
| | - Yuanda Jiang
- National Center of Space Science, Chinese Academy of Sciences, Beijing, China
| | - Cuicui Wang
- Institute of Cell and Development Biology, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, China
| | - Baoming Geng
- National Center of Space Science, Chinese Academy of Sciences, Beijing, China
| | - Yanqiu Wang
- National Center of Space Science, Chinese Academy of Sciences, Beijing, China
| | - Jianling Chen
- Institute of Cell and Development Biology, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, China
| | - Fei Liu
- Institute of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, China
| | - Peng Qiu
- National Center of Space Science, Chinese Academy of Sciences, Beijing, China
| | - Guangjie Zhai
- National Center of Space Science, Chinese Academy of Sciences, Beijing, China
| | - Ping Chen
- Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.,Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Renfu Quan
- Institute of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, China
| | - Jinfu Wang
- Institute of Cell and Development Biology, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, China
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Moya A, Larochette N, Bourguignon M, El-Hafci H, Potier E, Petite H, Logeart-Avramoglou D. Osteogenic potential of adipogenic predifferentiated human bone marrow-derived multipotent stromal cells for bone tissue-engineering. J Tissue Eng Regen Med 2017; 12:e1511-e1524. [PMID: 28875591 DOI: 10.1002/term.2571] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 07/13/2017] [Accepted: 09/01/2017] [Indexed: 12/16/2022]
Abstract
In the present study, we evaluated the benefits of an adipogenic predifferentiation, the pathway most closely related to osteoblastogenesis, on the pro-osteogenic potential of human adult multipotent bone marrow stromal cells (hBMSCs), both in vitro and in vivo. Adipogenic differentiation of hBMSCs for 14 days resulted in a heterogeneous cell population from which the most adipogenic-committed cells were eliminated by their lack of readhesion ability. Our results provided evidence that the select adherent adipogenic differentiated hBMSCs (sAD+ cells) express a gene profile characteristic of both adipogenic and osteogenic lineages. In vitro, when cultured in osteogenic medium, sAD+ differentiated along the osteogenic lineage faster than undifferentiated hBMSCs. In vivo, in an ectopic mouse model, sAD+ exhibited a significantly higher bone formation capability compared with undifferentiated hBMSCs. We sought, then, to investigate the underlying mechanisms responsible for such beneficial effects of adipogenic predifferentiation on bone formation and found that this outcome was not linked to a better cell survival post-implantation. The secretome of sAD+ was both proangiogenic and chemoattractant, but its potential did not supersede the one of undifferentiated hBMSCs. However, using co-culture systems, we observed that the sAD+ paracrine factors were pro-osteogenic on undifferentiated hBMSCs. In conclusion, adipogenic priming endows hBMSCs with high osteogenic potential as well as pro-osteogenic paracrine-mediated activity. This preconditioning appears as a promising strategy for bone tissue engineering technology in order to improve the hBMSC osteogenic potency in vivo.
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Affiliation(s)
- Adrien Moya
- UMR 7052 CNRS University Paris Diderot, Sorbonne Paris Cité, Paris, France
| | | | | | - Hanane El-Hafci
- UMR 7052 CNRS University Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Esther Potier
- UMR 7052 CNRS University Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Hervé Petite
- UMR 7052 CNRS University Paris Diderot, Sorbonne Paris Cité, Paris, France
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38
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Xue D, Chen E, Zhang W, Gao X, Wang S, Zheng Q, Pan Z, Li H, Liu L. The role of hesperetin on osteogenesis of human mesenchymal stem cells and its function in bone regeneration. Oncotarget 2017; 8:21031-21043. [PMID: 28423500 PMCID: PMC5400563 DOI: 10.18632/oncotarget.15473] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 02/08/2017] [Indexed: 11/28/2022] Open
Abstract
Hesperetin has been suggested to be involved in bone strength. We aimed to investigate the effects of hesperetin on the osteogenic differentiation of human mesenchymal stem cells and its related mechanisms. We showed that hesperetin promoted osteogenic differentiation of human mesenchymal stem cells in vitro. It potentially exerts its effects via the ERK and Smad signaling pathways. Using a rat osteotomy model, we showed that human mesenchymal stem cells combined with a hesperetin/gelatin sponge scaffold resulted in accelerated fracture healing in vivo. Due to the low cost of hesperetin, it could be used as a growth factor for bone tissue engineering or surgical fracture treatment.
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Affiliation(s)
- Deting Xue
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Erman Chen
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Wei Zhang
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Xiang Gao
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Shengdong Wang
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Qiang Zheng
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Zhijun Pan
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Hang Li
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China
| | - Ling Liu
- Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, P.R. China
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Westhauser F, Senger AS, Reible B, Moghaddam A. * In Vivo Models for the Evaluation of the Osteogenic Potency of Bone Substitutes Seeded with Mesenchymal Stem Cells of Human Origin: A Concise Review. Tissue Eng Part C Methods 2017; 23:881-888. [PMID: 28747099 DOI: 10.1089/ten.tec.2017.0164] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Research concerning bone substitutes is one of the most challenging fields in orthopedic research and has a high clinical relevance, especially since the currently available bone substitutes are limited in their osteostimulative capabilities. In vitro models for the evaluation of the properties of bone substitutes allow the use of human mesenchymal stem cells (hMSCs) seeded onto scaffolds, but suffer from the lack of a physiological environment for those cells. Most in vivo models include the use of non-hMSC and are therefore lacking in clinical relevance. To overcome these issues, in vivo models were created that allow the evaluation of hMSC-seeded bone substitutes, combining the advantages of the use of human cells with the physiological conditions of an organism in vivo. In brief, models usually aim for bone formation in immunocompromised rodents. The subcutaneous implantation of scaffolds is most widely performed, showing low complication rates along with good results, but suffering from inferior vascularization of the implants and the absence of the realistic structural and mechanical conditions of bone. Orthotopic implantation, for example in calvarian or long bone defects, provides the most appropriate surrounding for hMSC-seeded scaffolds. However, parallel host-induced bone formation is a major limitation. This review summarizes in vivo models for the evaluation of the osteogenic potency of bone substitutes seeded with mesenchymal stem cells of human origin.
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Affiliation(s)
- Fabian Westhauser
- 1 HTRG-Heidelberg Trauma Research Group, Center of Orthopedics, Traumatology, and Spinal Cord Injury, Heidelberg University Hospital , Heidelberg, Germany
| | - Anne-Sophie Senger
- 1 HTRG-Heidelberg Trauma Research Group, Center of Orthopedics, Traumatology, and Spinal Cord Injury, Heidelberg University Hospital , Heidelberg, Germany
| | - Bruno Reible
- 1 HTRG-Heidelberg Trauma Research Group, Center of Orthopedics, Traumatology, and Spinal Cord Injury, Heidelberg University Hospital , Heidelberg, Germany
| | - Arash Moghaddam
- 2 Clinic for Orthopedic Surgery, Trauma Surgery, and Hand Surgery, Klinikum Aschaffenburg-Alzenau , Aschaffenburg, Germany
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Improved Bone Regeneration With Multiporous PLGA Scaffold and BMP-2-Transduced Human Adipose-Derived Stem Cells by Cell-Permeable Peptide. IMPLANT DENT 2017; 26:4-11. [PMID: 27893514 DOI: 10.1097/id.0000000000000523] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Currently, much work has focused on the engineering of bone using adipose-derived stem cells (ADSCs), which differentiate into osteogenic cells. This study was conducted to assess the bone-regenerating capacity of ADSCs with genetic modification. MATERIALS AND METHODS ADSCs were cultured and transduced with recombinant adenovirus-expressing bone morphogenetic protein-2 (rAd/BMP-2). Two 5-mm full-thickness bone defects were created on the parietal bones of 24 rats. The defects were left empty (n = 12), restored with a scaffold alone (n = 12), transplanted with ADSCs in osteogenic media (n = 12), or transplanted with rAd/BMP-2-transduced ADSCs (n = 12). Six defects from each group were assessed by histologic observation, histomorphometric analysis, and microcomputed tomography (micro-CT) imaging at 4 and 8 weeks after transplantation. RESULTS Increased new bone formation was observed in the rAd/BMP-2-transduced ADSC groups, compared with the other groups. On micro-CT, significant differences were noted in bone volume-to-tissue volume ratios between rAd/BMP-2-transduced ADSCs group and the other groups at both time points (P < 0.05). CONCLUSION The result demonstrates that transferring BMP-2 promotes the osteogenic differentiation of ADSCs and enhances bone regeneration. Under limitation of this study, genetic modification of ADSCs with BMP-2 could be adopted in clinical application.
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de Oliveira LSDS, de Araújo AA, de Araújo Júnior RF, Barboza CAG, Borges BCD, da Silva JSP. Low-level laser therapy (780 nm) combined with collagen sponge scaffold promotes repair of rat cranial critical-size defects and increases TGF-β, FGF-2, OPG/RANK and osteocalcin expression. Int J Exp Pathol 2017; 98:75-85. [PMID: 28556971 DOI: 10.1111/iep.12226] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 02/09/2017] [Indexed: 12/15/2022] Open
Abstract
The aim of this study was to evaluate the effect of collagen sponge scaffold (CSS) implantation associated with low-level laser therapy (LLLT) on repairing bone defects. A single 5-mm cranial defect was surgically created in forty Wistar rats, which then received one of the following four interventions (n = 10 per group): no treatment (G0); bone defect implanted with collagen sponge scaffold (CSS) alone (G1); defect treated with low-level laser therapy (LLLT) (wavelength 780 nm; total energy density 120 J/cm2 ; power 50 mW) alone (G2); and CSS associated with LLLT treatment (G3). After surgery, animals in each group were euthanized at 21 days and 30 days (n = 5 per euthanasia time group). Bone formation was monitored by X-ray imaging analysis. Biopsies were collected and processed for histological analysis and immunohistochemical evaluation of transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2), osteoprotegerin (OPG) and receptor activator of nuclear factor ƙ (RANK). Osteocalcin (OCN) was detected by immunofluorescence analysis. Compared to the G0 group, defects in the 30-day G3 group exhibited increased bone formation, both by increase in radiopaque areas (P < 0.01) and by histomorphometric analysis (P < 0.001). The histopathological analysis showed a decreased number of inflammatory cells (P < 0.001). The combined CCS + LLLT (G3) treatment also resulted in the most intense immunostaining for OPG, RANK, FGF-2 and TGF-β, and the most intense and diffuse OCN immunofluorescent labelling at 30 days postsurgery (G3 vs. G0 group, P < 0.05). Therefore, the use of CCS associated with LLLT could offer a synergistic advantage in improving the healing of bone fractures.
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Affiliation(s)
| | - Aurigena Antunes de Araújo
- Department of Biophysics and Pharmacology, Post Graduation Program in Public Health/Post Graduation Program in Pharmaceutical Science, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Raimundo Fernandes de Araújo Júnior
- Department of Morphology, Post Graduation Program in Health Science/Post Graduation Program in Functional and Structural Biology, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Carlos Augusto Galvão Barboza
- Department of Morphology, Post-Graduation Program in Oral Pathology, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Boniek Castillo Dutra Borges
- Department of Dentistry, Post-Graduation Program in Public Health, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - José Sandro Pereira da Silva
- Department of Dentistry, Post-Graduation Program in Public Health, Federal University of Rio Grande do Norte, Natal, RN, Brazil
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Ezirganli S, Kazancioglu HO, Ozdemir H, Inan DS, Tek M. The Effects of Nigella Sativa Seed Extract on Bone Healing in an Experimental Model. J Craniofac Surg 2017; 27:1905-1909. [PMID: 27513784 DOI: 10.1097/scs.0000000000002986] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The purpose of this study was to histologically evaluate the effects on bone healing of nigella sativa seed extract applied on calvarial defects in an ovariectomized rat model. The study included 32 female rats weighing 280 to 310 g with an average age of 3 months. A defect was created with a trephine burr on each rat calvarium. The rats were divided into 2 groups (control and study) of 8 animals each. All the defects were grafted with a gelatin sponge mixed with normal saline. In the study group, nigella sativa seed extract was applied systemically using an oro-gastric tube. Half of the animals in each group were sacrificed after 2 weeks, and the others after 4 weeks. In the control groups, the defects were not completely filled with regenerated bone. Osteoblast cells were observed more in the study groups. A higher rate of osteoclasts was determined in the control groups. In addition, the nigella sativa group had a statistically greater amount of bone formation than the others group at both 2 weeks and 4 weeks (P <0.05). The systemic application of nigella sativa seed extract demonstrated incredibly positive effects on enhanced bone healing in this experimental osteoporotic model.
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Affiliation(s)
- Seref Ezirganli
- *Nişantasi University †Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Bezmialem Vakif University, Istanbul ‡Department of Periodontology, Faculty of Dentistry, Eskişehir Osmangazi University, Eskişehir §Department of Histology and Embryology, Faculty of Medicine, Cumhuriyet University, Sivas
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Abant Izzet Baysal University, Bolu, Turkey
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Adipose Derived Stem Cells Conditioned Media in Combination with Bioceramic-Collagen Scaffolds Improved Calvarial Bone Healing in Hypothyroid Rats. IRANIAN RED CRESCENT MEDICAL JOURNAL 2017. [DOI: 10.5812/ircmj.45516] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Huynh NCN, Everts V, Nifuji A, Pavasant P, Ampornaramveth RS. Histone deacetylase inhibition enhances in-vivo bone regeneration induced by human periodontal ligament cells. Bone 2017; 95:76-84. [PMID: 27871909 DOI: 10.1016/j.bone.2016.11.017] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 11/16/2016] [Accepted: 11/17/2016] [Indexed: 01/12/2023]
Abstract
UNLABELLED Periodontal ligament cells have the potential to differentiate into bone forming osteoblasts and thus represent a good cellular candidate for bone regeneration. This study aimed to investigate the effect of inhibition of histone deacetylases, using the inhibitor Trichostatin A (TSA), on bone regeneration by human periodontal ligament cells (hPDLCs) in a mouse calvaria bone defect. METHODS RUNX2 protein and its acetylation was analyzed by immunoprecipitation and western blotting. The effect of TSA on osteogenic differentiation of hPDLCs was investigated using in vitro 3D cultures. hPDLCs were pre-incubated with and without TSA and implanted in mouse calvaria defects with polycaprolactone/polyethylene glycol (PCL/PEG) co-polymer scaffold. Micro-CT scanning and bone histomorphometric analysis were used to quantify the amount of bone. Survival of hPDLCs as xenogenic grafts was verified by immunohistochemistry with anti-human β1-integrin. The immunological response of mice against hPDLCs xenografts was evaluated by measuring total IgG and hPDLCs-specific IgG. RESULTS Beside affecting histone protein, TSA also induced hyper-acetylation of RUNX2 which might be a crucial mechanism for enhancing osteogenesis by hPDLCs. TSA enhanced mineral deposition by hPDLCs in in vitro 3D cultures and had no effect on cell viability. In vivo bone regeneration of mouse calvaria defects was significantly enhanced by TSA pre-treated hPDLCs. By using anti-human ß1 integrin hPDLCs were shown to differentiate into osteocyte-like cells that were present in newly formed bone. hPDLCs, as a xenograft, slightly but not significantly induced an immunological response in recipient mice as demonstrated by the level of total IgG and hPDLCs-specific IgG. CONCLUSION Inhibition of histone deacetylases by TSA enhanced in vivo bone regeneration by hPDLCs. The data strongly suggest a novel approach to regenerate bone tissue.
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Affiliation(s)
- Nam Cong-Nhat Huynh
- Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Dental Basic Sciences, Faculty of Odonto-Stomatology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Vincent Everts
- Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
| | - Akira Nifuji
- Department of Pharmacology, School of Dental Medicine, Tsurumi University, Yokohama, Japan
| | - Prasit Pavasant
- Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
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Johari B, Kadivar M, Lak S, Gholipourmalekabadi M, Urbanska AM, Mozafari M, Ahmadzadehzarajabad M, Azarnezhad A, Afshari S, Zargan J, Kargozar S. Osteoblast-seeded bioglass/gelatin nanocomposite: a promising bone substitute in critical-size calvarial defect repair in rat. Int J Artif Organs 2016; 39:524-533. [PMID: 27901555 DOI: 10.5301/ijao.5000533] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2016] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Amid the plethora of methods to repair critical bone defects, there is no one perfect approach. In this study, we sought to evaluate a potent 3-dimensional (3D) bioactive SiO2-CaO-P2O5 glasses (bioglass)/gelatin (gel) scaffold for its biocompatibility by seeding cells as well as for its regenerative properties by animal implantation. METHODS Osteoblast cells were seeded onto nanocomposite scaffolds to investigate the process of critical-size calvarial defect via new bone formation. Scanning electron microscopy (SEM) was used to validate topography of the scaffolds, its homogeneity and ideal cellular attachment. Proliferation assay and confocal microscopy were used to evaluate its biocompatibility. To validate osteogenesis of the bioactive nanocomposite scaffolds, they were first implanted into rats and later removed and analyzed at different time points post mortem using histological, immunohistochemical and histomorphometric methods. RESULTS Based on in vitro results, we showed that our nanocomposite is highly cell-compatible material and allows for osteoblasts to adhere, spread and proliferate. In vivo results indicate that our nanocomposite provides a significant contribution to bone regeneration and is highly biodegradable and biocompatible. So, seeded scaffolds with osteoblasts enhanced repair of critical bone defects via osteogenesis. CONCLUSIONS We demonstrate the feasibility of engineering a nanocomposite scaffold with an architecture resembling the human bone, and provide proof-of-concept validation for our scaffold using a rat animal model.
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Affiliation(s)
- Behrooz Johari
- Biology Group, Faculty of Basic Sciences, Imam Hossein Comprehensive University, Tehran - Iran
- Department of Biochemistry, Pasteur Institute of Iran, Tehran - Iran
| | - Mehdi Kadivar
- Department of Biochemistry, Pasteur Institute of Iran, Tehran - Iran
| | - Shirin Lak
- Department of Biochemistry, Pasteur Institute of Iran, Tehran - Iran
| | - Mazaher Gholipourmalekabadi
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran - Iran
| | - Aleksandra M Urbanska
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY - USA
| | - Masoud Mozafari
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran - Iran
- Cellular and Molecular Research Center (CMRC), Iran University of Medical Sciences, Tehran - Iran
| | - Maryam Ahmadzadehzarajabad
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran - Iran
| | - Asaad Azarnezhad
- Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj - Iran
| | - Samane Afshari
- Department of Biochemistry, Pasteur Institute of Iran, Tehran - Iran
| | - Jamil Zargan
- Biology Group, Faculty of Basic Sciences, Imam Hossein Comprehensive University, Tehran - Iran
| | - Saeid Kargozar
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran - Iran
- National Cell Bank, Pasteur Institute of Iran, Tehran - Iran
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Castillo-Dalí G, Castillo-Oyagüe R, Terriza A, Saffar JL, Batista A, Barranco A, Cabezas-Talavero J, Lynch CD, Barouk B, Llorens A, Sloan AJ, Cayón RV, Gutiérrez-Pérez JL, Torres-Lagares D. In vivo comparative model of oxygen plasma and nanocomposite particles on PLGA membranes for guided bone regeneration processes to be applied in pre-prosthetic surgery: a pilot study. J Dent 2016; 42:1446-57. [PMID: 24814137 DOI: 10.1016/j.jdent.2014.04.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 04/22/2014] [Accepted: 04/28/2014] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVES To evaluate the bone regeneration potential of a new membrane fabricated with polyglycolide acid (PLGA) after being treated with oxygen plasma (PO2), and/or being functionalized with silicon dioxide (SiO2) or titanium dioxide (TiO2) nanoparticles. METHODS Bone defects (5 mm 3 mm) were produced on the top of 3 experimentation rabbits’ skulls and were covered with variously modified PLGA scaffolds. After the animals were sacrificed, neoformed bone (%), mineralized bone (mm), bone resorption (%), osteoclasts/mm2, and intensity of osteosynthetic activity, were assessed under microscope. RESULTS The following groups were formed depending on the type of membrane: PLGA (control); PLGA/PO2; PLGA/SiO2; PLGA/TiO2; PLGA/PO2/SiO2; and PLGA/PO2/TiO2. The histological sections showed bone layers in advanced stages of formation. The highest percentages of neoformed bone corresponded to PLGA/PO2/SiO2 membranes (59.07%; p = 0.31) followed by PLGA/PO2 barriers (50.27%). The controls showed the lowest mineralization (13.89 mm; p = 0.24). PLGA/TiO2 scaffolds exhibited the least bone resorption (4.45%; p = 0.77) and osteoclasts/ mm2 (1.58; p = 0.86). PLGA/SiO2 and PLGA/TiO2 membranes stimulated the maximum osteosynthetic activity. CONCLUSIONS The treatment of PLGA barriers with PO2 increased bone regeneration in rabbits. When comparing the effect of PO2/SiO2 and PO2/TiO2, higher percentages of neoformed bone were encountered after silicon-dioxide coating. CLINICAL SIGNIFICANCE The incorporation of SiO2 nanoparticles onto PO2-treated PLGA membranes was the most promising technique out of those investigated to promote bone formation in rabbits. The addition of SiO2 or TiO2 layers to PLGA substrates may stimulate the osteosynthetic activity, which might be useful to restore bone dimensions in preparation for naturally appearing dental prostheses.
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Shao W, He J, Han Q, Sang F, Wang Q, Chen L, Cui S, Ding B. A biomimetic multilayer nanofiber fabric fabricated by electrospinning and textile technology from polylactic acid and Tussah silk fibroin as a scaffold for bone tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2016; 67:599-610. [PMID: 27287159 DOI: 10.1016/j.msec.2016.05.081] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Revised: 04/15/2016] [Accepted: 05/18/2016] [Indexed: 11/28/2022]
Abstract
To engineer bone tissue, a scaffold with good biological properties should be provided to approximate the hierarchical structure of collagen fibrils in natural bone. In this study, we fabricated a novel scaffold consisting of multilayer nanofiber fabrics (MLNFFs) by weaving nanofiber yarns of polylactic acid (PLA) and Tussah silk fibroin (TSF). The yarns were fabricated by electrospinning, and we found that spinnability, as well as the mechanical properties of the resulting scaffold, was determined by the ratio between polylactic acid and Tussah silk fibroin. In particular, a 9:1 mixture can be spun continuously into nanofiber yarns with narrow diameter distribution and good mechanical properties. Accordingly, woven scaffolds based on this mixture had excellent mechanical properties, with Young's modulus 417.65MPa and tensile strength 180.36MPa. For nonwoven scaffolds fabricated from the same materials, the Young's modulus and tensile strength were 2- and 4-fold lower, respectively. Woven scaffolds also supported adhesion and proliferation of mouse mesenchymal stem cells, and promoted biomineralization via alkaline phosphatase and mineral deposition. Finally, the scaffolds significantly enhanced the formation of new bone in damaged femoral condyle in rabbits. Thus, the scaffolds are potentially suitable for bone tissue engineering because of biomimetic architecture, excellent mechanical properties, and good biocompatibility.
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Affiliation(s)
- Weili Shao
- Key Laboratory of Advanced Textile Composites, Ministry of Education, Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387, China; Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007, China; Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007, China
| | - Jianxin He
- Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007, China; Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007, China.
| | - Qiming Han
- Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007, China; Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007, China
| | - Feng Sang
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China
| | - Qian Wang
- Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007, China; Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007, China
| | - Li Chen
- Key Laboratory of Advanced Textile Composites, Ministry of Education, Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387, China
| | - Shizhong Cui
- Key Laboratory of Advanced Textile Composites, Ministry of Education, Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387, China; Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007, China; Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007, China
| | - Bin Ding
- Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007, China; Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007, China; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201600, China.
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Zang S, Jin L, Kang S, Hu X, Wang M, Wang J, Chen B, Peng B, Wang Q. Periodontal Wound Healing by Transplantation of Jaw Bone Marrow-Derived Mesenchymal Stem Cells in Chitosan/Anorganic Bovine Bone Carrier Into One-Wall Infrabony Defects in Beagles. J Periodontol 2016; 87:971-81. [PMID: 27153292 DOI: 10.1902/jop.2016.150504] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND This study aims to evaluate the performance of chitosan/anorganic bovine bone (C/ABB) scaffold seeded with human jaw bone marrow-derived mesenchymal stem cells (hJBMMSCs) in supporting the healing/repair of 1-wall critical-size periodontal defects. METHODS Physical properties of the C/ABB scaffold were compared with those of the chitosan scaffold. hJBMMSCs were obtained from healthy human alveolar bone during the extraction of third molar impacted teeth. One-wall (7 × 4 mm) infrabony defects were surgically created at the bilateral mandibular third premolars and first molars in six beagles. The defects were randomly assigned to six groups and implanted with different scaffolds: 1) chitosan (C) scaffold; 2) C scaffold with hJBMMSCs (C + cell); 3) C/ABB scaffold (C/ABB); 4) C/ABB scaffold with hJBMMSCs (C/ABB + cell); 5) ABB scaffold (ABB); and 6) open flap debridement (control). The animals were euthanized 8 weeks after surgery for histologic analysis. RESULTS The C/ABB scaffold had a porous structure and increased compressive strength. Both C/ABB and C/ABB + cell exhibited the newly formed cellular mixed-fiber cementum, woven/lamellar bone, and periodontal ligament. Cementum formation was significantly greater in group C/ABB + cell than in group C/ABB (2.64 ± 0.50 mm versus 0.91 ± 0.55 mm, P <0.05). For new bone (NB) height, group C/ABB + cell and C/ABB showed mean ± SD values of 2.83 ± 0.29 mm and 2.65 ± 0.52 mm and for NB area 8.89 ± 1.65 mm and 8.73 ± 1.94 mm(2), respectively. For NB (height and area), there was no significant difference between the two groups. CONCLUSIONS The combination of hJBMMSCs and C/ABB scaffolds could promote periodontal repair. Future studies are expected to further optimize the combination and lead to an ideal periodontal regeneration.
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Affiliation(s)
- Shengqi Zang
- Department of Periodontology, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.,Department of Stomatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lei Jin
- Department of Stomatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Shuai Kang
- Department of Periodontology, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xin Hu
- Department of Periodontology, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Meng Wang
- Department of Periodontology, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Jinjin Wang
- Department of Periodontology, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Bo Chen
- Department of Operative Dentistry and Endodontics, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Fourth Military Medical University
| | - Bo Peng
- Department of Periodontology, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Qintao Wang
- Department of Periodontology, State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
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Current View on Osteogenic Differentiation Potential of Mesenchymal Stromal Cells Derived from Placental Tissues. Stem Cell Rev Rep 2016; 11:570-85. [PMID: 25381565 PMCID: PMC4493719 DOI: 10.1007/s12015-014-9569-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Mesenchymal stromal cells (MSC) isolated from human term placental tissues possess unique characteristics, including their peculiar immunomodulatory properties and their multilineage differentiation potential. The osteogenic differentiation capacity of placental MSC has been widely disputed, and continues to be an issue of debate. This review will briefly discuss the different MSC populations which can be obtained from different regions of human term placenta, along with their unique properties, focusing specifically on their osteogenic differentiation potential. We will present the strategies used to enhance osteogenic differentiation potential in vitro, such as through the selection of subpopulations more prone to differentiate, the modification of the components of osteo-inductive medium, and even mechanical stimulation. Accordingly, the applications of three-dimensional environments in vitro and in vivo, such as non-synthetic, polymer-based, and ceramic scaffolds, will also be discussed, along with results obtained from pre-clinical studies of placental MSC for the regeneration of bone defects and treatment of bone-related diseases.
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Electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/hydroxyapatite scaffold with unrestricted somatic stem cells for bone regeneration. ASAIO J 2016; 61:357-65. [PMID: 25710767 DOI: 10.1097/mat.0000000000000205] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The combination of scaffolds and cells can be useful in tissue reconstruction. In this study, nanofibrous poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/nanohydroxyapatite (nano-HAp) scaffolds, filled with unrestricted somatic stem cells (USSCs), were used for healing calvarial bone in rat model. The healing effects of these scaffolds, with and without stem cells, in bone regeneration were investigated by computed tomography (CT) analysis and pathology assays after 28 days of grafting. The results of CT analysis showed that bone regeneration on the scaffolds, and the amounts of regenerated new bone for polymer/nano-HAp scaffold with USSC, was significantly greater than the scaffold without cell and untreated control samples. Therefore, the combination of scaffold especially with USSC could be considered as a useful method for bone regeneration.
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