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Jacob RGM, Ervolino da Silva AC, Chaushu L, Lang NP, Borges Duailibe de Deus C, Botticelli D, Rangel Garcia Júnior I. Evaluation of Two Configurations of Hydroxyapatite and Beta-Tricalcium Phosphate in Sinus Grafts with Simultaneous Implant Installation: An Experimental Study in Rabbits. Dent J (Basel) 2023; 11:121. [PMID: 37232771 PMCID: PMC10217008 DOI: 10.3390/dj11050121] [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: 03/08/2023] [Revised: 04/20/2023] [Accepted: 04/28/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND This study aimed to evaluate peri-implant bone formation in rabbits after sinus grafting mediated by hydroxyapatite and beta-tricalcium phosphate (HA + β-TCP) in granule or paste configurations, concomitant with immediate implant installation. MATERIAL & METHODS Thirty-four rabbit maxillary sinuses were grafted with HA + β-TCP, half of which were applied in a granule and half in a paste composition. Implant placement was performed simultaneously. At 7 and 40 days postoperatively, the animals were euthanized, and samples were prepared for tomographic, microtomographic, histological, histometric (hematoxylin and eosin staining, HE), and immunohistochemical (labeling of transcription factor Runx-2 [RUNX2], vascular endothelial growth factor [VEGF], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analysis. Implant removal torque was also measured. RESULTS On tomography, maintenance of sinus membrane integrity was observed in both the groups. Higher values of morphometric parameters evaluated by micro-CT were found in the "paste group" after seven days. At 40 days, there were no significant differences between the groups in most of the microtomographic parameters evaluated. In histological sections stained with HE, a higher percentage of newly formed bone was observed in the "granule group" after 40 days. Similar positive immunolabeling was observed for both RUNX2 and OCN in both the experimental groups. TRAP immunolabeling was similar in both groups as well. VEGF labeling increased in the "granule group", indicating a higher osteoconductive potential in this biomaterial. Similar removal torque values were observed in both groups. Thus, the two HA + β-TCP configurations showed similar healing patterns of simultaneously installed implants adjacent to sinus floor elevation. However, significantly higher bone values were observed for the "granule configuration". CONCLUSIONS The HA + β-TCP granules and paste presentations showed favorable long-term healing results, with bone formation in similar quantities and quality adjacent to the implants.
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Affiliation(s)
- Ricardo Garcia Mureb Jacob
- Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (UNESP), Rua José Bonifácio 1193, Araçatuba 16015-050, SP, Brazil; (R.G.M.J.); (A.C.E.d.S.); (C.B.D.d.D.); (I.R.G.J.)
- Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Rua José Bonifácio 1193, Araçatuba 16015-050, SP, Brazil
| | - Ana Cláudia Ervolino da Silva
- Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (UNESP), Rua José Bonifácio 1193, Araçatuba 16015-050, SP, Brazil; (R.G.M.J.); (A.C.E.d.S.); (C.B.D.d.D.); (I.R.G.J.)
| | - Liat Chaushu
- Department of Periodontology and Implant Dentistry, The Maurice and Gabriela Goldschleger School of Dentistry, Tel Aviv University, Tel Aviv 69978, Israel;
| | - Niklaus Peter Lang
- School of Dental Medicine, University of Berne, CH-3010 Berne, Switzerland
| | - Ciro Borges Duailibe de Deus
- Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (UNESP), Rua José Bonifácio 1193, Araçatuba 16015-050, SP, Brazil; (R.G.M.J.); (A.C.E.d.S.); (C.B.D.d.D.); (I.R.G.J.)
- Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Rua José Bonifácio 1193, Araçatuba 16015-050, SP, Brazil
| | | | - Idelmo Rangel Garcia Júnior
- Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (UNESP), Rua José Bonifácio 1193, Araçatuba 16015-050, SP, Brazil; (R.G.M.J.); (A.C.E.d.S.); (C.B.D.d.D.); (I.R.G.J.)
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Qin L, Liu N, Bao CLM, Yang DZ, Ma GX, Yi WH, Xiao GZ, Cao HL. Mesenchymal stem cells in fibrotic diseases-the two sides of the same coin. Acta Pharmacol Sin 2023; 44:268-287. [PMID: 35896695 PMCID: PMC9326421 DOI: 10.1038/s41401-022-00952-0] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 06/29/2022] [Indexed: 02/06/2023]
Abstract
Fibrosis is caused by extensive deposition of extracellular matrix (ECM) components, which play a crucial role in injury repair. Fibrosis attributes to ~45% of all deaths worldwide. The molecular pathology of different fibrotic diseases varies, and a number of bioactive factors are involved in the pathogenic process. Mesenchymal stem cells (MSCs) are a type of multipotent stem cells that have promising therapeutic effects in the treatment of different diseases. Current updates of fibrotic pathogenesis reveal that residential MSCs may differentiate into myofibroblasts which lead to the fibrosis development. However, preclinical and clinical trials with autologous or allogeneic MSCs infusion demonstrate that MSCs can relieve the fibrotic diseases by modulating inflammation, regenerating damaged tissues, remodeling the ECMs, and modulating the death of stressed cells after implantation. A variety of animal models were developed to study the mechanisms behind different fibrotic tissues and test the preclinical efficacy of MSC therapy in these diseases. Furthermore, MSCs have been used for treating liver cirrhosis and pulmonary fibrosis patients in several clinical trials, leading to satisfactory clinical efficacy without severe adverse events. This review discusses the two opposite roles of residential MSCs and external MSCs in fibrotic diseases, and summarizes the current perspective of therapeutic mechanism of MSCs in fibrosis, through both laboratory study and clinical trials.
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Affiliation(s)
- Lei Qin
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Nian Liu
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Chao-le-meng Bao
- CASTD Regengeek (Shenzhen) Medical Technology Co. Ltd, Shenzhen, 518000 China
| | - Da-zhi Yang
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Gui-xing Ma
- grid.263817.90000 0004 1773 1790Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, 518055 China
| | - Wei-hong Yi
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Guo-zhi Xiao
- grid.263817.90000 0004 1773 1790Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, 518055 China
| | - Hui-ling Cao
- grid.263817.90000 0004 1773 1790Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, 518055 China
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Tangsuksant T, Ummartyotin S, Pongprayoon T, Arpornmaeklong P, Apinyauppatham K. Property and biological effects of the cuttlebone derived calcium phosphate particles, a potential bioactive bone substitute material. J Biomed Mater Res B Appl Biomater 2023; 111:1207-1223. [PMID: 36718607 DOI: 10.1002/jbm.b.35226] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 12/16/2022] [Accepted: 01/13/2023] [Indexed: 02/01/2023]
Abstract
Cuttlebone (CB) is a marine waste-derived biomaterial and a rich source of calcium carbonate for the biosynthesis of the calcium phosphate (CaP) particles. The current study aimed to synthesize CB derived biphasic calcium phosphate (CB-BCP) and investigate biological activity of the CB-CaP: hydroxyapatite (CB-HA), beta-tricalcium phosphate (CB-b-TCP) and biphasic 60:40 (w/w) HA/b-TCP (CB-BCP) with the human dental pulp stem cells (hDPSCs). The particles were synthesized using solid state reactions under mild condition and properties of the particles were compared with a commercial BCP as a reference material. Morphology, particle size, physicochemical properties, mineral contents, and the ion released patterns of the particles were examined. Then the particle/cell interaction, cell cytotoxicity and osteogenic property of the particles were investigated in the direct and indirect cell culture models. It was found that an average particles size of the CB-HA was 304.73 ± 4.19 nm, CB-b-TCP, 503.17 ± 23.06 nm and CB-BCP, 1394.67 ± 168.19 nm. The physicochemical characteristics of the CB-CaP were consistent with the HA, b-TCP and BCP. The highest level of calcium (Ca) was found in the mineral contents and the preincubated medium of the CB-BCP and traces of fluoride, magnesium, strontium, and zinc were identified in the CB-CaP. The cell cytotoxicity and osteogenic property of the particles were dose dependent. The particles adhered on cell surface and were internalized into the cell cytoplasm. The CB-BCP and CB-HA indirectly and directly promote osteoblastic differentiations of the hDPSCs in stronger levels than other groups. The CB-BCP and CB-HA were potential bioactive bone substitute materials.
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Affiliation(s)
- Thanin Tangsuksant
- Master of Science Program in Dental Implantology, Faculty of Dentistry, Thammasat University Rangsit Campus, Khlong Luang, Thailand
| | - Sarute Ummartyotin
- Department of Materials and Textile Technology, Faculty of Science and Technology, Thammasat University Rangsit Campus, Khlong Luang, Thailand
| | - Thirawudh Pongprayoon
- Department of Chemical Engineering, Faculty of Engineering, King Mongkut's University of Technology North Bangkok (KMUTNB), Bangkok, Thailand
| | - Premjit Arpornmaeklong
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Thammasat University Rangsit Campus, Khlong Luang, Thailand
| | - Komsan Apinyauppatham
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Thammasat University Rangsit Campus, Khlong Luang, Thailand
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Al‐allaq AA, Kashan JS. A review: In vivo studies of bioceramics as bone substitute materials. NANO SELECT 2022. [DOI: 10.1002/nano.202200222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Affiliation(s)
- Ali A. Al‐allaq
- Ministry of Higher Education and Scientific Research Office Reconstruction and Projects Baghdad Iraq
| | - Jenan S. Kashan
- Biomedical Engineering Department University of Technology Baghdad Iraq
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Camacho-Alonso F, Tudela-Mulero MR, Buendía AJ, Navarro JA, Pérez-Sayáns M, Mercado-Díaz AM. Bone regeneration in critical-sized mandibular symphysis defects using bioceramics with or without bone marrow mesenchymal stem cells in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats. Dent Mater 2022; 38:1283-1300. [PMID: 35717229 DOI: 10.1016/j.dental.2022.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 05/14/2022] [Accepted: 06/05/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVES To compare new bone formation in mandibular critical-sized bone defects (CSBDs) in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats filled with bioceramics (BCs) with or without bone marrow mesenchymal stem cells (BMSCs). METHODS A total of 64 adult female Sprague-Dawley rats were randomized into four groups (n = 16 per group): Group 1 healthy, Group 2 diabetic, Group 3 osteoporotic, and Group 4 diabetic-osteoporotic rats. Streptozotocin was used to induce type 1 diabetes in Group 2 and 4, while bilateral ovariectomy was used to induce osteoporosis in Group 3 and 4. The central portion of the rat mandibular symphysis was used as a physiological CSBD. In each group, eight defects were filled with BC (hydroxypatatite 60% and β-tricalcium phosphate 40%) alone and eight with BMSCs cultured on BC. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS In all groups (healthy, diabetics, osteoporotics, and diabetics-osteoporotics), the CSBDs filled with BC + BMSCs showed greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with CSBDs treated with BC alone (at 4 and 8 weeks). CONCLUSIONS Application of BMSCs cultured on BCs improves bone regeneration in CSBDs compared with application of BCs alone in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats.
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Affiliation(s)
- F Camacho-Alonso
- Department of Oral Surgery, University of Murcia, Murcia, Spain.
| | | | - A J Buendía
- Department of Histology and Pathological Anatomy, University of Murcia, Murcia, Spain
| | - J A Navarro
- Department of Histology and Pathological Anatomy, University of Murcia, Murcia, Spain
| | - M Pérez-Sayáns
- Department of Oral Medicine, Oral Surgery and Implantology, University of Santiago de Compostela, Spain. MedOralRes Group, Health Research Institute of Santiago de Compostela (IDIS). Santiago de Compostela, Spain
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Uday Chandrika K, Kacha S, Nair AS, Jamwal VS, Sandilya S, Singh S. Tissue Engineering of Cartilage Using Collagen Scaffold Enriched with Plant Polysaccharides. Cartilage 2021; 13:650S-662S. [PMID: 33906475 PMCID: PMC8804724 DOI: 10.1177/19476035211007899] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Degenerative diseases associated with articular cartilage pose a huge burden on health care economics. The nature of the tissue involved and the changes therein do not allow self-healing; and most of these problems are progressive. Tissue engineering offers some solutions provided we focus on the right kind of cells and the appropriate surrounding niches created for a particular tissue. The present study deals with the formation of polysaccharide rich stable scaffold of collagen after cross-linking with oxidized gum arabic. The scaffold was tested for its biocompatibility and ability to support cells. The in vitro cytotoxicity of the scaffolds toward induced pluripotent stem cells and chondrocytes was evaluated. Evaluation of expression of lineage specific markers indicates differentiation of induced pluripotent stem cells to chondrogenic lineage and maintenance of chondrocytes per se when grown in the scaffold. Animal studies were carried out to study the efficacy of the scaffold to repair the knee injuries. Cells along with the scaffold appeared to be the best filling, in repair of injured cartilage. These studies show that these scaffolds are potential candidates in applications such as tissue engineering of cartilage.
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Affiliation(s)
| | - Sapna Kacha
- CSIR Centre for Cellular and Molecular
Biology, Hyderabad, India
| | - Anuja S. Nair
- CSIR Centre for Cellular and Molecular
Biology, Hyderabad, India
| | | | - Shruti Sandilya
- CSIR Centre for Cellular and Molecular
Biology, Hyderabad, India
| | - Shashi Singh
- CSIR Centre for Cellular and Molecular
Biology, Hyderabad, India
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Kulus M, Sibiak R, Stefańska K, Zdun M, Wieczorkiewicz M, Piotrowska-Kempisty H, Jaśkowski JM, Bukowska D, Ratajczak K, Zabel M, Mozdziak P, Kempisty B. Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues-Origins, Characteristics, Signaling Pathways, and Clinical Trials. Cells 2021; 10:cells10123278. [PMID: 34943786 PMCID: PMC8699543 DOI: 10.3390/cells10123278] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/13/2021] [Accepted: 11/19/2021] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.
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Affiliation(s)
- Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
| | - Rafał Sibiak
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
- Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Katarzyna Stefańska
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
| | - Maciej Zdun
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
| | - Maria Wieczorkiewicz
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
| | - Hanna Piotrowska-Kempisty
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
- Department of Toxicology, Poznan University of Medical Sciences, 60-631 Poznan, Poland
| | - Jędrzej M. Jaśkowski
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (J.M.J.); (D.B.)
| | - Dorota Bukowska
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (J.M.J.); (D.B.)
| | - Kornel Ratajczak
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
| | - Maciej Zabel
- Division of Anatomy and Histology, University of Zielona Gora, 65-046 Zielona Gora, Poland;
| | - Paul Mozdziak
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA;
| | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA;
- Department of Anatomy, Poznan University of Medical Sciences, 60-781 Poznan, Poland
- Correspondence:
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Brunello G, Panda S, Schiavon L, Sivolella S, Biasetto L, Del Fabbro M. The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E1500. [PMID: 32218290 PMCID: PMC7177381 DOI: 10.3390/ma13071500] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 03/20/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023]
Abstract
Bioceramic scaffolds are appealing for alveolar bone regeneration, because they are emerging as promising alternatives to autogenous and heterogenous bone grafts. The aim of this systematic review is to answer to the focal question: in critical-sized bone defects in experimental animal models, does the use of a bioceramic scaffolds improve new bone formation, compared with leaving the empty defect without grafting materials or using autogenous bone or deproteinized bovine-derived bone substitutes? Electronic databases were searched using specific search terms. A hand search was also undertaken. Only randomized and controlled studies in the English language, published in peer-reviewed journals between 2013 and 2018, using critical-sized bone defect models in non-medically compromised animals, were considered. Risk of bias assessment was performed using the SYRCLE tool. A meta-analysis was planned to synthesize the evidence, if possible. Thirteen studies reporting on small animal models (six studies on rats and seven on rabbits) were included. The calvarial bone defect was the most common experimental site. The empty defect was used as the only control in all studies except one. In all studies the bioceramic materials demonstrated a trend for better outcomes compared to an empty control. Due to heterogeneity in protocols and outcomes among the included studies, no meta-analysis could be performed. Bioceramics can be considered promising grafting materials, though further evidence is needed.
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Affiliation(s)
- Giulia Brunello
- Department of Management and Engineering, University of Padova, Stradella San Nicola 3, 36100 Vicenza Italy; (G.B.); (L.B.)
- Section of Dentistry, Department of Neurosciences, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (L.S.); (S.S.)
| | - Sourav Panda
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Commenda 10, 20122 Milan, Italy;
- Department of Periodontics and Oral Implantology, Institute of Dental Sciences, Siksha O Anusandhan University, Bhubaneswar, 751003 Odisha, India
| | - Lucia Schiavon
- Section of Dentistry, Department of Neurosciences, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (L.S.); (S.S.)
| | - Stefano Sivolella
- Section of Dentistry, Department of Neurosciences, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (L.S.); (S.S.)
| | - Lisa Biasetto
- Department of Management and Engineering, University of Padova, Stradella San Nicola 3, 36100 Vicenza Italy; (G.B.); (L.B.)
| | - Massimo Del Fabbro
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Commenda 10, 20122 Milan, Italy;
- Dental Clinic, I.R.C.C.S. Orthopedic Institute Galeazzi, Via Galeazzi 4, 20161 Milan, Italy
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Brokesh AM, Gaharwar AK. Inorganic Biomaterials for Regenerative Medicine. ACS APPLIED MATERIALS & INTERFACES 2020; 12:5319-5344. [PMID: 31989815 DOI: 10.1021/acsami.9b17801] [Citation(s) in RCA: 124] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Regenerative medicine leverages the innate potential of the human body to efficiently repair and regenerate damaged tissues using engineered biomaterials. By designing responsive biomaterials with the appropriate biophysical and biochemical characteristics, cellular response can be modulated to direct tissue healing. Recently, inorganic biomaterials have been shown to regulate cellular responses including cell-cell and cell-matrix interactions. Moreover, ions released from these mineral-based biomaterials play a vital role in defining cell identity, as well as driving tissue-specific functions. The intrinsic properties of inorganic biomaterials, such as the release of bioactive ions (e.g., Ca, Mg, Sr, Si, B, Fe, Cu, Zn, Cr, Co, Mo, Mn, Au, Ag, V, Eu, and La), can be leveraged to induce phenotypic changes in cells or modulate the immune microenvironment to direct tissue healing and regeneration. Biophysical characteristics of biomaterials, such as topography, charge, size, electrostatic interactions, and stiffness can be modulated by addition of inorganic micro- and nanoparticles to polymeric networks have also been shown to play an important role in their biological response. In this Review, we discuss the recent emergence of inorganic biomaterials to harness the innate regenerative potential of the body. Specifically, we will discuss various biophysical or biochemical effects of inorganic-based materials in directing cellular response for regenerative medicine applications.
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Affiliation(s)
- Anna M Brokesh
- Biomedical Engineering, Dwight Look College of Engineering , Texas A&M University , College Station , Texas 77843 , United States
| | - Akhilesh K Gaharwar
- Biomedical Engineering, Dwight Look College of Engineering , Texas A&M University , College Station , Texas 77843 , United States
- Material Science and Engineering, Dwight Look College of Engineering , Texas A&M University , College Station , Texas 77843 , United States
- Center for Remote Health Technologies and Systems , Texas A&M University , College Station , Texas 77843 , United States
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Zhao R, Chen S, Yuan B, Chen X, Yang X, Song Y, Tang H, Yang X, Zhu X, Zhang X. Healing of osteoporotic bone defects by micro-/nano-structured calcium phosphate bioceramics. NANOSCALE 2019; 11:2721-2732. [PMID: 30672553 DOI: 10.1039/c8nr09417a] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The micro-/nano-structured calcium phosphate bioceramic exhibited a higher new bone substitution rate in an osteoporotic bone defect rat model.
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Affiliation(s)
- Rui Zhao
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Siyu Chen
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Bo Yuan
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Xuening Chen
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Xi Yang
- Department of Orthopaedics
- West China Hospital of Sichuan University
- Chengdu 610041
- China
| | - Yueming Song
- Department of Orthopaedics
- West China Hospital of Sichuan University
- Chengdu 610041
- China
| | - Hai Tang
- Department of Orthopedics
- Beijing Friendship Hospital
- Capital Medical University
- Beijing 100050
- China
| | - Xiao Yang
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Xiangdong Zhu
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
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Abstract
Calcium phosphate bioceramics has recently experienced increased interest in bone reconstruction. Mimicking of natural structure of bone, like the use of nanomaterials, is an attractive approach for generating scaffolds for bone regeneration. The aim of present study was to evaluate the effect of nanonization on the biphasic calcium phosphate (BCP) ceramic in the repair of bone cavities in the canine mandible. A commercial BCP was dry-milled in a high energy planetary ball mill with zirconia balls and container. Three holes (8 mm in diameter) were outlined to the depth of cortical bone of mandibular angle of 5 dogs bilaterally. The first hole (positive control group A, n = 10) was filled in with commercial BCP material. The second hole was loaded with the nanonized BCP (experimental group C, n = 10) and the third one was left untreated (negative control group B, n = 10). The defects were allowed to regenerate for 8 weeks. New bone formation was greater in groups A and C than in B. No difference was seen between group A and group C (P = 0.676). The residual bone material in group C (19.34 ± 8.03) was as much as one-half of that in group A (38.69 ± 7.90%) (P = 0.000). The negative control group B presented the highest amount of soft tissue within the bone defects. The least percentage of marrow space was found in the positive control group (13.23 ± 13.52). Our results depicted that the rate of resorption increased significantly after nanonization even though the nano-sized BCP failed to make a superior regeneration than the ordinary BCP.
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Köse S, Kankilic B, Gizer M, Ciftci Dede E, Bayramli E, Korkusuz P, Korkusuz F. Stem Cell and Advanced Nano Bioceramic Interactions. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1077:317-342. [PMID: 30357696 DOI: 10.1007/978-981-13-0947-2_17] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Bioceramics are type of biomaterials generally used for orthopaedic applications due to their similar structure with bone. Especially regarding to their osteoinductivity and osteoconductivity, they are used as biodegradable scaffolds for bone regeneration along with mesenchymal stem cells. Since chemical properties of bioceramics are important for regeneration of tissue, physical properties are also important for cell proliferation. In this respect, several different manufacturing methods are used for manufacturing nano scale bioceramics. These nano scale bioceramics are used for regeneration of bone and cartilage both alone or with other types of biomaterials. They can also act as carrier for the delivery of drugs in musculoskeletal infections without causing any systemic toxicity.
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Affiliation(s)
- Sevil Köse
- Faculty of Health Sciences, Department of Nutrition and Dietetics, Atilim University, Ankara, Turkey.
| | - Berna Kankilic
- Head of Certification, Directorate of Directives, Turkish Standards Institution, Ankara, Turkey
| | - Merve Gizer
- Department of Bioengineering, Hacettepe University, Ankara, Turkey
| | - Eda Ciftci Dede
- Department of Bioengineering, Hacettepe University, Ankara, Turkey
| | - Erdal Bayramli
- Department of Chemistry, Middle East Technical University, Ankara, Turkey
| | - Petek Korkusuz
- Department of Histology and Embryology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Feza Korkusuz
- Department of Sports Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
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Rh Owen G, Dard M, Larjava H. Hydoxyapatite/beta-tricalcium phosphate biphasic ceramics as regenerative material for the repair of complex bone defects. J Biomed Mater Res B Appl Biomater 2017; 106:2493-2512. [PMID: 29266701 DOI: 10.1002/jbm.b.34049] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 10/27/2017] [Accepted: 10/31/2017] [Indexed: 01/07/2023]
Abstract
Bone is a composite material composed of collagen and calcium phosphate (CaP) mineral. The collagen gives bone its flexibility while the inorganic material gives bone its resilience. The CaP in bone is similar in composition and structure to the mineral hydroxyapatite (HA) and is bioactive, osteoinductive and osteoconductive. Therefore synthetic versions of bone apatite (BA) have been developed to address the demand for autologous bone graft substitutes. Synthetic HA (s-HA) are stiff and strong, but brittle. These lack of physical attributes limit the use of synthetic apatites in situations where no physical loading of the apatite occurs. s-HA chemical properties differ from BA and thus change the physical and mechanical properties of the material. Consequently, s-HA is more chemically stable than BA and thus its resorption rate is slower than the rate of bone regeneration. One solution to this problem is to introduce a faster resorbing CaP, such as β-tricalcium phosphate (β-TCP), when synthesizing the material creating a biphasic (s-HA and β-TCP) formulation of calcium phosphate (BCP). The focus of this review is to introduce the major differences between BCP and biological apatites and how material scientists have overcome the inadequacies of the synthetic counterparts. Examples of BCP performance in vitro and in vivo following structural and chemical modifications are provided as well as novel ultrastructural data. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2493-2512, 2018.
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Affiliation(s)
- Gethin Rh Owen
- Department of Oral, Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver V6T 1Z3, Canada
| | - Michel Dard
- College of Dentistry, New York University, New York, New York
| | - Hannu Larjava
- Department of Oral, Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver V6T 1Z3, Canada
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Bone integration behavior of hydroxyapatite/β-tricalcium phosphate graft implanted in dental alveoli: a histomorphometric and scanning electron microscopy study. IMPLANT DENT 2016; 23:710-5. [PMID: 25343320 DOI: 10.1097/id.0000000000000172] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE This study investigated the bone integration ability of a biphasic calcium phosphate bioceramic implanted in dental alveolus of rats. MATERIALS AND METHODS A total of 21 male rats were submitted to upper right incisor extraction and implanted with a synthetic bioceramic (Straumann Bone Ceramic). The animals were killed on 7th, 21st, and 42nd day after surgery for light and scanning electron microscopy (SEM) analysis of bone, bioceramic, and soft tissue volume as well as the quality of graft in its interface. RESULTS Light histology results showed no persistent inflammatory and foreign body reactions, a newly formed bone adhered on the ceramic surface without interposition of soft tissue, which was confirmed by SEM analysis. Histometrically, reduction/resorption, between 7 and 42 days, in the percentage of bioceramic implanted (α = 1%) left gaps for a gradual increase in vital bone formation (α = 1%) around the particles. CONCLUSIONS The bioceramic in question is biocompatible, has good bone integration, being gradually resorbed and replaced by it, featuring a viable bone substitute for grafting procedures.
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15
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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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16
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Komakula SSB, Raut S, Verma NP, Raj TA, Kumar MJ, Sinha A, Singh S. Assessment of injectable and cohesive nanohydroxyapatite composites for biological functions. Prog Biomater 2015; 4:31-38. [PMID: 29470792 PMCID: PMC5151109 DOI: 10.1007/s40204-014-0034-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 12/04/2014] [Indexed: 11/30/2022] Open
Abstract
Pressing need for utilization of injectables/fillers in various forms of orthopaedic treatments/surgeries commands an equal demand for better graft material. Injectable bone graft material based on biomimetically synthesized nanohydroxyapatite was developed and subjected to ball milling for different times; three materials thus produced were evaluated for their biological properties. The three composites tested were found to have some difference in proliferation and differentiation on mesenchymal stem cells in cultures. In vivo studies were performed by implanting the graft materials with or without cells in the bone drill hole injury created in the femur of Wistar rats. Our studies show that the composites lead to well-healed injury site with normal histology without inflammation or fibrous tissue formation and bone deformity. This material needs to be tested on large animals for further ascertaining its applicability in clinical use.
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Affiliation(s)
| | - Snehal Raut
- CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India
| | | | - T Avinash Raj
- CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India
| | - Mahesh J Kumar
- CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India
| | - Arvind Sinha
- CSIR-National Metallurgical Laboratory, Jamshedpur, 831 007, India
| | - Shashi Singh
- CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India.
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17
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Wei CC, Lin AB, Hung SC. Mesenchymal stem cells in regenerative medicine for musculoskeletal diseases: bench, bedside, and industry. Cell Transplant 2015; 23:505-12. [PMID: 24816447 DOI: 10.3727/096368914x678328] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Human bone marrow-derived mesenchymal stem cells (MSCs) can self-renew and differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs have effectively emerged as a promising tool for clinical applications, specifically in musculoskeletal diseases. This article reviews the status of preclinical animal studies, clinical trials, and the efforts of the industry in using MSCs to treat musculoskeletal diseases such as bone fractures, bone defects, focal chondral lesions, osteoarthritis, spinal diseases, and tendon injuries. We also discuss the current problems encountered and potential of using MSCs in future clinical studies.
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Affiliation(s)
- Chih-Chang Wei
- Stem Cell Laboratory, Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
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18
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Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. Bone Res 2014; 2:14017. [PMID: 26273526 PMCID: PMC4472121 DOI: 10.1038/boneres.2014.17] [Citation(s) in RCA: 187] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 07/25/2014] [Accepted: 07/29/2014] [Indexed: 02/05/2023] Open
Abstract
Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.
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19
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Romagnoli C, Brandi ML. Adipose mesenchymal stem cells in the field of bone tissue engineering. World J Stem Cells 2014; 6:144-152. [PMID: 24772241 PMCID: PMC3999772 DOI: 10.4252/wjsc.v6.i2.144] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 12/19/2013] [Accepted: 03/04/2014] [Indexed: 02/06/2023] Open
Abstract
Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians. Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility, biodegradability and osteoinductivity. Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells (MSCs). In particular, a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue. These adipose stem cells (ASCs) can be obtained in large quantities with little donor site morbidity or patient discomfort, in contrast to the invasive and painful isolation of bone marrow MSCs. The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models, with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients. Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration, the lack of standardization in applied techniques makes the comparison between studies difficult. Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns, which must be resolved to permit application in regenerative medicine.
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20
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Fan R, Deng X, Zhou L, Gao X, Fan M, Wang Y, Guo G. Injectable thermosensitive hydrogel composite with surface-functionalized calcium phosphate as raw materials. Int J Nanomedicine 2014; 9:615-26. [PMID: 24489468 PMCID: PMC3904811 DOI: 10.2147/ijn.s52689] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
In this study, L-lactide was used to modify the tricalcium phosphate (β-TCP) and tetracalcium phosphate (TTCP) surface which can form functionalized poly(l-lactic acid) (PLLA)-grafted β-TCP (g-β-TCP) and PLLA-grafted TTCP (g-TTCP) particles. The g-β-TCP and g-TTCP obtained were incorporated into a PEG-PCL-PEG (PECE) matrix to prepare injectable thermosensitive hydrogel composites. The morphology of the hydrogel composites showed that the g-β-TCP and g-TTCP particles dispersed homogeneously into the polymer matrix, and each hydrogel composite had a three-dimensional network structure. Rheologic analysis showed that the composite had good thermosensitivity. Changes in calcium concentration and pH in simulated body fluid solutions confirmed the feasibility of surface-functionalized calcium phosphate for controlled release of calcium. All the results indicate that g-β-TCP/PECE and g-TTCP/PECE hydrogels might be a promising protocol for tissue engineering.
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Affiliation(s)
- RangRang Fan
- State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - XiaoHui Deng
- Department of Human Anatomy, Xinxiang Medical University, Xinxiang, People's Republic of China
| | - LiangXue Zhou
- State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Xiang Gao
- State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Min Fan
- State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - YueLong Wang
- State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Gang Guo
- State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
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21
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Castilho M, Moseke C, Ewald A, Gbureck U, Groll J, Pires I, Teßmar J, Vorndran E. Direct 3D powder printing of biphasic calcium phosphate scaffolds for substitution of complex bone defects. Biofabrication 2014; 6:015006. [PMID: 24429776 DOI: 10.1088/1758-5082/6/1/015006] [Citation(s) in RCA: 105] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The 3D printing technique based on cement powders is an excellent method for the fabrication of individual and complex bone substitutes even in the case of large defects. The outstanding bone remodeling capacity of biphasic calcium phosphates (BCPs) containing hydroxyapatite (HA) as well as tricalcium phosphate (TCP) in varying ratios makes the adaption of powder systems resulting in BCP materials to this fabrication technique a desirable aim. This study presents the synthesis and characterization of a novel powder system for the 3D printing process, intended for the production of complexly shaped BCP scaffolds by a hydraulic setting reaction of calcium carbonate and TCP with phosphoric acid. The HA/TCP ratio in the specimens could be tailored by the calcium/phosphate ratio of the starting powder. The scaffolds could be fabricated with a dimensional accuracy of >96.5% and a minimal macro pore size of 300 µm. Independent of the phase composition the printed specimens showed a microporosity of approximately 68%, while the compressive strength strongly depended on the chemical composition and increased with rising TCP content in the scaffolds to a maximum of 1.81 MPa. Post-treatment of the scaffolds with a polylactic-co-glycolic acid-solution enhanced the mechanical properties by a factor of 8. In vitro studies showed that all BCP scaffolds were cytocompatible and enhanced the cell viability as well as the cell proliferation, as compared with pure TCP. Cell proliferation is even better on BCP when compared to HA and cell viability is in a similar range on these materials.
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Affiliation(s)
- Miguel Castilho
- Institute of Mechanical Engineering/IST, Technical University of Lisbon, Portugal
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22
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Liu X, Peng W, Wang Y, Zhu M, Sun T, Peng Q, Zeng Y, Feng B, Lu X, Weng J, Wang J. Synthesis of an RGD-grafted oxidized sodium alginate-N-succinyl chitosan hydrogel and an in vitro study of endothelial and osteogenic differentiation. J Mater Chem B 2013; 1:4484-4492. [PMID: 32261121 DOI: 10.1039/c3tb20552e] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hydrophilic surfaces for hydrogels as bone tissue engineering scaffolds are not beneficial for the adsorption of protein and not conducive to the adhesion and growth of cells. In this study, we proposed to use an oxidized sodium alginate-N-succinyl chitosan hydrogel as a bone tissue engineering scaffold material and to overcome this issue by using RGD to modify this kind of hydrogel. The physicochemical properties of the obtained hydrogels were characterized and an in vitro endothelial differentiation and osteogenic differentiation study of bone-marrow-derived mesenchymal stem cells (BMSCs) was conducted to evaluate it. The results showed that the RGD-grafted oxidized sodium alginate-N-succinyl chitosan hydrogel not only had a good degradability but also enhanced cell adhesion and proliferation and promoted endothelial differentiation and osteogenic differentiation of BMSCs. Based on the results, it can be expected that RGD-grafted oxidized sodium alginate-N-succinyl chitosan hydrogel might be an optimal material for bone tissue engineering scaffold whenever it is used alone, or composed with other materials in the future.
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Affiliation(s)
- Xia Liu
- Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, P. R. China
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23
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He X, Dziak R, Mao K, Genco R, Swihart M, Swithart M, Li C, Yang S. Integration of a novel injectable nano calcium sulfate/alginate scaffold and BMP2 gene-modified mesenchymal stem cells for bone regeneration. Tissue Eng Part A 2012; 19:508-18. [PMID: 22994418 DOI: 10.1089/ten.tea.2012.0244] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
The repair of craniofacial bone defects is surgically challenging due to the complex anatomical structure of the craniofacial skeleton. Current strategies for bone tissue engineering using a preformed scaffold have not resulted in the expected clinical regeneration due to difficulty in seeding cells into the deep internal space of scaffold, and the inability to inject them in minimally invasive surgeries. In this study, we used the osteoconductive and mechanical properties of nano-scale calcium sulfate (nCS) and the biocompatibility of alginate to develop the injectable nCS/alginate (nCS/A) paste, and characterized the effect of this nCS/A paste loaded with bone morphogenetic protein 2 (BMP2) gene-modified rat mesenchymal stem cells (MSCs) on bone and blood vessel growth. Our results showed that the nCS/A paste was injectable under small injection forces. The mechanical properties of the nCS/A paste were increased with an increased proportion of alginate. MSCs maintained their viability after the injection, and MSCs and BMP2 gene-modified MSCs in the injectable pastes remained viable, osteodifferentiated, and yielded high alkaline phosphatase activity. By testing the ability of this injectable paste and BMP2-gene-modified MSCs for the repair of critical-sized calvarial bone defects in a rat model, we found that BMP2-gene-modified MSCs in nCS/A (nCS/A+M/B2) showed robust osteogenic activity, which resulted in consistent bone bridging of the bone defects. The vessel density in nCS/A+M/B2 was significantly higher than that in the groups of blank control, nCS/A alone, and nCS/A mixed with MSCs (nCS/A+M). These results indicate that BMP2 promotes MSCs-mediated bone formation and vascularization in nCS/A paste. Overall, the results demonstrated that the combination of injectable nCS/A paste and BMP2-gene-modified MSCs is a new and effective strategy for the repair of bone defects.
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Affiliation(s)
- Xiaoning He
- Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York 14214, USA
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Alves Cardoso D, Jansen JA, Leeuwenburgh SCG. Synthesis and application of nanostructured calcium phosphate ceramics for bone regeneration. J Biomed Mater Res B Appl Biomater 2012; 100:2316-26. [PMID: 23015272 DOI: 10.1002/jbm.b.32794] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Revised: 07/13/2012] [Accepted: 07/14/2012] [Indexed: 01/02/2023]
Abstract
In the past two decades, nanotechnology has entered the field of regenerative medicine, resulting in the development of a novel generation of instructive, nanostructured biomaterials that are able to orchestrate cellular behavior by presenting specific morphological and biological cues. Using nanotechnology, materials containing nanosized features (e.g., pores, patterns, textures, grain sizes) can be obtained that exhibit properties that are considerably altered compared with micron-structured materials. Inspired by the hierarchical nanostructure of bone, the application of nanostructured materials for bone regeneration is gaining increasing interest in the field of biomaterials research. Because crystallographic and chemical studies have shown that synthetic hydroxyapatite closely resembles the inorganic phase found in bone and teeth, synthesis and applications of nanostructured calcium phosphate ceramics have been reviewed. Synthesis techniques for the preparation of calcium phosphate nanoparticles include precipitation, sol-gel, and hydrothermal processes, whereas four main biomedical applications of nanostructured calcium phosphate ceramics in bone regeneration have been addressed in more detail, that is, (1) polymer/calcium phosphate nanocomposites, (2) nanostructured monophasic calcium phosphate bone fillers, (3) nanostructured precursor phases for calcium phosphate cements, and (4) nanostructured calcium phosphate coatings.
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Affiliation(s)
- D Alves Cardoso
- Department of Biomaterials, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands
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25
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Zanetti AS, Sabliov C, Gimble JM, Hayes DJ. Human adipose-derived stem cells and three-dimensional scaffold constructs: a review of the biomaterials and models currently used for bone regeneration. J Biomed Mater Res B Appl Biomater 2012; 101:187-99. [PMID: 22997152 DOI: 10.1002/jbm.b.32817] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Revised: 07/28/2012] [Accepted: 08/07/2012] [Indexed: 12/24/2022]
Abstract
In the past decade, substantial strides have been taken toward the use of human adipose-derived stromal/stem cells (hASC) in the regeneration of bone. Since the discovery of the hASC osteogenic potential, many models have combined hASC with biodegradable scaffold materials. In general, rats and immunodeficient (nude) mice models for nonweight bearing bone formation have led the way to assess hASC osteogenic potential in vivo. The goal of this review is to present an overview of the recent literature describing hASC osteogenesis in conjunction with three-dimensional scaffolds for bone regeneration.
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Affiliation(s)
- Andrea S Zanetti
- Department of Biological and Agricultural Engineering, Louisiana State University and LSU AgCenter, Louisiana, USA
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