α-hemihydrate calcium sulfate/octacalcium phosphate combined with sodium hyaluronate promotes bone marrow-derived mesenchymal stem cell osteogenesis in vitro and in vivo

Drug Design, Development and Therapy, Oct 2018

α-hemihydrate calcium sulfate/octacalcium phosphate combined with sodium hyaluronate promotes bone marrow-derived mesenchymal stem cell osteogenesis in vitro and in vivo Changshun Chen,1 Chen Zhu,2 Xiang Hu,1 Qiuli Yu,3 Qianjin Zheng,1 Shengxiang Tao,1 Lihong Fan2 1Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; 2School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China; 3School of Health Sciences, Wuhan University, Wuhan, Hubei, China Purpose: The aims of this research were to combine a-hemihydrate calcium sulfate/octacalcium phosphate (α-CSH/OCP) with sodium hyaluronate (SH) or SH sulfate (SHS) to determine whether these composites can be used as a new type of bone repair material. This study may provide a theoretical basis and new ideas for the construction of active bone repair materials and their clinical application.Methods: In this study, we combined α-CSH/OCP with SH or SHS. Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and the wettability test were performed, and porosity, setting time, in vitro degradation, and the mechanical properties of these composite materials were analyzed to evaluate the ultrastructural and physicochemical properties. We evaluated the histocompatibility of these composites by MTT assay, hemolysis, acute toxicity, and pyrogenic and intracutaneous stimulation tests. In addition, the osteogenic differentiation ability of these materials was detected in vitro using Western blot analysis and in vivo using an animal model of bone defect.Results: The α-CSH/OCP/SH composite had a compressive strength of 13.72 MPa, a porous rate of 27.45%, and the 28-day degradation rate of 64%. The MTT assay results showed that the relative proliferation rates of the α-CSH/OCP/SH group were greater than 90%. The results of the α-CSH/OCP/SH composite in the hemolysis, acute toxicity, pyrogenic, and intracutaneous stimulation tests were within the normal range. Western blot analysis indicated that the expression of bone extracellular matrix (ECM) proteins was notably upregulated and always higher in the α-CSH/OCP/SH group than in the other groups. XRD of the rabbit radius-defect model indicated that bone healing in the area implanted with α-CSH/OCP/SH was excellent approximately 9 weeks after repair.Conclusion: α-CSH/OCP/SH has very good biocompatibility and exhibits clear advantages in the induction of bone regeneration and self-repair, and this compound shows promise in the field of bone tissue engineering. Keywords: sodium hyaluronate, characterization, BMSCs, biocompatibility, osteogenic differentiation

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α-hemihydrate calcium sulfate/octacalcium phosphate combined with sodium hyaluronate promotes bone marrow-derived mesenchymal stem cell osteogenesis in vitro and in vivo

Authors Chen C, Zhu C, Hu X, Yu Q, Zheng Q, Tao S, Fan L Received 7 May 2018 Accepted for publication 27 July 2018 Published 2 October 2018 Volume 2018:12 Pages 3269—3287 DOI https://doi.org/10.2147/DDDT.S173289 Checked for plagiarism Yes Review by Single-blind Peer reviewers approved by Dr Colin Mak Peer reviewer comments 2 Editor who approved publication: Professor Manfred Ogris Changshun Chen,1 Chen Zhu,2 Xiang Hu,1 Qiuli Yu,3 Qianjin Zheng,1 Shengxiang Tao,1 Lihong Fan2 1Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; 2School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China; 3School of Health Sciences, Wuhan University, Wuhan, Hubei, China Purpose: The aims of this research were to combine a-hemihydrate calcium sulfate/octacalcium phosphate (α-CSH/OCP) with sodium hyaluronate (SH) or SH sulfate (SHS) to determine whether these composites can be used as a new type of bone repair material. This study may provide a theoretical basis and new ideas for the construction of active bone repair materials and their clinical application. Methods: In this study, we combined α-CSH/OCP with SH or SHS. Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and the wettability test were performed, and porosity, setting time, in vitro degradation, and the mechanical properties of these composite materials were analyzed to evaluate the ultrastructural and physicochemical properties. We evaluated the histocompatibility of these composites by MTT assay, hemolysis, acute toxicity, and pyrogenic and intracutaneous stimulation tests. In addition, the osteogenic differentiation ability of these materials was detected in vitro using Western blot analysis and in vivo using an animal model of bone defect. Results: The α-CSH/OCP/SH composite had a compressive strength of 13.72 MPa, a porous rate of 27.45%, and the 28-day degradation rate of 64%. The MTT assay results showed that the relative proliferation rates of the α-CSH/OCP/SH group were greater than 90%. The results of the α-CSH/OCP/SH composite in the hemolysis, acute toxicity, pyrogenic, and intracutaneous stimulation tests were within the normal range. Western blot analysis indicated that the expression of bone extracellular matrix (ECM) proteins was notably upregulated and always higher in the α-CSH/OCP/SH group than in the other groups. XRD of the rabbit radius-defect model indicated that bone healing in the area implanted with α-CSH/OCP/SH was excellent approximately 9 weeks after repair. Conclusion: α-CSH/OCP/SH has very good biocompatibility and exhibits clear advantages in the induction of bone regeneration and self-repair, and this compound shows promise in the field of bone tissue engineering. Keywords: sodium hyaluronate, characterization, BMSCs, biocompatibility, osteogenic differentiation Introduction Bone defects have become a serious clinical problem1 due to their prevalence in clinical orthopedics cases and the common need to resect the affected parts of the bone.2 Numerous methods are used to treat bone defects, such as autografts, alloplastic materials, and allografts.3 At present, the gold-standard treatment for bone defects is autogenous bone grafting. However, autogenous bone graft material is limited and donor site complications include pain and infection.4,5 Bone tissue engineering provides an alternative method for the treatment of bone defects that aims to regenerate damaged bone tissues by combining cells with bone repair materials, which act as templates for tissue regeneration and guide new tissue growth.6 Because of its unlimited supply and lack of risk for spreading disease, engineered bone is considered as a potential alternative to traditional bone grafts.7 In the field of bone tissue engineering, synthetic materials show promise due to their potential bone engineering characteristics; these materials include composites, stimuli-responsive materials, gels, and scaffolding. Stimuli-responsive materials can change their shapes from a 2D flat-planar structure to 3D structure with various morphologies with small or modest variations in their physical environment, such as temperature, pH, and magnetic fields. However, there are some concerns regarding the use of programmable adaptive materials in clinical applications.8 Gels and scaffold materials show good biocompatibility, biodegradability, mechanical properties, vascularization, and innervation. However, these materials are imperfect and require additional studies.9 Bone tissue engineering has become an attractive therapeutic approach with great potential for repairing bone defects.10 In bone tissue engineering, bone repair materials serve as matrices for tissue formation, thus playing a pivotal role in bone repair. An excellent bone rep (...truncated)


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Changshun Chen, Chen Zhu, Xiang Hu, Qiuli Yu, Qianjin Zheng, Shengxiang Tao, Lihong Fan. α-hemihydrate calcium sulfate/octacalcium phosphate combined with sodium hyaluronate promotes bone marrow-derived mesenchymal stem cell osteogenesis in vitro and in vivo, Drug Design, Development and Therapy, 2018, pp. 3269-3287, DOI: 10.2147/DDDT.S173289