International Journal of Nanomedicine (Feb 2018)
Guided osteoporotic bone regeneration with composite scaffolds of mineralized ECM/heparin membrane loaded with BMP2-related peptide
Abstract
Tingfang Sun,1,* Man Liu,2,* Sheng Yao,1 Yanhui Ji,1 Lei Shi,3 Kai Tang,1 Zekang Xiong,1 Fan Yang,1 Kaifang Chen,1 Xiaodong Guo1 1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 2Department of Gastroenterology and Hepatology, Taikang Tongji Hospital, Wuhan 430050, China; 3State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China *These authors contributed equally to this work Introduction: At present, the treatment of osteoporotic defects poses a great challenge to clinicians, owing to the lower regeneration capacity of the osteoporotic bone as compared with the normal bone. The guided bone regeneration (GBR) technology provides a promising strategy to cure osteoporotic defects using bioactive membranes. The decellularized matrix from the small intestinal submucosa (SIS) has gained popularity for its natural microenvironment, which induces cell response. Materials and methods: In this study, we developed heparinized mineralized SIS loaded with bone morphogenetic protein 2 (BMP2)-related peptide P28 (mSIS/P28) as a novel GBR membrane for guided osteoporotic bone regeneration. These mSIS/P28 membranes were obtained through the mineralization of SIS (mSIS), followed by P28 loading onto heparinized mSIS. The heparinized mSIS membrane was designed to improve the immobilization efficacy and facilitate controlled release of P28. P28 release from mSIS-heparin-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells from ovariectomized rats (rBMSCs-OVX) were investigated in vitro. Furthermore, a critical-sized OVX calvarial defect model was used to assess the bone regeneration capability of mSIS-heparin-P28 in vivo. Results: In vitro results showed that P28 release from mSIS-heparin-P28 occurred in a controlled manner, with a long-term release time of 40 days. Moreover, mSIS-heparin-P28 promoted cell proliferation and viability, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes in rBMSCs-OVX without the addition of extra osteogenic components. In vivo experiments revealed that mSIS-heparin-P28 dramatically stimulated osteoporotic bone regeneration. Conclusion: The heparinized mSIS loaded with P28 may serve as a potential GBR membrane for repairing osteoporotic defects. Keywords: osteoporotic defect, guided bone regeneration, decellularized matrix, heparin, BMP2-related peptide, control release
