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A cell-engineered small intestinal submucosa-based bone mimetic construct for bone regeneration.

Research paper by Mei M Li, Chi C Zhang, Yuxing Y Mao, Yi Y Zhong, Jiyuan J Zhao

Indexed on: 11 Jan '18Published on: 11 Jan '18Published in: Tissue engineering. Part A



Abstract

Extracellular matrix (ECM)-ornamented biomaterials have attracted attention due to their high potential to improve the bio-functionality of original materials. It is thought that ECM with a bone mimetic microenvironment generated by the specific induction of osteoblasts would be more beneficial for bone regeneration than regular ECM. In this study, we developed an osteogenic and mineralized ECM construct (Os/M-ECM-SIS) under the guidance of osteoblasts on a small intestinal submucosa (SIS) scaffold co-treated with icariin and calcium. The generated Os/M-ECM-SIS scaffolds exhibited similar morphology and inorganic components as natural bone and higher mechanical strength than ECM-SIS. Cell adhesion, proliferation and differentiation of osteoblasts and fibroblasts were also enhanced in the cells cultured on the Os/M-ECM-SIS scaffolds. The Os/M-ECM-SIS scaffolds even promoted trans-differentiation of fibroblasts with an up-regulation of osteogenic differentiation markers. In a calvarial defect model, new bone formation was greatly enhanced in defects implanted with the Os/M-ECM-SIS scaffolds compared to ECM-SIS scaffolds. Further study showed that the Os/M-ECM-SIS scaffolds promoted bone regeneration in vitro and in vivo via the Bmp/Smad-signaling pathway. Thus, this work proposes a valuable method for generating a mineralized bone mimetic-scaffold with SIS as off-the-shelf bone graft substitutes that provides an excellent osteogenic microenvironment, making it suitable for application in bone tissue engineering.