Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo

微孔多糖多层涂层BCP复合支架与固定骨化三醇在体内和体外促进骨质疏松骨再生

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作者:Qian Tang, Zhichao Hu, Haiming Jin, Gang Zheng, XingFang Yu, Gang Wu, Haixiao Liu, Zhenzhong Zhu, Huazi Xu, Changqing Zhang, Liyan Shen

Conclusion

A composite scaffold based on BCP, created by simply combining a biomimetic PEM coating and Cal immobilisation, could be clinically useful and has marked advantages as a targeted, off-the-shelf, cell-free treatment option for osteoporotic bone regeneration.

Methods

The ovariectomy-induced functional changes in bone marrow mesenchymal stem cells (BMSCs), protective effects of Cal, and the potential mechanism were all verified. A PEM film composed of hyaluronic acid (HA) and chitosan (Chi) was prepared through layer-by-layer self-assembly. The morphology, growth behaviour, and drug retention capability of the composite scaffolds were characterised, and their biocompatibility and therapeutic efficacy for bone regeneration were systematically explored in vitro and in vivo.

Results

The osteogenic differentiation, adhesion, and proliferation abilities of ovariectomised rat BMSCs (OVX-rBMSCs) decreased, in accordance with the deficiency of CaSR. Cal effectively activated osteogenesis in these OVX-rBMSCs by binding specifically to the active pocket of the CaSR structure, while the biomimetic PEM coating augmented OVX-rBMSCs proliferation and adhesion due to its porous surface structure. The PEM-coated scaffolds showed advantages in Cal loading and retention, especially at lower drug concentrations. HA/Chi PEM synergised with Cal to improve the proliferation, adhesion, and osteogenesis of OVX-rBMSCs and promote bone regeneration and BCP degradation in the critical-size calvarial bone defect model of OVX rats.

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