Blockade of adrenergic β-receptor activation through local delivery of propranolol from a 3D collagen/polyvinyl alcohol/hydroxyapatite scaffold promotes bone repair in vivo

通过 3D 胶原蛋白/聚乙烯醇/羟基磷灰石支架局部输送普萘洛尔来阻断肾上腺素能 β 受体激活,促进体内骨修复

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作者:Hao Wu, Yue Song, Junqin Li, Xing Lei, Shuaishuai Zhang, Yi Gao, Pengzhen Cheng, Bin Liu, Sheng Miao, Long Bi, Liu Yang, Guoxian Pei

Conclusions

This study demonstrates that local adrenergic β-receptor blockade can effectively enhance the treatment of bone defects by stimulating osteogenic differentiation, inhibiting osteoclastogenesis and enhancing BMSCs migration.

Methods

Collagen/PVA/propranolol/hydroxyapatite(CPPH)composite scaffolds were fabricated with 3D printing technique and characterized by scanning electron microscope (SEM). Micro-CT analysis and bone formation histology were performed to detect new bone formation. Osteogenic differentiation of bone marrow stromal cells (BMSCs) and osteoclastogenesis of bone marrow monocytes cultured with scaffolds extract were performed for further verification.

Results

Intraperitoneal injection of propranolol did not significantly improve bone repair, as indicated by micro-CT analysis and bone formation histology. However, CPPH scaffolds exhibited sustained release of propranolol in vitro and significantly enhanced bone regeneration compared with vehicle collagen/PVA/hydroxyapatite (CPH) scaffolds in vivo. Moreover, in vitro experiments indicated the scaffolds containing propranolol promoted the osteogenic differentiation and migration of rat BMSCs and inhibited osteoclastogenesis by preventing β-receptor activation. Conclusions: This study demonstrates that local adrenergic β-receptor blockade can effectively enhance the treatment of bone defects by stimulating osteogenic differentiation, inhibiting osteoclastogenesis and enhancing BMSCs migration.

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