Open AccessBlockade of adrenergic β‐receptor activation through local delivery of propranolol from a 3D collagen/polyvinyl alcohol/hydroxyapatite scaffold promotes bone repair in vivo
Author(s) -
Wu Hao,
Song Yue,
Li Junqin,
Lei Xing,
Zhang Shuaishuai,
Gao Yi,
Cheng Pengzhen,
Liu Bin,
Miao Sheng,
Bi Long,
Yang Liu,
Pei Guoxian
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12725
Subject(s) - bone healing , in vivo , chemistry , stromal cell , regeneration (biology) , propranolol , bone marrow , microbiology and biotechnology , biomedical engineering , medicine , anatomy , biology
Objectives Activation of the sympathetic system and adrenergic β‐receptors following traumatic bone defects negatively impairs bone regeneration. Whether preventing β‐receptor activation could potentially improve bone defect repair is unknown. In this study, we investigated the effect of systematic administration and local delivery of propranolol through composite scaffolds on bone healing. Materials and methods Collagen/PVA/propranolol/hydroxyapatiteCPPHcomposite 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.