Enhanced bone regeneration using an insulin-loaded nano-hydroxyapatite/collagen/PLGA composite scaffold

Xing Wang,1,* Guilan Zhang,2,* Feng Qi,3 Yongfeng Cheng,1 Xuguang Lu,1 Lu Wang,1 Jing Zhao,1 Bin Zhao1 1Shanxi Medical University Stomatological Hospital, Taiyuan, 2Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 3Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, MO, USA *These authors contributed equally to this work Abstract: Insulin is widely considered as a classical hormone and drug in maintaining energy and glucose homeostasis. Recently, insulin has been increasingly recognized as an indispensable factor for osteogenesis and bone turnover, but its applications in bone regeneration have been restricted because of the short periods of activity and uncontrolled release. In this study, we incorporated insulin-loaded poly lactic-co-glycolic-acid (PLGA) nanospheres into nano-hydroxyapatite/collagen (nHAC) scaffolds and investigated the bioactivity of the composite scaffolds in vitro and in vivo. Bioactive insulin was successfully released from the nanospheres within the scaffold, and the release kinetics of insulin could be efficiently controlled by uniform-sized nanospheres. The physical characterizations of the composite scaffolds demonstrated that incorporation of nanospheres in nHAC scaffolds using this method did not significantly change the porosity, pore diameters, and compressive strengths of nHAC. In vitro, the insulin-loaded nHAC/PLGA composite scaffolds possessed favorable biological function for bone marrow mesenchymal stem cells adhesion and proliferation, as well as the differentiation into osteoblasts. In vivo, the optimized bone regenerative capability of this composite scaffold was confirmed in rabbit mandible critical size defects. These results demonstrated successful development of a functional insulin–PLGA–nHAC composite scaffold that enhances the bone regeneration capability of nHAC. Keywords: insulin, composite scaffold, drug delivery system, bone tissue engineering&nbsp