Surface Functionalization with Proanthocyanidins Provides an Anti-Oxidant Defense Mechanism That Improves the Long-Term Stability and Osteogenesis of Titanium Implants

Abstract

Jiahao Tang,1,2 Liang Chen,1,2 Deyi Yan,1,2 Zijian Shen,1,2 Bingzhang Wang,1,2 Sheji Weng,1,2 Zongyi Wu,1,2 Zhongjie Xie,1,2 Jiancan Shao,1,2 Lei Yang,1,2 Liyan Shen1,2 1The Second School of Medicine Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 2Key Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of ChinaCorrespondence: Lei Yang; Liyan ShenKey Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 109, Xueyuan West Road, Lucheng District, Wenzhou, Zhejiang 325000, People’s Republic of ChinaFax [phone]Email [email protected]; [email protected]: Aseptic loosening is a major complication after total joint replacement. Reactive oxygen species generated by local tissue cells and liberated from implant surfaces have been suggested to cause implant failures. Surface modification of titanium (Ti)-based implants with proanthocyanidins (PAC) is a promising approach for the development of anti-oxidant defense mechanism to supplement the mechanical functions of Ti implants. In this study, a controlled PAC release system was fabricated on the surface of Ti substrates using the layer-by-layer (LBL) assembly.Materials and Methods: Polyethyleneimine (PEI) base layer was fabricated to enable layer-by-layer (LBL) deposition of hyaluronic acid/chitosan (HA/CS) multi-layers without or with the PAC. Surface topography and wettability of the fabricated HA/CS-PAC substrates were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FTIR) and contact angle measurement. PAC release profiles were investigated using drug release assays. MC3T3-E1 pre-osteoblast cells were used to assess the osteo-inductive effects of HA/CS-PAC substrates under conditions H2O2-induced oxidative stress in vitro. A rat model of femoral intramedullary implantation evaluated the osseo-integration and osteo-inductive potential of the HA/CS-PAC coated Ti implants in vivo.Results: SEM, AFM, FTIR and contact angle measurements verified the successful fabrication of Ti surfaces with multi-layered HA/CS-PAC coating. Drug release assays revealed controlled and sustained release of PAC over 14 days. In vitro, cell-based assays showed high tolerability and enhanced the osteogenic potential of MC3T3-E1 cells on HA/CS-PAC substrates when under conditions of H2O2-induced oxidative stress. In vivo evaluation of femoral bone 14 days after femoral intramedullary implantation confirmed the enhanced osteo-inductive potential of the HA/CS-PAC coated Ti implants.Conclusion: Multi-layering of HA/CS-PAC coating onto Ti-based surfaces by the LBL deposition significantly enhances implant osseo-integration and promotes osteogenesis under conditions of oxidative stress. This study provides new insights for future applications in the field of joint arthroplasty.Keywords: proanthocyanidins, anti-oxidant, ROS, layer-by-layer methodology, surface modification of titanium, osteogenesis

Keywords

• proanthocyanidins
• anti-oxidant
• ros
• layer-by-layer methodology
• surface modification of titanium
• osteogenesis