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A programmed surface on polyetheretherketone for sequentially dictating osteoimmunomodulation and bone regeneration to achieve ameliorative osseointegration under osteoporotic conditions

Year: 2022

Journal: Bioact. Mater., Volume 14, AUG, page 364–376

Authors: Zheng, Yanyan; Gao, Ang; Bai, Jiaxiang; Liao, Qing; Wu, Yuzheng; Zhang, Wei; Guan, Min; Tong, Liping; Geng, Dechun; Zhao, Xin; Chu, Paul K.; Wang, Huaiyu

Organizations: National Natural Science Foundation of China [31922040, 82001965]; Shenzhen Science and Technology Research Funding [SGLH20180625144002074, JCYJ20180507182637685, JCYJ20190806165616542]; Youth Innovation Promotion Association of Chinese Academy of Sciences [2017416, 2020353]; Guangdong Basic and Applied Basic Research Foundation [2020B1515120078]; China Postdoctoral Science Foundation [2019M663190]; SIAT Innovation Program for Excellent Young Researchers [E1G034]; Nanchong Science and Technology Project [20SXQT0302]; City University of Hong Kong Strategic Research Grant (SRG) [7005505]

Keywords: Polyetheretherketone; Surface modification; Osteoimmunomodulation; Sequential release; Osteoporosis; Osseointegration

Polyetheretherketone (PEEK) is a desirable alternative to conventional biomedical metals for orthopedic implants due to the excellent mechanical properties. However, the inherent bioinertness of PEEK contributes to inferior osseointegration of PEEK implants, especially under pathological conditions of osteoporosis. Herein, a programmed surface is designed and fabricated on PEEK to dictate osteoimmunomodulation and bone regeneration sequentially. A degradable hybrid coating consisting of poly(lactide-co-glycolide) and alendronate (ALN) loaded nano-hydroxyapatite is deposited on PEEK and then interleukin-4 (IL-4) is grafted onto the outer surface of the hybrid coating with the aid of N-2 plasma immersion ion implantation and subsequent immersion in IL-4 solution. Dominant release of IL-4 together with ALN and Ca2+ during the first few days synergistically mitigates the early acute inflammatory reactions and creates an osteoimmunomodulatory microenvironment that facilitates bone regeneration. Afterwards, slow and sustained delivery of ALN and Ca2+ in the following weeks boosts osteogenesis and suppresses osteoclastogenesis simultaneously, consequently ameliorating bone-implant osseointegration even under osteoporotic conditions. By taking into account the different phases in bone repair, this strategy of constructing advanced bone implants with sequential functions provides customizable and clinically viable therapy to osteoporotic patients.