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

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.