Enhancing Immunomodulation and Osseointegration of Bone Implants via Thrombin‐Activated Platelet‐Rich Plasma Self‐Assembly

A multifunctional biointerface is created through the grafting of thrombin onto the polyetheretherketone (PEEK) surface using N,N'-Disuccinimidyl Carbonate (DSC) linkers, thereby activating platelet-rich plasma (PRP) self-assembly. The PRP gel sustainably releases growth factors over 16 days, promoting cell growth, osteogenesis, vascularization, and specific macrophage polarization. The biointerface enhances in vivo bone formation, angiogenesis, and immunomodulation, with biological activity increasing in accordance with platelet enrichment ratios.

Abstract

Platelet-rich plasma (PRP) is characterized by elevated concentrations of growth factors that facilitate bone repair. Nonetheless, the effective integration of PRP with bone implants and the sustained release of its active constituents pose significant challenges. In this study, thrombin is grafted onto the surface of polyetheretherketone (PEEK) via an N,N'-Disuccinimidyl Carbonate (DSC) linker and the retained enzymatic activity of thrombin enables the controlled activation of PRP self-assembly, resulting in the formation of a functional bio-gel layer. The optimal thrombin concentration to be 100 U/ mL⁻¹ is determined, at which point both the grafting amount and enzymatic activity of thrombin reaches their peak, with no further increases observed at higher concentrations. PRP solutions with varying platelet enrichment ratios are subsequently activated on the thrombin-grafted PEEK surface, yielding self-assembled bio-gels capable of sustained growth factor release for up to 16 days. The thrombin-activated PRP bio-gel on PEEK surface not only enhances in vitro cell adhesion, proliferation, osteogenic differentiation, vascularization and specific polarization of macrophages, but also effectively facilitates in vivo angiogenesis, immunomodulation and bone formation in a platelet dose-dependent manner. Consequently, the thrombin-activated PRP gel presents a promising strategy for the biological functionalization of PEEK implants in orthopedic applications.