Int J Biol Macromol. 2026 Aug 21:154150. doi: 10.1016/j.ijbiomac.2026.154150. Online ahead of print.
ABSTRACT
Polyetheretherketone (PEEK) implants exhibit excellent mechanical biocompatibility yet remain inherently bioinert, resulting in fibrous encapsulation that compromises osseointegration and long-term stability. Conventional surface modification strategies employing exogenous bone morphogenetic protein-2 (BMP-2) loading suffer from burst-release kinetics, supraphysiological dosing risks, and coating delamination under physiological conditions, which are fundamentally misaligned with endogenous bone healing dynamics. Here, we present an endogenous homing strategy that transforms bioinert PEEK into osteoinductive scaffolds through in situ hydrogel assembly of dual-functional self-assembling peptides. Our design integrates RADA16 self-assembling domains with BMP-2-binding motifs (B2P), which upon covalent immobilization spontaneously assemble into nanofibrous hydrogel coatings that recapitulate native extracellular matrix architecture. This modification creates a hydrophilic bioactive interface that actively sequesters endogenous BMP-2 from the local microenvironment, thereby amplifying osteogenic signaling without exogenous supplementation. In vitro experiments reveal that B2P-functionalized PEEK significantly enhanced preosteoblast migration, proliferation, and osteogenic differentiation compared with unmodified controls. In a critical-sized beagle tibial defect model, PEEK-B2P implants achieved superior osseointegration with increased bone volume fraction and bone-implant contact, forming continuous lamellar bone without fibrous interposition. These findings establish an endogenous homing paradigm that converts bioinert PEEK into bioactive implants, offering a translatable strategy for enhanced bone regeneration and implant stability.
PMID:42628859 | DOI:10.1016/j.ijbiomac.2026.154150

