A poly(ether-ketone-ketone) composite scaffold simulating the immune-osteogenic cascade for <i>in situ</i> bone regeneration

The process of bone repair is intrinsically associated with the immune response. Following scaffold implantation, the pro-inflammatory response initiates the immune-osteogenic cascade. Efficient recruitment and timely conversion of macrophages to an anti-inflammatory phenotype are critical for promoting subsequent bone regeneration. Poly(ether-ketone-ketone) (PEKK) is an attractive orthopaedic material, but exhibits biological inertness. In this study, an immunomodulatory PEKK/bioglass composite scaffold was fabricated by fused deposition modeling and a soft cryogel containing monocyte chemotactic protein-1 (MCP-1) was infilled into the macropores of the scaffold (PBCM). The rapid release of MCP-1 from PBCM initially mobilized endogenous macrophages, which subsequently recruited rat mesenchymal stem cells (rMSCs). Continuous release of bioactive ions not only facilitated the polarization of macrophages towards the M2 phenotype, thereby establishing a favorable anti-inflammatory microenvironment conducive to bone formation, but also stimulated the osteogenic differentiation of rMSCs. Moreover, cytokines secreted by macrophages further promoted osteogenesis. <i>In vivo</i> experiments demonstrated excellent bone regeneration following PBCM implantation. Taken together, this study aimed to develop a novel immunomodulatory PEKK composite scaffold that can simulate the immune-osteogenic cascade for timely recruitment of endogenous cells, efficient immunomodulation of macrophages and superior osteogenic abilities, potentially serving as potent implants for tissue engineering applications.