Anti-inflammatory peptide-modified β-TCP scaffolds enhance the hyperglycemic inflammatory microenvironment

Chronic hyperglycemia in diabetic patients induces a sustained systemic inflammatory microenvironment that critically impairs bone regeneration and delays healing. In this study, we developed a β-tricalcium phosphate (β-TCP) scaffold functionalized with the anti-inflammatory peptide KAFAKAARLYRKALARQLGVAA (KAFAK), aiming to regulate the local hyperglycemic inflammatory milieu and enhance bone regeneration. Polydopamine (PDA) was applied as a bioadhesive coating to facilitate the efficient immobilization of KAFAK on the scaffold surface. The physicochemical properties and biocompatibility of the modified scaffolds were systematically characterized. A hyperglycemic inflammatory model was established using lipopolysaccharide (LPS) and glucose to simulate diabetic conditions. In this model, KAFAK-functionalized β-TCP scaffolds significantly downregulated the expression of key pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, in RAW264.7 macrophages. Furthermore, the scaffold effectively modulated macrophage behavior, exhibiting notable immunomodulatory and anti-inflammatory activity. Overall, this study demonstrates that KAFAK-functionalized β-TCP scaffolds hold strong potential for bone regeneration under hyperglycemic inflammatory conditions and offer a novel strategy for immunomodulatory therapy in metabolic bone disorders.