HDL-Functionalized Biomaterial Coatings Provide Favorable Immunomodulation and Enhance Osteogenesis

Chronic inflammation and oxidative stress at implant interfaces impair osseointegration, particularly in patients with systemic comorbidities. To address these challenges, we developed bioactive coatings by immobilizing high-density lipoprotein (HDL) onto poly(2-oxazoline) (POX) films prepared by plasma polymerization. Surface characterization confirmed stable immobilization of HDL. Functional assays revealed that the POX–HDL surfaces promoted macrophage polarization toward an anti-inflammatory, M2-like phenotype, characterized by reduced TNF-α and IL-6 expression, increased secretion of IL-10 and IL-13, and markedly lower reactive oxygen species production. Importantly, mesenchymal stem cells cultured on the POX–HDL surfaces exhibited enhanced osteogenic differentiation, demonstrated by elevated calcium deposition and upregulation of RUNX2, ALP, and COL1A1. Furthermore, macrophage-conditioned media collected from POX–HDL surfaces enhanced MSC mineralization, underscoring the dual, direct, and indirect immunomodulatory effects of these coatings. This study provides evidence that immobilizing HDL onto biomaterial surfaces can simultaneously regulate immune responses and stimulate bone regeneration. Such multifunctional coatings offer a promising strategy to enhance osseointegration and long-term implant success, especially in high-risk patient groups such as individuals with diabetes or cancer.