A compartmentalized hyaluronic acid/PHB core–shell scaffold for differential delivery of curcumin and amniotic membrane-derived bioactive factors: Immunomodulatory and endothelial responses invitro

Chronic wounds remain a major clinical challenge due to prolonged inflammation, oxidative stress, and impaired tissue regeneration. In this study, a coaxial electrospun nanofibrous scaffold was developed for the compartmentalized delivery of curcumin (Cur) and amniotic membrane extract (AME) using a hyaluronic acid (HA) core and poly(3-hydroxybutyrate) (PHB) shell architecture, referred to as HPCA. The designed core–shell structure enabled spatial separation of hydrophilic and hydrophobic bioactive components and provided distinct release behaviors for AME and Cur. The developed HPCA scaffolds exhibited favorable physicochemical characteristics, including appropriate nanofibrous morphology, enhanced surface hydrophilicity after bioactive incorporation, and sustained release profiles. Biological evaluations demonstrated that the HPCA scaffold improved fibroblast viability and proliferation compared with non-loaded and single-loaded formulations. Moreover, HPCA regulated macrophage inflammatory responses by reducing pro-inflammatory cytokine expression and enhancing anti-inflammatory responses. The scaffold also promoted endothelial cell organization and vascular-like network formation, indicating improved angiogenic potential. Overall, the combination of HA-mediated hydration, PHB-based structural support, and compartmentalized delivery of Cur and AME created a favorable regenerative microenvironment for chronic wound treatment. The developed HPCA coaxial electrospun platform provides a multifunctional strategy integrating controlled bioactive delivery, immunomodulatory regulation, and angiogenesis promotion.