Ellagic acid-grafted carboxymethyl chitosan/graphene oxide-coated nanofibrous membrane for immunomodulatory periosteal regeneration

To enhance the clinical value of carboxymethyl chitosan (CMCS) as an osteogenic material, improving its bioactivity and mechanical strength is crucial. Meanwhile, ellagic acid (EA) has strong bioactivities but low bioavailability due to its hydrophobicity. In this study, by introducing EA units into CMCS molecules, a near-infrared (NIR) light-mediated nanofiber membrane based on polycaprolactone (PCL)/EA-CMCS blended nanofibers coated with an EA-CMCS/graphene oxide (GO) layer (PCL/EA-CMCS@EA-CMCS/GO) was designed. The bioactivity of CMCS and bioavailability of EA could be significantly improved by covalent coupling of EA with CMCS. Blending EA-CMCS with PCL significantly enhanced the mechanical properties of nanofiber membranes. The coated nanofibrous membrane featured a multi-level structure of coating and blending. By leveraging the photothermal conversion effect of GO, it enabled the programmed and sustained release of EA-CMCS from both the coating and the nanofibers. Moreover, the membrane exhibited excellent biomineralization and antioxidant capabilities. It effectively regulated macrophage polarization and promoted the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 osteoblasts. These properties enabled the membrane to regulate the harsh osteogenic immune microenvironment and promote bone regeneration. This biomimetic periosteum holds great potential as a substitute for periosteal grafts and offers a novel strategy for developing artificial periosteum.