Preparation of fibroblast growth factor 2-incorporated carboxymethyl cellulose nanoparticles for tissue repair and regeneration

Fibroblast growth factor 2 (FGF-2) is a protein that plays an important role in the skin wound healing process. However, the biomedical application of this protein has some limitations due to its instability. To address this problem, this study developed carboxymethyl cellulose (CMC) nanoparticles (NPs) as a nano-carrier for FGF-2 encapsulation and stabilization to improve the bioavailability of this therapeutic protein. Using aluminum chloride (AlCl₃) as a cross-linking agent, sphere-shaped CMC NPs were successfully created with a size of 85.60 ± 12.15 nm and no cytotoxicity on NIH/3T3 cell line. In FGF-2 encapsulation, the pre-gelation FGF-2 concentration at 50 μg/mL resulted in the highest FGF-2 loading efficiency at over 90%. FGF-2-incorporated CMC NPs (CMC:FGF-2 NPs) exhibited the same size (88.06 ± 13.51 nm) with CMC NPs, release rates at approximately 30% in aqueous solution after 48 h, preservation of FGF-2 biological activity on NIH/3T3 cell line, and FGF-2 protection from protease hydrolytic action. In burn treatment on mice, CMC:FGF-2 NPs displayed an acceleration of wound closure, growth of granulation tissue, re-epithelialization, and angiogenesis compared to CMC NPs and naked FGF-2. Collectively, this study was a groundwork for the further clinical study of CMC:FGF-2 NPs in burn treatment.