Mesoporous Silica-Loaded PCL-CHT Hybrid Membranes for Skin Regeneration

An innovative multifunctional membrane, combining polymeric materials with inorganic nanoparticles and bioactive molecules, was developed for skin tissue application. The strategy was to synthesize a hybrid polymeric/silica membrane in which SiO₂ nanoparticles are dispersed inside the membrane matrix. To this end, hexagonal calcined mesoporous silica nanoparticles (MSNs) with a uniform structure, 187.6 ± 4.6 nm diameter, and 5.1 nm pore size were synthesized to accommodate molecules of pharmaceutical interest in the silica mesopores. MSNs were then loaded with daidzein, a prominent isoflavone well-known for its anti-inflammatory, antioxidant, and antidiabetic activity, through chemical-physical interactions to investigate its role as a drug carrier. The hybrid membranes were created by combining chitosan (CHT) and polycaprolactone (PCL) polymers with mesoporous silica nanoparticles, optimizing the polymer-to-silica molar ratio up to 5:1, for which enhanced hydrophilicity (WCA = 55.5 ± 2.9°), moisture permeability (WVTR = 32.2 ± 4.4 g/m²·h), and swelling capacity (68 ± 11%) were achieved. Drug release studies on the hybrid membrane incorporating daidzein-preloaded silica confirmed sustained delivery of the active compound, releasing 88.9 ± 0.9 μM/cm² after 48 hours. The physical-chemical and morphological-structural properties of the membranes favored the adhesion and growth of human keratinocytes, providing biomimetic cues to facilitate epidermal maturation. In the developed epidermal models, oxygen consumption, which is representative of an active cellular metabolic state, rises over time, leveling off at day 7. The highest oxygen uptake activity was observed in the hybrid membrane PCL-CHT/MSN, achieving values of 161 ± 3 μmol/L at day 11. Hybrid epidermal-membrane constructs enhance keratinocyte proliferation and differentiation, as evidenced by specific cytokeratins, matrix metalloproteinases, and cyclin D1 expression, suggesting improved stratification and epidermal remodeling.