Pig skin-derived reconstituted lipid nanoparticles loaded sodium alginate hydrogel for wound healing

Chronic non-healing wounds pose a clinical burden, necessitating advanced dressings that modulate the healing microenvironment and accelerate tissue regeneration. Herein, we developed a hydrogel-based dressing by integrating pig skin-derived reconstituted lipid nanoparticles (PS-rLNPs) with FDA-approved sodium alginate (SA), termed PS-rLNPs-SA. PS-rLNPs were fabricated via a solvent injection method with lipids from fresh pig skin, which were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and liquid chromatography-mass spectrometry (LC-MS). PS-rLNPs exhibited uniform spherical morphology with hydrated particle size of 91.3 nm, excellent colloidal stability in physiological environments, and were mainly composed of triglycerides (77.9%) and phosphatidylcholine (11.6%)-lipids that synergistically support cell metabolism and membrane interaction. In vitro, PS-rLNPs promoted proliferation and migration of 3 T3 and L929 fibroblasts in a concentration-dependent manner (optimal at 300 μg/mL) without cytotoxicity, primarily via clathrin-mediated endocytosis and lysosomal escape. PS-rLNPs-SA hydrogel, prepared via in-situ calcium crosslinking, displayed shear-thinning behavior, injectability, and biocompatibility, enabling sustained release of PS-rLNPs at the wound site. In murine full-thickness skin defect model, PS-rLNPs-SA significantly accelerated wound closure (healing rate of 93.26% on Day 10), outperforming free PS-rLNPs and blank SA hydrogel. Histopathological and immunohistochemical analyses showed PS-rLNPs-SA enhanced regeneration, reduced inflammatory infiltration, promoted collagen deposition, and increased neovascularization (CD31⁺ vessels) and cell proliferation (Ki-67⁺ cells). Furthermore, in vitro hemolysis assays and in vivo major organ histology verified the biosafety of PS-rLNPs-SA. This work introduces promising natural lipid-based nanoplatform for wound repair, offering a novel strategy for developing clinically translatable wound dressings.