Fish Skin-Derived Acellular Matrix with pH-Modulating Nanogels for Wound Healing

Fish skin-derived acellular dermal matrices (FS-ADMs) are promising wound dressings due to their low zoonotic risk and minimal chemical processing. This study investigated the combined effects of pH modulation as a chemical intervention and FS-ADM as a physical scaffold on wound healing. Carp skin was selected for its favorable lipid composition and high exudate absorption capacity.

Hyaluronic acid (HA)-based nanogels composed of HA and L-lysine, with or without tannic acid (TA), were synthesized and characterized using FTIR spectroscopy and light scattering. Full-thickness excisional wounds were created in 30 Wistar rats and evaluated over 21 days for re-epithelialization, collagen organization, neovascularization, inflammation, and appendage regeneration. Animals were divided into five groups: negative control, FS-ADM alone (SC), FS-ADM with HA nanogel (SC+NC), and FS-ADM with two TA-loaded HA nanogel formulations (SC+NP1 and SC+NP2). Data were analyzed using GraphPad Prism 9.0.

The nanogels exhibited sustained acidifying behavior, reducing pH by approximately 1.5 units over seven days in vitro. Degradation studies showed scaffold breakdown of 37% within three days and 60% by day 21, indicating suitable biodegradation kinetics. Medicated FS-ADMs demonstrated excellent biocompatibility, maintaining 96% L929 fibroblast viability. The SC+NC group exhibited the most effective healing (9.67±0.58), achieving complete epithelialization, organized collagen deposition, and sebaceous gland regeneration by day 21. The SC+NP2 group also showed substantial healing, including hair follicle regeneration. HA nanogel without TA outperformed TA-loaded systems, suggesting a dominant role of HA in enhancing tissue repair.

Combining FS-ADM with pH-modulating nanogels significantly accelerates wound healing through sustained acidification and represents a promising strategy for chronic wounds such as diabetic ulcers.