Biomimetic macroporous hydrogel with a triple-network structure for full-thickness skin regeneration

Abstract

Full-thickness skin repair is still a challenge in clinical practice because it is extremely difficult for dermal reconstruction and calls for a promising strategy to achieve quick sutureless closure and high-quality dermal restoration for large acute skin defects. Inspired by the unique composition, mechanical properties and microscopic architecture of skin tissue, a novel biomimetic hydrogel with a triple-network structure that mimics the extracellular matrix (ECM) composition has been reported. A composite biomimetic hydrogel was prepared using ECM-derived biopolymers, gelatin methacryloyl (GelMA) and N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2‑methoxy-5-nitro-sophenoxy) butanamide (NB)-linked sodium alginate (Alg-NB) and the photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). This biomimetic hydrogel can undergo rapid gelling under UV irradiation (approximately 3 s), has strong mechanical properties (mechanical strength ≈530 kPa) with UV-ionic-crosslinking, and shows strong adhesion to wet tissue. In vitro two-dimensional culture of human skin fibroblasts (HSFs) confirmed that the biomimetic hydrogel has excellent biocompatibility, and HSFs on the surface grow into cell clusters because of the macroporous structures of the hydrogel (pore diameter ≈160 μm). The subcutaneous implantation of the biomimetic hydrogel in Sprague-Dawley (SD) rats confirmed its biocompatibility and low biodegradation in vivo. Moreover, in an SD rat full-thickness skin defect model, this engineered biomimetic hydrogel not only could be used for sutureless wound closure strategies but also could accelerate the reconstitution of dermal tissue with skin appendages. This study provides an effective strategy of quick sutureless wound closure and highly efficient repair for full-thickness skin defects and shows enormous potential for tissue regeneration in clinical applications.