A “Frost Formation”-Inspired Near-Infrared Responsive Nitric Oxide Releasing Hydrogel for Enhancing Fat Graft Survival

Abstract Soft tissue defects represent a major challenge in plastic surgery, for which autologous fat grafting remains the standard treatment. However, in the early post-transplant period, the grafted fat tissue undergoes ischemia and hypoxia, leading to low and markedly unpredictable survival rates that consequently compromise the aesthetic outcomes. Nitric oxide (NO), an endogenous gasotransmitter, play a vital role in mediating angiogenesis and vascular remodeling. Therefore, we developed a near-infrared (NIR)-responsive hydrogel that releases NO on demand to promote adipocytes vascularization and thereby improve graft retention and enable precise volumetric filling. To ensure high-filling, the platform incorporates a photosensitive Gelatin Methacryloyl (GelMA) hydrogel inspired by the rapid solidification of “Frost Formation”. The hydrogel can be precisely delivered to the target area and photocrosslinked in situ to form a three-dimensional network that supports cell growth. Notably, this photocrosslinking process does not require ultraviolet (UV) irradiation, thereby eliminating the associated risks and significantly greatly enhancing the safety of adipose remodeling and filling technologies. Experimental studies conducted both in vitro and in vivo have validated that this hydrogel platform ensures precise grafting, promotes graft integration, and significantly improves the long-term survival of transplanted adipose tissue.