Prevascularized Hydrogel Enhancing Innervation and Repair of Full‐Thickness Volumetric Muscle Loss in Abdominal Wall Defects

Implant degradation rate is more crucial than vascular density for muscle repair in abdominal wall volumetric muscle loss (VML). Fast-degrading gelatin hydrogels with adequate vessel density (51.2 ± 16 vessels mm^{− 2}) achieve 70% repair of 55% VML defects in one month. By contrast, slower-degrading implants result in only 50% repair despite higher vascular density, highlighting the key importance of degradation rate over vascular density.

Abstract

Current materials for repairing abdominal peritoneal defects face rapid degradation, infection risk, insufficient vascular ingrowth, slow muscle regeneration, and suboptimal postoperative integration, often causing fibrotic healing and hindering volumetric muscle loss (VML) repair exceeding 30%. To address these issues, photo-cross-linkable gelatin hydrogels are combined with blood vessel–forming cells to reconstruct vascular networks, providing temporary nutrient and gas channels that support cell repair. By developing a polymer-chain propagation time technique, hydrogel properties are optimized, avoiding limitations of conventional light exposure. These gels guide blood-vessel formation in vitro and promote robust microvessel and neural development in vivo. Precise control of light exposure and propagation times balances cross-linking and degradation, fostering blood vessel growth and host motor neuron ingrowth. In 55% VML, these hydrogels enable full-thickness abdominal muscle regeneration, restoring up to 70% of lost muscle while mimicking healthy tissue's strength and structure. Achieving higher degradation rates and a vascular density exceeding 50 vessels/mm⁻² is essential for functional muscle repair. These strategies effectively bridge current clinical gaps, advancing regenerative medicine. The ability to fine-tune degradation and stiffness underscores gelatin hydrogels' potential as cell carriers, allowing the reconstruction of temporary vascular and neural channels at injury sites and significantly enhancing muscle tissue regeneration.