<i>In Situ</i> Printing of Adhesive Hydrogel Scaffolds for the Treatment of Skeletal Muscle Injuries

TLDR

Reconstructive surgery for volumetric muscle loss is limited by variable defect geometry and the time‑intensive imaging and printing required for 3D scaffolds, making immediate post‑traumatic interventions difficult. The study proposes printing gelatin‑based hydrogels directly into muscle defects and cross‑linking them in situ to enable rapid, geometry‑matched reconstruction. A handheld 3D printer deposits the gelatin‑based bioink into the defect and cross‑links it in situ. Ex vivo and in vitro tests confirmed the bioink’s adhesion to muscle and its suitability for cell delivery, while in vivo mouse studies showed acellular scaffolds adhered to defect sites and promoted muscle hypertrophy, demonstrating the handheld printer’s potential for rapid, precise defect filling.

Abstract

Reconstructive surgery remains inadequate for the treatment of volumetric muscle loss (VML). The geometry of skeletal muscle defects in VML injuries varies on a case-by-case basis. Three-dimensional (3D) printing has emerged as one strategy that enables the fabrication of scaffolds that match the geometry of the defect site. However, the time and facilities needed for imaging the defect site, processing to render computer models, and printing a suitable scaffold prevent immediate reconstructive interventions post-traumatic injuries. In addition, the proper implantation of hydrogel-based scaffolds, which have generated promising results in vitro, is a major challenge. To overcome these challenges, a paradigm is proposed in which gelatin-based hydrogels are printed directly into the defect area and cross-linked in situ. The adhesiveness of the bioink hydrogel to the skeletal muscles was assessed ex vivo. The suitability of the in situ printed bioink for the delivery of cells is successfully assessed in vitro. Acellular scaffolds are directly printed into the defect site of mice with VML injury, exhibiting proper adhesion to the surrounding tissue and promoting remnant skeletal muscle hypertrophy. The developed handheld printer capable of 3D in situ printing of adhesive scaffolds is a paradigm shift in the rapid yet precise filling of complex skeletal muscle tissue defects.