He, X.; Luo, Z.; He, S.

Functional regeneration of volumetric muscle loss (VML) remains a significant challenge in the field of regenerative medicine. We have developed a novel biomimetic scaffold (0.4 mm thick hernia patch) derived from soluble collagen. This biomimetic scaffold exhibits exceptional strength, low immunogenicity, and structurally mimics the natural muscle fiber arrangement. The scaffold is utilized to repair a VML rabbit model (30 x 30 mm defect in abdominal wall) using nylon sutures for connection. It was observed that the VML site was gradually covered by regenerated tissue, which consisted of 2-3 mm thick functional muscle. By 32 weeks post-surgery, the newly formed muscle tissue had covered the majority of the VML area, as evidenced by morphological observations and histological evaluations. Approximately 24 weeks after surgery, the scaffold underwent complete degradation. This degradation exhibited a strong correlation with muscle regeneration. Furthermore, it was observed that the nylon sutures gradually migrated towards the VML center as muscle regeneration progressed, and nylon sutures exhibited an adverse impact on muscle regeneration. The study did not employ exogenous cells or growth factors. However, the collagen scaffold effectively stimulated endogenous muscle regeneration. In contrast to the previous limited partial recovery or fibrotic scar healing, the collagen scaffold successfully induced genuine structural and functional muscle regeneration. The 0.4 mm thick scaffold (hernia patch) exhibits a different structure from the 2-3 mm thick natural abdominal muscle wall. This suggests that a simple scaffold can regenerate functional tissue with a complex structure. This research represents the first successful functional regeneration of VML in clinically relevant animal models through the utilization of artificial materials. This technology possesses transformative potential in the treatment of muscle defects arising from trauma, tumor resection, hernia, or congenital anomalies. Furthermore, it holds substantial medical potentials in addressing neuromuscular diseases, such as Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA), by collaborating with advanced technologies including CRISPR-Cas9, adeno-associated virus (AAV) gene therapy, and stem cell technology.