Development and Evaluation of a Novel Hyaluronic Acid-Based Biomaterial System, MuscleMatrix™, for Repair of Craniofacial and Extremity Volumetric Muscle Loss Injuries 4 views

Volumetric muscle loss (VML) is a devastating injury resulting from traumatic or surgical loss of skeletal muscle, leading to muscle weakness, impaired function, and long-term disability. Unlike many other forms of muscle injury, VML injuries are unable to regenerate via intrinsic mechanisms. Despite the clinical significance of this problem, as VML impacts both military and civilian populations, there are currently no treatments that fully restore muscle form and function after injury. This dissertation addresses this unmet need through utilization of biologically relevant experimental models of VML and application of rigorous cell- and tissue-level metrics to improve understanding of the pathophysiology of VML injury as well as the therapeutic potential of a novel hyaluronic acid-based biomaterial system: MuscleMatrix™ (MM). Two formulations of this biomaterial—hydrogel (MM-h) and cryogel (MM-c)—were tested across multiple preclinical models in the Lewis rat to explore how injury location, time, and biomaterial design influence muscle regeneration. Long-term functional recovery (3–6 months) was investigated in well-established hindlimb VML models of the tibialis anterior and gastrocnemius muscles. This work also developed a novel craniofacial VML model in the masseter muscle alongside a method for functional evaluation of the jaw. In addition to these long-term studies, early wound healing mechanisms (1–4 weeks) were characterized through histological analyses, providing insights into the cellular and tissue-level processes that underlie repair. Rather than focusing on biomaterial synthesis, the emphasis of this work is placed on elucidating the biological, biomechanical, and translational principles essential for developing effective therapeutics. The overarching goal of this dissertation is to deepen our understanding of VML injury and repair in order to better guide the creation of next-generation regenerative biomaterials capable of restoring muscle structure and function.

PHD (Doctor of Philosophy)

volumetric muscle loss; hyaluronic acid; tissue engineering; regenerative medicine; hydrogel; biomaterials

English

2025-12-01