Recent advances in implantable biomaterials for the treatment of volumetric muscle loss.

Background: Volumetric muscle loss (VML) causes pain and disability in patients who sustain traumatic injury from invasive surgical procedures, vehicle accidents, and battlefield wounds. Clinical treatment of VML injuries is challenging and although options such as free-flap autologous grafting exist, patients inevitably develop excessive scarring and fatty infiltration, leading to muscle weakness and reduced quality of life.

Summary: New bioengineering approaches, including cell therapy, drug delivery, and biomaterial implantation, have emerged as therapies to restore muscle function and structure to pre-injury levels. Of these, acellular biomaterial implants have attracted wide interest owing to their broad potential design space and high translational potential as medical devices. Implantable biomaterials fill the VML defect and create a conduit that permits the migration of regenerative cells from intact muscle tissue to the injury site. Invading cells and regenerating myofibers are sensitive to the biomaterial's structural and biochemical properties, which can play instructive roles in guiding cell fate and organization into functional tissue.

Key messages: Many diverse biomaterials have been developed for skeletal muscle regeneration with variations in biophysical and biochemical properties and while many have been tested in vitro, few have proven their regenerative potential in clinically relevant in vivo models. Here, we provide an overview of recent advances in the design, fabrication, and application of acellular biomaterials made from synthetic or natural materials for the repair of VML defects. We specifically focus on biomaterials with rationally designed structural (i.e., porosity, topography, alignment) and biochemical (i.e., proteins, peptides, growth factors) components, highlighting their regenerative effects in clinically relevant VML models.