Old and new biomarkers for volumetric muscle loss

Abstract

Volumetric muscle loss (VML) impacts skeletal muscles and causes damage to associated tissues such as blood vessels and other structural tissues. Despite progress in the VML field, current preclinical approaches are often ineffective at restoring muscle volume. Additional research is paramount to develop strategies that improve muscle mass and function, while restoring supporting tissues. We highlight mechanisms that govern normal muscle function that are also key players for VML, including intracellular calcium signaling/homeostasis, mitochondria signaling (calcium, reactiove oxidative species (ROS)/oxidative stress), and angiogenesis. We propose an integration of these processes within the context of emerging biomaterials that provide structural support for muscle regeneration. We posit that new biomarkers (i.e. myokines and lipid signaling mediators) may serve as sentinels of early muscle injury and regeneration. We conclude that as new ideas, approaches, and models come together, new treatments will emerge to allow the full rebuilding of skeletal muscles and functional recovery of skeletal muscles after VML.

Figure 1

Primary and secondary injuries during VML. In addition to skeletal muscle, nerves, tendons, bone, and blood vessels are all injured, impaired, or destroyed during initial injury, which further cause second injury in several ways. These pathological conditions in second injury have been observed in other muscle diseases.

Figure 2

Potential new biomarkers in VML tissue regeneration. During VML tissue regeneration, effective biomaterial and tissue engineering is essential for reconstruction of the complex functioning system, including skeletal muscles, bone, blood vessels, and nerves. New biomarkers can serve as sentinels of muscle injury and monitor the regeneration. Our understanding of cross talk between bone and muscle and the pathophysiological conditions in other muscle diseases will shed light to identify new biomarkers in VML.