Mechanically Induced Damage in Tissue Engineered Skeletal Muscle

INTRODUCTION Engineered tissues offer strong possibilities as model systems for studying tissue responses to physical, chemical or biological stimuli. Moreover, they can be used to investigate specific pathologies or clinical treatments with less ethical considerations and better experimental control than animal models or human studies. We use the concept of tissue engineering to design in-vitro models for studying the etiology and prevention of mechanically induced damage in skeletal muscle, as is common in pressure sores. Previous studies have demonstrated that skeletal muscle is highly susceptible to sustained compression, leading to tissue breakdown within 2 h of straining [1]. This breakdown starts at the cellular level with disintegration of contractile proteins and damage to the cell membrane and nucleus, followed by inflammatory reactions [2]. Although it is clear that both the duration and magnitude of compression affect cellular breakdown, the mechanobiological pathways whereby tissue compression leads to cell damage are poorly understood. Theories focusing on impaired oxygen transport and metabolism within the tissue can only partly explain the onset of pressure sores and have to date not been fully verified. Recently, we demonstrated that sustained deformation of the cells inside the tissue is an additional trigger for muscle breakdown [3]. Using a hierarchy of complementary model systems, ranging from single cells to animal models, we aim to elucidate the multi-factorial etiology of pressure sore related muscle damage. The present study employs tissue engineered skeletal muscle to investigate the relationship between gross tissue compression and cell damage.