From scrawny to brawny: the quest for neomusculogenesis; smart surfaces and scaffolds for muscle tissue engineering

The successful generation of functional muscle tissues requires both an in-depth knowledge of muscle tissue physiology and advanced engineering practices. The inherent contractile functionality of muscle is a result of its high-level cellular and matrix organization over a multitude of length scales. While there have been many attempts to produce artificial muscle, a method to fabricate a highly organized construct, comprised of multiple cell types and capable of delivering contractile strengths similar to that of native smooth, skeletal or cardiac muscle has remained elusive. This is largely due to a lack of control over phenotype and spatial organization of cells. This paper covers state-of-the-art approaches to generating both 2D and 3D substrates that provide some form of higher level organization or multiple biochemical, mechanical or electrical cues to cells in order to successfully manipulate their behavior, in a manner that is conducive to the production of contractile muscle tissue. These so-called 'smart surfaces' and 'smart scaffolds' represent vital steps towards surface-engineered substrates for the engineering of muscle tissues, showing confidently that cellular behavior can be effectively and reproducibly manipulated through the design of the physical, chemical and electrical properties of the substrates on which cells are grown. However, many challenges remain to be overcome prior to reaching the ultimate goal of fully functional 3D vascularized engineered muscle.