Vascularization of tissue-engineered skeletal muscle constructs.

Skeletal muscle tissue can be created in vitro by tissue engineering approaches, based on differentiation of muscle stem cells. Several approaches exist and generally result in three dimensional constructs composed of multinucleated myofibers to which we refer as myooids. Engineering methods date back to 3 decades ago and meanwhile a wide range of cell types and scaffold types have been evaluated. Nevertheless, in most approaches, myooids remain very small to allow for diffusion-mediated nutrient supply and waste product removal, typically less than 1 mm thick. One of the shortcomings of current in vitro skeletal muscle organoid development is the lack of a functional vascular structure, thus limiting the size of myooids. This is a challenge which is nowadays applicable to almost all organoid systems. Several approaches to obtain a vascular structure within myooids have been proposed. The purpose of this review is to give a concise overview of these approaches.