Reconstructive surgery remains inadequate for the treatment of volumetric muscle loss (VML). The geometry of skeletal muscle defects in VML injuries varies on a case-by-case basis. Three-dimensional (3D) printing has emerged as one strategy that enables the fabrication of scaffolds that match the geometry of the defect site. However, the time and facilities needed for imaging the defect site, processing to render computer models, and printing a suitable scaffold prevent immediate reconstructive interventions post-traumatic injuries. In addition, the proper implantation of hydrogel-based scaffolds, which have generated promising results in vitro, is a major challenge. To overcome these challenges, a paradigm is proposed in which gelatin-based hydrogels are printed directly into the defect area and cross-linked in situ. The adhesiveness of the bioink hydrogel to the skeletal muscles was assessed ex vivo. The suitability of the in situ printed bioink for the delivery of cells is successfully assessed in vitro. Acellular scaffolds are directly printed into the defect site of mice with VML injury, exhibiting proper adhesion to the surrounding tissue and promoting remnant skeletal muscle hypertrophy. The developed handheld printer capable of 3D in situ printing of adhesive scaffolds is a paradigm shift in the rapid yet precise filling of complex skeletal muscle tissue defects.
Engineering functional skeletal muscle tissue is an ongoing challenge because of the complexity of the in vivo microenvironment and the various factors that contribute to the development and maintenance of the native tissue. However, the growing understanding of the natural skeletal muscle's microenvironment in vivo, as well as the ability to successfully reproduce these factors in vitro, are contributing to the formation of engineered skeletal muscle tissues (SMTs) with greater biomimetic structure and function. This review first summarizes the structure of skeletal muscle tissue. The role of various hydrogels, biomaterials, and scaffolds as building blocks of complex skeletal muscle structures is then explored. Additionally, the role of external stimuli and regulators that can be applied during in vitro culture that lead to the formation of SMT models with higher functionality is examined. These include various physical, biochemical, electrical, mechanical, and magnetic stimulations, as well as biological stimulation through coculture with fibroblasts, endothelial, or neuronal cells. Finally, examples of recently developed functional tissue models that have been developed for in vitro and in vivo applications and the future outlook for this field are discussed.
This study reports the fabrication of highly porous electrospun self‐folding bilayers, which fold into tubular structures with excellent mechanical stability, allowing them to be easily manipulated and handled. Two kinds of bilayers based on biocompatible and biodegradable soft (PCL, polycaprolactone) and hard (PHB, poly‐hydroxybutyrate) thermoplastic polymers have been fabricated and compared. Multi‐scroll structures with tunable diameter are obtained after the shape transformation of the bilayer in aqueous media, where PCL‐based bilayer rolled longitudinally and PHB‐based one rolled transversely with respect to the fiber direction. A combination of higher elastic modulus and transverse orientation of fibers with respect to rolling direction allowed precise temporal control of shape transformation of PHB‐bilayer – stress produced by swollen methacrylated hyaluronic acid (HA‐MA) do not relax with time and folding is not affected by the fact that bilayer is fixed in unfolded state in cell culture medium for more than 1 h. This property of PHB‐bilayer allowed cell culturing without a negative effect on its shape transformation ability. Moreover, PHB‐based tubular structure demonstrated superior mechanical stability compared to PCL‐based ones and do not collapse during manipulations that happened to PCL‐based one. Additionally, PHB/HA‐MA bilayers showed superior biocompatibility, degradability, and long‐term stability compared to PCL/HA‐MA.
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