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Opportunely arranged microscaled fibers offer an attractive 3D architecture for tissue regeneration as they may enhance and stimulate specific tissue regrowth. Among different scaffolding options, encapsulating cells in degradable hydrogel microfibers appears as particularly attractive strategy. Hydrogel patches, in fact, offer a highly hydrated environment, allow easy incorporation of biologically active molecules, and can easily adapt to implantation site. In addition, microfiber architecture is intrinsically porous and can improve mass transport, vascularization, and cell survival after grafting. Anionic polysaccharides, as pectin or the more popular alginate, represent a particularly promising choice for the fabrication of cell-laden patches, due to their extremely mild gelation in the presence of divalent ions and widely accepted biocompatibility. In this study, to combine the favorable properties of hydrogel and fibrous architecture, a simple coaxial flow wet-spinning system was used to prepare cell-laden, 3D fibrous patches using RGD-modified pectin. Rapid fabrication of coherent self-standing patches, with diameter in the range of 100-200 μm and high cell density, was possible by accurate choice of pectin and calcium ions concentrations. Cells were homogeneously dispersed throughout the microfibers and remained highly viable for up to 2 weeks, when the initial stage of myotubes formation was observed. Modified-pectin microfibers appear as promising scaffold to support muscle tissue regeneration, due to their inherent porosity, the favorable cell-material interaction, and the possibility to guide cell alignment toward a functional tissue., (© 2021 Wiley Periodicals LLC.)

Bioengineered functional muscle tissues are beneficial for regenerative medicine due to their treatment potential for various debilitating disorders, including myopathy and traumatic injuries. However, the contractile properties of engineered muscle constructs are lacking compared with their native counterparts. Here, we used microfluidic spinning to fabricate photocrosslinkable gelatin methacryloyl (GelMA) hydrogel fibres with well-defined surface morphologies for engineering muscle tissues. We examined whether the combination of topographical cues from surface micropatterning and biochemical stimulation with recombinant agrin can improve the generation of bioengineered muscle tissue. Topographical cues on micropatterned fibres promoted alignment of C2C12 myoblasts and augmented myotube formation during differentiation, as assessed by increased myotube length, aspect ratio, and the elevated mRNA expression of myogenic genes. Moreover, agrin treatment significantly increased acetylcholine receptor expression/clustering and myotube formation and upregulated dystrophin expression in differentiated C2C12 myotubes. Interestingly, the combination of topographical cues with agrin treatment further enhanced myotube maturation and functionality as shown by improved contractility under electrical stimulation. Thus, combining topographical cues and agrin treatment improved functions of engineered muscle tissue, which has potential in biorobotics, drug screening, tissue engineering, and regenerative medicine., (© 2018 John Wiley & Sons, Ltd.)

The availability of three-dimensional bioactive scaffolds with enhanced angiogenic capacity that have the capability to recruit tissue specific resident progenitors is of great importance for the regeneration of impaired skeletal muscle. Here, we have investigated whether introduction of chemoattractant factors to tissue specific extracellular matrix promotes cellular behaviour in vitro as well as muscle progenitor recruitment and vascularization in vivo. We developed an interconnective macroporous sponge from decellularized skeletal muscle with maintained biochemical traits of the intact muscle. SDF-1α, a potent cell homing factor involved in muscle repair, was physically adsorbed or chemically immobilized in these muscle-derived sponges. The immobilized sponges showed significantly higher SDF-1α conjugation efficiency along with improved metabolism and infiltration of muscle-derived stem cells in vitro, and thus generated uniform cellular constructs. In vivo, femoral muscle implantation in rats revealed a negligible immune response in all scaffold groups. We observed enhanced engraftment, neovascularization, and infiltration of CXCR4 + cells in the immobilized-SDF-1α sponge compared with nonimmobilized controls. Although Pax7 + cells identified adjacent to the immobilized-SDF-1α implantation site, other factors appear to be necessary for efficient penetration of Pax7 + cells into the sponge. These findings suggest that immobilization of cell homing factors via chemical mediators can result in recruitment of cells to the microenvironment with subsequent improvement in angiogenesis., (Copyright © 2017 John Wiley & Sons, Ltd.)