Matured Myofibers in Bioprinted Constructs with In Vivo Vascularization and Innervation.

For decades, the study of tissue-engineered skeletal muscle has been driven by a clinical need to treat neuromuscular diseases and volumetric muscle loss. The in vitro fabrication of muscle offers the opportunity to test drug-and cell-based therapies, to study disease processes, and to perhaps, one day, serve as a muscle graft for reconstructive surgery. This study developed a biofabrication technique to engineer muscle for research and clinical applications. A bioprinting protocol was established to deliver primary mouse myoblasts in a gelatin methacryloyl (GelMA) bioink, which was implanted in an in vivo chamber in a nude rat model. For the first time, this work demonstrated the phenomenon of myoblast migration through the bioprinted GelMA scaffold with cells spontaneously forming fibers on the surface of the material. This enabled advanced maturation and facilitated the connection between incoming vessels and nerve axons in vivo without the hindrance of a scaffold material. Immunohistochemistry revealed the hallmarks of tissue maturity with sarcomeric striations and peripherally placed nuclei in the organized bundles of muscle fibers. Such engineered muscle autografts could, with further structural development, eventually be used for surgical reconstructive purposes while the methodology presented here specifically has wide applications for in vitro and in vivo neuromuscular function and disease modelling.

Strategies for neural control of prosthetic limbs: from electrode interfacing to 3D printing.

Limb amputation is a major cause of disability in our community, for which motorised prosthetic devices offer a return to function and independence. With the commercialisation and increasing availability of advanced motorised prosthetic technologies, there is a consumer need and clinical drive for intuitive user control. In this context, rapid additive fabrication/prototyping capacities and biofabrication protocols embrace a highly-personalised medicine doctrine that marries specific patient biology and anatomy to high-end prosthetic design, manufacture and functionality. Commercially-available prosthetic models utilise surface electrodes that are limited by their disconnect between mind and device. As such, alternative strategies of mind-prosthetic interfacing have been explored to purposefully drive the prosthetic limb. This review investigates mind to machine interfacing strategies, with a focus on the biological challenges of long-term harnessing of the user's cerebral commands to drive actuation/movement in electronic prostheses. It covers the limitations of skin, peripheral nerve and brain interfacing electrodes, and in particular the challenges of minimising the foreign-body response, as well as a new strategy of grafting muscle onto residual peripheral nerves. In conjunction, this review also investigates the applicability of additive tissue engineering at the nerve-electrode boundary, which has led to pioneering work in neural regeneration and bioelectrode development for applications at the neuroprosthetic interface.