Engineered Regenerative Isolated Peripheral Nerve Interface for Targeted Reinnervation

초록

A regenerative peripheral nerve interface (RPNI) offers a therapeutic solution for nerve injury through reconstruction of the target muscle. However, implanting a transected peripheral nerve into an autologous skeletal muscle graft in RPNI causes donor-site morbidity, highlighting the need for tissue-engineered skeletal muscle constructs. Here, an engineered regenerative isolated peripheral nerve interface (eRIPEN) is developed using 3D skeletal cell printing combined with direct electrospinning to create a nanofiber membrane envelop for host nerve implantation. In this in vivo study, after over 8 months of RPNI surgery, the eRIPEN exhibits a minimum Feret diameter of 15-20 mu m with a cross-sectional area of 100-500 mu m2, representing the largest distribution of myofibers. Furthermore, neuromuscular junction formation and muscle contraction with a force of approximate to 28 N are observed. Notably, the decreased hypersensitivity to mechanical/thermal stimuli and an improved tibial functional index from -77 to -56 are found in the eRIPEN group. The present novel concept of eRIPEN paves the way for the utilization and application of tissue-engineered constructs in RPNI, ultimately realizing neuroprosthesis control through synaptic connections. An engineered regenerative isolated peripheral nerve interface (eRIPEN) is developed using 3D bioprinting of myoblasts and skeletal-muscle-derived decellularized extracellular matrix bioink, along with direct electrospinning to create a nanofiber membrane envelope for in vivo host nerve implantation. After regenerative peripheral nerve interface (RPNI) surgery, the eRIPEN demonstrates long-term contractility for skeletal muscle tissue and positive effect on pain alleviation through innervation. image

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