Abstract
Given the increasing use of regenerative free muscle flaps for various reconstructive procedures and neuroprosthetic applications, there is great interest and value in their enhanced regeneration, revascularization, and reinnervation for improved functional recovery. Here, we implant polyimide-based mircroelectrodes on free flap grafts and perform electrical stimulation for 6 weeks in a murine model. Using electrophysiological and histological assessments, we compare outcomes of stimulated grafts with unstimulated control grafts. We find delayed reinnervation and abnormal electromyographic (EMG) signals, with significantly more polyphasia, lower compound muscle action potentials and higher fatigability in stimulated animals. These metrics are suggestive of myopathy in the free flap grafts stimulated with the electrode. Additionally, active inflammatory processes and partial necrosis are observed in grafts stimulated with the implanted electrode. The results suggest that under this treatment protocol, implanted epimysial electrodes and electrical stimulation to deinnervated, and devascularized flaps during the early recovery phase may be detrimental to regeneration. Future work should determine the optimal implantation and stimulation window for accelerating free muscle graft regeneration.
Highlights
Peripheral nerve regeneration is a promising and important area of clinical development and plays an integral role in the functionality of reinnervated organs [1,2,3]
Based on the volume of evidence documenting mechanisms that promote both nerve and muscle regeneration, we investigate the use of chronic Functional electrical stimulation (FES) to promote regeneration, reinnervation, and revascularization of regenerative muscle grafts
We explore the effect of chronic stimulation via a PI-based epimysial electrode on the regeneration, reinnervation, and revascularization of a regenerative free muscle graft that is neurotized during surgery to form a peripheral nerve interface (Figure 1A)
Summary
Peripheral nerve regeneration is a promising and important area of clinical development and plays an integral role in the functionality of reinnervated organs [1,2,3]. Over time, implanted devices may become isolated within a thick fibrotic capsule, drastically reducing the functional capabilities of electrical signal transfer for both stimulation and recording [38] For applications such as those in the field of neuroprostheses, inflammation caused by the foreign body response can preclude the required longevity [39]. This polyimide film-based electrode platform has been successfully used in prior studies for stimulating neuromuscular tissues without any major biocompatibility or foreign body concerns [42] In this murine study, we explore the effect of chronic stimulation via a PI-based epimysial electrode on the regeneration, reinnervation, and revascularization of a regenerative free muscle graft (deinnervated and devascularized) that is neurotized during surgery to form a peripheral nerve interface (Figure 1A). We compared these to established cases in which no electrode was implanted
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