We tested the hypothesis that denervated muscle fibers account for part of the specific force (sF_o) deficit observed in muscles from old adult (OA) mammals. Whole muscle force (F_o) was quantified for extensor digitorum longus (EDL) muscles of OA and young adult (YA) rats. EDL muscle sF_o was calculated by dividing F_o by either total muscle fiber cross-sectional area (CSA) or by innervated fiber CSA. Innervated fiber CSA was estimated from EDL muscle cross sections labeled for neural cell adhesion molecules, whose presence is a marker for muscle fiber denervation. EDL muscles from OA rats contained significantly more denervated fibers than muscles from YA rats (5.6% vs 1.1% of total CSA). When compared with YA muscle, OA muscle demonstrated deficits of 34.1% for F_o, 28.3% for sF_o, and 24.9% for sF_o calculated by using innervated CSA as the denominator. Denervated muscle fibers accounted for 11.3% of the specific force difference between normal YA and OA skeletal muscle. Other mechanisms in addition to denervation account for the majority of the sF_o deficit with aging.

Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation.Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n=25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry.Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs.Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation.

Objective. Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. Approach. Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. Main Results. Raw RPNI signals were active during walking, with amplitudes of 1 mV _PP , and quiet during standing, with amplitudes less than 0.1 mV _PP . RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. Significance. In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control.

Introduction: This review summarizes current understanding about the role of adipose‐derived tissues in peripheral nerve regeneration and discusses potential advances that would translate this approach into the clinic.Methods: We searched PubMed for in vivo, experimental studies on the regenerative effects of adipose‐derived tissues on peripheral nerve injuries. We summarized the methods and results for the 42 experiments.Results: Adipose‐derived tissues enhanced peripheral nerve regeneration in 86% of the experiments. Ninety‐five percent evaluated purified, cultured, or differentiated adipose tissue. These approaches have regulatory and scaling burdens, restricting clinical usage. Only one experiment tested the ability of adipose tissue to enhance nerve regeneration in conjunction with nerve autografts, the clinical gold standard.Conclusion: Scientific studies illustrate that adipose‐derived tissues enhance regeneration of peripheral nerves. Before this approach achieves clinical acceptance, fat processing must become automated and regulatory approval achieved. Animal studies using whole fat grafts are greatly needed for clinical translation. © 2015 Wiley Periodicals, Inc. Microsurgery 36:81–88, 2016.

Background: The goal of the authors is to restore fine motor control and sensation for high-arm amputees. They developed a regenerative peripheral nerve interface with the aim of attaining closed loop neural control by integrating directly with the amputee's residual motor and sensory peripheral nerves. PEDOT, poly(3,4-ethylenedioxythiophene), has both electrical and ionic conduction characteristics. This hybrid character could help bridge the salutatory conduction of the nervous system to an electrode. The purpose of this study was to determine whether electrodes polymerized with PEDOT have improved ability to both record and stimulate peripheral nerve action potentials. Methods: Impedance spectroscopy and cyclic voltammetry were performed on electrodes before and after polymerization to measure electrode impedance and charge capacity. Both recording needle and bipolar stimulating electrodes were polymerized with PEDOT. Plain and PEDOT electrodes were tested using rat (n = 18) in situ nerve conduction studies. The peroneal nerve was stimulated using a bipolar electrode at multiple locations along the nerve. Action potentials were measured in the extensor digitorum longus muscle. Results: Bench testing showed PEDOT electrodes had a higher charge capacity and lower impedance than plain electrodes, indicating significantly improved electrode fidelity. Nerve conduction testing indicated a significant reduction in the stimulus threshold for both PEDOT recording and PEDOT stimulatory electrodes when compared with plain electrodes, indicating an increase in sensitivity. Conclusions: PEDOT electrochemical polymerization improves electrode fidelity. Electrodes that have been electropolymerized with PEDOT show improved sensitivity when recording or stimulating action potentials at the tissue–electrode interface.