In Situ Polymerization of a Conductive Polymer in Acellular Muscle Tissue Constructs

We present a method to chemically deposit a conductive polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), on acellularized muscle tissue constructs. Morphology and structure of the deposition was characterized using optical and scanning electron microscopies (SEM). The micrographs showed elongated, smooth, tubular PEDOT structures completely penetrating and surrounding the tissue fibers. The chemical polymerization was performed using iron chloride, a mild oxidizer. Remaining iron and chlorine in the tissue constructs were reduced to acceptable metabolic levels, while preserving the structural integrity of the tissue. We expect that these acellular, polymerized tissue implants will remain essentially unmodified in cellular environments in vitro and in vivo because of the chemical and thermal stability of the PEDOT polymer depositions. Our results indicate that in situ polymerization occurs throughout the tissue, converting it into an extensive acellular, non-antigenic substrate of interest for in vivo experiments related to nerve repair and bioartificial prosthesis. We expect these conducting polymer scaffolds to be useful for direct integration with electronically and ionically active tissues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63276/1/tea.2007.0123.pd

Regenerative peripheral nerve interfaces for real-time, proportional control of a Neuroprosthetic hand

Abstract Introduction Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. Methods Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. Results Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). Conclusion EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.https://deepblue.lib.umich.edu/bitstream/2027.42/146521/1/12984_2018_Article_452.pd

Dermal Sensory Regenerative Peripheral Nerve Interface for Reestablishing Sensory Nerve Feedback in Peripheral Afferents in the Rat

Background: Without meaningful, intuitive sensory feedback, even the most advanced myoelectric devices require significant cognitive demand to control. The dermal sensory regenerative peripheral nerve interface (DS-RPNI) is a biological interface designed to establish high-fidelity sensory feedback from prosthetic limbs. Methods: DS-RPNIs were constructed in rats by securing fascicles of residual sensory peripheral nerves into autologous dermal grafts, with the objectives of confirming regeneration of sensory afferents within DS-RPNIs and establishing the reliability of afferent neural response generation with either mechanical or electrical stimulation. Results: Two months after implantation, DS-RPNIs were healthy and displayed well-vascularized dermis with organized axonal collaterals throughout and no evidence of neuroma. Electrophysiologic signals were recorded proximal from DS-RPNI's sural nerve in response to both mechanical and electrical stimuli and compared with (1) full-thickness skin, (2) deepithelialized skin, and (3) transected sural nerves without DS-RPNI. Mechanical indentation of DS-RPNIs evoked compound sensory nerve action potentials (CSNAPs) that were like those evoked during indentation of full-thickness skin. CSNAP firing rates and waveform amplitudes increased in a graded fashion with increased mechanical indentation. Electrical stimuli delivered to DS-RPNIs reliably elicited CSNAPs at low current thresholds, and CSNAPs gradually increased in amplitude with increasing stimulation current. Conclusions: These findings suggest that afferent nerve fibers successfully reinnervate DS-RPNIs, and that graded stimuli applied to DS-RPNIs produce proximal sensory afferent responses similar to those evoked from normal skin. This confirmation of graded afferent signal transduction through DS-RPNI neural interfaces validate DS-RPNI's potential role of facilitating sensation in human-machine interfacing. Clinical Relevance Statement: The DS-RPNI is a novel biotic-abiotic neural interface that allows for transduction of sensory stimuli into neural signals. It is expected to advance the restoration of natural sensation and development of sensorimotor control in prosthetics.</p

Neural Tissue Engineering: Hybrid Conducting Polymer–Hydrogel Conduits for Axonal Growth and Neural Tissue Engineering (Adv. Healthcare Mater. 6/2012)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94249/1/11110_ftp.pd

Development of a Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb

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

Regenerative peripheral nerve interface free muscle graft mass and function

BackgroundRegenerative peripheral nerve interfaces (RPNIs) transduce neural signals to provide high‐fidelity control of neuroprosthetic devices. Traditionally, rat RPNIs are constructed with ~150 mg of free skeletal muscle grafts. It is unknown whether larger free muscle grafts allow RPNIs to transduce greater signal.MethodsRPNIs were constructed by securing skeletal muscle grafts of various masses (150, 300, 600, or 1200 mg) to the divided peroneal nerve. In the control group, the peroneal nerve was transected without repair. Endpoint assessments were conducted 3 mo postoperatively.ResultsCompound muscle action potentials (CMAPs), maximum tetanic isometric force, and specific muscle force were significantly higher for both the 150 and 300 mg RPNI groups compared to the 600 and 1200 mg RPNIs. Larger RPNI muscle groups contained central areas lacking regenerated muscle fibers.ConclusionsElectrical signaling and tissue viability are optimal in smaller as opposed to larger RPNI constructs in a rat model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166376/1/mus27138.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166376/2/mus27138_am.pd

Incisional Herniation Induces Decreased Abdominal Wall Compliance via Oblique Muscle Atrophy and Fibrosis

OBJECTIVE: The purpose of this study is to measure abdominal wall myopathic histologic and mechanical changes during incisional herniation and its effect on incisional hernia repairs. SUMMARY BACKGROUND DATA: Unloaded skeletal muscles undergo characteristic atrophic changes, including change in fiber type composition, decreased cross-sectional area, and pathologic fibrosis. We hypothesize that these atrophic changes decrease muscle elastic properties and may contribute to the high laparotomy wound failure rate observed following incisional hernia repair. METHODS: A rat model of chronic incisional hernia formation was used. Failing midline laparotomy incisions developed into incisional hernias. Controls were uninjured and sham laparotomy (healed) groups. Internal oblique muscles were harvested for fiber typing, measurement of cross-sectional area, collagen deposition, and mechanical analysis. Mesh hernia repairs were performed on a second group of rats with chronic incisional hernias or acute anterior abdominal wall myofascial defects. RESULTS: The hernia group developed lateral abdominal wall shortening and oblique muscle atrophy. This was associated with a change in the distribution of oblique muscle fiber types, decreased cross-sectional area, and pathologic fibrosis consistent with myopathic disuse atrophy. These muscles exhibited significant decreased extensibility and increased stiffness. The healed (sham) laparotomy group expressed an intermediate phenotype between the uninjured and hernia groups. Recurrent hernia formation was most frequent in the chronic hernia model, and hernia repairs mechanically disrupted at a lower force compared with nonherniated abdominal walls. CONCLUSIONS: The internal oblique muscles of the abdominal wall express a pattern of changes consistent with those seen in chronically unloaded skeletal muscles. The internal oblique muscles become fibrotic during herniation, reducing abdominal wall compliance and increasing the transfer of load forces to the midline wound at the time of hernia repair