The regenerative peripheral nerve interface remains viable over seven months in the presence of an implanted electrode. Electrodes with and without conductive polymer reliably transduced signals from the regenerative peripheral nerve interface. Electrodes with a conductive polymer coating resulted in recording more of the regenerative peripheral nerve interface signal.

Background:Originally designed for prosthetic control, regenerative peripheral nerve interfaces (RPNIs) prevent neuroma formation by providing free muscle grafts as physiological targets for peripheral nerve ingrowth. We report the first series of patients undergoing RPNI implantation for treatment of symptomatic postamputation neuromas.Methods:A retrospective case series of all amputees undergoing RPNI implantation for treatment of symptomatic neuromas between November 2013 and June 2015 is presented. Data were obtained via chart review and phone interviews using questions derived from the Patient Reported Outcomes Measurement Information System instruments. Statistical analyses were performed using dependent sample t tests with a significance threshold of P < 0.01.Results:Forty-six RPNIs were implanted into 16 amputees for neuroma relief (3 upper extremities and 14 lower extremities). Mean age was 53.5 years (6 females and 10 males). All patients participated in postoperative phone interviews at 7.5 ± 3.4 (range: 3–15) months. Patients reported a 71% reduction in neuroma pain and a 53% reduction in phantom pain. Most patients felt satisfied or highly satisfied with RPNI surgery (75%), reporting decreased (56%) or stable (44%) levels of analgesic use. Most patients would strongly recommend RPNI surgery to a friend (88%) and would do it again if given the option (94%). Complications included delayed wound healing (n = 4) and neuroma pain at a different site (n = 2).Conclusions:RPNI implantation carries a reasonable complication profile while offering a simple, effective treatment for symptomatic neuromas. Most patients report a significant reduction in neuroma and phantom pain with a high level of satisfaction. The physiological basis for preventing neuroma recurrence is an intriguing benefit to this approach.

Peripheral nerves provide a promising source of motor control signals for neuroprosthetic devices. Unfortunately, the clinical utility of current peripheral nerve interfaces is limited by signal amplitude and stability. Here, we showed that the regenerative peripheral nerve interface (RPNI) serves as a biologically stable bioamplifier of efferent motor action potentials with long-term stability in upper limb amputees. Ultrasound assessments of RPNIs revealed prominent contractions during phantom finger flexion, confirming functional reinnervation of the RPNIs in two patients. The RPNIs in two additional patients produced electromyography signals with large signal-to-noise ratios. Using these RPNI signals, subjects successfully controlled a hand prosthesis in real-time up to 300 days without control algorithm recalibration. RPNIs show potential in enhancing prosthesis control for people with upper limb loss.

The rat infarct model is widely used in heart failure research, but few echocardiographic indexes of left ventricular (LV) function are validated in this model. Accordingly, the objective of this study was to validate a 13-segment LV wall motion score index (WMSI) and the myocardial performance index (MPI) in infarcted rats. Twenty-nine male Wistar rats underwent left coronary artery ligation or sham operation and were evaluated with two-dimensional and Doppler flow echocardiography 8 wk later. After echocardiography, invasive indexes were obtained using a high-fidelity catheter. WMSI and MPI were correlated with the invasive and noninvasive measurements of LV function. WMSI and MPI significantly correlated directly with end-diastolic pressure (r=0.72 and 0.42 for WMSI and MPI, respectively) and the time constant of isovolumic relaxation (r=0.68 and 0.48) and inversely with peak rate of rise of LV pressure (+dP/dt; r=-0.68 and -0.50), peak rate of decline in LV pressure (r=-0.57 and -0.44), LV developed pressure (r=-0.58 and -0.42), area fractional shortening (r=-0.85 and -0.53), and cardiac index (r=-0.74 and -0.74). Stepwise linear regression analyses revealed that LV end-diastolic pressure, +dP/dt, area fractional shortening, and cardiac index were independent determinants of WMSI (r=0.994) and that cardiac index and +dP/dt were independent determinants of MPI (r=0.781). We conclude that the 13-segment WMSI and MPI are reproducible and correlate strongly with established echocardiographic and invasive indexes of systolic and diastolic function. These findings support the use of WMSI and MPI as indexes of global LV function in the rat infarction model of heart failure.

Background: Postamputation pain affects a large number of individuals living with major limb loss. Regenerative peripheral nerve interfaces are constructs composed of a transected peripheral nerve implanted into an autologous free muscle graft. The authors have previously shown that regenerative peripheral nerve interfaces can be used to treat symptomatic end neuromas that develop after major limb amputation. In this study, they investigated the potential of prophylactic interfaces to prevent the formation of symptomatic neuromas and mitigate phantom limb pain. Methods: Patients who underwent limb amputation with and without prophylactic regenerative peripheral nerve interface implantation were identified. A retrospective review was performed to ascertain patient demographics, level of amputation, and postoperative complications. Documentation of symptomatic neuromas and phantom limb pain was noted. Results: Postoperative outcomes were evaluated in a total of 90 patients. Forty-five patients underwent interface implantation at the time of primary amputation, and 45 control patients underwent amputation without interfaces. Six control patients (13.3 percent) developed symptomatic neuromas in the postoperative period compared with zero (0.0 percent) in the prophylactic interface group (p = 0.026). Twenty-three interface patients (51.1 percent) reported phantom limb pain, compared with 41 control patients (91.1 percent; p < 0.0001). Conclusions: Prophylactic regenerative peripheral nerve interfaces in major limb amputees resulted in a lower incidence of both symptomatic neuromas and phantom limb pain compared with control patients undergoing amputation without regenerative peripheral nerve interfaces, suggesting that prevention of peripheral neuromas following amputation may diminish the central pain mechanisms that lead to phantom limb pain. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Lymphedema is an incurable disease caused by insufficient lymphatic drainage leading to abnormal accumulation of interstitial fluid within the soft tissues. Although this condition may result from a primary structural defect of the lymphatic system, most cases in developed countries are secondary to iatrogenic causes. The diagnosis of lymphedema can be made readily by performing a clinical history and physical examination and may be confirmed by imaging studies such as lymphoscintigraphy, magnetic resonance lymphangiography, or indocyanine green lymphangiography. Nonsurgical treatment continues to be the mainstay of lymphedema management. However, advances in microsurgical techniques have revolutionized surgical options for treating lymphedema, and emerging evidence suggests that reconstructive methods may be performed to restore lymphatic flow. Procedures such as lymphaticovenular anastomosis and vascularized lymph node transfer can potentially offer a more permanent solution to chronic lymphedema, and initial studies have demonstrated promising results.

Painful terminal neuromas resulting from nerve injury following amputation are common. However, there is currently no universally accepted gold standard of treatment for this condition. A comprehensive literature review is presented on the treatment of terminal neuromas. Four categories of terminal neuroma surgical procedures are assessed: epineurial closure; nerve transposition with implantation; neurorrhaphy, and alternate target reinnervation. Significant patient and case studies are highlighted in each section, focusing on surgical technique and patient outcome metrics. Studies presented consisted of a PubMed search for "terminal neuromas," without year limitation. The current available research supports the use of implantation into muscle for the surgical treatment of terminal neuromas. However, this technique has several fundamental flaws that limit its utility, as it does not address the underlying physiology behind neuroma formation. Regenerative peripheral nerve interfaces and targeted muscle reinnervation are 2 techniques that seem to offer the most promise in preventing and treating terminal neuroma formation. Both techniques are also capable of generating control signals which can be used for both motor and sensory prosthetic control. Such technology has the potential to lead to the future restoration of lost limb function in amputees. Further clinical research employing larger patient groups with high-quality control groups and reproducible outcome measures is needed to determine the most effective and beneficial surgical treatment for terminal neuromas. Primary focus should be placed on investigating techniques that most closely approximate the theoretically ideal neuroma treatment, including targeted muscle reinnervation and regenerative peripheral nerve interfaces.

Peripheral nerve injury remains a major cause of morbidity in trauma patients. Despite advances in microsurgical techniques and improved understanding of nerve regeneration, obtaining satisfactory outcomes after peripheral nerve injury remains a difficult clinical problem. There is a growing body of evidence in preclinical animal studies demonstrating the supportive role of stem cells in peripheral nerve regeneration after injury. The characteristics of both mesoderm‐derived and ectoderm‐derived stem cell types and their role in peripheral nerve regeneration are discussed, specifically focusing on the presentation of both foundational laboratory studies and translational applications. The current state of clinical translation is presented, with an emphasis on both ethical considerations of using stems cells in humans and current governmental regulatory policies. Current advancements in cell‐based therapies represent a promising future with regard to supporting nerve regeneration and achieving significant functional recovery after debilitating nerve injuries.