Regenerative peripheral nerve interface prevents neuroma formation after peripheral nerve transection

Neuroma formation after peripheral nerve transection often leads to severe neuropathic pain.Regenerative peripheral nerve interface has been shown to reduce painful neuroma in the clinic.However,no reports have investigated the underlying mechanisms,and no comparative animal studies on regenerative peripheral nerve interface and other means of neuroma prevention have been conducted to date.In this study,we established a rat model of left sciatic nerve transfection,and subsequently interfered with the model using the regenerative peripheral nerve interface or proximal nerve stump implantation inside a fully innervated muscle.Results showed that,compared with rats subjected to nerve stump implantation inside the muscle,rats subjected to regenerative peripheral nerve interface intervention showed greater inhibition of the proliferation of collagenous fibers and irregular regenerated axons,lower expressions of the fibrosis markerα-smooth muscle actin and the inflammatory marker sigma-1 receptor in the proximal nerve stump,lower autophagy behaviors,lower expressions of c-fos and substance P,higher expression of glial cell line-derived neurotrophic factor in the ipsilateral dorsal root ganglia.These findings suggested that regenerative peripheral nerve interface inhibits peripheral nerve injury-induced neuroma formation and neuropathic pain possibly via the upregulation of the expression of glial cell line-derived neurotrophic factor in the dorsal root ganglia and reducing neuroinflammation in the nerve stump.

Optical read-out and modulation of peripheral nerve activity

Numerous clinical and research applications necessitate the ability to interface with peripheral nerve fibers to read and control relevant neural pathways. Visceral organ modulation and rehabilitative prosthesis are two areas which could benefit greatly from improved neural interfacing approaches. Therapeutic neural interfacing, or ‘bioelectronic medicine’, has potential to affect a broad range of disorders given that all the major organs of the viscera are neurally innervated. However, a better understanding of the neural pathways that underlie function and a means to precisely interface with these fibers are required. Existing peripheral nerve interfaces, consisting primarily of electrode-based designs, are unsuited for highly specific （individual axon） communication and/or are invasive to the tissue. Our laboratory has explored an optogenetic approach by which optically sensitive reporters and actuators are targeted to specific cell （axon） types. The nature of such an approach is laid out in this short perspective, along with associated technologies and challenges.

Regenerative peripheral nerve interfaces(RPNIs):current status and future direction

Despite significant advancements in neuroprosthetic control strategies,current peripheral nerve interfacing techniques are limited in their ability to facilitate accurate and reliable long-term control.The regenerative peripheral nerve interface(RPNI)is a biologically stable bioamplifier of efferent motor action potentials with demonstrated long-term stability.This innovative,straightforward,and reproducible surgical technique has shown enormous potential in improving prosthetic control for individuals with upper limb amputations.The RPNI consists of an autologous free muscle graft secured around the end of a transected peripheral nerve or individual fascicles within a residual limb.This construct facilitates EMG signal transduction from the residual peripheral nerve to a neuroprosthetic device using indwelling bipolar electrodes on the muscle surface.This review article focuses on the development of the RPNI and its use for intuitive and enhanced prosthetic control and sensory feedback.In addition,this article also highlights the use of RPNIs for the prevention and treatment of postamputation pain.

Advances in upper limb loss rehabilitation:the role of targeted muscle reinnervation and regenerative peripheral nerve interfaces

Upper limb loss results in significant physical and psychological impairment and is a major financial burden for both patients and healthcare services.Current myoelectric prostheses rely on electromyographic(EMG)signals captured using surface electrodes placed directly over antagonistic muscles in the residual stump to drive a single degree of freedom in the prosthetic limb(e.g.,hand open and close).In the absence of the appropriate muscle groups,patients rely on activation of biceps/triceps muscles alone(together with a mode switch)to control all degrees of freedom of the prosthesis.This is a non-physiological method of control since it is non-intuitive and contributes poorly to daily function.This leads to the high rate of prosthetic abandonment.Targeted muscle reinnervation(TMR)reroutes the ends of nerves in the amputation stump to nerves innervating“spare”muscles in the amputation stump or chest wall.These then become proxies for the missing muscles in the amputated limb.TMR has revolutionised prosthetic control,especially for high-level amputees(e.g.,after shoulder disarticulation),resulting in more intuitive,fluid control of the prosthesis.TMR can also reduce the intensity of symptoms such as neuroma and phantom limb pain.Regenerative peripheral nerve interface(RPNI)is another technique for increasing the number of control signals without the limitations of finding suitable target muscles imposed by TMR.This involves wrapping a block of muscle around the free nerve ending,providing the regenerating axons with a target organ for reinnervation.These RPNIs act as signal amplifiers of the previously severed nerves and their EMG signals can be used to control prosthetic limbs.RPNI can also reduce neuroma and phantom limb pain.In this review article,we discuss the surgical technique of TMR and RPNI and present outcomes from our experience with TMR.

Lower extremity amputation:the emerging role of targeted muscle reinnervation(TMR)and regenerative peripheral nerve interface(RPNI)

Lower extremity amputation is increasingly prevalent in the United States,with growing numbers of patients suffering from diabetes and peripheral vascular disease.Amputation has significant functional sequelae as more than half of patients are unable to ambulate at one year postoperatively.Improving mobility and decreasing chronic post-amputation pain can significantly improve the quality of life for these patients and reduce the cost burden on the healthcare system.Plastic and reconstructive surgery has been at the forefront of“reconstructive amputation”,in which nerve pedicles can be surgically guided to decrease painful neuroma formation as well as provide targets for myoelectric prosthesis use.We herein review post-amputation outcomes,epidemiology of chronic,post-amputation pain,and current treatments,including total muscle reinnervation and regenerative peripheral nerve interface,which are at the forefront of multidisciplinary treatment of lower extremity amputees.

Design of shared bus DSP board in vector network analyzer

Currently,the mainstream vector network analyzer employs embedded computer module with a digital intermediate frequency(IF)board to form a high performance windows platform.Under this structure,the vector network analyzer needs a powerful encoding system to arbitrate the bus acquirement,which is usually realized by field-programmable gate array(FPGA)chip.The paper explores the shared bus design method of the digital signal processing(DSP)board in network analyzer.Firsty,it puts an emphasis on the system structure,and then the shared bus communication method is described in detail;Finally,the advantages of the shared bus communication mechanism are summanzed.

Management of symptomatic neuromas:a narrative review of the most common surgical treatment modalities in amputees

Symptomatic neuromas are an all-too-common complication following limb amputation or extremity trauma,leading to chronic and debilitating pain for patients.Surgical resection of symptomatic neuromas has proven to be the superior method of intervention,but traditional methods of neuroma resection do not address the underlying pathophysiology leading to the formation of a future symptomatic neuroma and lead to high reoperation rates.Novel approaches employ the physiology of peripheral nerve injury to harness the regeneration of nerves to their advantage.This review explores the underlying pathophysiology of neuroma formation and centralization of pain signaling.It compares the traditional surgical approach for symptomatic neuroma resection and describes three novel surgical strategies that harness this pathophysiology of neuroma formation to their advantage.The traditional resection of symptomatic neuromas is currently the standard of care for amputation patients,but new techniques including the regenerative peripheral nerve interface,targeted muscle reinnervation,and intraosseous transposition have shown promise in improving patient pain outcomes for postamputation pain and residual limb pain.Symptomatic neuromas are a chronic and debilitating complication following amputation procedures and trauma,and the current standard of care does not address the underlying pathophysiology leading to the formation of the neuroma.New techniques are under development that may provide improved patient pain outcomes and a higher level of care for symptomatic neuroma resection.