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 invest...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.展开更多
Complications following amputation can be devastating for patients,including debilitating neuropathic pain,the inability to perform activities of daily living(ADLs)or gain meaningful employment.While prosthesis use al...Complications following amputation can be devastating for patients,including debilitating neuropathic pain,the inability to perform activities of daily living(ADLs)or gain meaningful employment.While prosthesis use allows patients to restore independence and reintegrate into daily activities,patients often abandon these devices.Despite the immense advancements in prosthetic technology,there is still a need for an interface that can provide a natural experience with accurate and reliable long-term control.The Regenerative Peripheral Nerve Interface(RPNI)is a simple surgical technique that offers real-time control of myoelectric prosthetic devices to restore extremity function.This stable,biological nerve interface successfully amplifies efferent motor action potentials,provides sensory feedback,and offers a more functional prosthetic device experience.Based on the principles of RPNI,novel surgical approaches have been developed to expand its applications and improve outcomes.This review article summarizes the utilization of the RPNI and its recent modifications of different neural interfaces in the setting of major limb amputation and musculoskeletal injuries.展开更多
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 regenerativ...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.展开更多
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)signa...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.展开更多
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...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.展开更多
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 t...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.展开更多
Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic i...Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic injuries,and neurological diseases.Neural machine interface technology establishes direct connections with the brain or peripheral nervous system to restore impaired motor,sensory,and cognitive functions,significantly improving patients'quality of life.This review analyzes the chronological development and integration of various neural machine interface technologies,including regenerative peripheral nerve interfaces,targeted muscle and sensory reinnervation,agonist–antagonist myoneural interfaces,and brain–machine interfaces.Recent advancements in flexible electronics and bioengineering have led to the development of more biocompatible and highresolution electrodes,which enhance the performance and longevity of neural machine interface technology.However,significant challenges remain,such as signal interference,fibrous tissue encapsulation,and the need for precise anatomical localization and reconstruction.The integration of advanced signal processing algorithms,particularly those utilizing artificial intelligence and machine learning,has the potential to improve the accuracy and reliability of neural signal interpretation,which will make neural machine interface technologies more intuitive and effective.These technologies have broad,impactful clinical applications,ranging from motor restoration and sensory feedback in prosthetics to neurological disorder treatment and neurorehabilitation.This review suggests that multidisciplinary collaboration will play a critical role in advancing neural machine interface technologies by combining insights from biomedical engineering,clinical surgery,and neuroengineering to develop more sophisticated and reliable interfaces.By addressing existing limitations and exploring new technological frontiers,neural machine interface technologies have the potential to revolutionize neuroprosthetics and neurorehabilitation,promising enhanced mobility,independence,and quality of life for individuals with neurological impairments.By leveraging detailed anatomical knowledge and integrating cutting-edge neuroengineering principles,researchers and clinicians can push the boundaries of what is possible and create increasingly sophisticated and long-lasting prosthetic devices that provide sustained benefits for users.展开更多
This article presents a comprehensive strategy for both the prevention and treatment of neuropathic pain at the radial forearm(RF)donor site.This strategy is presented within the framework of RF phalloplasty,based on ...This article presents a comprehensive strategy for both the prevention and treatment of neuropathic pain at the radial forearm(RF)donor site.This strategy is presented within the framework of RF phalloplasty,based on the senior author’s practice and the premise that of all RF reconstructions,phalloplasty holds the greatest potential for postoperative neuropathic pain due to flap size and the inherent division of multiple antebrachial cutaneous nerves to provide for flap sensation.This proposed protocol offers a thorough care pathway that integrates techniques in peripheral nerve surgery with perioperative clinical strategies to prevent and treat neuropathic pain.Specific technical recommendations for the prevention and treatment of postoperative neuromas,compression neuropathies,and hyperalgesia of each peripheral nerve involved in RF phalloplasty flap harvest are proposed.These strategies can be adapted and applied to RF flaps utilized in other reconstructive areas.展开更多
Amputation is a historically well-grounded procedure,but such a traumatic operation invites a litany of postoperative complications,such as the formation of agonizing neuromas.Developments in mitigating these complica...Amputation is a historically well-grounded procedure,but such a traumatic operation invites a litany of postoperative complications,such as the formation of agonizing neuromas.Developments in mitigating these complications include the clinically successful targeted muscle reinnervation(TMR)and regenerative peripheral nerve interface(RPNI),which showcased the potential for utilizing peripheral nerves'regenerative capabilities to circumvent neuroma formation and isolate neural activity for control of a sophisticated prosthetic device.Nevertheless,these techniques only record the aforementioned neural activity from the reinnervated muscle,not the nerve itself,which may ultimately limit the degree of functionality they can restore to amputees.Alternatively,regenerative sieve electrodes are non-biological end targets for reinnervation that utilize their porous structure to isolate regenerating axons into discrete transient zones lined with stimulating and recording electrodes.Albeit more invasive,such direct contact with the once-damaged nerve opens the door for highly selective,bi-directional neural interfaces with the capacity to restore higher degrees of sensorimotor functionality to patients for enhanced rehabilitation outcomes.By expanding the definition of innervation to include non-biological targets,clinicians can make room for these advancements in neural interfacing to revolutionize patient care.展开更多
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 t...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.展开更多
基金supported by the Health Commission of Hubei Province Medical Leading Talent Project,No.LJ20200405(to AXY)。
文摘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.
基金The Institutional Review Board at the University of Michigan approved this study(HUM00124839).
文摘Complications following amputation can be devastating for patients,including debilitating neuropathic pain,the inability to perform activities of daily living(ADLs)or gain meaningful employment.While prosthesis use allows patients to restore independence and reintegrate into daily activities,patients often abandon these devices.Despite the immense advancements in prosthetic technology,there is still a need for an interface that can provide a natural experience with accurate and reliable long-term control.The Regenerative Peripheral Nerve Interface(RPNI)is a simple surgical technique that offers real-time control of myoelectric prosthetic devices to restore extremity function.This stable,biological nerve interface successfully amplifies efferent motor action potentials,provides sensory feedback,and offers a more functional prosthetic device experience.Based on the principles of RPNI,novel surgical approaches have been developed to expand its applications and improve outcomes.This review article summarizes the utilization of the RPNI and its recent modifications of different neural interfaces in the setting of major limb amputation and musculoskeletal injuries.
文摘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.
文摘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.
文摘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.
基金financially supported in part by funds administered through VA Eastern Colorado Health Care System-Denver VA Medical Centerfunds from the NIH SPARC initiative administered through the Office of the Director:1OT2OD023852-01
文摘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.
基金supported in part by the National Natural Science Foundation of China,Nos.81927804(to GL),82260456(to LY),U21A20479(to LY)Science and Technology Planning Project of Shenzhen,No.JCYJ20230807140559047(to LY)+3 种基金Key-Area Research and Development Program of Guangdong Province,No.2020B0909020004(to GL)Guangdong Basic and Applied Research Foundation,No.2023A1515011478(to LY)the Science and Technology Program of Guangdong Province,No.2022A0505090007(to GL)Ministry of Science and Technology,Shenzhen,No.QN2022032013L(to LY)。
文摘Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic injuries,and neurological diseases.Neural machine interface technology establishes direct connections with the brain or peripheral nervous system to restore impaired motor,sensory,and cognitive functions,significantly improving patients'quality of life.This review analyzes the chronological development and integration of various neural machine interface technologies,including regenerative peripheral nerve interfaces,targeted muscle and sensory reinnervation,agonist–antagonist myoneural interfaces,and brain–machine interfaces.Recent advancements in flexible electronics and bioengineering have led to the development of more biocompatible and highresolution electrodes,which enhance the performance and longevity of neural machine interface technology.However,significant challenges remain,such as signal interference,fibrous tissue encapsulation,and the need for precise anatomical localization and reconstruction.The integration of advanced signal processing algorithms,particularly those utilizing artificial intelligence and machine learning,has the potential to improve the accuracy and reliability of neural signal interpretation,which will make neural machine interface technologies more intuitive and effective.These technologies have broad,impactful clinical applications,ranging from motor restoration and sensory feedback in prosthetics to neurological disorder treatment and neurorehabilitation.This review suggests that multidisciplinary collaboration will play a critical role in advancing neural machine interface technologies by combining insights from biomedical engineering,clinical surgery,and neuroengineering to develop more sophisticated and reliable interfaces.By addressing existing limitations and exploring new technological frontiers,neural machine interface technologies have the potential to revolutionize neuroprosthetics and neurorehabilitation,promising enhanced mobility,independence,and quality of life for individuals with neurological impairments.By leveraging detailed anatomical knowledge and integrating cutting-edge neuroengineering principles,researchers and clinicians can push the boundaries of what is possible and create increasingly sophisticated and long-lasting prosthetic devices that provide sustained benefits for users.
文摘This article presents a comprehensive strategy for both the prevention and treatment of neuropathic pain at the radial forearm(RF)donor site.This strategy is presented within the framework of RF phalloplasty,based on the senior author’s practice and the premise that of all RF reconstructions,phalloplasty holds the greatest potential for postoperative neuropathic pain due to flap size and the inherent division of multiple antebrachial cutaneous nerves to provide for flap sensation.This proposed protocol offers a thorough care pathway that integrates techniques in peripheral nerve surgery with perioperative clinical strategies to prevent and treat neuropathic pain.Specific technical recommendations for the prevention and treatment of postoperative neuromas,compression neuropathies,and hyperalgesia of each peripheral nerve involved in RF phalloplasty flap harvest are proposed.These strategies can be adapted and applied to RF flaps utilized in other reconstructive areas.
文摘Amputation is a historically well-grounded procedure,but such a traumatic operation invites a litany of postoperative complications,such as the formation of agonizing neuromas.Developments in mitigating these complications include the clinically successful targeted muscle reinnervation(TMR)and regenerative peripheral nerve interface(RPNI),which showcased the potential for utilizing peripheral nerves'regenerative capabilities to circumvent neuroma formation and isolate neural activity for control of a sophisticated prosthetic device.Nevertheless,these techniques only record the aforementioned neural activity from the reinnervated muscle,not the nerve itself,which may ultimately limit the degree of functionality they can restore to amputees.Alternatively,regenerative sieve electrodes are non-biological end targets for reinnervation that utilize their porous structure to isolate regenerating axons into discrete transient zones lined with stimulating and recording electrodes.Albeit more invasive,such direct contact with the once-damaged nerve opens the door for highly selective,bi-directional neural interfaces with the capacity to restore higher degrees of sensorimotor functionality to patients for enhanced rehabilitation outcomes.By expanding the definition of innervation to include non-biological targets,clinicians can make room for these advancements in neural interfacing to revolutionize patient care.
文摘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.
