Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Robotic-Assisted Anastomosis in Orthoplastic Surgery: Preliminary Data.

BACKGROUND: The evolution of microsurgery has relied on advancements in operating microscopes and surgical instruments. Pioneering advancements, however, especially within the domain of "super-microsurgery", challenge the limits of human dexterity by dealing with anastomoses between vessels smaller than 0.8 mm. Based on these premises, the Symani robotic system was designed and developed. This platform utilizes teleoperation and motion-scaled movement to provide surgeons with precision and accuracy in manipulating millimetre and submillimetre-sized anatomical structures. In this study, we present our experience in performing robotic-assisted anastomoses using the Symani Surgical System in free flap reconstruction. METHODS: We present a comprehensive analysis of all reconstructive procedures involving microsurgical free flaps performed using the Symani robotic platform at the orthoplastic unit of the Rizzoli Orthopaedic Institute from 1 October 2022 to 1 May 2023. RESULTS: Sixteen microsurgical reconstructions using free flaps were performed, involving a total of 40 anastomoses on vessel calibres ranging from 0.6 mm to 2.5 mm. In each case, the anastomosis was executed with the assistance of the robotic platform, achieving a 100+% success rate in patent anastomoses, and no major complications occurred.Conclusion The Symani system has proven to be safe and reliable in performing microsurgical anastomoses. While this platform demonstrated successful in various vessel calibres, its most promising potential lies in anastomoses below the size of a millimetre. Larger patient cohorts and extended investigation periods will be essential to explore whether robotics in microsurgery offers advantages across all microsurgical procedures or should be reserved for selected cases.

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Cutting Edge Bionics in Highly Impaired Individuals: A Case of Challenges and Opportunities.

Highly impaired individuals stand to benefit greatly from cutting-edge bionic technology, however concurrent functional deficits may complicate the adaptation of such technology. Here, we present a case in which a visually impaired individual with bilateral burn injury amputation was provided with a novel transradial neuromusculoskeletal prosthesis comprising skeletal attachment via osseointegration and implanted electrodes in nerves and muscles for control and sensory feedback. Difficulties maintaining implant hygiene and donning and doffing the prosthesis arose due to his contralateral amputation, ipsilateral eye loss, and contralateral impaired vision necessitating continuous adaptations to the electromechanical interface. Despite these setbacks, the participant still demonstrated improvements in functional outcomes and the ability to control the prosthesis in various limb positions using the implanted electrodes. Our results demonstrate the importance of a multidisciplinary, iterative, and patient-centered approach to making cutting-edge technology accessible to patients with high levels of impairment.

Targeted muscle reinnervation in bionic upper limb reconstruction: current status and future directions.

Selective nerve transfers are used in the setting of upper limb amputation to improve myoelectric prosthesis control. This surgical concept is referred to as targeted muscle reinnervation (TMR) and describes the rerouting of the major nerves of the arm onto the motor branches of the residual limb musculature. Aside from providing additional myosignals for prosthetic control, TMR can treat and prevent neuroma pain and possibly also phantom limb pain. This article reviews the history and current applications of TMR in upper limb amputation, with a focus on practical considerations. It further explores and identifies technological innovations to improve the man-machine interface in amputation care, particularly regarding implantable interfaces, such as muscle electrodes and osseointegration. Finally, future clinical directions and possible scientific avenues in this field are presented and critically discussed.

A highly integrated bionic hand with neural control and feedback for use in daily life.

Restoration of sensorimotor function after amputation has remained challenging because of the lack of human-machine interfaces that provide reliable control, feedback, and attachment. Here, we present the clinical implementation of a transradial neuromusculoskeletal prosthesis-a bionic hand connected directly to the user's nervous and skeletal systems. In one person with unilateral below-elbow amputation, titanium implants were placed intramedullary in the radius and ulna bones, and electromuscular constructs were created surgically by transferring the severed nerves to free muscle grafts. The native muscles, free muscle grafts, and ulnar nerve were implanted with electrodes. Percutaneous extensions from the titanium implants provided direct skeletal attachment and bidirectional communication between the implanted electrodes and a prosthetic hand. Operation of the bionic hand in daily life resulted in improved prosthetic function, reduced postamputation, and increased quality of life. Sensations elicited via direct neural stimulation were consistently perceived on the phantom hand throughout the study. To date, the patient continues using the prosthesis in daily life. The functionality of conventional artificial limbs is hindered by discomfort and limited and unreliable control. Neuromusculoskeletal interfaces can overcome these hurdles and provide the means for the everyday use of a prosthesis with reliable neural control fixated into the skeleton.

Improved control of a prosthetic limb by surgically creating electro-neuromuscular constructs with implanted electrodes.

Remnant muscles in the residual limb after amputation are the most common source of control signals for prosthetic hands, because myoelectric signals can be generated by the user at will. However, for individuals with amputation higher up the arm, such as an above-elbow (transhumeral) amputation, insufficient muscles remain to generate myoelectric signals to enable control of the lost arm and hand joints, thus making intuitive control of wrist and finger prosthetic joints unattainable. We show that severed nerves can be divided along their fascicles and redistributed to concurrently innervate different types of muscle targets, particularly native denervated muscles and nonvascularized free muscle grafts. We engineered these neuromuscular constructs with implanted electrodes that were accessible via a permanent osseointegrated interface, allowing for bidirectional communication with the prosthesis while also providing direct skeletal attachment. We found that the transferred nerves effectively innervated their new targets as shown by a gradual increase in myoelectric signal strength. This allowed for individual flexion and extension of all five fingers of a prosthetic hand by a patient with a transhumeral amputation. Improved prosthetic function in tasks representative of daily life was also observed. This proof-of-concept study indicates that motor neural commands can be increased by creating electro-neuromuscular constructs using distributed nerve transfers to different muscle targets with implanted electrodes, enabling improved control of a limb prosthesis.

Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial.

BACKGROUND: Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation - commonly known as neuroma pain - and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP. METHODS: One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12 months post-surgery) and in long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site. DISCUSSION: A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0-10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment. TRIAL REGISTRATION: ClincialTrials.gov NCT05009394.

Soft Tissue Reconstruction of the Posterior Trunk after Tumor Excision: A Surgical Algorithm.

BACKGROUND: The posterior trunk has been considered a challenging area to reconstruct following soft tissue tumor excision because of the shortage of local donor sites. The advent of innovative procedures such as perforator flaps has radically changed this perspective and offered a new approach to the problem. METHODS: Upon a review of the literature and the personal experiences of the senior author, an algorithm is developed according to the most updated procedure, combined with more conventional options that maintain a role in decision-making. RESULTS: The upper back latissimus dorsi and trapezium flap are still the most reliable approaches, while perforator flaps based either on the circumflex scapular arteries or the transverse cervical artery represent a more refined option. In the middle third, few indications remain for the reverse latissimus dorsi, while the gold standard is represented by local perforator flaps based on the posterior intercostal system. In the lower back, conventional VY advancement flaps are still a safe and effective option in the sacral area, and perforator flaps based on posterior intercostal arteries, lumbar arteries and superior gluteal arteries are the first choice in most cases. CONCLUSIONS: Using perforator flaps significantly improved soft tissue reconstruction in the posterior trunk.

The profunda artery perforator flap for upper limb reconstruction: A case report and literature review on the flap applications in reconstruction.

The profunda femoris artery perforator (PAP) flap has been recently popularized as an alternative option for microsurgical reconstruction. The use of PAP flap has never been reported and described for reconstruction of the upper extremities, in particular the forearm. The purpose of this case report is to describe a case suggesting the PAP flap as a further reconstructive option in the upper limb. A 16-year-old girl who sustained a traumatic injury to her right dominant forearm resulting in subtotal circumferential tissue loss following a road traffic accident was referred to the authors' department 2 years post-trauma. The disabling fibrotic sequelae on her volar forearm (15 × 10 cm) resulted in a nonfunctional hand. She was unable to perform any active movement of her wrist or digits. Passive movements in the finger joints were preserved. Following debridement and reconstruction of nerves and tendons, soft tissues were resurfaced with a PAP flap. The transverse skin paddle, 12 × 7 cm, was placed distally with the adipofascial portion positioned proximally above the muscle bellies and anastomoses site. A small raw area (4 × 3 cm) was covered with an acellular dermal matrix (ADM). The postoperative course was uneventful. At 9 months postoperatively, the patient demonstrated active flexion and extension of the fingers with independent function. The patient reported satisfaction with the flap donor site and forearm resurfacing. The PAP flap can be a further option for areas requiring soft tissue coverage in patients refusing visible scars. This flap had both the advantage of reducing the morbidity and visibility of the donor site, as well as the ability to resurface a large recipient site with soft and pliable tissue, covering exposed nerves and tendons.

Does pediatric hand transplantation undermine a child's right to an open future?

To date, pediatric hand transplantations have only been performed twice. The ethical issue most often discussed in the literature on this surgery concerns the risks of immunosuppression. While these risks are significant, they can be at least partially mitigated by selecting for patients who are already immunocompromised. Nevertheless, as we will argue, pediatric hand transplantation raises ethical issues that go beyond the risks of immunosuppression. In this paper, we focus on three additional ethical issues: the fact that pediatric hand transplantation aims to improve, rather than save life; the fact that it is an experimental surgery; and the fact that it will be performed on non-autonomous patients whose 'right to an open future' may potentially be undermined by the surgery. Taken together, we think that these considerations suggest that transplantation should be postponed until a child is mature enough to make their own decision about it.

The Myokinetic Control Interface: How Many Magnets Can be Implanted in an Amputated Forearm? Evidence From a Simulated Environment.

We recently introduced the concept of a new human-machine interface (the myokinetic control interface) to control hand prostheses. The interface tracks muscle contractions via permanent magnets implanted in the muscles and magnetic field sensors hosted in the prosthetic socket. Previously we showed the feasibility of localizing several magnets in non-realistic workspaces. Here, aided by a 3D CAD model of the forearm, we computed the localization accuracy simulated for three different below-elbow amputation levels, following general guidelines identified in early work. To this aim we first identified the number of magnets that could fit and be tracked in a proximal (T1), middle (T2) and distal (T3) representative amputation, starting from 18, 20 and 23 eligible muscles, respectively. Then we ran a localization algorithm to estimate the poses of the magnets based on the sensor readings. A sensor selection strategy (from an initial grid of 840 sensors) was also implemented to optimize the computational cost of the localization process. Results showed that the localizer was able to accurately track up to 11 (T1), 13 (T2) and 19 (T3) magnetic markers (MMs) with an array of 154, 205 and 260 sensors, respectively. Localization errors lower than 7% the trajectory travelled by the magnets during muscle contraction were always achieved. This work not only answers the question: "how many magnets could be implanted in a forearm and successfully tracked with a the myokinetic control approach?", but also provides interesting insights for a wide range of bioengineering applications exploiting magnetic tracking.

Neural feedback strategies to improve grasping coordination in neuromusculoskeletal prostheses.

Conventional prosthetic arms suffer from poor controllability and lack of sensory feedback. Owing to the absence of tactile sensory information, prosthetic users must rely on incidental visual and auditory cues. In this study, we investigated the effect of providing tactile perception on motor coordination during routine grasping and grasping under uncertainty. Three transhumeral amputees were implanted with an osseointegrated percutaneous implant system for direct skeletal attachment and bidirectional communication with implanted neuromuscular electrodes. This neuromusculoskeletal prosthesis is a novel concept of artificial limb replacement that allows to extract control signals from electrodes implanted on viable muscle tissue, and to stimulate severed afferent nerve fibers to provide somatosensory feedback. Subjects received tactile feedback using three biologically inspired stimulation paradigms while performing a pick and lift test. The grasped object was instrumented to record grasping and lifting forces and its weight was either constant or unexpectedly changed in between trials. The results were also compared to the no-feedback control condition. Our findings confirm, in line with the neuroscientific literature, that somatosensory feedback is necessary for motor coordination during grasping. Our results also indicate that feedback is more relevant under uncertainty, and its effectiveness can be influenced by the selected neuromodulation paradigm and arguably also the prior experience of the prosthesis user.

Self-Contained Neuromusculoskeletal Arm Prostheses.

We report the use of a bone-anchored, self-contained robotic arm with both sensory and motor components over 3 to 7 years in four patients after transhumeral amputation. The implant allowed for bidirectional communication between a prosthetic hand and electrodes implanted in the nerves and muscles of the upper arm and was anchored to the humerus through osseointegration, the process in which bone cells attach to an artificial surface without formation of fibrous tissue. Use of the device did not require formal training and depended on the intuitive intent of the user to activate movement and sensory feedback from the prosthesis. Daily use resulted in increasing sensory acuity and effectiveness in work and other activities of daily life. (Funded by the Promobilia Foundation and others.).

Grip control and motor coordination with implanted and surface electrodes while grasping with an osseointegrated prosthetic hand.

BACKGROUND: Replacement of a lost limb by an artificial substitute is not yet ideal. Resolution and coordination of motor control approximating that of a biological limb could dramatically improve the functionality of prosthetic devices, and thus reduce the gap towards a suitable limb replacement. METHODS: In this study, we investigated the control resolution and coordination exhibited by subjects with transhumeral amputation who were implanted with epimysial electrodes and an osseointegrated interface that provides bidirectional communication in addition to skeletal attachment (e-OPRA Implant System). We assessed control resolution and coordination in the context of routine and delicate grasping using the Pick and Lift and the Virtual Eggs Tests. Performance when utilizing implanted electrodes was compared with the standard-of-care technology for myoelectric prostheses, namely surface electrodes. RESULTS: Results showed that implanted electrodes provide superior controllability over the prosthetic terminal device compared to conventional surface electrodes. Significant improvements were found in the control of the grip force and its reliability during object transfer. However, these improvements failed to increase motor coordination, and surprisingly decreased the temporal correlation between grip and load forces observed with surface electrodes. We found that despite being more functional and reliable, prosthetic control via implanted electrodes still depended highly on visual feedback. CONCLUSIONS: Our findings indicate that incidental sensory feedback (visual, auditory, and osseoperceptive in this case) is insufficient for restoring natural grasp behavior in amputees, and support the idea that supplemental tactile sensory feedback is needed to learn and maintain the motor tasks internal model, which could ultimately restore natural grasp behavior in subjects using prosthetic hands.

The microsurgical training programme in Gothenburg, Sweden: early experiences.

OBJECTIVE: Microsurgical techniques are increasingly used in routine surgical practice as well as in biomedical research. The training opportunities at standardised training courses are limited, and no microsurgical training facility or programme existed in Scandinavia before 2013. METHODS: A microsurgery laboratory was set up and two different courses were started, aiming separately at biomedical researchers and surgeons. The course for biomedical researchers teaches basic microsurgical skills such as vessel isolation, cannulation, and arterial microvascular suture under magnification. The more advanced course for surgeons focuses on various techniques of microvascular and nerve anastomosis. Both courses use a combination of theory and practice, with emphasis on the practical part, the course for surgeons also includes clinically relevant information. RESULTS: Twelve 5-day courses using both non-living models and exercises on laboratory animals have been conducted and attended by 49 researchers and 44 surgeons. The organisation and the programme of the training courses as well as 'The 4E concept' behind the course (educational curriculum, equipment, ergonomy, and evaluation) are further detailed. CONCLUSIONS: We have successfully established the first training laboratory and series of microsurgical training courses in Scandinavia at two different levels. The experience from the first 12 courses shows the need for this type of structured training, and confirms that the microsurgical education curriculums needs to be adapted to participants' prerequisites and expectations, and various difficulty levels should be considered.