Nerve Implantation Research Articles

Biomechanical modelling infers that collagen content within peripheral nerves is a greater indicator of axial Young's modulus than structure.

The mechanical behaviour of peripheral nerves is known to vary between different nerves and nerve regions. As the field of nerve tissue engineering advances, it is vital that we understand the range of mechanical regimes future nerve implants must match to prevent failure. Data on the mechanical behaviour of human peripheral nerves are difficult to obtain due to the need to conduct mechanical testing shortly after removal from the body. In this work, we adapt a 3D multiscale biomechanical model, developed using asymptotic homogenisation, to mimic the micro- and macroscale structure of a peripheral nerve. This model is then parameterised using experimental data from rat peripheral nerves and used to investigate the effect of varying the collagen content, the fibril radius and number density, and the macroscale cross-sectional geometry of the peripheral nerve on the effective axial Young's moduli of the whole nerve. Our results indicate that the total amount of collagen within a cross section has a greater effect on the axial Young's moduli compared to other measures of structure. This suggests that the amount of collagen in a cross section of a peripheral nerve, which can be measured through histological and imaging techniques, is one of the key metrics that should be recorded in the future experimental studies on the biomechanical properties of peripheral nerves.

Engineered Regenerative Isolated Peripheral Nerve Interface for Targeted Reinnervation.

A regenerative peripheral nerve interface (RPNI) offers a therapeutic solution for nerve injury through reconstruction of the target muscle. However, implanting a transected peripheral nerve into an autologous skeletal muscle graft in RPNI causes donor-site morbidity, highlighting the need for tissue-engineered skeletal muscle constructs. Here, an engineered regenerative isolated peripheral nerve interface (eRIPEN) is developed using 3D skeletal cell printing combined with direct electrospinning to create a nanofiber membrane envelop for host nerve implantation. In this in vivo study, after over 8 months of RPNI surgery, the eRIPEN exhibits a minimum Feret diameter of 15-20µm with a cross-sectional area of 100-500 µm2, representing the largest distribution of myofibers. Furthermore, neuromuscular junction formation and muscle contraction with a force of ≈28 N are observed. Notably, the decreased hypersensitivity to mechanical/thermal stimuli and an improved tibial functional index from -77 to -56 are found in the eRIPEN group. The present novel concept of eRIPEN paves the way for the utilization and application of tissue-engineered constructs in RPNI, ultimately realizing neuroprosthesis control through synaptic connections.

Biocompatible antibiotic-coupled nickel-titanium nanoparticles as a potential coating material for biomedical devices

The challenges facing metallic implants for reconstructive surgery include the leaching of toxic metal ions, a mismatch in elastic modulus between the implant and the treated tissue, and the risk of infection. These problems can be addressed by passivating the metal surface with an organic substrate and incorporating antibiotic molecules. Nitinol (NiTi), a nickel-titanium alloy, is used in devices for biomedical applications due to its shape memory and superelasticity. However, unmodified NiTi carries a risk of localized nickel toxicity and inadequately supports angiogenesis or neuroregeneration due to limited cell adhesion, poor biomineralization, and little antibacterial activity. To address these challenges, NiTi nanoparticles were modified using self-assembled phosphonic acid monolayers and functionalized with the antibiotics ceftriaxone and vancomycin via the formation of an amide. Surface modifications were monitored to confirm that phosphonic acid modifications were present on NiTi nanoparticles and 100% of the samples formed ordered films. Modifications were stable for more than a year. Elemental composition showed the presence of nickel, titanium, and phosphorus (1.9% for each sample) after surface modifications. Dynamic light scattering analysis suggested some agglomeration in solution. However, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy confirmed a particle size distribution of <100 nm, the even distribution of nanoparticles on coverslips, and elemental composition before and after cell culture. B35 neuroblastoma cells exhibited no inhibition of survival and extended neurites of approximately 100 μm in total length when cultured on coverslips coated with only poly-l-lysine or with phosphonic acid-modified NiTi, indicating high biocompatibility. The ability to support neural cell growth and differentiation makes modified NiTi nanoparticles a promising coating for surfaces in metallic bone and nerve implants. NiTi nanoparticles functionalized with ceftriaxone inhibited Escherichia coli and Serratia marcescens (SM6) at doses of 375 and 750 μg whereas the growth of Bacillus subtilis was inhibited by a dose of only 37.5 μg. NiTi-vancomycin was effective against B. subtilis at all doses even after mammalian cell culture. These are common bacteria associated with infected implants, further supporting the potential use of functionalized NiTi in coating reconstructive implants.

Economic Cost-Benefit Analysis of Nerve Implanted into Muscle versus Targeted Muscle Reinnervation versus Regenerative Peripheral Nerve Interface, for Treatment of the Painful Neuroma.

This study investigated the relative cost utility of three techniques for the management of symptomatic neuromas after neuroma excision: (1) implantation of nerve into muscle, (2) targeted muscle reinnervation (TMR), and (3) regenerative peripheral nerve interface (RPNI). The costs associated with each procedure were determined using Common Procedural Terminology codes in combination with data from the Centers for Medicaid and Medicare Services Physician and Facility 2020 Fee Schedules. The relative utility of the three procedures investigated was determined using changes in Patient-Reported Outcomes Measurement Information System (PROMIS) and Numeric Rating Scale (NRS) pain scores as reported per procedure. The relative utility of each procedure was reported in terms of quality-adjusted life years (QALYs), as is standard in the literature. The least expensive option for the surgical treatment of painful neuromas was nerve implantation into an adjacent muscle. In contrast, for the treatment of four neuromas, as is common postamputation, TMR without a microscope was found to cost $50,061.55 per QALY gained, TMR with a microscope was found to cost $51,996.80 per QALY gained, and RPNI was found to cost $14,069.28 per QALY gained. While RPNI was more expensive than nerve implantation into muscle, it was still below the standard willingness-to-pay threshold of $50,000 per QALY, while TMR was not. Evaluation of costs and utilities associated with the various surgical options for the management of painful neuromas suggest that nerve implantation into muscle is the least expensive option with the best improvement in QALY, while demonstrating comparable outcomes to TMR and RPNI with regard to pain symptoms.

Supercritical Carbon Dioxide Decellularization of Porcine Nerve Matrix for Regenerative Medicine.

Tissue engineering scaffolds are often made from the decellularization of tissues. The decellularization of tissues caused by prolonged contact with aqueous detergents might harm the microstructure and leave cytotoxic residues. In this research, we developed a new technique to use supercritical carbon dioxide (Sc-CO2)-based decellularization for porcine nerve tissue. The effect of decellularization was analyzed by histological examination, including Hematoxylin and Eosin, Masson's Trichrome staining, and 4',6-diamidino-2-phenylindole staining. Moreover, biochemical analysis of the decellularized tissues was also performed by measuring DNA content, amount of collagen, and glycosaminoglycans (GAGs) after decellularization. The results showed that the tissue structure was preserved, cells were removed, and the essential components of extracellular matrix, such as collagen fibers, elastin fibers, and GAG fibers, remained after decellularization. In addition, the DNA content was decreased compared with native tissue, and the concentration of collagen and GAGs in the decellularized nerve tissue was the same as in native tissue. The in vivo experiment in the rat model showed that after 6 months of decellularized nerve implantation, the sciatic function index was confirmed to recover in decellularized nerve. Morphological analysis displayed a range of infiltrated cells in the decellularized nerve, similar to that in native tissue, and the number of Schwann cells that play essential for motor function and sensory in the decellularized nerve was confirmed. These findings indicate that tissue decellularization using Sc-CO2 has been successfully used in tissue engineering.

Development of a feline model for preclinical research of a new translabyrinthine auditory nerve implant.

Cochlear implants are among the most successful neural prosthetic devices to date but exhibit poor frequency selectivity and the inability to consistently activate apical (low frequency) spiral ganglion neurons. These issues can limit hearing performance in many cochlear implant patients, especially for understanding speech in noisy environments and in perceiving or appreciating more complex inputs such as music and multiple talkers. For cochlear implants, electrical current must pass through the bony wall of the cochlea, leading to widespread activation of auditory nerve fibers. Cochlear implants also cannot be implanted in some individuals with an obstruction or severe malformations of the cochlea. Alternatively, intraneural stimulation delivered via an auditory nerve implant could provide direct contact with neural fibers and thus reduce unwanted current spread. More confined current during stimulation can increase selectivity of frequency fiber activation. Furthermore, devices such as the Utah Slanted Electrode Array can provide access to the full cross section of the auditory nerve, including low frequency fibers that are difficult to reach using a cochlear implant. However, further scientific and preclinical research of these Utah Slanted Electrode Array devices is limited by the lack of a chronic large animal model for the auditory nerve implant, especially one that leverages an appropriate surgical approach relevant for human translation. This paper presents a newly developed transbullar translabyrinthine surgical approach for implanting the auditory nerve implant into the cat auditory nerve. In our first of a series of studies, we demonstrate a surgical approach in non-recovery experiments that enables implantation of the auditory nerve implant into the auditory nerve, without damaging the device and enabling effective activation of the auditory nerve fibers, as measured by electrode impedances and electrically evoked auditory brainstem responses. These positive results motivate performing future chronic cat studies to assess the long-term stability and function of these auditory nerve implant devices, as well as development of novel stimulation strategies that can be translated to human patients.

Regulating Schwann cells and endothelial cells by YIGSR functionalized porous chitosan scaffolds for nerve regeneration

Numerous artificial nerve implants for repair of peripheral nerve injury has been developed while their performance still needs to be further improved. In this study, the Tyr-Ile-Gly-Ser-Arg (YIGSR, YR) functionalized porous chitosan scaffolds were prepared by freeze-drying technique and surface biomodification for simultaneous regulation of Schwann cells (SCs) and endothelial cells (ECs), which play important role in nerve regeneration. The physicochemical properties were characterized, including morphology, composition, wettability, mechanical properties, porosity, etc. The culture of SCs and ECs were used to evaluate the pro-neural and endothelial cell growth effects of the grafts, as well as the constitutive relationship between YR-regulated SCs and ECs. Then, the mechanisms involved were explored using molecular biology experiments. The results showed that the YR-grafted chitosan scaffolds could be successfully prepared with aggregated dopamine and YR particles on the surface of the scaffolds. The scaffolds showed a uniform porous structure, YR grafting decreased the porosity of the scaffolds but increased the mechanical properties of the scaffolds, and YR displayed a relatively stable release behavior. Further on, all YR-grafted scaffolds were proven no cytotoxicity and significantly promoted the proliferation and spreading of SCs and ECs, up-regulated the gene expression of Tumor Necrosis Factor-alpha (TNF-α) and Recombinant Contactin 2 (Cntn2), and facilitated the release of growth factors such as brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF). Thus, this YR-functionalized scaffold is expected to simultaneously promote both neuronal cell growth and vascularization in peripheral nerve regeneration. This study provides a strategy for the development of biofunctionalized nerve grafts.

Finite element analysis of the angle range in trans-inferior alveolar nerve implantation at the mandibular second molar

BackgroundTrans- inferior alveolar nerve (IAN) implantation technique was wildly used while the potential appropriate angle range in which the residual alveolar bone can bear the stress without absorption are currently unclear. This study aimed to evaluate the stress distribution pattern of the interface between bone and implant by finite element analysis (FEA) to determine the appropriate range of the implant tilt angle.MethodsCone beam computed tomography (CBCT) images of 120 patients with missing mandibular second molars and vertical bone height < 9 mm in the edentulous area were selected. The distances from the mandibular nerve canal to the buccal cortex, the lingual cortex and the alveolar ridge crest were measured by using a combination of software. The angular ranges of the buccal-lingual inclination of simulated trans-IAN implants were measured and three-dimensional finite element models were constructed in the mandibular second molar area according to the differences of the inclination angles. A vertical load (200N) was then applied to analyze the biomechanical conditions of the implant-bone interface during median occlusion.ResultsThe distance at the second molar from the nerve canal to the buccal cortex, lingual cortex and alveolar crest were 6.861 ± 1.194 mm, 2.843 ± 0.933 mm and 7.944 ± 0.77 mm. Trans-IAN implantation was feasible in 73.33% of patients. The minimum angle and maximum angles of the buccal-lingual inclination of the simulated implant were 19.135 ± 6.721° and 39.282 ± 6.581°. When a vertical static load of 200N was applied, the tensile stress in cortical bone gradually increased with the increase of the implant tilt angle. When the inclination angle reached 30°, the tensile stress (105.9 MPa) exceeded the yield strength (104 MPa) of cortical bone. Compared with the conventional implants, the stress peak value of the vertical ultra-short implant in cortical bone was greater than the stress peak value of the conventional implants at 10°(79.81 MPa) and 20°(82.83 MPa) and was smaller than the stress of the implant at 30°(105.9 MPa) and 40°(107.8 MPa). Therefore, when the bone mass allows, conventional-length implants should be selected whenever possible, and an operative range of the trans-IAN implantation in the mandibular second molar could be retained with an inclination angle of < 30°.ConclusionsThe mandibular nerve canal at the mandibular second molar was obviously biased to the lingual side, which ensured sufficient bone mass at the buccal side. In most patients with severe mandibular atrophy, it was possible to maintain a safe distance from the nerve canal with conventional-length implants via the trans-IAN implantation technique.

Design of a novel millimeter size wireless electrical stimulator and its targeting effect on the Schaffer-CA1 pathway in rat hippocampus

Traditional tethered nerve implants have many limitations since they rely on physical wires for power and signal transmission. Wireless stimulation technology can promote the exploration of neurological diseases and meet patient requirements, stemming from its portability and efficiency. In this paper, the link transmission characteristics of a sub-millimeter inductor are investigated by simulation, electrical tests, and theoretical analysis. The inductor acts as the receiving coil of a wireless stimulation device, and the wireless energy transmission process based on magnetic induction coupling is analyzed. Second, a novel millimeter-scale wireless stimulator device for neuromodulation is designed based on the parameters of transmitting and receiving coils obtained from the simulation. Finally, rat electrophysiological experiments are conducted to assess the feasibility of the device. The field Excitatory Post Synaptic Potential baseline is first recorded in the CA1 radiation area for 10 min, followed by the addition of high-frequency stimulation, and after successful induction of long-term potentiation (LTP) and recording for 10 min, the two coils are fixed at a distance of 1 cm and the hippocampal Schaffer-CA1 pathway is added. The experimental results show that the addition of wireless stimulation can modulate the transmission of synaptic electrical activity in the hippocampal Schaffer-CA1 pathway and significantly increase the level of (LTP) induction. A millimeter-scale wireless stimulation device is investigated and designed in this paper, the feasibility of the device is demonstrated through ex vivo electrophysiological experiments, and its effects on the targeted modulation of the Schaffer-CA1 pathway in the rat hippocampus are described.

Dual-bionic regenerative microenvironment for peripheral nerve repair.

Autologous nerve grafting serves is considered the gold standard treatment for peripheral nerve defects; however, limited availability and donor area destruction restrict its widespread clinical application. Although the performance of allogeneic decellularized nerve implants has been explored, challenges such as insufficient human donors have been a major drawback to its clinical use. Tissue-engineered neural regeneration materials have been developed over the years, and researchers have explored strategies to mimic the peripheral neural microenvironment during the design of nerve catheter grafts, namely the extracellular matrix (ECM), which includes mechanical, physical, and biochemical signals that support nerve regeneration. In this study, polycaprolactone/silk fibroin (PCL/SF)-aligned electrospun material was modified with ECM derived from human umbilical cord mesenchymal stem cells (hUMSCs), and a dual-bionic nerve regeneration material was successfully fabricated. The results indicated that the developed biomimetic material had excellent biological properties, providing sufficient anchorage for Schwann cells and subsequent axon regeneration and angiogenesis processes. Moreover, the dual-bionic material exerted a similar effect to that of autologous nerve transplantation in bridging peripheral nerve defects in rats. In conclusion, this study provides a new concept for designing neural regeneration materials, and the prepared dual-bionic repair materials have excellent auxiliary regenerative ability and further preclinical testing is warranted to evaluate its clinical application potential.

Artificial nerve conduit for guiding peripheral nerve growth (cadaveric study)

At present, the search for effective ways of restoring peripheral nerves with anatomical damage continues. Autoplasty still remains the gold standard, which, however, is not without its drawbacks. The use of nerve implants for promoting directional axon growth is essential and promising.Objective: to study the biomechanical properties of laboratory samples of an artificial nerve conduit (NGC) made of hybrid biomaterials and to, on cadaveric material, assess the technical feasibility of using them in surgical practice to repair extended peripheral nerve defects.Material and methods. The objects of the study were three electrospun NGC samples: from synthetic material (polycaprolactone, PCL) and hybrid biomaterials (PCL + gelatin or PCL + collagen). The work compared the physical and mechanical properties of NGC: stiffness, plasticity, elasticity, brittleness, resistance to chemical attack, their ability to be impregnated with liquid media, permeability, possibility of making an anastomosis between the implant and the nerve during surgical procedure. Cadaveric material was the object of the study: we used a dissected superficial sensory branch of the human right radial nerve, 2 mm in diameter, isolated on the forearm, about 12 cm in length, because it most corresponded to the diameter of the NGC samples tested. After surgery, the echogenic features of the implants and their anastomoses with the nerve were assessed by ultrasound imaging.Results. It was found that hybrid NGC samples, based on their biomechanical properties, are fundamentally suitable for use in surgical practice, to ensure growth and replacement of a peripheral nerve defect. However, the best composition of a nerve guide can be established after comparative preclinical study of the biocompatible and functional properties of hybrid material samples.Conclusion. The physical and mechanical properties of the investigated NGC samples made of hybrid biomaterials meet the technical requirements for implantable nerve conduits for surgical application.

Micron track chitosan conduit fabricated by 3D-printed model topography provides bionic microenvironment for peripheral nerve regeneration.

The micron track conduit (MTC) and nerve factor provide a physical and biological model for simulating peripheral nerve growth and have potential applications for nerve injury. However, it has rarely been reported that they synergize on peripheral nerves. In this study, we used bioderived chitosan as a substrate to design and construct a neural repair conduit with micron track topography using threedimensional (3D) printing topography. We loaded the MTC with neurotrophin-3 (NT-3) to promote the regeneration of sensory and sympathetic neurons in the peripheral nervous system. We found that the MTC@NT3 composite nerve conduit mimicked the microenvironment of peripheral nerves and promoted axonal regeneration while inducing the targeted growth of Schwann cells, which would promote functional recovery in rats with peripheral nerve injury. Artificial nerve implants with functional properties can be developed using the strategy presented in this study.

Anatomical Variations of Modiolus in Relation with Vestibular and Cranial Morphology on CT Scans

Background: Fundamental knowledge of the anatomy and physiology of the inner ear is necessary to understand otologic diseases and therapeutic strategies. Aim: Evaluate the inter- and intraindividual variability of the modiolar position in relation to vestibular landmarks and cranial morphology on computed tomography scans (CT scan). Methods: Thirty CT scans of normal temporal bones (25 adults, 5 children) were analyzed after multiplanar reconstruction (MPR). The measurements for each ear included the angle of each semicircular canal (SCC) made by a line passing through the chosen plane and a line passing between the apex and the ampulla of the SCC studied and the angle of the modiolus in the transverse and sagittal planes. Results: Intraindividual asymmetries with a moderate to good right/left correlation were observed for the lateral SCC in the transverse plane, posterior SCC in the frontal plane, and the superior SCC in the sagittal plane and for the modiolus in the transverse plane. Conclusions: An anatomical variability in the cochlea, independent of other surrounding anatomical elements, seems to exist, but the SCCs seem to remain symmetrical. Significance: The orientation of the modiolus is an important knowledge to acquire during presurgical planning prior to transmodiolar auditory nerve implantation.

Multifaceted understanding of human nerve implants to design optimized electrodes for bioelectronics

Bioelectronic medicine is a promising venue for treatment of disabilities using implantable neural interfaces. Peripheral neurostimulation of residual nerves recently enabled multiple functional benefits in amputees. Despite the preliminary promising impact on patients' life, the over-time stability of implants and the related nerve reactions are unclear. To unveil the mechanisms and inform the design of better nerve-electrode interfaces, we engaged a multifaceted approach, merging functional responses from patients, their histological data, and corresponding computational modelling. Neurostimulation evoked different selective sensation locations and qualities over-time, with respective perceptual thresholds, that showed different degree of time stabilities dependent from the stimulating active sites. The histological analysis after explant showed mild tissue reactions, while electromechanically active sites and substrates remained conserved. Computational models, based on patients' histology, revealed the direct influence of the simulated tissue reaction to change of thresholds and type of perceived sensations. Novel insights of electrode biocompatibility was observed compared to animals and the increase of thresholds could be predicted computationally. This multifaced framework suggest that future intraneural implants should have easier implantation and higher biocompatibility counteracting the sensations changes through AI-based stimulations and electrode coatings.

Design and Functional Test of Transistor Inverter Based on Polyvinyl Alcohol and Graphene Oxide Electrolyte

Eco‐friendly “green” electronics are attracting increasing interest in recent years. For example, neural prostheses, nerve implants, drug delivery devices, and diagnostic electronics, as well as some green materials (paper, silk, and polysaccharides) with bioabsorbable and biocompatible transistors, load inverters, and other devices. Here, biodegradable polyvinyl alcohol (PVA)/graphene oxide (GO) electric double‐layer (EDL) transistors are prepared on glass substrates. PVA film treated with GO solution is used as a gate dielectric. Oxide EDL transistors show good performance. A resistive load inverter is also constructed, which shows full swing characteristics and high voltage gain at low operating voltage. The waveform conversion is realized, including the conversion from sine wave to rectangular wave, and the conversion from noise signal to two‐bit output. In addition, PVA/GO transistors can be easily dissolved in water. The proposed PVA/GO oxide transistors may have potential applications in “green” portable devices.

Nerve implants with bioactive interfaces enhance neurite outgrowth and nerve regeneration in vivo

Nerve implants functionalized with growth factors and stem cells are critical to promote neurite outgrowth, regulate neurodifferentiation, and facilitate nerve regeneration. In this study, human umbilical cord mesenchymal stem cells (hUCMSCs) and 3,4-hydroxyphenalyalanine (DOPA)-containing insulin-like growth factor 1 (DOPA-IGF-1) were simultaneously applied to enhance the bioactivity of poly(lactide-co-glycolide) (PLGA) substrates which will be potentially utilized as nerve implants. In vitro and in vivo evaluations indicated that hUCMSCs and DOPA-IGF-1 could synergistically regulate neurite outgrowth of PC12 cells, improve intravital recovery of motor functions, and promote conduction of nerve electrical signals in vivo. The enhanced functional and structural nerve regeneration of injured spinal cord might be mainly attributable to the synergistically enhanced biofunctionality of hUCMSCs and DOPA-IGF-1/PLGA on the bioactive interfaces. Findings from this study demonstrate the potential of hUCMSC-seeded, DOPA-IGF-1-modified PLGA implants as promising candidates for promoting axonal regeneration and motor functional recovery in spinal cord injury treatment.

A finite element model of the mechanical interactions between peripheral nerves and intrafascicular implants

Objective. Intrafascicular peripheral nerve implants are key components in the development of bidirectional neuroprostheses such as touch-enabled bionic limbs for amputees. However, the durability of such interfaces is hindered by the immune response following the implantation. Among the causes linked to such reaction, the mechanical mismatch between host nerve and implant is thought to play a decisive role, especially in chronic settings. Approach. Here we focus on modeling mechanical stresses induced on the peripheral nerve by the implant’s micromotion using finite element analysis. Through multiple parametric sweeps, we analyze the role of the implant’s material, geometry (aspect-ratio and shape), and surface coating, deriving a set of parameters for the design of better-integrated implants. Main results. Our results indicate that peripheral nerve implants should be designed and manufactured with smooth edges, using materials at most three orders of magnitude stiffer than the nerve, and with innovative geometries to redistribute micromotion-associated loads to less delicate parts of the nerve such as the epineurium. Significance. Overall, our model is a useful tool for the peripheral nerve implant designer that is mindful of the importance of implant mechanics for long term applications.

Evaluation of Pneumatic Insertion Stability of Utah Slanted Electrode Arrays in Rat Sciatic Nerve.

The Utah Electrode Array (UEA) and its variants (e.g., the Utah Slanted Electrode Array, or USEA) have been prominent contributors to advances in the field of neural engineering over the past decade. The most common means of inserting UEA and USEA devices into neural tissue is pneumatic insertion performed by an insertion wand and a pneumatic controller. As design changes from the well-established standards occur to better suit specialized surgical applications, it becomes essential to verify that the alterations do not compromise the structural integrity of the device during insertion. This paper characterizes and demonstrates the reliability of specialized USEAs and insertion wands designed for auditory nerve implants following pneumatic insertion into a rat sciatic nerve. The results show that proposed changes in the USEA form factor and pneumatic insertion ergonomics do not compromise implant stability and device structural viability.

Surgical Approaches for Prevention of Neuroma at Time of Peripheral Nerve Injury.

Painful neuroma is a frequent sequela of peripheral nerve injury which can result in pain and decreased quality of life for the patient, often necessitating surgical intervention. End neuromas are benign neural tumors that commonly form after nerve transection, when axons from the proximal nerve stump regenerate in a disorganized manner in an attempt to recreate nerve continuity. Inflammation and collagen remodeling leads to a bulbous end neuroma which can become symptomatic and result in decreased quality of life. This review covers surgical prophylaxis of end neuroma formation at time of injury, rather than treatment of existing neuroma and prevention of recurrence. The current accepted methods to prevent end neuroma formation at time of injury include different mechanisms to inhibit the regenerative response or provide a conduit for organized regrowth, with mixed results. Approaches include proximal nerve stump capping, nerve implantation into bone, muscle and vein, various pharmacologic methods to inhibit axonal growth, and mechanisms to guide axonal growth after injury. This article reviews historical treatments that aimed to prevent end neuroma formation as well as current and experimental treatments, and seeks to provide a concise, comprehensive resource for current and future therapies aimed at preventing neuroma formation.

Complex regional pain syndrome patient treated with a below knee amputation, implanting nerves directly into muscle: A case report

Persistent, disabling lower extremity pain, outside the distribution of a single nerve, is termed chronic regional pain syndrome (CRPS), but, in reality, this chronic pain is often due to multiple peripheral nerve injuries. It is the purpose of this report to describe the first application of the "traditional," nerve implantation into muscle, usually used in the treatment of a painful neuroma, as a pre-emptive surgical technique in doing a below knee amputation (BKA). In 2011, a 51-year-old woman developed severe, disabling CRPS, after a series of operations to treat an enchondroma of the left fifth metatarsal. When appropriate peripheral nerve surgeries failed to relieve distal pain, a BKA was elected. The approach to the BKA included implantation of each transected peripheral nerve directly into an adjacent muscle. At 5.0 years after the patient's BKA, the woman reported full use of this extremity, using the prosthesis, and was free of phantom limb and residual limb pain. This anecdotal experience gives insight that long-term relief of lower extremity CRPS can be achieved by a traditional BKA utilizing the approach of implanting each transected nerve into an adjacent muscle.