Nerve Autograft Research Articles

Assessing Survival, Distribution, and Optimal Loading Technique of Schwann Cell-Derived Exosomes Into Second-generation Axon Guidance Channels.

Peripheral nerve injury (PNI) occurs in approximately 3% of all trauma patients and can be challenging to treat, particularly when injury is severe such as with a long-segmental gap. Although peripheral nerves can regenerate after injury, functional recovery is often insufficient, leading to deficits in the quality of life of patients with PNI. Although nerve autografts are the gold standard of care, there are several disadvantages to their use, namely a lack of autologous nerve material for repair. This has led to the pursuit of alternative treatment methods such as axon guidance channels (AGCs). Second-generation AGCs have been shown to be able to deliver growth-enhancing substrates for nerve repair directly to the injury site. Although our laboratory has had success with second-generation AGCs filled with Schwann cells (SCs), SCs have their own set of issues clinically. Because of this, we have begun to utilize SC-derived exosomes as an alternative, as they have the appropriate protein markers, associate to axons in high concentrations, and are able to improve nerve regeneration. However, it is unknown how SC-derived exosomes may react within second-generation AGCs; thus, the aim of the present study was to assess the ability of SC-derived exosomes to be loaded into a second-generation AGC and how they would distribute within it. A total of 4 dry second-generation AGCs were loaded with SC-derived exosomes that were derived from green fluorescent protein (GFP)-labeled SCs. They were subsequently frozen and sliced before imaging. Here, we present findings that SC-derived exosomes can be loaded into second-generation AGCs through our established loading method utilizing negative pressure and are able to survive and equally distribute along the length of the AGC. Although only 4 second-generation AGCs were utilized, these findings indicate a potential use for SC-derived exosomes within second-generation AGCs to treat severe PNI. Future research should focus on exploring this in greater detail and in different contexts to assess the ability of SC-derived exosomes to survive at the site of injury and treat PNI.

Socioeconomic factors and outcome after repair and reconstruction of digital and major nerve trunk injuries in the upper limb

Peripheral nerve injuries in the upper limb can lead to substantial disability and pain. We aimed to assess how socioeconomic factors affect outcomes after repaired or reconstructed digital or major nerve trunk injuries in the upper limb. We identified 670 individuals, who underwent surgical nerve repair or reconstruction using sensory nerve autografts, in the Swedish National Quality Registry for Hand Surgery 2010–2018. Socioeconomic factors, including education, cohabitation, type of work, sick leave, immigrant status and income, were gathered from the Swedish statistical agency (www.scb.se) and National Diabetes Register (NDR). We calculated prevalence ratios (PR) to assess the relationship between socioeconomic factors and surgical outcomes for the nerve injuries. Individuals with a major nerve trunk injury had higher QuickDASH scores and lower income compared to those with digital nerve injury. Individuals with immigration background (adjusted PR = 2.0, 95% CI 1.2–3.2), history of > 4 weeks of sick leave the year before surgery (adjusted PR = 1.8, 95% CI 1.1–3.1), or education level below tertiary (adjusted PR = 2.8, 95% CI 1.7–4.7) had significantly higher QuickDASH scores. Recognizing impact of non-biological factors, including immigration, prior sick leave, and education level, on outcome after nerve surgery is crucial for improving prognosis in socioeconomically deprived individuals.

Recent advances in biomaterial design for nerve guidance conduits: a narrative review

Researchers have made significant strides in developing biomaterials for nerve guiding conduits, exploring natural polymers like chitosan, collagen, and silk, along with synthetic counterparts such as silicone, poly(lactic-co-glycolic acid), polycaprolactone, and poly(L-lactic acid). Each material offers distinct benefits, necessitating further study for refinement. Diverse conduit designs, including hollow/non-porous, porous, grooved, multi-channel, and fiber/hydrogel-filled conduits, have been created. Multi-channel and aligned fiber designs stand out for providing effective topographical cues guiding axon formation. Various manufacturing methods, from solvent casting to three-dimensional printing techniques like electrohydrodynamic jet and digital light processing, enable scaffold manipulation. Positive outcomes in laboratory (in vitro) and live animal (in vivo) experiments indicate the effectiveness of biomaterial-based conduits in connecting nerve gaps and promoting regeneration. However, research remains predominantly in the preclinical phase, with challenges like inadequate mechanical characteristics and the absence of biological signals. Addressing these constraints requires material refinement and the introduction of biological functionality. Future prospects involve intelligent conduits using nanocomposite biomaterials, stem cells, controlled release of neurotrophic factors, and integration of electrical and optical stimulation. Comprehensive preclinical validation is crucial before clinical translation. Despite advancements, further study is essential to fully leverage biomaterials as nerve autograft substitutes, with multidisciplinary collaboration key to continued progress in this promising field. The main goal is to present a thorough overview of the most recent developments, cutting-edge research gaps, and future prospects in the engineering and design of biomaterial-based nerve guiding conduits for the repair of peripheral nerve injury.

Reduced Graphene Oxide Fibers Combined with Electrical Stimulation Promote Peripheral Nerve Regeneration.

The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo. rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated. rGOFs exhibited aligned micro- and nano-channels with excellent mechanical and electrical properties. They are biocompatible in vitro and in vivo. All 6 groups exhibited PNI repair outcomes in view of neurological and morphological recovery. The SGC+ES group achieved similar therapeutic effects as nerve autograft group (P > 0.05), significantly outperformed other treatment groups. Immunohistochemical analysis showed that the expression of proteins related to axonalregeneration and angiogenesis were relatively higher in the SGC+ES. The rGOFs had good biocompatibility combined with excellent electrical and mechanical properties. Combined with ES, the rGOFs provided superior motor nerve recovery for a 10-mm nerve gap in a murine acute transection injury model, indicating its excellent repairing ability. That the similar therapeutic effects as autologous nerve transplantation make us believe this method is a promising way to treat peripheral nerve defects, which is expected to guide clinical practice in the future.

Peripheral nerve injury repair by electrical stimulation combined with graphene-based scaffolds.

Peripheral nerve injury (PNI) is a common clinical problem, which due to poor recovery often leads to limb dysfunction and sensory abnormalities in patients. Tissue-engineered nerve guidance conduits (NGCs) that are designed and fabricated from different materials are the potential alternative to nerve autografts. However, translation of these NGCs from lab to commercial scale has not been well achieved. Complete functional recovery with the aid of NGCs in PNI becomes a topic of general interest in tissue engineering and regeneration medicine. Electrical stimulation (ES) has been widely used for many years as an effective physical method to promote nerve repair in both pre-clinical and clinical settings. Similarly, ES of conductive and electroactive materials with a broad range of electrical properties has been shown to facilitate the guidance of axons and enhance the regeneration. Graphene and its derivatives possess unique physicochemical and biological properties, which make them a promising outlook for the development of synthetic scaffolds or NGCs for PNI repair, especially in combination with ES. Considering the discussion regarding ES for the treatment of PNI must continue into further detail, herein, we focus on the role of ES in PNI repair and the molecular mechanism behind the ES therapy for PNI, providing a summary of recent advances in context of graphene-based scaffolds (GBSs) in combination with ES. Future perspectives and some challenges faced in developing GBSs are also highlighted with the aim of promoting their clinical applications.

Management of “Long” Nerve Gaps

Long-gap nerve injuries offer unique physiological and logistical treatment challenges to the reconstructive surgeon. Options include nerve autograft, processed nerve allograft, nerve transfers, and tendon transfers. This review provides an evidence-framed discussion regarding the pros and cons of these diverse approaches.

The effectiveness of acellular nerve allografts compared to autografts in animal models: A systematic review and meta-analysis.

Treatment of nerve injuries proves to be a worldwide clinical challenge. Acellular nerve allografts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous nerve graft. To systematically review the efficacy of the acellular nerve allograft, its difference from the gold standard (the nerve autograft) and to discuss its possible indications. PubMed, Embase and Web of Science were systematically searched until the 4th of January 2022. Original peer reviewed paper that presented 1) distinctive data; 2) a clear comparison between not immunologically processed acellular allografts and autologous nerve transfers; 3) was performed in laboratory animals of all species and sex. Meta analyses and subgroup analyses (for graft length and species) were conducted for muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count diameter, tetanic contraction and amplitude using a Random effects model. Subgroup analyses were conducted on graft length and species. Fifty articles were included in this review and all were included in the meta-analyses. An acellular allograft resulted in a significantly lower muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count and smaller diameter, tetanic contraction compared to an autologous nerve graft. No difference was found in amplitude between acellular allografts and autologous nerve transfers. Post hoc subgroup analyses of graft length showed a significant reduced muscle weight in long grafts versus small and medium length grafts. All included studies showed a large variance in methodological design. Our review shows that the included studies, investigating the use of acellular allografts, showed a large variance in methodological design and are as a consequence difficult to compare. Nevertheless, our results indicate that treating a nerve gap with an allograft results in an inferior nerve recovery compared to an autograft in seven out of eight outcomes assessed in experimental animals. In addition, based on our preliminary post hoc subgroup analyses we suggest that when an allograft is being used an allograft in short and medium (0-1cm, > 1-2cm) nerve gaps is preferred over an allograft in long (> 2cm) nerve gaps.

The Medial Antebrachial Cutaneous Nerve Is a Low-Morbidity Alternative to the Standard Sural Nerve Autograft.

Nerve interposition grafting is an important technique in nerve reconstructive surgery that is used when a primary repair is not feasible without significant tension. This study sought to evaluate the long-term morbidity of the medial antebrachial cutaneous (MABC) nerve as an alternative donor nerve in comparison with sural nerve harvest. A single surgeon and institution retrospective chart review was performed to identify all patients who underwent nerve autografting using the sural and MABC as donor nerves between January 1, 2000 and December 31, 2019. Surveys assessed overall patient satisfaction with surgery, as well as donor and recipient site morbidity, satisfaction, pain, numbness, and cold sensitivity. Of the 73 patients contacted, 54 agreed to participate, and 43 of 73 (58.9%) ultimately completed the survey: 28 MABC (65.1%) and 15 sural (34.9%). There were no significant differences between the sural and MABC groups in overall satisfaction with surgery, donor and recipient site satisfaction, pain, cold sensitivity, and effect on quality of life. Even though 66.7% of sural donor sites and 75% of MABC donor sites had residual numbness, the effect this had on quality of life was very low (2 and 3, respectively). The MABC is a safe alternative to the traditional sural nerve autograft. A small subset of patients undergoing nerve autograft harvest will experience long-term morbidity in the form of pain. Conversely, the more common presence of numbness is not reported as bothersome.

The Effect of Local Purified Exosome Product, Stem Cells, and Tacrolimus on Neurite Extension

The combination of cellular and noncellular treatments has been postulated to improve nerve regeneration through a processed nerve allograft. This study aimed to evaluate the isolated effect of treatment with purified exosome product (PEP), mesenchymal stem cells (MSCs), and tacrolimus (FK506) alone and in combination when applied in decellularized allografts. A three-dimensional invitro-compartmented cell culture system was used to evaluate the length of regenerating neurites from the neonatal dorsal root ganglion into the adjacent peripheral nerve graft. Decellularized nerve allografts were treated with undifferentiated MSCs, 5% PEP, 100 ng/mL FK506, PEP and FK506 combined, or MSCs and FK506 combined (N= 9/group) and compared with untreated nerve autografts (positive control) and nerve allografts (negative control). Neurite extension was measured to quantify nerve regeneration after 48 hours, and stem cell viability was evaluated. Stem cell viability was confirmed in all MSC-treated nerve grafts. Treatments with PEP, PEP+ FK506, and MSCs+ FK506 combined were found to be superior to untreated allografts and not significantly different from autografts. Combined PEP and FK506 treatment resulted in the greatest neurite extension. Treatment with FK506 and MSCs was significantly superior to MSC alone. The combined treatment groups were not found to be statistically different. Although all treatments improved neurite outgrowth, treatments with PEP, PEP+ FK506, and MSCs+ FK506 combined had superior neurite growth compared with untreated allografts and were not found to be significantly different from autografts, the current gold standard. Purified exosome product, a cell-free exosome product, is a promising adjunct to enhance nerve allograft regeneration, with possible future avenues for clinical translation.

Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries

Recent studies suggest that acellular nerve allografts (ANA) have similar efficacy as nerve autografts in certain applications of nerve surgery. However, multiple studies also demonstrate the limitations of nerve allografts, resulting in poor patient outcomes. This submission discusses a recent case series of patients who failed allograft use with subsequent histologic analyses of these allografts. Recommendations on the treatment of nerve gaps are presented, drawing from our current understanding of allograft and autograft utility in reconstruction. Factors taken into account include recipient critical nerve function, existent nerve gap, and nerve diameter.

Comparative Analysis of Various Spider Silks in Regard to Nerve Regeneration: Material Properties and Schwann Cell Response.

Peripheral nerve reconstruction through the employment of nerve guidance conduits with Trichonephila dragline silk as a luminal filling has emerged as an outstanding preclinical alternative to avoid nerve autografts. Yet, it remains unknown whether the outcome is similar for silk fibers harvested from other spider species. This study compares the regenerative potential of dragline silk from two orb-weaving spiders, Trichonephila inaurata and Nuctenea umbratica, as well as the silk of the jumping spider Phidippus regius. Proliferation, migration, and transcriptomic state of Schwann cells seeded on these silks are investigated. In addition, fiber morphology, primary protein structure, and mechanical properties are studied. The results demonstrate that the increased velocity of Schwann cells on Phidippus regius fibers can be primarily attributed to the interplay between the silk's primary protein structure and its mechanical properties. Furthermore, the capacity of silk fibers to trigger cells toward a gene expression profile of a myelinating Schwann cell phenotype is shown. The findings for the first time allow an in-depth comparison of the specific cellular response to various native spider silks and a correlation with the fibers' material properties. This knowledge is essential to open up possibilities for targeted manufacturing of synthetic nervous tissue replacement.

Nerve regeneration using decellularized tissues: challenges and opportunities.

In tissue engineering, the decellularization of organs and tissues as a biological scaffold plays a critical role in the repair of neurodegenerative diseases. Various protocols for cell removal can distinguish the effects of treatment ability, tissue structure, and extracellular matrix (ECM) ability. Despite considerable progress in nerve regeneration and functional recovery, the slow regeneration and recovery potential of the central nervous system (CNS) remains a challenge. The success of neural tissue engineering is primarily influenced by composition, microstructure, and mechanical properties. The primary objective of restorative techniques is to guide existing axons properly toward the distal end of the damaged nerve and the target organs. However, due to the limitations of nerve autografts, researchers are seeking alternative methods with high therapeutic efficiency and without the limitations of autograft transplantation. Decellularization scaffolds, due to their lack of immunogenicity and the preservation of essential factors in the ECM and high angiogenic ability, provide a suitable three-dimensional (3D) substrate for the adhesion and growth of axons being repaired toward the target organs. This study focuses on mentioning the types of scaffolds used in nerve regeneration, and the methods of tissue decellularization, and specifically explores the use of decellularized nerve tissues (DNT) for nerve transplantation.

Utilization Trends of Nerve Autograft Alternatives for the Reconstruction of Peripheral Nerve Defects.

Autologous nerve grafting is the time-honored reconstruction method for peripheral nerve gaps. However, it is associated with donor-site morbidities. A growing number of studies have demonstrated the effective use of decellularized nerve allograft and synthetic conduits, which are convenient options with no donor deficit. The specific aim of this study was to characterize changes in practice trends for peripheral nerve defect reconstruction. The authors queried the 2015 to 2020 Merative MarketScan Databases for patients who underwent nerve autograft, allograft, synthetic conduit, and/or vein graft reconstruction. Patient demographic data (ie, location, indication) and hospital characteristics (ie, facility, provider type) were recorded. Regression analysis identified changes in trends over the study period. A total of 4331 patients underwent one or more nerve gap reconstructive procedures over the study period. Since the introduction of allograft CPT code in 2018, segmented mixed effect longitudinal modeling revealed that allograft utilization significantly increased from 21.5% to 29.6% after 2018 ( P < 0.001), whereas nerve autograft use decreased from 18.6% to 15.8% and conduit use decreased from 60% to 54.7% ( P = 0.09 and P = 0.03, respectively). When stratifying autograft by size, use of autograft less than or equal to 4 cm significantly decreased from 10.6% to 7.7% after 2018 ( P = 0.03), and autograft greater than 4 cm did not. When stratifying by state, there is heterogeneity in utilization rates of each product. After creation of a designated allograft CPT code in 2018, there was an increase in allograft use with concomitant decrease in conduit and short length autograft use, suggesting that allograft replaced a portion of procedures used in short nerve gap reconstruction.

Updates in peripheral nerve surgery of the upper extremity: diagnosis and treatment options.

The loss of function resulting from peripheral nerve injuries confers a significant burden to the patient and society. The treatment of peripheral nerve injuries requires an accurate diagnosis and formulation of a functional reconstructive plan. Advances in peripheral nerve imaging complement electrodiagnostic studies, and provide us with detailed information regarding the status of nerve injury, repair, and regeneration in order to prognosticate recovery and determine the need for surgical intervention. When direct nerve repair is not possible, the methods for bridging a nerve gap are the nerve autograft, allograft and conduit. While current research supports the use of conduits and nerve allografts for shorter nerve gaps, the nerve autograft still remains the gold standard for bridging a nerve gap. When direct nerve repair or nerve grafting fails, or is anticipated to be insufficient, nerve transfers are an alternative for reconstruction. Knowledge of axonal counts, upper limb innervation patterns, location and clustering of upper limb peripheral nerves allows for the design of new nerve transfers. The options of nerve transfers for radial, ulnar and median nerve injuries are outlined, as well as their outcomes. Nerve transfers are an attractive option for restoring motor and sensory function while minimizing donor site morbidity. However, one must consider their limitations, and preserve donor sites for secondary tendon transfer options. This article presents the latest information regarding the imaging of peripheral nerves, methods to bridge a nerve gap, and nerve transfers to aid the peripheral nerve surgeon in choosing a reconstructive plan.

The Porous Structure of Peripheral Nerve Guidance Conduits: Features, Fabrication, and Implications for Peripheral Nerve Regeneration.

Porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits the infiltration of cells, nutrients, and molecular signals and the discharge of metabolic waste. Porous structures with precisely customized pore sizes, porosities, and connectivities are being used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs for the replacement of traditional nerve autografts in the treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and the classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs, including biodegradation, mechanical performance, and permeability, were analyzed. Pore structure affects the biological behavior of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. The construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalize, summarize, and analyze methods for the preparation of porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide the development of medical nerve repair materials.

Advances in Biomimetic Nerve Guidance Conduits for Peripheral Nerve Regeneration.

Injuries to the peripheral nervous system are a common clinical issue, causing dysfunctions of the motor and sensory systems. Surgical interventions such as nerve autografting are necessary to repair damaged nerves. Even with autografting, i.e., the gold standard, malfunctioning and mismatches between the injured and donor nerves often lead to unwanted failure. Thus, there is an urgent need for a new intervention in clinical practice to achieve full functional recovery. Nerve guidance conduits (NGCs), providing physicochemical cues to guide neural regeneration, have great potential for the clinical regeneration of peripheral nerves. Typically, NGCs are tubular structures with various configurations to create a microenvironment that induces the oriented and accelerated growth of axons and promotes neuron cell migration and tissue maturation within the injured tissue. Once the native neural environment is better understood, ideal NGCs should maximally recapitulate those key physiological attributes for better neural regeneration. Indeed, NGC design has evolved from solely physical guidance to biochemical stimulation. NGC fabrication requires fundamental considerations of distinct nerve structures, the associated extracellular compositions (extracellular matrices, growth factors, and cytokines), cellular components, and advanced fabrication technologies that can mimic the structure and morphology of native extracellular matrices. Thus, this review mainly summarizes the recent advances in the state-of-the-art NGCs in terms of biomaterial innovations, structural design, and advanced fabrication technologies and provides an in-depth discussion of cellular responses (adhesion, spreading, and alignment) to such biomimetic cues for neural regeneration and repair.

Targeted Nipple Reinnervation in Gender-affirming Mastectomy Using Autologous Nerve Graft.

Our team recently described targeted nipple reinnervation (TNR) during female-to-male gender-affirming mastectomy with free nipple grafting using either direct nerve coaptation or nerve allograft. The goals of TNR are to improve sensation (including erogenous sensation) and prevent numbness, paresthesias, chronic pain, and phantom sensation. Here, we describe our modified technique, which has evolved to use autologous intercostal nerve branches as donor nerves for reinnervation if direct nerve coaptation cannot be achieved. During TNR, the T3-T5 sensory branches are preserved and coapted to the repositioned nipple-areolar complex (NAC). In patients with donor nerves that were not adequate in length to allow for direct coaptation, autologous intercostal nerve branches were not used for coaptation (branches present along the chest wall that would otherwise be lost) or one of the T3-T5 branches were harvested. An end-to-end nerve repair between the autograft and donor nerves was done, and the donor nerve/autograft complex was coapted to the NAC. Targeted muscle reinnervation was performed after autograft harvest to prevent neuroma formation. TNR with intercostal nerve autograft is technically feasible in female-to-male gender-affirming mastectomy with free nipple grafting when direct coaptation is not possible. Chest reinnervation using autologous intercostal nerve branches as donor nerves is another option for reinnervation when the nerves are too short for direct coaptation. Because the collection of long-term data is ongoing, the effectiveness of NAC reinnervation using our technique will be described in a future publication.

Histologic Comparison of the Fascicular Area of Processed Nerve Allograft Versus Cabled Sural Nerve Autograft.

The use of multiple cables of sural nerve autograft is common for peripheral nerve reconstruction when injured nerve caliber exceeds the nerve graft caliber. Although the optimal matching of neural to nonneural elements and its association with functional outcomes are unknown, it is reasonable to consider maximizing the neural tissue structure available for nerve regeneration. No prior studies have compared directly the cross-sectional fascicular area between cabled nerve autografts and size-selected nerve allografts. This study evaluated the cross-sectional fascicular area between native nerve stumps and two reconstructive nerve grafting methods: cabled sural nerve autograft (CSNA) and processed nerve allograft (PNA). CSNA from matched cadaveric specimens and PNA were used to reconstruct nerve defects in the median and ulnar nerves of six pairs of cadaveric specimens. Nerve reconstructions were done by fellowship-trained hand surgeons. The total nerve area, fascicular area, and nonfascicular area were measured histologically. The CSNA grafts had significantly less fascicular area than PNA and caliber-matched native nerve. The PNA grafts had a significantly higher percent fascicular area compared with the intercalary CNSA graft. Fascicular area was significantly greater in PNA versus CSNA. The PNA consistently demonstrated a match in fascicular area closer to the native nerve stumps than CSNA, where CSNA had significantly smaller fascicular area compared with native nerve stumps.

Challenges in Nerve Repair and Reconstruction.

Peripheral nerve injuries may substantially impair a patient's function and quality of life. Despite appropriate treatment, outcomes often remain poor. Direct repair remains the standard of care when repair is possible without excessive tension. For larger nerve defects, nerve autografting is the gold standard. However, a considerable challenge is donor site morbidity. Processed nerve allografts and conduits are other options, but evidence supporting their use is limited to smaller nerves and shorter gaps. Nerve transfer is another technique that has seen increasing popularity. The future of care may include novel biologics and pharmacologic therapy to enhance regeneration.

Local Administration of Minocycline Improves Nerve Regeneration in Two Rat Nerve Injury Models.

Peripheral nerve injuries are quite common and often require a surgical intervention. However, even after surgery, patients do not often regain satisfactory sensory and motor functions. This, in turn, results in a heavy socioeconomic burden. To some extent, neurons can regenerate from the proximal nerve stump and try to reconnect to the distal stump. However, this regenerating capacity is limited, and depending on the type and size of peripheral nerve injury, this process may not lead to a positive outcome. To date, no pharmacological approach has been used to improve nerve regeneration following repair surgery. We elected to investigate the effects of local delivery of minocycline on nerve regeneration. This molecule has been studied in the central nervous system and was shown to improve the outcome in many disease models. In this study, we first tested the effects of minocycline on SCL 4.1/F7 Schwann cells in vitro and on sciatic nerve explants. We specifically focused on the Schwann cell repair phenotype, as these cells play a central role in orchestrating nerve regeneration. Finally, we delivered minocycline locally in two different rat models of nerve injury, a sciatic nerve transection and a sciatic nerve autograft, demonstrating the capacity of local minocycline treatment to improve nerve regeneration.