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Background/Objectives: Microsurgery employs techniques requiring optical magnification and specialized instruments to operate on small anatomical structures, including small vessels. These methods are integral to plastic surgery, enabling procedures such as free tissue transfer, nerve reconstruction, replantation, and lymphatic surgery. This paper explores the historical development, advancements, and current applications of microsurgery in plastic surgery. Methods: The databases MEDLINE (via PubMed) and Web of Science were selectively searched with the term "(((microsurgery) OR (advances)) OR (robotic)) OR (AI)) AND (((lymphatic surgery) OR (peripheral nerve surgery)) OR (allotransplantation))" and manually checked for relevance. Additionally, a supplementary search among the references of all publications included was performed. Articles were included that were published in English or German up to June 2024. Results: Modern microsurgical techniques have revolutionized plastic surgery, enabling precise tissue transfers, improved nerve reconstruction, and effective lymphedema treatments. The evolution of robotic-assisted surgery, with systems like da Vinci and MUSA, has enhanced precision and reduced operative times. Innovations in imaging, such as magnetic resonance (MR) lymphography and near-infrared fluorescence, have significantly improved surgical planning and outcomes. Conclusions: The continuous advancements in microsurgery, including supermicrosurgical techniques and robotic assistance, have significantly enhanced the capabilities and outcomes of plastic surgery. Future developments in AI and robotics promise further improvements in precision and efficiency, while new imaging modalities and surgical techniques expand the scope and success of microsurgical interventions. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability. Herein, we selected induced pluripotent stem cells (iPSCs) derived exosomes to supplement acellular nerve grafts (ANGs) with the aim of restoring long-distance peripheral nerve defects. Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4, Sox2, Klf4, and c-Myc. The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4, SSEA4, Nanog, Sox2, which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells (SCs) in vitro. After isolation and biological characteristics of iPSCs-derived exosomes, we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination. After that, we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats. Owing to the promotion of iPSCs-derived exosomes, satisfactory regenerative outcomes were achieved including gait behavior analysis, electrophysiological assessment, and morphological analysis of regenerated nerves. Especially, motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers. Taken together, our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects, and thus represents a cell-free strategy for future clinical applications.

The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form. This review aims to provide an overview of the scientific evidence on the biology of adipose tissue, the role of adipose-derived stem cells, and the indications of adipose tissue grafting in peripheral nerve surgery. Adipose tissue is easily accessible through the lower abdomen and inner thighs. Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress, resulting in variable survival of adipocytes within the first 24 hours. Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts. Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization, and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue. In clinical studies, the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results. Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new, more studies are needed to explore safety and long-term effects on peripheral nerve regeneration. The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated, enzyme-free, and used in the same surgical procedure, e.g. adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction. Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival. Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.

Modern end-to-side (ETS) nerve transfers have undergone several permutations since the early 1990's. Preclinical data have revealed important mechanisms and patterns of donor axon outgrowth into the recipient nerves and target reinnervation. The versatility of ETS nerve transfers can also potentially address several processes that limit functional recovery after nerve injury by babysitting motor end-plates and/or supporting the regenerative environment within the denervated nerve. Further clinical and basic science work is required to clarify the ideal clinical indications, contraindications, and mechanisms of action for these techniques in order to maximize their potential as reconstructive options., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There are several possibilities for repairing a nerve defect. These include nerve grafting, tissues for bridging, biological or synthetic nerve conduits. Such conduits, alone or filled with different tissues or substances, may be the key for a major breakthrough in the modern treatment of nerve defects. The easiest way to research these new methods is by experimental in vivo research on live animals – such as the Wistar rats. The following article aims to compare 4 different types of repairs for nerve defects: the nerve graft, a biologic nerve conduit (rat aorta), rat aorta with platelet rich plasma and rat aorta with stem cells.

Abstract Background Even though several studies reported donor autologous nerve grafts for digital nerve defects, there is no report in the literature regarding acceptable graft for thumb nerves. The purpose of this study is to provide guidelines for autologous nerve graft selection by detecting similarities between thumb nerve zones and donor nerve with regard to the number of fascicles and cross-sectional area. Materials and methods Five cadavers were used in this study. An anatomical zoning system was defined for thumb nerves (zones 1, 2, 3). Sural nerve (SN), medial antebrachial cutaneous nerve (MABCN), lateral antebrachial cutaneous nerve (LABCN), posterior interosseous nerve (PIN), and anterior interosseous nerve (AIN) were selected as donor nerve grafts. The number of fascicles and surface area (mm2) was defined. Results The mean of the fascicle number in zone 1, zone 2, zone 3, AIN, PIN, LABCN, MABCN, and SN were 3.8, 4.7, 6.1, 2.2, 1.8, 4.5, 3.1, and 6.4, respectively. The mean of the surface area in zone 1, zone 2, zone 3, AIN, PIN, LABCN, MABCN, and SN were 2.19, 6.26, 4.04, 1.58, 0.71, 5.00, 3.01, and 8.06, respectively. Conclusions LABCN is the best choice for all zones that has fascicular matching with all three zones of thumb nerves and caliber matching with zones 2 and 3. In zone 1, the best nerve graft is MABCN which has both suitable caliber and fascicle count.

Background The rabbit sciatic nerve injury model may represent a valuable alternative for critical gap distance seen in humans but often leads to automutilation. In this study, we modified the complete sciatic nerve injury model for avoiding autophagy. Materials and Methods In 20 adult female New Zealand White rabbits, instead of transecting the complete sciatic nerve, we unilaterally transected the tibial portion and preserved the peroneal portion. Thereby loss of sensation in the dorsal aspect of the paw was avoided. The tibial portion was repaired in a reversed autograft approach in a length of 2.6 cm. In an alternative repair approach, a gap of 2.6 cm in length was repaired with a chitosan-based nerve guide. Results During the 6-month follow-up period, there were no incidents of autotomy. Nerve regeneration of the tibial portion of the sciatic nerve was evaluated histologically and morphometrically. A clear difference between the distal segments of the healthy contralateral and the repaired tibial portion of the sciatic nerve was detectable, validating the model. Conclusion By transecting the isolated tibial portion of the rabbit sciatic nerve and leaving the peroneal portion intact, it was possible to eliminate automutilation behavior.

Background  Robotic-assisted techniques are a tremendous revolution in modern surgery, and the advantages and indications were well discussed in different specialties. However, the use of robotic technique in plastic and reconstructive surgery is still very limited, especially in the field of peripheral nerve reconstruction. This study aims to identify current clinical applications for peripheral nerve reconstruction, and to evaluate the advantages and disadvantages to establish potential uses in the future. Methods  A review was conducted in the literatures from PubMed focusing on currently published robotic peripheral nerve intervention techniques. Eligible studies included related animal model, cadaveric and human studies. Reviews on robotic microsurgical technique unrelated to peripheral nerve intervention and non-English articles were excluded. The differences of wound assessment and nerve management between robotic-assisted and conventional approach were compared. Results  Total 19 studies including preclinical experimental researches and clinical reports were listed and classified into brachial plexus reconstruction, peripheral nerve tumors management, peripheral nerve decompression or repair, peripheral nerve harvesting, and sympathetic trunk reconstruction. There were three animal studies, four cadaveric studies, eight clinical series, and four studies demonstrating clinical, animal, or cadaveric studies simultaneously. In total 53 clinical cases, only 20 (37.7%) cases were successfully approached with minimal invasive and intervened robotically; 17 (32.1%) cases underwent conventional approach and the nerves were intervened robotically; 12 (22.6%) cases converted to open approach but still intervened the nerve by robot; and 4 (7.5%) cases failed to approach robotically and converted to open surgery entirely. Conclusion  Robotic-assisted surgery is still in the early stage in peripheral nerve surgery. We believe the use of the robotic system in this field will develop to become popular in the future, especially in the fields that need cooperation with other specialties to provide the solutions for challenging circumstances. [ABSTRACT FROM AUTHOR]

Homuncular organization, i.e., the neuronal representation of the human body within the primary motor cortex, is one of the most fundamental principles of the human brain. Despite this, in rare peripheral nerve surgery patients, the transformation of a monofunctional (diaphragm activation) into a bifunctional motor area (diaphragm and arm activation is controlled by the same cortical area) has previously been demonstrated. The mechanisms behind this transformation are not fully known. To investigate this transformation of a monofunctional area we investigate functional connectivity changes in a unique and highly instructive pathophysiological patient model. These patients suffer from complete brachial plexus avulsion with arm paralysis and had been treated with reconnection of the end of the musculocutaneous nerve to the side of a fully functional phrenic nerve to regain function. Task-based functional connectivity between the arm representations and the diaphragm (phrenic nerve) representations were examined in six patients and 12 aged matched healthy controls at ultra-high field MRI while they either performed or tried isolated elbow flexion or conducted forced abdominal inspiration. Functional connectivity values are considerably increased between the diseased arm and the bilateral diaphragm areas while trying strong muscle tension in the diseased arm as compared to the healthy arm. This effect was not found as compared to the healthy arm in the patient group. This connectivity was stronger between ipsilateral than between corresponding contralateral brain regions. No corresponding differences were found in healthy subjects. Our data suggests that the increased functional connectivity between the deprived arm area and the diaphragm area drives biceps muscle function. From this findings we infer that this new rehabilitative mechanism in the primary motor cortex may establish new intrahemispheric connections within the brain and the motor cortex in particular to reroute the output of a completely denervated motor area. This study extend current knowledge about neuroplasticity within the motor cortex.

Homuncular organization, i.e., the neuronal representation of the human body within the primary motor cortex, is one of the most fundamental principles of the human brain. Despite this, in rare peripheral nerve surgery patients, the transformation of a monofunctional (diaphragm activation) into a bifunctional motor area (diaphragm and arm activation is controlled by the same cortical area) has previously been demonstrated. The mechanisms behind this transformation are not fully known. To investigate this transformation of a monofunctional area we investigate functional connectivity changes in a unique and highly instructive pathophysiological patient model. These patients suffer from complete brachial plexus avulsion with arm paralysis and had been treated with reconnection of the end of the musculocutaneous nerve to the side of a fully functional phrenic nerve to regain function. Task-based functional connectivity between the arm representations and the diaphragm (phrenic nerve) representations were examined in six patients and 12 aged matched healthy controls at ultra-high field MRI while they either performed or tried isolated elbow flexion or conducted forced abdominal inspiration. Functional connectivity values are considerably increased between the diseased arm and the bilateral diaphragm areas while trying strong muscle tension in the diseased arm as compared to the healthy arm. This effect was not found as compared to the healthy arm in the patient group. This connectivity was stronger between ipsilateral than between corresponding contralateral brain regions. No corresponding differences were found in healthy subjects. Our data suggests that the increased functional connectivity between the deprived arm area and the diaphragm area drives biceps muscle function. From this findings we infer that this new rehabilitative mechanism in the primary motor cortex may establish new intrahemispheric connections within the brain and the motor cortex in particular to reroute the output of a completely denervated motor area. This study extend current knowledge about neuroplasticity within the motor cortex. [ABSTRACT FROM AUTHOR]

Cortical reorganization in response to peripheral nervous system damage is only poorly understood. In patients with complete brachial plexus avulsion and subsequent reconnection of the end of the musculocutaneous nerve to the side of a phrenic nerve, reorganization leads to a doubled arm representation in the primary motor cortex. Despite, homuncular organization being one of the most fundamental principles of the human brain, movements of the affected arm now activate 2 loci: the completely denervated arm representation and the diaphragm representation. Here, we investigate the details behind this peripherally triggered reorganization, which happens in healthy brains. fMRI effective connectivity changes within the motor network were compared between a group of patients and age matched healthy controls at 7 Tesla (6 patients and 12 healthy controls). Results show the establishment of a driving input of the denervated arm area to the diaphragm area which is now responsible for arm movements. The findings extend current knowledge about neuroplasticity in primary motor cortex: a denervated motor area may drive an auxilliary area to reroute its motor output.

Summary While systematic reviews are regarded as the strongest level of medical evidence, inconsistency in the quality and rigor of systematic reviews raises concerns about their use as a tool in guiding quality delivery in evidence-based clinical practice. The objective of this present study was to assess methodological soundness of systematic reviews with a particular focus on peripheral nerve repair and reconstruction. We performed a comprehensive search using PubMed and Scopus to identify all systematic reviews published on peripheral nerve reconstruction in 9 high-impact surgical journals. Two authors independently performed literature searches, screened abstracts, and extracted data. Discrepancies were resolved by discussion and consensus. The quality of systematic reviews was assessed using AMSTAR criteria. Initial search retrieved 184 articles. After screening duplicates, titles, abstracts, and conducting full text reviews, 26 studies met inclusion criteria. Of those, 18 (65%) were published by Plastic Surgery, 7 (27%) by Orthopedic Surgery, and 1 (4%) by Occupational Therapy. The total number of systematic reviews published on peripheral nerves each year has shown an increasing trend from 2004 through 2015. The overall median AMSTAR score was 5, reflecting a "fair" quality. There was no evidence of AMSTAR score improvement over time. Although the number of systematic reviews published on peripheral nerve repair has risen over the last decade, their quality has not exhibited the same increase. This highlights the necessity to increase familiarity with and conform to methodological quality criteria in order to improve the integrity of evidence-based medicine in peripheral nerve repair and reconstruction. [ABSTRACT FROM AUTHOR]

Introduction: Nerve autograft is the gold standard for reconstruction of peripheral nerve loss. The alternative is the interposition of a synthetic regeneration conduit. The purpose of the study was to evaluate the in vivo feasibility and interest of Adipose-Derived Stem Cells (ADSCs) using the Nanofat technique and chitosan conduit for peripheral nerve defect repair., Material and Methods: In vivo, after the creation of a 10 mm defect of the sciatic nerve, 2 groups were defined according to the nerve repair in rats: "chitosan" group (n = 10) and "chitosan and ADSCs" group (n = 10) with a clinical and paraclinical evaluation at 7 weeks., Results: The in vivo results seem to show that the adjunction of ADSCs was favorable clinically, histologically and functionally compare to a chitosan reconstruction alone., Discussion: Peripheral nerve repair with defect using a chitosan conduit associated with ADSCs would constitute a surgical alternative in a single surgical step., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form. This review aims to provide an overview of the scientific evidence on the biology of adipose tissue, the role of adipose-derived stem cells, and the indications of adipose tissue grafting in peripheral nerve surgery. Adipose tissue is easily accessible through the lower abdomen and inner thighs. Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress, resulting in variable survival of adipocytes within the first 24 hours. Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts. Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization, and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue. In clinical studies, the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results. Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new, more studies are needed to explore safety and long-term effects on peripheral nerve regeneration. The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated, enzyme-free, and used in the same surgical procedure, e.g. adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction. Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival. Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.

Summary: In spite of great recent advancements, the definition of the optimal strategy for bridging a nerve defect, especially across long gaps, still remains an open issue since the amount of autologous nerve graft material is limited while the outcome after alternative tubulization techniques is often unsatisfactory. The aim of this study was to investigate a new tubulization technique based on the employment of vein conduits filled with whole subcutaneous adipose tissue obtained by lipoaspiration. In adult rats, a 1cm-long defect of the left median nerve was repaired by adipose tissue–vein-combined conduits and compared with fresh skeletal muscle tissue-vein-combined conduits and autologous nerve grafts made by the excised nerve segment rotated by 180°. Throughout the postoperative period, functional recovery was assessed using the grasping test. Regenerated nerve samples were withdrawn at postoperative month-6 and processed for light and electron microscopy and stereology of regenerated nerve fibers. Results showed that functional recovery was significantly slower in the adipose tissue-enriched group in comparison to both control groups. Light and electron microscopy showed that a large amount of adipose tissue was still present inside the vein conduits at postoperative month-6. Stereology showed that all quantitative morphological predictors analyzed performed significantly worse in the adipose tissue-enriched group in comparison to the two control groups. On the basis of this experimental study in the rat, the use of whole adipose tissue for tissue engineering of peripheral nerves should be discouraged. Pre-treatment of adipose tissue aimed at isolating stromal vascular fraction and/or adipose derived stem/precursor cells should be considered a fundamental requisite for nerve repair. [Copyright &y& Elsevier]

Background  The rabbit sciatic nerve injury model may represent a valuable alternative for critical gap distance seen in humans but often leads to automutilation. In this study, we modified the complete sciatic nerve injury model for avoiding autophagy. Materials and Methods  In 20 adult female New Zealand White rabbits, instead of transecting the complete sciatic nerve, we unilaterally transected the tibial portion and preserved the peroneal portion. Thereby loss of sensation in the dorsal aspect of the paw was avoided. The tibial portion was repaired in a reversed autograft approach in a length of 2.6 cm. In an alternative repair approach, a gap of 2.6 cm in length was repaired with a chitosan-based nerve guide. Results  During the 6-month follow-up period, there were no incidents of autotomy. Nerve regeneration of the tibial portion of the sciatic nerve was evaluated histologically and morphometrically. A clear difference between the distal segments of the healthy contralateral and the repaired tibial portion of the sciatic nerve was detectable, validating the model. Conclusion  By transecting the isolated tibial portion of the rabbit sciatic nerve and leaving the peroneal portion intact, it was possible to eliminate automutilation behavior., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Summary: Different bioartificial tubes were recommended for peripheral nerve reconstruction in the past. In order to replace autologous nerve grafts this materials are still under review in different animal studies. Most of them are dealing with the rodent peripheral nerves. One very popular animal model to study different materials is the rat median nerve model. With its easy excess, simple behavioral tests and reliable long term results it is attractive to many scientists in this field. This review gives an overview about the past, current and future options in this model for bioartificial nerve tubes. It summarizes the evolution of successful implantation of different materials across short nerve gaps and demonstrates the obstacles arising from long nerve gaps and the problems associated to them. [Copyright &y& Elsevier]

Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability. Herein, we selected induced pluripotent stem cells (iPSCs) derived exosomes to supplement acellular nerve grafts (ANGs) with the aim of restoring long-distance peripheral nerve defects. Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4, Sox2, Klf4, and c-Myc. The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4, SSEA4, Nanog, Sox2, which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells (SCs) in vitro. After isolation and biological characteristics of iPSCs-derived exosomes, we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination. After that, we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats. Owing to the promotion of iPSCs-derived exosomes, satisfactory regenerative outcomes were achieved including gait behavior analysis, electrophysiological assessment, and morphological analysis of regenerated nerves. Especially, motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers. Taken together, our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects, and thus represents a cell-free strategy for future clinical applications., Competing Interests: None declared., (© 2021 The Authors.)

The successful reconstruction of supercritical peripheral nerve injuries remains a major challenge in modern medicine. Progress in tissue engineering has enabled the development of nerve guidance conduits as an alternative to autologous nerve transplantation and the enrichment of conduits with fibrous materials or hydrogels has shown great potential in bridging nerve defects. The application of the dragline silk of spider genus Nephila as a filament for nerve guidance conduits has led to promising results. However, the use of spider silk has been phenomenological so far and the reasons for its success are still not identified. This renders a targeted tuning of synthetic fibrous luminal fillings such as recombinant silk out of reach. In this work the existing research was extended and in addition to dragline, the cocoon silk of Nephila edulis , as well as the connecting and attaching silk of Avicularia avicularia were investigated. Scanning electron microscopy revealed a difference in size and morphology of the spider silks. However, in vitro experiments indicated that Schwann cells adhere to the four fibers, independent of these two attributes. Raman spectroscopy in native state and aqueous environment demonstrated similar secondary protein structures for dragline, cocoon, and connecting silk. In contrast, the attaching silk showed a significant lower conformation of β-sheets, crucial for the stiffness of the silk. This was in line with the in vitro experiments, where the flexible attaching silk fibers adhered to each other when placed in liquid. This resulted in their inability to guide Schwann cells, leading to the generation of cell agglomerations. This direct comparison demonstrated the crucial role of β-sheets conformation for the guidance properties of natural spider silk, providing essential insights into the necessary material properties for the integration of fibrous luminal fillings in nerve guidance conduits. Unlabelled Image • The diameter and the morphology of spider silk does not affect the adhesion of rat Schwann cells • Secondary protein structure of connecting silk from A. avicularia is similar to dragline and cocoon silk from N. edulis • The attaching silk of A. avicularia has a smaller β-sheets conformation • The β-sheets are crucial for the guiding properties of natural spider silk [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve reconstruction is a difficult problem to solve. Acellular nerve allografts (ANAs) have been widely tested and are a promising alternative to the autologous gold standard. However, current reconstructive methods still yield unpredictable and unsuccessful results. Consequently, numerous studies have been carried out studying alternatives to plain ANAs, but it is not clear if nerve regeneration potential exists between current biological, chemical, and physical enrichment modes., Objective: To systematically review the effects of cell-enhanced ANAs on regeneration of peripheral nerve injuries., Methods: PubMed, ScienceDirect, Medline, and Scopus databases were searched for related articles published from 2007 to 2017. Inclusion criteria of selected articles consisted of (1) articles written in English; (2) the topic being cell-enhanced ANAs in peripheral nerve regeneration; (3) an in vivo study design; and (4) postgrafting neuroregenerative assessment of results. Exclusion criteria included all articles that (1) discussed central nervous system ANAs; (2) consisted of xenografts as the main topic; and (3) consisted of case series, case reports or reviews., Results: Forty papers were selected, and categorization included the animal model; the enhancing cell types; the decellularization method; and the neuroregenerative test performed. The effects of using diverse cellular enhancements combined with ANAs are discussed and also compared with the other treatments such as autologous nerve graft, and plain ANAs., Conclusion: ANAs cellular enhancement demonstrated positive effects on recovery of nerve function. Future research should include clinical translation, in order to increase the level of evidence available on peripheral nerve reconstruction., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background Acellular nerve allografts (ANAs) have been established as promising alternatives to autologous nerve grafts, which represent the reference standard. Our research group recently performed a systematic review of reported cell-based–enriching methods for recellularization of ANAs. Recellularization results in consistent improvement of peripheral neuroregeneration compared with plain ANAs. We systematically reviewed the effects on nerve regeneration when ANA enrichment was obtained through biological, chemical, and physical modification instead of cells. Methods The PubMed, ScienceDirect, Medline, and Scopus databases were searched for reports of noncellular modification of ANAs, reported from January 2007 to December 2017. The inclusion criteria were English language, noncellular enrichment of ANAs in peripheral nerve regeneration, an in vivo study design, and postgrafting neuroregenerative outcomes assessment. The exclusion criteria were the central nervous system as the site of ANA application, nerve conduits, xenografts, case series, case reports, and reviews. Results Only animal studies were found to be eligible. We included 16 studies, which were analyzed regarding the animal model, decellularization method, graft-enriching mode, and neuroregenerative tests performed. Conclusions Noncellular-based stimulation of ANAs demonstrated positive effects on recovery of nerve function compared with nerve grafting compared with plain ANAs. The neuroregenerative effect of autografting still appeared superior to ANAs, even with noncellular enrichment of ANAs. However, we found that in a few studies, modified ANAs closely approached or even outperformed autografts. Future research should include more preclinical investigations of this promising tool and clinical translation to increase the level of evidence available in the challenging field of peripheral nerve reconstruction. [ABSTRACT FROM AUTHOR]