Biocompatible 3D-Printed Devices With Adipose Stem Cells in the Regenerative Process of Sciatic Nerve Lesions in Rodent Models: An Experimental Study.

INTRODUCTION: Peripheral nerve injuries are a significant clinical challenge. The rat sciatic nerve serves as an ideal model for studying nerve regeneration. Extensive research has been conducted to unravel the intricate mechanisms involved in peripheral nerve regeneration, aiming to develop effective therapeutic strategies for nerve injury patients. Research including different types of materials that can be used as nerve guides like synthetic polymers have been investigated for their biocompatibility and molding properties. Among multiple stem cell types, adipose-derived stem cells (ASCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), and induced pluripotent stem cells (iPSCs) have shown neuroprotective and regenerative important properties. METHODS: The purposes of our study were to develop a protocol for rat sciatic nerve injury treated with 3D-printed guide and adipose stem cells to investigate nerve regeneration through histologic examination and biomechanical characteristics of muscular tissue. We use 20 (100%) male Wistar rats, measuring between 350 g ± 35 g, who underwent complete transection of the right sciatic nerve, resulting in a 1 cm defect. The group was separated into three subgroups: the first subgroup (n = 8) was treated with a 3D-printed guide with adipose stem cells, the second subgroup (n = 8) was treated with a 3D-printed guide without adipose stem cells, and the third subgroup (n = 4) was the control group. At four, eight, and 12 weeks, we measured with ultrasonography the grade of muscular atrophy. At 12 weeks, we harvested the sciatic nerve and performed a histological examination and mechanical investigation of the tibialis anterior muscle. RESULTS: On the examined specimen of the first subgroup, cross-sectioned nerve structures were present, surrounded by a mature fibro-adipose connective tissue, with blood vessels. In the second subgroup, no nerve structure was observed on the examined sections, but in the polymorphic inflammatory infiltrate and control group, no signs of regeneration were found. CONCLUSIONS: The present study shows a promising potential when utilizing adipose stem cell-based therapies for promoting peripheral nerve regeneration following large (>1 cm) nerve defects knowing that at this size, regeneration is impossible with known treatments.

Conductive and alignment-optimized porous fiber conduits with electrical stimulation for peripheral nerve regeneration.

Autologous nerve transplantation (ANT) is currently considered the gold standard for treating long-distance peripheral nerve defects. However, several challenges associated with ANT, such as limited availability of donors, donor site injury, mismatched nerve diameters, and local neuroma formation, remain unresolved. To address these issues comprehensively, we have developed porous poly(lactic-co-glycolic acid) (PLGA) electrospinning fiber nerve guide conduits (NGCs) that are optimized in terms of alignment and conductive coating to facilitate peripheral nerve regeneration (PNR) under electrical stimulation (ES). The physicochemical and biological properties of aligned porous PLGA fibers and poly(3,4-ethylenedioxythiophene):polystyrene sodium sulfonate (PEDOT:PSS) coatings were characterized through assessments of electrical conductivity, surface morphology, mechanical properties, hydrophilicity, and cell proliferation. Material degradation experiments demonstrated the biocompatibility in vivo of electrospinning fiber films with conductive coatings. The conductive NGCs combined with ES effectively facilitated nerve regeneration. The designed porous aligned NGCs with conductive coatings exhibited suitable physicochemical properties and excellent biocompatibility, thereby significantly enhancing PNR when combined with ES. This combination of porous aligned NGCs with conductive coatings and ES holds great promise for applications in the field of PNR.

[Clinical characteristics and prognosis of two anastomosis techniques in the treatment of facial nerve defects].

Objective:To investigate the characteristics and prognosis of two anastomosis techniques in repairing facial nerve defects. Methods:A retrospective analysis was conducted on 30 patients who underwent facial nerve anastomosis（direct or rerouting） for facial nerve defects in our department from January 2012 to December 2021. Among them, 21 were male and 9 were female, with an average age of（37.53±11.33） years, all with unilateral onset. Preoperative House-Brackmann（H-B） facial nerve function grades were Ⅳ in 2 cases, Ⅴ in 9 cases, and Ⅵin 19 cases. The duration of facial paralysis before surgery was within 6 months in 21 cases, 6-12 months in 6 cases, and over 1 year in 3 cases. The causes of facial paralysis included 14 cases of cholesteatoma, 6 cases of facial neurioma, 6 cases of trauma, and 4 cases of middle ear surgery injury. Surgical approaches included 9 cases of the middle cranial fossa approach, 8 cases of labyrinthine-otic approach, 7 cases of mastoid-epitympanum approach, and 6 cases of retroauricular lateral neck approach. Results:All patients were followed up for more than 2 years. The direct anastomosis was performed in 10 cases: 6 cases with defects located in the extratemporal segment and 4 cases in the tympanic segment. Rerouting anastomosis was performed in 20 cases: 11 cases with defects located in the labyrinthine-geniculate ganglion, 4 cases from the internal auditory canal to the geniculate ganglion, 3 cases in the internal auditory canal, and 2 cases in the horizontal-pyramid segment. Postoperative H-B facial nerve grades were Ⅱ in 2 cases, Ⅲ in 20 cases, and Ⅳ in 8 cases, with 73.3%（22/30） of patients achieving H-B grade Ⅲ or better. Conclusion:Both direct and rerouting anastomosis techniques can effectively repair facial nerve defects, with no significant difference in efficacy between the two techniques. Most patients can achieve H-B grade Ⅲ or better facial nerve function recovery. Preoperative facial nerve function and duration of facial paralysis are the main prognostic factors affecting the outcome of facial nerve anastomosis.

[Femoral nerve repair with autografts for proximal retroperitoneal damage (case report and literature review)]. / Autoplastika bedrennogo nerva pri ego proksimal'nom zabryushinnom povrezhdenii (klinicheskoe nablyudenie i obzor literatury).

Femoral nerve damage, especially in proximal retroperitoneal space, is rare. Therefore, surgical strategy is still unclear for these patients. Various specialists discuss repair with autografts or neurotization by the obturator nerve or its muscular branch. OBJECTIVE: To demonstrate the diagnostic algorithm for proximal femoral nerve injury and favorable outcomes after repair with long autografts. MATERIAL AND METHODS: We assessed movements and sensitivity using a five-point scale, as well as ultrasound, magnetic resonance imaging and electroneuromyography data in a patient with extended iatrogenic femoral nerve damage before and after repair with long autografts (10.5 cm). RESULTS AND DISCUSSION: The patient had complete femoral nerve interruption in proximal retroperitoneal space with 10-cm defect that required repair with five autografts from two sural nerves. Postoperative ultrasound and magnetic resonance imaging revealed signs of graft survival and no neuroma within the nerve suture lines. The first signs of motor recovery occurred after 10 months. After 14 months, strength of quadriceps femoris muscle comprised 4 points, and electroneuromyography confirmed re-innervation. CONCLUSION: Femoral nerve repair with autografts for complete proximal anatomical interruption can provide sufficient restoration of movements and sensitivity. Therefore, this surgical option should be preferred instead of neurotization. Ultrasound, MRI and ENMG are valuable to clarify the diagnosis and state of the autografts.

Tetramethylpyrazine promotes angiogenesis and nerve regeneration and nerve defect repair in rats with spinal cord injury.

Objective: This study evaluated the regulatory effect of Tetramethylpyrazine (TMP) on the spinal cord injury (SCI) rat model and clarified the neuroprotective mechanism of TMP on SCI. Methods: An SCI rat model was generated and treated with TMP injections for two weeks. miR-497-5p and EGFL7 expression changes were evaluated, motor function recovery after SCI was assessed by BBB score test and footprint analysis, lesions of rat spinal cord were assessed by HE staining and TUNEL staining; angiogenesis was assessed by immunoblotting for CD31; inflammatory factor levels were detected by ELISA. EGFL7 was verified as a target of miR-497-5p by bioinformatics website analysis and luciferase reporter gene assay. H2O2-injured neurons were cultured in vitro to explore the effect of TMP. Results: After SCI, miR-497-5p was upregulated while EGFL7 was downregulated in rats. TMP inhibited apoptosis and promoted angiogenesis, nerve regeneration, and repair of nerve defects by reducing miR-497-5p and increasing EGFL7 expression. miR-497-5p targeted EGFL7. In addition, TMP hindered neuronal inflammation and apoptosis induced by H2O2in vitro. Conclusion: TMP promotes angiogenesis by downregulating miR-497-5p to target EGFL7, and promotes nerve regeneration and repair of nerve defects in rats with SCI.

Exosomes combined with biosynthesized cellulose conduits improve peripheral nerve regeneration.

Peripheral nerve injury is one of the more common forms of peripheral nerve disorders, and the most severe type of peripheral nerve injury is a defect with a gap. Biosynthetic cellulose membrane (BCM) is a commonly used material for repair and ligation of nerve defects with gaps. Meanwhile, exosomes from mesenchymal stem cells can promote cell growth and proliferation. We envision combining exosomes with BCMs to leverage the advantages of both to promote repair of peripheral nerve injury. Prepared exosomes were added to BCMs to form exosome-loaded BCMs (EXO-BCM) that were used for nerve repair in a rat model of sciatic nerve defects with gaps. We evaluated the repair activity using a pawprint experiment, measurement and statistical analyses of sciatica function index and thermal latency of paw withdrawal, and quantitation of the number and diameter of regenerated nerve fibers. Results indicated that EXO-BCM produced comprehensive and durable repair of peripheral nerve defects that were similar to those for autologous nerve transplantation, the gold standard for nerve defect repair. EXO-BCM is not predicted to cause donor site morbidity to the patient, in contrast to autologous nerve transplantation. Together these results indicate that an approach using EXO-BCM represents a promising alternative to autologous nerve transplantation, and could have broad applications for repair of nerve defects.

Potential of an artificial nerve graft containing Schwann cells for the treatment of a 20-mm nerve defect in rats.

OBJECTIVE: In a previous study, the authors showed that the migration of Schwann cells (SCs) through end-to-side (ETS) neurorrhaphy promotes axonal regrowth within an acellular nerve graft. In the present study, the authors investigated whether a similar strategy using an artificial nerve (AN) would allow reconstruction of a long nerve gap (20 mm) in rats. METHODS: Forty-eight 8- to 12-week-old Sprague Dawley rats were divided into control (AN) and experimental (SC migration-induced AN [SCiAN]) groups. Prior to the experiment, the ANs used in the SCiAN group were populated in vivo with SCs over a 4-week period by ETS neurorrhaphy onto the sciatic nerve. In both groups, a 20-mm sciatic nerve defect was reconstructed in an end-to-end fashion using 20-mm ANs. Sections from the nerve graft and distal sciatic nerve in both groups underwent assessments at 4 weeks for SC migration by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. At 16 weeks, axonal elongation was assessed by immunohistochemical analysis, histomorphometry, and electron microscopy. The number of myelinated fibers was counted, the g-ratio was calculated, and myelin sheath thickness and axon diameter were measured. Furthermore, functional recovery was evaluated at 16 weeks using the Von Frey filament test for sensory recovery and by calculating the muscle fiber area for motor recovery. RESULTS: The area occupied by SCs at 4 weeks and by axons at 16 weeks was significantly larger in the SCiAN group than in the AN group. Histomorphometric evaluation of the distal sciatic nerve revealed a significantly greater number of axons. At 16 weeks, plantar perception in the SCiAN group was significantly better, demonstrating improvement in sensory function. However, no tibialis anterior muscle motor improvement was observed in either group. CONCLUSIONS: The induction of SC migration into an AN by ETS neurorrhaphy is a useful technique for repairing 20-mm nerve defects in rats, with better nerve regeneration and sensory recovery. No motor recovery was observed in either group; however, motor recovery might require a longer period of time than the lifespan of the AN used in this study. Future studies should investigate whether structural and material reinforcement of the AN, to lower its decomposition rate, can improve functional recovery.

Experimental study on the repair of peripheral nerve injuries via simultaneously coapting the proximal and distal ends of peripheral nerves to the side of nearby intact nerves.

Introduction: Peripheral nerve defect is a difficult disease to treat in clinical practice. End-to-side anastomosis is a useful method to treat it. At present, the end-to-side anastomosis method does not involve the proximal nerve, which results in a waste of proximal donor nerves, and even the formation of traumatic neuromas at the proximal end. The patients suffer from traumatic neuralgia and the curative effect is unsatisfactory. Methods: In this study, an improved end-to-side anastomosis technique was proposed in this study: both the proximal and distal ends of the damaged common peroneal nerve were sutured to an adjacent normal tibial nerve. Moreover, the possible role and mechanism of the proposed technique were explained at the physiological and anatomical levels. In this study, a 10 mm common peroneal nerve defect was made in SD rats, and the rats were randomly divided into three groups. In Group I, the distal end of the common peroneal nerve was attached end-to-side to the fenestrated tibial nerve adventitia, and the proximal end was ligated and fixed in the nearby muscle. In Group II, the tibial nerve adventitia was fenestrated and the epineurial end-to-end anastomosis surgery was performed to suture the proximal and distal ends of the common peroneal nerve. Rats in Group III were taken as control and received sham operation. Twelve weeks after the operation, the recovery of the repaired nerve and distal effector functions were examined by the sciatic functional index, electrophysiology, osmic acid staining, the muscle wet weight ratio, and the muscle fiber cross-sectional area. Results: It was found that these results in Group II were similar to those in Group III, but better than those in Group I. Through retrograde tracing of neurons and Electrophysiological examination in Group II, the study also found that the proximal common peroneal nerve also could establish a connection with tibialis anterior, even gastrocnemius. Discussion: Therefore, it is inferred that fostering both the proximal and distal ends of defective peripheral nerves on normal peripheral nerves using the end-to-side anastomosis technique is a more effective approach to repairing injured nerves.

Effects of subepineural hyaluronic acid injection on nerve recovery in a rat sciatic nerve defect model.

BACKGROUND: Maintenance of epineural integrity is very important for nerve healing. Reports on the use of substances consid-ered to have positive effects on nerve healing in experimental nerve defect models are increasing. The present study assessed the effects of sub-epineural hyaluronic acid injection in a rat sciatic nerve defect model that was created while maintaining epineural integrity. METHODS: The study included 40 Sprague Dawley rats. The rats were randomly divided into a control group and three experimental groups (10 rats in each group). In the control group, the sciatic nerve was dissected and no additional surgery was performed. In experimental group 1, the sciatic nerve was transected in the middle, and then, primary repair was performed. In experimental group 2, a 1-cm defect was created while preserving the epineurium, and then, the defect was repaired with end-to-end suturing of the pre-served epineurium. In experimental group 3, the surgical procedure for experimental group 2 was performed, and then, sub-epineural hyaluronic acid injection was carried out. Functional and histological evaluations were performed. RESULTS: On functional evaluation, there was no statistically significant difference among the groups during the 12-week follow-up period. On histological evaluation, nerve recovery was poorer in experimental group 2 than in experimental groups 1 and 3 (p<0.05). CONCLUSION: Although the functional analysis did not reveal any significant results, the histological findings suggest that hyaluronic acid increases the regeneration capacity of axons through its anti-fibrotic and anti-inflammatory effects.

Outcome After Reconstruction of 43 Digital Nerve Defects With Muscle-in-Vein Conduits.

PURPOSE: Muscle-in-vein conduits provide an alternative for bridging digital nerve defects when tension-free suture is not possible. Low donor site morbidity and absence of additional costs are favorable advantages compared with autografts or conduits. METHODS: We retrospectively reviewed 37 patients with 43 defects of proper palmar digital nerves. Primary repair by muscle-in-vein conduits was performed in 22 cases, whereas 21 cases underwent secondary reconstruction. Recovery of sensibility was assessed using static and moving 2-point discrimination and Semmes-Weinstein monofilament testing. Results were compared with the contralateral side serving as a control. Outcome data were stratified according to international guidelines and evaluated for differences in terms of age, gap length, time of reconstruction, and concomitant injuries. RESULTS: The median gap length was 20 mm (range, 9-60 mm). After a median follow-up of 25.0 months (interquartile range, 29.0 months), the median static and moving 2-point discrimination were 7.0 mm and 5.0 mm (interquartile range, 3.0 mm), respectively. The evaluation with Semmes-Weinstein monofilament revealed a median reduction of sensibility of 2 levels compared with the contralateral side. According to the American Society for Surgery of the Hand guidelines, 81.4% of the results were classified as excellent or good, whereas fair and poor results were noted in 9.3% of the cases each. The modified Highet and Sander's criteria rated complete clinical recovery in 13 cases; 23 results were regarded as S3+. CONCLUSIONS: Muscle-in-vein conduits can be considered for primary and secondary reconstruction of digital nerves. Successful sensory recovery in terms of measurable 2-point discrimination was achieved in 91% of all cases. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model.

Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells (ADSPCs) in peripheral nerve recovery. Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs. This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned (2% oxygen for 72 hours) autologous ADSPCs (n = 9). This treatment mode was compared with three others: fibrin conduit seeded with ADSPCs cultivated under normoxic conditions (n = 9); non-cell-carrying conduit (n = 9); and nerve autograft only (n = 9). A 16-week follow-up included functional testing (sciatic functional index and static sciatic index) as well as postmortem muscle mass analyses and morphometric nerve evaluations (histology, g-ratio, axon density, and diameter). At 8 weeks, the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups, indicating faster functional regeneration. Furthermore, histologic evaluation showed significantly increased axon outgrowth/branching, axon density, remyelination, and a reduced relative connective tissue area. Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts. Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.

Nanozymes for Regenerative Medicine.

Nanozymes refer to nanomaterials that catalyze enzyme substrates into products under relevant physiological conditions following enzyme kinetics. Compared to natural enzymes, nanozymes possess the characteristics of higher stability, easier preparation, and lower cost. Importantly, nanozymes possess the magnetic, fluorescent, and electrical properties of nanomaterials, making them promising replacements for natural enzymes in industrial, biological, and medical fields. On account of the rapid development of nanozymes recently, their application potentials in regeneration medicine are gradually being explored. To highlight the achievements in the regeneration medicine field, this review summarizes the catalytic mechanism of four types of representative nanozymes. Then, the strategies to improve the biocompatibility of nanozymes are discussed. Importantly, this review covers the recent advances in nanozymes in tissue regeneration medicine including wound healing, nerve defect repair, bone regeneration, and cardiovascular disease treatment. In addition, challenges and prospects of nanozyme researches in regeneration medicine are summarized.

Direct End-to-End Neurorrhaphy for Wrist-Level Long Nerve Defect with Fixation of the Wrist in Flexion: Technique Note.

Background For a nerve gap, end-to-end neurorrhaphy would either be difficult or would include tension. The use of a nerve graft or conduit could be a solution, but it might compromise the reinnervation. We describe a method for wrist-level ulnar and/or median long nerve injury by fixing the wrist in the flexion position with K-wire (s) to make possible an end-to-end and tension-free neurorrhaphy. Patients and Methods Two patients had wrist-level ulnar nerve injury for 2 and 3 months and nerve gaps of 2.5 cm and 3.5 cm, respectively, after the neuroma excision. K-wires were used to transfix from the radius to carpal bones, in order to keep their wrists in flexion of 45 and 65 degrees, respectively, with which the tension-free end-to-end neurorrhaphy could be achieved. The K-wires were removed in 6 weeks after surgery, and their wrists were kept in the splint for a progressive extension program. Results Both patients were noted to have an improved claw hand deformity 4 months after the surgery. The ulnar nerve motor and sensory function could be recovered mostly in the 12-month follow-up. The wrist flexion and extension motion arc both achieved, at least, 150 degree in the 12-month follow-up. There were no complications related to the K-wire fixation. Conclusion With the wrist fixed in a flexed position, maintaining a longer nerve gap to achieve a direct end-to-end and tension-free neurorrhaphy would be more likely and safer. Without the use of nerve graft, innervation of the injured nerve would be faster.

Defects of the sciatic nerve and its divisions treated by direct suturing in 90 degrees knee flexion: report on the first clinical series.

OBJECTIVE: To evaluate functional results after treatment of large defects of the sciatic nerve and its divisions by direct nerve suturing in high knee flexion. METHODS: A retrospective review was conducted in patients treated for lower extremity nerve defects between 2011 and 2019. Inclusion criteria were a defect > 2 cm with a minimal follow-up period of 2 years for the sciatic nerve and 1 year for its divisions. Nerve defects were bridged by an end-to-end suture with the knee flexed at 90° for 6 weeks. Functional results were assessed based on the Medical Research Council's grading system. RESULTS: Seventeen patients with a mean age of 27.6 years were included. They presented with seven sciatic nerve defects and ten division defects, including eight missile injuries. The mean time to surgery was 12.3 weeks and the mean nerve defect length was 5 cm. Overall, 21 nerve sutures were performed, with eight in the tibial distribution and 13 in the fibular distribution. Post-operatively, there was no significant knee stiffness related to the immobilization. The mean follow-up time was 24.5 months. Meaningful motor and sensory recovery were observed after 7 of 8 sutures in the tibial distribution and 11 of 13 sutures in the fibular distribution. A functional sural triceps muscle with protective sensibility of the sole was restored in all patients. There were no differences according to the injury mechanisms. CONCLUSION: Temporary knee flexion at 90° allows for direct coaptation of sciatic nerve defects up to 8 cm, with promising results no matter the level or mechanism of injury.

Peripheral nerve defects repaired with autogenous vein grafts filled with platelet-rich plasma and active nerve microtissues and evaluated by novel multimodal ultrasound techniques.

BACKGROUND: Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair. METHODS: In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects. RESULTS: Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively. CONCLUSION: Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.

Resurfacing the complex finger defect and sensation reconstruction with the free distal ulnar artery perforator flap: a self-controlled case series study.

Background: The purpose of this clinical research is to report our results using the free distal ulnar artery perforator flap for resurfacing complex tissue defects in the finger, and to provide empirical reference for the treatment of subsequent clinical cases. Methods: In our research, eight patients with complex skin defects were treated with free distal ulnar artery perforator flaps. There were 4 index, 3 long, and 2 ring fingers. All the flaps were raised from the ipsilateral ulnar lateral wrist. The donor sites were covered with a full thickness skin graft or closed by direct suture. Results: Comprehensive analysis of the clinical treatment process of eight patients, all flaps survived completely without any necrosis during the 6-18 months follow-up. The patients were satisfied with the finger mobility, the sensation function, and the aesthetic appearance. Conclusions: Resurfacing complex tissue defects in the finger using the free perforator flap in a single stage, especially when the defect is medium in size and accompanied by digit nerve loss, is a valuable technique to achieve satisfaction in both sensation and aesthetic appearance. The ulnar artery perforator flap seems to be a reliable and flexible flap for addressing complex hand injuries with tissue loss.

Effect of acellular nerve scaffold containing human umbilical cord-derived mesenchymal stem cells on nerve repair and regeneration in rats with sciatic nerve defect.

Background: The aim of the present study was to investigate the effect of acellular nerve scaffold (ANS) containing human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on nerve repair and regeneration in rats with sciatic nerve defect. Methods: Sciatic nerve trunks were removed from 6 female Sprague-Dawley (SD) rats, and ANS was prepared by lyophilization + enzymatic method and divided into A, B, C, D and E groups according to different treatment times. hUC-MSCs were isolated from the collected umbilical cords and cultured, and then ANS-hUC-MSCs complexes were made. The other 24 adult female SD rats were randomly divided into the control, autograft, ANS, and ANS-hUC-MSCs groups, and a rat model of sciatic nerve defect was established. Hematoxylin-eosin (HE) staining, Luxol fast blue (LFB) staining, Masson staining, and scanning electron microscopy were used to observe the morphology and tissue structure of ANS. The performance of ANS was evaluated by mechanical detection, and hydroxyproline (HYP) content was evaluated using a biochemical kit. Flow cytometry was adopted to detect the levels of hUC-MSCs surface antigens CD29, CD44, and CD34, as well as electrophysiological detection and muscle wet weight recovery rate for measuring rat muscle performance. Results: ANS was prepared according to group A method and had good mechanical properties, with less residues of cells and myelin, and higher HYP content, indicating that this scaffold had the best performance. ANS-hUC-MSCs significantly reduced myelin injury in the sciatic nerve, and increased axonal regeneration, effectively improving sciatic nerve injury in rats. In addition, ANS-hUC-MSCs significantly increased compound muscle action potential (CMAP), nerve conduction velocity (NCV), and muscle wet weight, and reduced muscle atrophy. Conclusions: ANS containing hUC-MSCs can promote nerve repair and regeneration in rats with sciatic nerve defects.

Treatment of upper extremity nerve defects by direct suturing in high elbow or wrist flexion.

PURPOSE: To evaluate functional outcomes after direct suturing of upper extremity nerve defects in high elbow or wrist flexion. METHODS: A retrospective review was conducted in patients treated for median, ulnar, or radial nerve defects between 2011 and 2019. Inclusion criteria were a defect > 1 cm and a minimal follow-up period of 1 year. Nerve defects were bridged by an end-to-end suture in 90° elbow flexion or 70° wrist flexion for 6 weeks. RESULTS: Nine patients with a mean age of 30.2 years were included. The patients presented with two ulnar nerve defects, four median nerve defects, and three radial nerve defects at various levels. The mean time to surgery was 13.5 weeks for recent injuries. The mean defect length was 2.9 cm, and the mean follow-up time was 22.4 months. Two patients had joint stiffness that was more likely related to the associated injuries than the 6-week immobilization. Successful outcomes were achieved in eight of the nine patients. Meaningful motor recovery was observed in seven patients, and all recovered meaningful sensation. Excellent nerve recovery was noted in pediatric patients and in those with distal nerve defects. CONCLUSION: Temporary high joint flexion allows for direct coaptation of upper extremity nerve defects up to 4 cm located near the elbow or wrist. In this small and heterogenous cohort, functional outcomes seemed to be comparable to those obtained with short autografting.

Intraoperative obturator nerve injury reconstructed using a PGA-collagen tube: Three case reports.

We herein report three cases of obturator nerve injury, which is rare in gynecological surgery. In all cases, it was difficult to suture both nerve ends without tension. Therefore, we used a PGA-collagen tube to interpose the nerve defect. After follow-ups of at least seven months, all three patients were able to adduct the hip joint and medial thigh sensations also improved. These results suggest the potential of a PGA-collagen tube in the treatment of obturator nerve injury.

Combined Use of Chitosan-PGLA Nerve Grafts and Bone Marrow Mononuclear Cells to Repair a 50-mm-long Median Nerve Defect Combined with an 80-mm-long Ulnar Nerve Defect in the Human Upper Arm.

BACKGROUND: Severe peripheral nerve injury, especially the long-distance peripheral nerve defect, causes severe functional disability in patients. There is always a lack of effective repair methods for clinic, and those in practice are associated with side effects. A case study was performed to observe the regenerative outcomes of the surgical repair of long-distance peripheral nerve defects in the upper arm with chitosan-poly(glycolide-co-lactide) (PGLA) nerve grafts combined with bone marrow mononuclear cells (BMMCs). METHODS: The right upper arm of a 29-year-old woman was injured, leaving a 50-mm-long median nerve defect, an 80-mm-long ulnar nerve defect, and muscle and blood vessel disruptions. The nerve defects were repaired by implanting BMMC-containing chitosan-PGLA nerve grafts on the 40th day after injury. A series of functional assessments were carried out from 2 weeks to 66 months after surgical repair. Sensory function was assessed by the pinprick test, two-point discrimination test and Semmes-Weinstein monofilament test. Motor function was evaluated by the range of motion of the wrist joint and muscle power. Autonomic function was monitored by laser-Doppler perfusion imaging (LDPI). Tissue morphology was observed through ultrasonic investigations. RESULTS: No adverse events, such as infection, allergy, or rejection, caused by the treatment were detected during the follow-up period. Sensory and pinprick nociception in the affected thumb, index, and middle fingers gradually restored at 6th month after surgery. The monofilament tactile sensation was 0.4 g in the terminal finger pulp of the thumb and index finger, 2.0 g in the middle finger, and greater than 300 g in the ring finger and little finger at the 66th month. Motor function recovery was detected at the 5th month after surgery, when the muscle strength of the affected forearm flexors began to recover. At the 66th month after surgery, the patient's forearm flexor strength was grade 4, with 80° of palmar flexion, 85° of dorsal extension, 8° of radial deviation, 40° of ulnar deviation, 40° of anterior rotation, and 85° of posterior rotation of the affected wrist. The patient could perform holding, picking up, and some other daily activities with the affected hand. The patient's sweating function of the affected hand was close to the level of the healthy hand. LDPI showed that the skin blood flow perfusion was significantly increased, with perfusion similar to on the normal side in some areas. Neuromusculoskeletal ultrasonography showed the presence of nerve structures. CONCLUSION: These results suggest that chitosan-PGLA nerve grafts combined with BMMCs could effectively repair long-distance nerve defects and achieve good clinical results.