Repair Of Nerve Defects Research Articles

E-jet 3D printed aligned nerve guidance conduits incorporated with decellularized extracellular matrix hydrogel encapsulating extracellular vesicles for peripheral nerve repair.

Peripheral nerve injury (PNI) as a common clinical issue that presents significant challenges for repair. Factors such as donor site morbidity from autologous transplantation, slow recovery of long-distance nerve damage, and deficiencies in local cytokines and extracellular matrix contribute to the complexity of effective PNI treatment. It is extremely urgent to develop functional nerve guidance conduits (NGCs) as substitutes for nerve autografts. We fabricate an aligned topological scaffold by combining the E-jet 3D printing and electrospinning to exert synergistic topographical cue for peripheral nerve regeneration. To address the limitation of NGCs with hollow lumens in repairing long-distance nerve defects, we modified the internal microenvironment by filling the lumen with umbilical cord-derived decellularized extracellular matrix (dECM) hydrogels and extracellular vesicles (EVs). This approach led to the development of a functional HE-NGC. Herein, the HE-NGCs provided obvious guidance and proliferation to SCs and PC12 in vitro due to the sustained-release effect of dECM hydrogels and the outstanding proliferation-promoting role of EVs. The HE-NGCs was surgically implanted in vivo to bridge 12-mm gap sciatic nerve defect in rats and it had a satisfactory effect in reestablishment of the sciatic nerve, including the recovery of motor functions and the myelination. Further studies revealed that HE-NGCs might promoted axon growth by activating the PI3K/Akt/mTOR and inhibiting the MAPK signaling pathways. These findings indicate that HE-NGCs effectively promote nerve regeneration, offering a promising strategy for applications in peripheral nerve repair. STATEMENT OF SIGNIFICANCE: This study introduces an approach using an E-jet 3D printing system to fabricate three-dimensional aligned scaffolds with varying gap sizes, optimizing the structure for Schwann cells migration. We present, for the first time, a comprehensive investigation into the effects of EVs derived from umbilical cord mesenchymal stem cells on Schwann cells behavior. By leveraging the natural extracellular matrix (ECM), we significantly enhanced the efficacy and longevity of EVs encapsulated within a dECM hydrogel. Our provided strategy involves utilizing EVs to support nerve cell migration and proliferation along aligned NGCs. As the dECM hydrogel degrades, EVs are gradually released, facilitating the deposition of new ECM and enabling the repair of nerve defects up to 12-mm in length.

Bioactive MgO/MgCO3/Polycaprolactone Multi-gradient Fibers Facilitate Peripheral Nerve Regeneration by Regulating Schwann Cell Function and Activating Wingless/Integrase-1 Signaling

AbstractPeripheral nerve defects present complex orthopedic challenges with limited efficacy of clinical interventions. The inadequate proliferation and dysfunction of Schwann cells within the nerve scaffold impede the effectiveness of nerve repair. Our previous studies suggested the effectiveness of a magnesium-encapsulated bioactive hydrogel in repairing nerve defects. However, its rapid release of magnesium ions limited its efficacy to long-term nerve regeneration, and its molecular mechanism remains unclear. This study utilized electrospinning technology to fabricate a MgO/MgCO3/polycaprolactone (PCL) multi-gradient nanofiber membrane for peripheral nerve regeneration. Our findings indicated that by carefully adjusting the concentration or proportion of rapidly degradable MgO and slowly degradable MgCO3, as well as the number of electrospun layers, the multi-gradient scaffold effectively sustained the release of Mg2+ over a period of 6 weeks. Additionally, this study provided insight into the mechanism of Mg2+-induced nerve regeneration and confirmed that Mg2+ effectively promoted Schwann cell proliferation, migration, and transition to a repair phenotype. By employing transcriptome sequencing technology, the study identified the Wingless/integrase-1 (Wnt) signaling pathway as a crucial mechanism influencing Schwann cell function during nerve regeneration. After implantation in 10 mm critically sized nerve defects in rats, the MgO/MgCO3/PCL multi-gradient nanofiber combined with a 3D-engineered PCL nerve conduit showed enhanced axonal regeneration, remyelination, and reinnervation of muscle tissue 12 weeks post-surgery. In conclusion, this study successfully developed an innovative multi-gradient long-acting MgO/MgCO3/PCL nanofiber with a tunable Mg2+ release property, which underscored the molecular mechanism of magnesium-encapsulated biomaterials in treating nervous system diseases and established a robust theoretical foundation for future clinical translation. Graphical abstract

Induced pluripotent stem cell-derived mesenchymal stem cells enhance acellular nerve allografts to promote peripheral nerve regeneration by facilitating angiogenesis.

Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells. However, adult tissue-derived mesenchymal stem cells encounter various obstacles, including limited tissue sources, invasive acquisition methods, cellular heterogeneity, purification challenges, cellular senescence, and diminished pluripotency and proliferation over successive passages. In this study, we used induced pluripotent stem cell-derived mesenchymal stem cells, known for their self-renewal capacity, multilineage differentiation potential, and immunomodulatory characteristics. We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury. Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation. Furthermore, the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats. Additionally, our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization. Collectively, our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats, offering promising therapeutic strategies for clinical translation.

PMMA-induced biofilm promotes Schwann cells migration and proliferation mediated by EGF/Tnc/FN1 to improve sciatic nerve defect

ObjectiveThe purpose of this study is to investigate the role of PMMA-induced biofilm in nerve regeneration compared with silicone-induced biofilm involved in the mechanism. MethodsPMMA or silicon rods were placed next to the sciatic nerve to induce a biological membrane which was assayed by PCR, Western blot, immunohistochemistry, immunofluorescence and proteomics. A 10 mm sciatic nerve gaps were repaired with the autologous nerve wrapped in an induced biological membrane. The repair effects were observed through general observation, functional evaluation of nerve regeneration, ultrasound examination, neural electrophysiology, the wet weight ratio of bilateral pretibial muscle and histological evaluation. Cell proliferation and migration of Schwann cells co-cultured with EGF-treated fibroblasts combined with siRNA were investigated. ResultsThe results indicated that expression of GDNF, NGF and VEGF along with neovascularization was similar in the silicone and PMMA group and as the highest at 6 weeks after operation. Nerve injury repair mediated by toluidine blue and S100β/NF200 expression, the sensory and motor function evaluation, ultrasound, target organ muscle wet-weight ratio, percentage of collagen fiber, electromyography and histochemical staining were not different between the two groups and better than blank group. EGF-treated fibroblasts promoted proliferation and migration may be Tnc expression dependently. ConclusionOur study suggested that PMMA similar to silicon induced biofilm may promote autogenous nerve transplantation to repair nerve defects through EGF/Tnc/FN1 to increase Schwann cells proliferation and migration.

Silicon-induced biofilm improves peripheral nerve defect in rats mediated by VEGF/VEGFR2/ERK

ABSTRACT Background: Injury of peripheral nerve capable of regeneration with much poorer prognosis affects people’s life quality. The recovery of nerve function after transplantation for peripheral nerve injury remain a worldwide problem. Silicon-induced biofilms as vascularized biological conduits can promote nerve regeneration by encapsulating autologous or allogeneic nerve graft. Objective: We proposed to explore the effect of silicon-induced biofilms on nerves regeneration and whether the VEGF/VEGFR2/ERK pathway was involved in the present study. Methods: Biofilms around the transplanted nerves in peripheral nerve injury rats were induced by silicon. Vascularization and proteins related to VEGF/VEGFR2/ERK were measured. Pathology and morphology of nerves were investigated after encapsulating the transplanted nerves by silicon-induced biofilms. Results: Our results indicated that the biofilms induced by silicon for 6 weeks showed the most intensive vascularization and the optimal effect on nerve regeneration. Moreover, silicon-induced biofilms for 4, 6 and 8 weeks could significantly secrete VEGF with the highest content at week 6 after induction. VEGFR2, VEGF, p-VEGFR2, ERK1, ERK2, p-ERK1 and p-ERK2 were expressed in the biofilms. p-VEGFR2, p-ERK1 and p-ERK2 expression were different at each time point and significantly increased at week 6 compared with that at week 4 or week 8 which was consistent with that 6 week of was the optimum time for biofilms induction to improve the nerve repair after peripheral nerve injury. Conclusion: Our results suggested that combination of silicon-induced autologous vascularized biofilm and autologous transplantation may promote the repair of rat sciatic nerve defect quickly through VEGF/VEGFR2/ERK pathway.

Repair of Sciatic Nerve Defect in Rats With Acellular Nerve Allograft Carrying Vascular Endothelial Cells.

Acellular nerve allografts (ANAs) were developed to replace the autologous nerve grafts (ANGs) to fill the peripheral nerve defects. Poor vascularization relative to ANGs has been a limitation of application of ANAs. A total of 60 female Sprague-Dawley rats were assigned 3 groups. The rats in A group received ANGs, the rats in B group received ANAs, and the rats in C group were transplanted with ANA carrying endothelial cells (ANA + ECs). In the 1st, 2nd, 4th, and 12th postoperative weeks, 5 rats were selected from each group for evaluating sciatic function index (SFI), electrophysiology, maximum tetanic force recovery rate, tibialis anterior muscle weights recovery rate, and microvessel density. In the 12th postoperative week, the nerves were harvested and stained with toluidine blue and observed under an electron microscope to compare nerve fibers, myelin width, and G-ratio. All the rats survived. In the first and second postoperative weeks, more microvessels were found in the ANA + EC group. In the 12th postoperative week, the nerve fibers were more numerous, and G-ratio was smaller in the C group compared with the B group. The compound muscle action potential and maximum tetanic force recovery rate in the tibialis anterior muscle in the C group were better than those in the B group in the 12th postoperative week. The A group showed better performances in electrophysiology, maximum tetanic force, muscle wet weight, and nerve regeneration. ANA + ECs can promote early angiogenesis, promoting nerve regeneration and neurological function recovery.

A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties.

JOURNAL/nrgr/04.03/01300535-202507000-00029/figure1/v/2024-09-09T124005Z/r/image-tiff Autografting is the gold standard for surgical repair of nerve defects > 5 mm in length; however, autografting is associated with potential complications at the nerve donor site. As an alternative, nerve guidance conduits may be used. The ideal conduit should be flexible, resistant to kinks and lumen collapse, and provide physical cues to guide nerve regeneration. We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them. Subsequently, we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen. The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers. The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability. Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model, suggesting that it has potential for clinical use in human nerve injuries.

The GDNF-gel/HA-Mg conduit promotes the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway

Magnesium (Mg)-based conduits have gained more attention in repairing peripheral nerve defects. However, they are limited due to poor corrosion resistance and rapid degradation rate. To tackle this issue, glial cell line-derived neurotrophic factor (GDNF)- Gelatin methacryloyl (Gel)/hydroxylapatite (HA)-Mg nerve conduit was developed and implanted in sciatic nerve defect model in Sprague-Dawley (SD) rats. The sciatic functional index measurement showed that the GDNF-Gel/HA-Mg nerve conduit effectively promoted the recovery of sciatic nerve function. The pathological examination results showed that there were more regenerated nerve tissues in GDNF-Gel/HA-Mg group, with a higher number of regenerating axons, and the thickness of the myelin sheath was significantly larger than that of control group (NC group). Immunofluorescence results revealed that the GDNF-Gel/HA-Mg conduit significantly promoted the expression of genes associated with nerve repair. RNA-seq and molecular test results indicated that GDNF-Gel/HA-Mg might be involved in the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway. Biological sciences; Neuroscience; Molecular neuroscience; Techniques in neuroscience.

Magnetic fibrin nanofiber hydrogel delivering iron oxide magnetic nanoparticles promotes peripheral nerve regeneration.

Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual's life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system, demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9 and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.

Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects

Autologous nerve transplantation (ANT) remains the gold standard for treating nerve defects. However, its efficacy in nerve repair still requires improvement. Mitochondrial dysfunction resulting from nerve injury may be a significant factor limiting nerve function restoration. This study investigated the impact of supplementing exogenous mitochondria (EM) in ANT and explored its effect on the efficacy of ANT in nerve repair. SD rats were used to prepare a model of a 10 mm sciatic nerve defect repaired by ANT (Auto group) and a model of ANT supplemented with EM (Mito group). At 12 weeks post-operation, functional, neurophysiological, and histological evaluations of the target organ revealed that the Mito group exhibited significantly better outcomes compared with the Auto group, with statistically significant differences (P < 0.05). In vitro experiments demonstrated that EM could be endocytosed by Schwann cells (SCs) and dorsal root ganglion neurons (DRGs) when co-cultured. After endocytosis by SCs, immunofluorescence staining of autophagy marker LC3II and mitochondrial marker Tomm20, as well as adenoviral fluorescence labeling of lysosomes and mitochondria, revealed that EM could promote autophagy in SCs. CCK8 and EDU assays also indicated that EM significantly promoted SCs proliferation and viability. After endocytosis by DRGs, EM could accelerate axonal growth rate. A sciatic nerve defect repair model prepared using Thy1-YFP-16 mice also revealed that EM could accelerate axonal growth in vivo, with statistically significant results (P < 0.05). This study suggests that EM enhances autophagy in SCs, promotes SCs proliferation and viability, and increases the axonal growth rate, thereby improving the efficacy of ANT. This research provides a novel therapeutic strategy for enhancing the efficacy of ANT in nerve repair.

Type I collagen extracellular matrix facilitates nerve regeneration via the construction of a favourable microenvironment.

The extracellular matrix (ECM) provides essential physical support and biochemical cues for diverse biological activities, including tissue remodelling and regeneration, and thus is commonly applied in the construction of artificial peripheral nerve grafts. Nevertheless, the specific functions of essential peripheral nerve ECM components have not been fully determined. Our research aimed to differentially represent the neural activities of main components of ECM on peripheral nerve regeneration. Schwann cells from sciatic nerves and neurons from dorsal root ganglia were isolated and cultured in vitro. The cells were seeded onto noncoated dishes, Matrigel-coated dishes, and dishes coated with the four major ECM components fibronectin, laminin, collagen I, and collagen IV. The effects of these ECM components on Schwann cell proliferation were determined via methylthiazolyldiphenyl-tetrazolium bromide (MTT), Cell Counting Kit-8, and 5-ethynyl-2'-deoxyuridine (EdU) assays, whereas their effects on cell migration were determined via wound healing and live-cell imaging. Neurite growth in neurons cultured on different ECM components was observed. Furthermore, the two types of collagen were incorporated into chitosan artificial nerves and used to repair sciatic nerve defects in rats. Immunofluorescence analysis and a behavioural assessment, including gait, electrophysiology, and target muscle analysis, were conducted. ECM components, especially collagen I, stimulated the DNA synthesis and movement of Schwann cells. Direct measurement of the neurite lengths of neurons cultured on ECM components further revealed the beneficial effects of ECM components on neurite outgrowth. Injection of collagen I into chitosan and poly(lactic-co-glycolic acid) artificial nerves demonstrated that collagen I facilitated axon regeneration and functional recovery after nerve defect repair by stimulating the migration of Schwann cells and the formation of new blood vessels. In contrast, collagen IV recruited excess fibroblasts and inflammatory macrophages and thus had disadvantageous effects on nerve regeneration. These findings reveal the modulatory effects of specific ECM components on cell populations of peripheral nerves, reveal the contributing roles of collagen I in microenvironment construction and axon regeneration, and highlight the use of collagen I for the healing of injured peripheral nerves.

Chitosan nerve conduit filled with ZIF-8-functionalized guide microfibres enhances nerve regeneration and sensory function recovery in sciatic nerve defects

Nerve conduits have shown promise as alternatives to autologous nerves, but their repair effects need to be improved. The topographical guidance and functionalization of scaffolds are crucial in nerve repair. In this work, a chitosan-based nerve graft filled with guiding fibres modified by ZIF-8 nanoparticles (CS@ZIF-8) was fabricated for defective nerve repair. An in vitro study demonstrated that CS@ZIF-8 exhibited excellent cytocompatibility and could significantly promote Schwann cell proliferation. In vivo, nerve conduits filled with CS@ZIF-8 were observed to guide stronger axonal longitudinal elongation. Rats bridged with the conduit filled with CS@ZIF-8 showed significant morphological and functional improvements in terms of regenerated nerve density, the number of myelinated nerve fibres, the number of myelin layers, the thickness of myelin sheath, target muscle recovery and sensory function compared to those transplanted with the hollow conduit and the conduit filled with pure chitosan fibres. The repair effects achieved by using the conduit filled with CS@ZIF-8 were similar to those of autografts. Altogether, the data here show that nerve conduits filled with ZIF-8-loaded guide fibres provide a promising approach for repairing nerve defects.

Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect.

Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.

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

ObjectiveThis 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. MethodsAn 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. ResultsAfter 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. ConclusionTMP promotes angiogenesis by downregulating miR-497-5p to target EGFL7, and promotes nerve regeneration and repair of nerve defects in rats with SCI.

A Bioresorbable and Conductive Scaffold Integrating Silicon Membranes for Peripheral Nerve Regeneration.

Peripheral nerve injury represents one of the most common types of traumatic damage, severely impairing motor and sensory functions, and posttraumatic nerve regeneration remains a major challenge. Electrical cues are critical bioactive factors that promote nerve regrowth, and bioartificial scaffolds incorporating conductive materials to enhance the endogenous electrical field have been demonstrated to be effective. The utilization of fully biodegradable scaffolds can eliminate material residues, and circumvent the need for secondary retrieval procedures. Here, a fully bioresorbable and conductive nerve scaffold integrating N-type silicon (Si) membranes is proposed, which can deliver both structural guidance and electrical cues for the repair of nerve defects. The entire scaffold is fully biodegradable, and the introduction of N-type Si can significantly promote the proliferation and production of neurotrophic factors of Schwann cells and enhance the calcium activity of dorsal root ganglion (DRG) neurons. The conductive scaffolds enable accelerated nerve regeneration and motor functional recovery in rodents with sciatic nerve transection injuries. This work sheds light on the advancement of bioresorbable and electrically active materials to achieve desirable neural interfaces and improved therapeutic outcomes, offering essential strategies for regenerative medicine.

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.

An effective technique in nerve defect repair: Analysis of sliding epineural tube graft technique and comparison with autologous nerve graft and turn-over epineural tube graft techniques

An effective technique in nerve defect repair: Analysis of sliding epineural tube graft technique and comparison with autologous nerve graft and turn-over epineural tube graft techniques

Nanozymes With Osteochondral Regenerative Effects: An Overview of Mechanisms and Recent Applications.

With the discovery of the intrinsic enzyme-like activity of metal oxides, nanozymes garner significant attention due to their superior characteristics, such as low cost, high stability, multi-enzyme activity, and facile preparation. Notably, in the field of biomedicine, nanozymes primarily focus on disease detection, antibacterial properties, antitumor effects, and treatment of inflammatory conditions. However, the potential for application in regenerative medicine, which primarily addresses wound healing, nerve defect repair, bone regeneration, and cardiovascular disease treatment, is garnering interest as well. This review introduces nanozymes as an innovative strategy within the realm of bone regenerative medicine. The primary focus of this approach lies in the facilitation of osteochondral regeneration through the modulation of the pathological microenvironment. The catalytic mechanisms of four types of representative nanozymes are first discussed. The pathological microenvironment inhibiting osteochondral regeneration, followed by summarizing the therapy mechanism of nanozymes to osteochondral regeneration barriers is introduced. Further, the therapeutic potential of nanozymes for bone diseases is included. To improve the therapeutic efficiency of nanozymes and facilitate their clinical translation, future potential applications in osteochondral diseases are also discussed and some significant challenges addressed.

Aligned Electroactive Electrospun Fibrous Scaffolds for Peripheral Nerve Regeneration.

Effective repair and functional recovery of large peripheral nerve deficits are urgent clinical needs. A biofunctional electroactive scaffold typically acts as a "bridge" for the repair of large nerve defects. In this study, we constructed a biomimetic piezoelectric and conductive aligned polypyrrole (PPy)/polydopamine (PDA)/poly-l-lactic acid (PLLA) electrospun fibrous scaffold to improve the hydrophilicity and cellular compatibility of PLLA and restore the weakened piezoelectric effect of PDA, which is beneficial in promoting Schwann cell differentiation and dorsal root ganglion neuronal extension and alignment. The aligned PPy/PDA/PLLA fibrous scaffold bridged the sciatic nerve of Sprague-Dawley rats with a 10 mm deficit, prevented autotomy, and promoted nerve regeneration and functional recovery, thereby activating the calcium and AMP-activated protein kinase signaling pathways. Therefore, electroactive fibrous scaffolds exhibit great potential for neural tissue regeneration.

Prospects of Using Chitosan-Based Biopolymers in the Treatment of Peripheral Nerve Injuries.

Peripheral nerve injuries are common neurological disorders, and the available treatment options, such as conservative management and surgical repair, often yield limited results. However, there is growing interest in the potential of using chitosan-based biopolymers as a novel therapeutic approach to treating these injuries. Chitosan-based biopolymers possess unique characteristics, including biocompatibility, biodegradability, and the ability to stimulate cell proliferation, making them highly suitable for repairing nerve defects and promoting nerve regeneration and functional recovery. Furthermore, these biopolymers can be utilized in drug delivery systems to control the release of therapeutic agents and facilitate the growth of nerve cells. This comprehensive review focuses on the latest advancements in utilizing chitosan-based biopolymers for peripheral nerve regeneration. By harnessing the potential of chitosan-based biopolymers, we can pave the way for innovative treatment strategies that significantly improve the outcomes of peripheral nerve injury repair, offering renewed hope and better prospects for patients in need.