Nerve Tissue Engineering Research Articles

A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats.

A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro, suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration. However, in vivo experiments have not been conducted. In this study, we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap. The Basso, Beattie, and Bresnahan locomotor rating scale, sciatic nerve compound muscle action potential recording, Fluoro-Gold retrograde tracing, growth related protein 43/S100 immunofluorescence staining, transmission electron microscopy, gastrocnemius muscle dry/wet weight ratio, and Masson's trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath, and recovery of the electrophysiological function and motor function as autologous nerve transplantation. The conduit results were superior to those of a bulk hydrogel or silicone tube transplant. These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve. The nerve conduits have the potential as a material for repairing peripheral nerve defects.

Potential application of let-7a antagomir in injured peripheral nerve regeneration.

Neurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. Considering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we evaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively achieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our study provides an experimental basis for potential in vivo application of let-7a.

Polylactic Acid/Polyaniline Nanofibers Subjected to Pre- and Post-Electrospinning Plasma Treatments for Refined Scaffold-Based Nerve Tissue Engineering Applications

Composite biopolymer/conducting polymer scaffolds, such as polylactic acid (PLA)/ polyaniline (PAni) nanofibers, have emerged as popular alternative scaffolds in the electrical-sensitive nerve tissue engineering (TE). Although mimicking the extracellular matrix geometry, such scaffolds are highly hydrophobic and usually present an inhomogeneous morphology with massive beads that impede nerve cell-material interactions. Therefore, the present study launches an exclusive combinatorial strategy merging successive pre- and post-electrospinning plasma treatments to cope with these issues. Firstly, an atmospheric pressure plasma jet (APPJ) treatment was applied on PLA and PLA/PAni solutions prior to electrospinning, enhancing their viscosity and conductivity. These liquid property changes largely eliminated the beaded structures on the nanofibers, leading to uniform and nicely elongated fibers having average diameters between 170 and 230 nm. After electrospinning, the conceived scaffolds were subjected to a N2 dielectric barrier discharge (DBD) treatment, which significantly increased their surface wettability as illustrated by large decreases in water contact angles for values above 125° to values below 25°. X-ray photoelectron spectroscopy (XPS) analyses revealed that 3.3% of nitrogen was implanted on the nanofibers surface in the form of C-N and N-C=O functionalities upon DBD treatment. Finally, after seeding pheochromocytoma (PC-12) cells on the scaffolds, a greatly enhanced cell adhesion and a more dispersive cell distribution were detected on the DBD-treated samples. Interestingly, when the APPJ treatment was additionally performed, the extension of a high number of long neurites was spotted leading to the formation of a neuronal network between PC-12 cell clusters. In addition, the presence of conducting PAni in the scaffolds further promoted the behavior of PC-12 cells as illustrated by more than a 40% increase in the neurite density without any external electrical stimulation. As such, this work presents a new strategy combining different plasma-assisted biofabrication techniques of conducting nanofibers to create promising scaffolds for electrical-sensitive TE applications.

Tissue-engineered grafts exploit axon-facilitated axon regeneration and pathway protection to enable recovery after 5-cm nerve defects in pigs.

Functional restoration following major peripheral nerve injury (PNI) is challenging, given slow axon growth rates and eventual regenerative pathway degradation in the absence of axons. We are developing tissue-engineered nerve grafts (TENGs) to simultaneously "bridge" missing nerve segments and "babysit" regenerative capacity by providing living axons to guide host axons and maintain the distal pathway. TENGs were biofabricated using porcine neurons and "stretch-grown" axon tracts. TENG neurons survived and elicited axon-facilitated axon regeneration to accelerate regrowth across both short (1 cm) and long (5 cm) segmental nerve defects in pigs. TENG axons also closely interacted with host Schwann cells to maintain proregenerative capacity. TENGs drove regeneration across 5-cm defects in both motor and mixed motor-sensory nerves, resulting in dense axon regeneration and electrophysiological recovery at levels similar to autograft repairs. This approach of accelerating axon regeneration while maintaining the pathway for long-distance regeneration may achieve recovery after currently unrepairable PNIs.

Mediate neurite outgrowth of PC-12 cells using polypyrrole-assisted laser-induced graphene flexible composite electrodes combined with electrical stimulation

Although electrical stimulation (ES) has been proved to be an effective strategy in promoting the regeneration and repair of injured peripheral nerve tissue, it is still a big challenge to encounter the risk of inflammation and infection when the conductive biological platform directly contacted with the damaged tissue. Therefore, it is a very promising solution to develop non-invasive flexible electrodes’ bio-scaffolds for clinical treatment of nerve tissue regeneration combined with ES. With such purpose, the flexible composite electrodes by depositing polypyrrole on laser-induced graphene (LIG) have been developed. The proliferation and differentiation of PC-12 cells incubated on the prepared composite electrodes combined with an ES of 400 mV/cm at different times have also been investigated. The results showed that the fabricated composite electrodes exhibited excellent conductivity and wettability. Moreover, the essence of ES was to induce a field effect, namely, the cell proliferation was independent of the conductivity of the composite electrodes. In addition, we observed that ES could significantly enhance proliferation and differentiation of PC-12 cells. With the prolongation of ES time, the increasing trend finally stabilized. Importantly, the cell growth through MTT value was 1.37 when ES time was 4 h, and the increment was the largest, reaching 0.3, compared with that of 2 h. Furthermore, the cell differentiation showed that the neurite outgrowth length at 8 h of ES was the broadest distribution (the half-width ca 33.83 μm). And the average neurite length reached 68.39 μm after 8 h of ES, which increased by 16.26 μm compared with that of 4 h. This work inspires the design and construction of a practical conductive platform, and provided a new theoretical basis and data support for clinical therapy in nerve tissue engineering combined with ES.

Instructive electroactive electrospun silk fibroin-based biomaterials for peripheral nerve tissue engineering.

Aligned sub-micron fibres are an outstanding surface for orienting and promoting neurite outgrowth; therefore, attractive features to include in peripheral nerve tissue scaffolds. A new generation of peripheral nerve tissue scaffolds is under development incorporating electroactive materials and electrical regimes as instructive cues in order to facilitate fully functional regeneration. Herein, electroactive fibres composed of silk fibroin (SF) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) were developed as a novel peripheral nerve tissue scaffold. Mats of SF with sub-micron fibre diameters of 190±50nm were fabricated by double layer electrospinning with thicknesses of ∼100μm (∼70-80μm random fibres and ∼20-30μm aligned fibres). Electrospun SF mats were modified with interpenetrating polymer networks (IPN) of PEDOT:PSS in various ratios of PSS/EDOT (α) and the polymerisation was assessed by hard X-ray photoelectron spectroscopy (HAXPES). The mechanical properties of electrospun SF and IPNs mats were characterised in the wet state tensile and the electrical properties were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The cytotoxicity and biocompatibility of the optimal IPNs (α=2.3 and 3.3) mats were ascertained via the growth and neurite extension of mouse neuroblastoma x rat glioma hybrid cells (NG108-15) for 7days. The longest neurite outgrowth of 300μm was observed in the parallel direction of fibre alignment on laminin-coated electrospun SF and IPN (α=2.3) mats which is the material with the lowest electron transfer resistance (Ret, ca. 330Ω). These electrically conductive composites with aligned sub-micron fibres exhibit promise for axon guidance and also have the potential to be combined with electrical stimulation treatment as a further step for the effective regeneration of nerves.

Scaffolds in the microbial resistant era: Fabrication, materials, properties and tissue engineering applications.

Due to microbial infections dramatically affect cell survival and increase the risk of implant failure, scaffolds produced with antimicrobial materials are now much more likely to be successful. Multidrug-resistant infections without suitable prevention strategies are increasing at an alarming rate. The ability of cells to organize, develop, differentiate, produce a functioning extracellular matrix (ECM) and create new functional tissue can all be controlled by careful control of the extracellular microenvironment. This review covers the present state of advanced strategies to develop scaffolds with antimicrobial properties for bone, oral tissue, skin, muscle, nerve, trachea, cardiac and other tissue engineering applications. The review focuses on the development of antimicrobial scaffolds against bacteria and fungi using a wide range of materials, including polymers, biopolymers, glass, ceramics and antimicrobials agents such as antibiotics, antiseptics, antimicrobial polymers, peptides, metals, carbon nanomaterials, combinatorial strategies, and includes discussions on the antimicrobial mechanisms involved in these antimicrobial approaches. The toxicological aspects of these advanced scaffolds are also analyzed to ensure future technological transfer to clinics. The main antimicrobial methods of characterizing scaffolds’ antimicrobial and antibiofilm properties are described. The production methods of these porous supports, such as electrospinning, phase separation, gas foaming, the porogen method, polymerization in solution, fiber mesh coating, self-assembly, membrane lamination, freeze drying, 3D printing and bioprinting, among others, are also included in this article. These important advances in antimicrobial materials-based scaffolds for regenerative medicine offer many new promising avenues to the material design and tissue-engineering communities.

The Effect of Vitamin C-Loaded Electrospun Polycaprolactone/Poly (Glycerol Sebacate) Fibers for Peripheral Nerve Tissue Engineering

Vitamin C (VC) is an essential supplement that plays a vital role in cellular processes and functions and has been applied for therapeutic purposes for many years. The beneficial effects of VC on peripheral nerve regeneration have been gained lots of attention. In this study, electrospun polycaprolactone (PCL)/polyglycerol sebacate (PGS) fibers incorporated with different concentrations of VC (5, 10, and 15 wt.%) were developed for peripheral nerve tissue engineering. The morphology of the fibers was investigated using scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), tensile analysis (Young’s modulus, ultimate tensile strength (UTS), and elongation at break), release profile of VC from the PCL/PGS fibers, in vitro degradation, water uptake behavior, and contact angle measurements were also studied. MTT assay and SEM were utilized to evaluate the attachment and viability of pheochromocytoma cells (PC12) on the scaffolds. The results showed that all scaffolds had a uniform diameter and mean diameter deceased from 1.24 to 0.88 µm followed by increasing VC. Young’s modulus and UTS enhanced with increasing in VC percentage. MTT assay demonstrated that PCL/PGS containing 5 wt.% VC had a greater viability rate among other scaffolds. Our outcome indicated possible applicability of VC containing scaffolds for nerve tissue engineering.

Electrical Stimulation-Mediated Differentiation of Neural Cells on Conductive Carbon Nanofiller-Based Scaffold

An important strategy in neural tissue engineering involves imparting electrical properties to the regenerative template to encourage cell proliferation and differentiation. Several clinical studies have confirmed that direct or indirect electrical stimulation therapy greatly impacts the treatment of peripheral and central nerve injury. Nerve regeneration can be accelerated by the application of electrical stimulations of different methods and with varying parameters. For a long period, electrical stimulation along with conventional conductive polymers have played an important role in nerve tissue regeneration, due to their conductivity. However, the low biocompatibility of these materials has brought attention toward the need for the alternative of the conductive polymers. Carbon nanofillers (graphene, nanotubes, and their derivatives) have been showing promising results in bioimaging, biosensing, and composites, simultaneously, proving themselves as a prospective biomaterial in neural tissue repair and regeneration due to their excellent electrical and mechanical properties, alongside, biocompatibility. Therefore, carbon nanofiller-based scaffolds synchronized with electrical stimulation may lead to a breakthrough in the treatment of nerve injury. This review article focuses on the influence of the electrical properties of carbon-based material on nerve tissue engineering. In this article, we explicitly focus on the different methods to deliver electrical stimulation and the pathways involved in the differentiation of neuronal cells. Emphasis is given to the analysis of the suitable fabrication strategies of carbon-based neural scaffold and the way its interfaces interact with neurons for promoting neuronal differentiation. Furthermore, this review summarizes the ongoing advancements to augment the conductivity and biological activities (cell adhesion, proliferation, neural differentiation, neurite outgrowth), as well as to reduce the potential toxicity in conductive carbon nanofiller-based scaffolds.

Recent advances and trends in the applications of MXene nanomaterials for tissue engineering and regeneration.

MXene, as a new two-dimensional nanomaterial, is endowed with lots of particular properties, such as large surface area, excellent conductivity, biocompatibility, biodegradability, hydrophilicity, antibacterial activity, and so on. In the past few years, MXene nanomaterials have become a rising star in biomedical fields including biological imaging, tumor diagnosis, biosensor, and tissue engineering. In this review, we sum up the recent applications of MXene nanomaterials in the field of tissue engineering and regeneration. First, we briefly introduced the synthesis and surface modification engineering of MXene. Then we focused on the application and development of MXene and MXene-based composites in skin, bone, nerve and heart tissue engineering. Uniquely, we also paid attention to some research on MXene with few achievements at present but might become a new trend in tissue engineering and regeneration in the future. Finally, this paper will also discuss several challenges faced by MXene nanomaterials in the clinical application of tissue engineering.

Electrospun Nanofibrous Scaffolds of Polycaprolactone/Gelatin Reinforced with Layered Double Hydroxide Nanoclay for Nerve Tissue Engineering Applications.

Nerve tissue engineering (NTE) is an effective approach for repairing damaged nerve tissue. In this regard, nanoparticle-incorporated electrospun scaffolds have aroused a great deal of interest in NTE applications. In this study, layered double hydroxide (LDH)-incorporated polycaprolactone (PCL)/gelatin (Gel) nanofibrous scaffolds were fabricated by an electrospinning technique. The physicochemical, mechanical, and biological properties of the scaffolds were examined. Also, the phase identification, morphology, and elemental composition were studied using X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy, respectively. The results revealed that the inclusion of LDH nanoparticles into the PCL/Gel scaffold has improved its mechanical strength and elongation at the break, while the degradation rate was enhanced in comparison with the pure PCL/Gel mat. The LDH-enriched electrospun PCL/Gel scaffolds exhibited a considerable impact on cell attachment and proliferation. The gene expression results showed that the neuron-specific (γγ) enolase (NSE) gene expression was significantly decreased in the scaffolds containing 1 and 10 wt % LDH compared to the scaffold without LDH, whereas in the scaffold with 0.1 wt % LDH, a slight increase in expression was observed. It can be deduced that electrospun PCL/Gel scaffolds containing LDH with optimum concentration can be a promising candidate for nerve tissue engineering applications.

Fabrication and characterization of methylprednisolone-loaded polylactic acid/hyaluronic acid nanofibrous scaffold for soft tissue engineering

Previous in vitro and in vivo studies have indicated that tissue engineering scaffolds, including Schwann cells, may improve axonal regeneration, particularly in combination with Methylprednisolone as an influential neuroprotective factor. The primary aim of this study was to design composite electrospun scaffolds based on polylactic acid (PLA)/hyaluronic acid (HA) containing various percentages (0.05–2% (w/v)) of Methylprednisolone (MP) with suitable mechanical and chemical properties for soft tissue especially to promote nerve growth. For the first time, MP was implicated in a PLA/HA nanofibrous and its effect on fiber’s properties was scrutinized as a candidate for nerve tissue engineering. In addition, morphology, chemical bonding, wettability, and degradation of the scaffolds were examined to evaluate their performance. The results showed the PLA/HA scaffolds had suitable morphological, physicochemical, and mechanical properties for nerve regeneration. Also, various percentages of MP were evaluated through physiochemical assay, drug release profile, and biological assays to find an optimum level of drug. These scaffolds may improve the growth and viability of Schwann cells. Results showed that composite scaffolds containing 0.5 w/v MP had lower cytotoxicity and higher biocompatibility.

Properties of Electrospun Aligned Poly(lactic acid)/Collagen Fibers with Nanoporous Surface for Peripheral Nerve Tissue Engineering

AbstractIt is important for the functional recovery of defective nerves to construct a suitable microenvironment for nerve regeneration by optimizing the topological structure and biological functions of nerve grafts. Electrospun fibers are employed to mimic the extracellular matrix (ECM) and the effect of the porous features on fiber surface draws much attention. Yet, little is known about the effect of the nanotopology of the fiber surface in conjunction with collagen I (COL) on neural cells. Herein, poly(lactic acid) (PLA)/COL hybrid fibrous membranes with a nanoporous structure on a fiber surface are fabricated. The performance of the obtained fibrous membranes is investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), water contact angle (WCA), and tensile test measurements. The cytotoxicity and biocompatibility of PLA/COL hybrid fibrous membranes and their effects on neural cells are systematically investigated. The physicochemical test results show that the PLA/COL hybrid fibrous membranes have appropriate mechanical properties and improved hydrophilicity. The MTT assay and hemolysis assay suggest the nontoxicity and good hemocompatibility of PLA/COL membranes. The nanoporous structure on the fiber surface and the introduction of COL synergistically promote proliferation and elongation of Schwann cells (SCs) and the extension of dorsal root ganglion (DRG) neurites.

Effect of Sulfonation Group on Polyaniline Copolymer Scaffolds for Tissue Engineering with Laminin Treatment under Electrical Stimulation.

Sulfonated copolyanilines (SPANs), SPAN-40 and SPAN-75, were prepared and applied in this tissue engineering study. SPAN scaffolds (SPANs) and control group polyaniline (PANI) were synthesized by performing oxidative polymerization. To further research the effects of neuron regeneration, PC12 cells were cultured on as-prepared PANI and SPANs with laminin (La) treatment under electrical stimulation. The effects on PC12 cell differentiation were investigated by controlling the amount of sulfonated groups (-SO3H) in the SPAN chain, the electrical stimulation voltage, and the presence or absence of La coating. The adhesion and proliferation of cells increased with the degree of sulfonation; La and electrical stimulation further promoted neuronal cell differentiation as increased neurite length was demonstrated in the micrograph analyses. In summary, the sulfonated copolyaniline coated with La had the best effect on neuronal differentiation under electrical stimulation, suggesting its potential as a substrate for nerve tissue engineering.

Physical Stimulation Combined with Biomaterials Promotes Peripheral Nerve Injury Repair.

Peripheral nerve injury (PNI) is a clinical problem with high morbidity that can cause severe damage. Surgical suturing or implants are usually required due to the slow speed and numerous factors affecting repair after PNI. An autologous nerve graft is the gold standard for PNI repair among implants. However, there is a potential problem of the functional loss of the donor site. Therefore, tissue-engineered nerve biomaterials are often used to bridge the gap between nerve defects, but the therapeutic effect is insufficient. In order to enhance the repair effect of nerve biomaterials for PNI, researchers are seeking to combine various stimulation elements, such as the addition of biological factors such as nerve growth factors or physical factors such as internal microstructural modifications of catheters and their combined application with physical stimulation therapy. Physical stimulation therapy is safer, is more convenient, and has more practical features than other additive factors. Its feasibility and convenience, when combined with nerve biomaterials, provide broader application prospects for PNI repair, and has therefore become a research hot spot. This paper will review the combined application of physical stimulation and biomaterials in PNI repair in recent years to provide new therapeutic ideas for the future use of physical stimulation in PNI repair.

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

BackgroundDeveloping 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.MethodsIn 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.ResultsOur 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.ConclusionOur 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.

Influence of Touch-Spun Nanofiber Diameter on Contact Guidance during Peripheral Nerve Repair.

Peripheral nerve regeneration across large gaps remains clinically challenging and scaffold design plays a key role in nerve tissue engineering. One strategy to encourage regeneration has utilized nanofibers or conduits to exploit contact guidance within the neural regenerative milieu. Herein, we report the effect of nanofiber topography on two key aspects of regeneration: Schwann cell migration and neurite extension. Substrates possessing distinct diameter distributions (300 ± 40 to 900 ± 70 nm) of highly aligned poly(ε-caprolactone) nanofibers were fabricated by touch-spinning. Cell migratory behavior and contact guidance were then evaluated both at the tissue level using dorsal root ganglion tissue explants and the cellular level using dissociated Schwann cells. Explant studies showed that Schwann cells emigrated significantly farther on fibers than control. However, both Schwann cells and neurites emigrated from the tissue explants directionally along the fibers regardless of their diameter, and the data were characterized by high variation. At the cellular level, dissociated Schwann cells demonstrated biased migration in the direction of fiber alignment and exhibited a significantly higher biased velocity (0.2790 ± 0.0959 μm·min-1) on 900 ± 70 nm fibers compared to other nanofiber groups and similar to the velocity found during explant emigration on 900 nm fibers. Therefore, aligned, nanofibrous scaffolds of larger diameters (900 ± 70 nm) may be promising materials to enhance various aspects of nerve regeneration via contact guidance alone. While cells track along with the fibers, this contact guidance is bidirectional along the fiber, moving in the plane of alignment. Therefore, the next critical step to direct regeneration is to uncover haptotactic cues that enhance directed migration.

Modulation of the Crosstalk between Schwann Cells and Macrophages for Nerve Regeneration: A Therapeutic Strategy Based on a Multifunctional Tetrahedral Framework Nucleic Acids System.

Peripheral nerve injury (PNI) is currently recognized as one of the most significant public health issues and affects the general well-being of millions of individuals worldwide. Despite advances in nerve tissue engineering, nerve repair still cannot guarantee complete functional recovery. In the present study, an innovative approach is adopted to establish a multifunctional tetrahedral framework nucleic acids (tFNAs) system, denoted as MiDs, which can integrate the powerful programmability, permeability, and structural stability of tFNAs, with the nerve regeneration potential of microRNA-22 to enhance the communication between Schwann cells (SCs) and macrophages for more effective functional rehabilitation of peripheral nerves. Relevant results demonstrate that MiDs can amplify the ability of SCs to recruit macrophages and facilitate their polarization into the pro-healing M2 phenotype to reconstruct the post-injury microenvironment. Furthermore, MiDs can initiate the adaptive intracellular reprogramming of SCs within a short period to further promote axon regeneration and remyelination. MiDs represent a new possibility for enhancing nerve repair and may have critical clinical applications in the future.

Knowledge Domain and Hotspots Predict Concerning Electroactive Biomaterials Applied in Tissue Engineering: A Bibliometric and Visualized Analysis From 2011 to 2021.

Objective: Electroactive biomaterials used in tissue engineering have been extensively studied. Electroactive biomaterials have unique potential advantages in cell culture and tissue regeneration, which have attracted the attention of medical researchers worldwide. Therefore, it is important to understand the global scientific output regarding this topic. An analysis of publications on electroactive biomaterials used in tissue engineering over the past decade was performed, and the results were summarised to track the current hotspots and highlight future directions. Methods: Globally relevant publications on electroactive biomaterials used in tissue engineering between 2011 and 2021 were extracted from the Web of Science database. The VOSviewer software and CiteSpace were employed to visualise and predict trends in research on the topic. Results: A total of 3,374 publications were screened. China contributed the largest number of publications (995) and citations (1581.95, actual value ×0.05). The United States achieved the highest H-index (440 actual values ×0.05). The journal Materials Science & Engineering C-materials for Biological Applications (IF = 7.328) published the most studies on this topic (150). The Chinese Academy of Science had the largest number of publications (107) among all institutions. The publication titled Nanotechnological strategies for engineering complex tissues by Dir, T of the United States had the highest citation frequency (985 times). Regarding the function of electroactive materials, the keyword “sensors” emerged in recent years. Regarding the characterisation of electroactive materials, the keyword “water contact angle” appeared lately. Regarding electroactive materials in nerve and cardiac tissue engineering, the keywords “silk fibroin and conductive hydrogel” appeared recently. Regarding the application of electroactive materials in bone tissue engineering, the keyword “angiogenesis” emerged in recent years. The current research trend indicates that although new functional materials are constantly being developed, attention should also be paid to their application and transformation in tissue engineering. Conclusion: The number of publications on electroactive biomaterials used in tissue engineering is expected to increase in the future. Topics like sensors, water contact angle, angiogenesis, silk fibroin, and conductive hydrogels are expected to be the focuses of research in the future; attention should also be paid to the application and transformation of electroactive materials, particularly bone tissue engineering. Moreover, further development of the field requires joint efforts from all disciplines.

Water-Soluble, Alanine-Modified Fullerene C60 Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells.

As carbon-based nanomaterials, water-soluble C60 derivatives have potential applications in various fields of biomedicine. In this study, a water-soluble fullerene C60 derivative bearing alanine residues (Ala-C60) was synthesized. The effects of Ala-C60 on neural stem cells (NSCs) as seed cells were explored. Ala-C60 can promote the proliferation of NSCs, induce NSCs to differentiate into neurons, and inhibit the migration of NSCs. Most importantly, the Ala-C60 can significantly increase the cell viability of NSCs treated with hydrogen peroxide (H2O2). The glutathioneperoxidase (GSH-Px) and superoxide dismutase (SOD) activities and glutathione (GSH) content increased significantly in NSCs treated even by 20 μM Ala-C60. These findings strongly indicate that Ala-C60 has high potential to be applied as a scaffold with NSCs for regeneration in nerve tissue engineering for diseases related to the nervous system.