Search Results (35)

This study investigated the chemical, thermal, and mechanical properties of segmented polyurethanes (SPUs) synthesized using less common biodegradable polyester polyols, specifically poly(adipate) (PAD) and poly(sebacate) (PSC), to evaluate their potential as nerve guidance conduits (NGCs) in peripheral nerve regeneration. The synthesis of novel 4,4′ methylene-bis-cyclohexyl diisocyanate (HMDI) SPUs was conducted in a two-step process: prepolymer formation and chain extension with 1,4-butanediol (BO) or 1,4-butanediamine (BA). SPUs were synthesized with two molar ratios—polyol:HMDI:BA/BO at 1:2:1 and 1:3:2 for the PAD:HMDI:BA system—to optimize mechanical properties. 1HRMN analysis verified the expected chemical structure of SPUs, whereas Raman and IR spectroscopy confirmed successful polyurethane synthesis. X-ray diffractograms showed that PAD-based SPUs (SPUPAD) were amorphous while PSC-based SPUs (SPUPSC) exhibited semi-crystalline behavior. SPUPAD showed only one degradation stage by TGA, while DSC showed one thermal event. In contrast, SPUPSC exhibited two degradation stages and three thermal events that confirmed phase separation. The longitudinal tensile properties of an NGC fabricated from SPUA-PAD-2 (PAD:HMDI:BA (1:3:2)) after 30 days of immersion in water (25 °C) showed a lower modulus (4.46 ± 0.5 MPa) than native intact nerves (15.87 ± 2.21 MPa) but a similar modulus to extracted nerves (8.19 ± 7.27 MPa). This system exhibited a longitudinal tensile force of 11.1 ± 1.6 N, which is lower than that of peripheral nerves (19.85 ± 7.21 N) but higher than that of commercial collagen-based nerve guide conduits (6.89 ± 2.6 N). The observed properties suggest that PUA-PAD-2 has potential as a biomaterial for nerve regeneration applications. Full article

Peripheral nerve injuries (PNIs) pose significant challenges to recovery, often resulting in impaired function and quality of life. To address these challenges, nerve guidance conduits (NGCs) are being developed as effective strategies to promote nerve regeneration by providing a supportive framework that guides axonal growth and facilitates reconnection of severed nerves. Among the materials being explored, graphene-based materials (GBMs) have emerged as promising candidates due to their unique properties. Their unique properties—such as high mechanical strength, excellent electrical conductivity, and favorable biocompatibility—make them ideal for applications in nerve repair. The integration of 3D printing technologies further enhances the development of GBM-based NGCs, enabling the creation of scaffolds with complex architectures and precise topographical cues that closely mimic the natural neural environment. This customization significantly increases the potential for successful nerve repair. This review offers a comprehensive overview of properties of GBMs, the principles of 3D printing, and key design strategies for 3D-printed NGCs. Additionally, it discusses future perspectives and research directions that could advance the application of 3D-printed GBMs in nerve regeneration therapies. Full article

The field of peripheral nerve regeneration is a dynamic and rapidly evolving area of research that continues to captivate the attention of neuroscientists worldwide. The quest for effective treatments and therapies to enhance the healing of peripheral nerves has gained significant momentum in recent years, as evidenced by the substantial increase in publications dedicated to this field. This surge in interest reflects the growing recognition of the importance of peripheral nerve recovery and the urgent need to develop innovative strategies to address nerve injuries. In this context, this article aims to contribute to the existing knowledge by providing a comprehensive review that encompasses both biomaterial and clinical perspectives. By exploring the utilization of nerve guidance conduits and pharmacotherapy, this article seeks to shed light on the remarkable advancements made in the field of peripheral nerve regeneration. Nerve guidance conduits, which act as artificial channels to guide regenerating nerves, have shown promising results in facilitating nerve regrowth and functional recovery. Additionally, pharmacotherapy approaches have emerged as potential avenues for promoting nerve regeneration, with various therapeutic agents being investigated for their neuroprotective and regenerative properties. The pursuit of advancing the field of peripheral nerve regeneration necessitates persistent investment in research and development. Continued exploration of innovative treatments, coupled with a deeper understanding of the intricate processes involved in nerve regeneration, holds the promise of unlocking the complete potential of these groundbreaking interventions. By fostering collaboration among scientists, clinicians, and industry partners, we can accelerate progress in this field, bringing us closer to the realization of transformative therapies that restore function and quality of life for individuals affected by peripheral nerve injuries. Full article

Nerve guidance conduits for peripheral nerve injuries can be improved using bioactive materials such as magnesium (Mg) and its alloys, which could provide both structural and trophic support. Therefore, we investigated whether exposure to Mg and Mg-1.6wt%Li thin films (Mg/Mg-1.6Li) would alter acute Schwann cell responses to injury. Using the RT4-D6P2T Schwannoma cell line (SCs), we tested extracts from freeze-killed cells (FKC) and nerves (FKN) as in vitro injury stimulants. Both FKC and FKN induced SC release of the macrophage chemoattractant protein 1 (MCP-1), a marker of the repair SC phenotype after injury. Next, FKC-stimulated cells exposed to Mg/Mg-1.6Li reduced MCP-1 release by 30%, suggesting that these materials could have anti-inflammatory effects. Exposing FKC-treated cells to Mg/Mg-1.6Li reduced the gene expression of the nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), and myelin protein zero (MPZ), but not the p75 neurotrophin receptor. In the absence of FKC, Mg/Mg-1.6Li treatment increased the expression of NGF, p75, and MPZ, which can be beneficial to nerve regeneration. Thus, the presence of Mg can differentially alter SCs, depending on the microenvironment. These results demonstrate the applicability of this in vitro nerve injury model, and that Mg has wide-ranging effects on the repair SC phenotype. Full article

Tissue engineering constitutes the most promising method of severe peripheral nerve injuries treatment and is considered as an alternative to autografts. To provide appropriate conditions during recovery special biomaterials called nerve guide conduits are required. An ideal candidate for this purpose should not only be biocompatible and protect newly forming tissue but also promote the recovery process. In this article a novel, multilayered biomaterial based on polyvinylpyrrolidone, collagen and chitosan of gradient structure modified with conductive nanoparticles is presented. Products were obtained by the combination of electrospinning and electrospraying techniques. Nerve guide conduits were subjected to FT-IR analysis, morphology and elemental composition study using SEM/EDS as well as biodegradation. Furthermore, their effect on 1321N1 human cell line was investigated by long-term cell culture. Lack of cytotoxicity was confirmed by XTT assay and morphology study. Obtained results confirmed a high potential of newly developed biomaterials in the field of nerve tissue regeneration with a special focus on injured nerves recovery. Full article

Background: Peripheral nerve injuries (PNIs) represent a significant clinical problem, and standard approaches to nerve repair have limitations. Recent breakthroughs in 3D printing and stem cell technologies offer a promising solution for nerve regeneration. The main purpose of this study was to examine the biomechanical characteristics in muscle tissue distal to a nerve defect in a murine model of peripheral nerve regeneration from physiological stress to failure. Methods: In this experimental study, we enrolled 18 Wistar rats in which we created a 10 mm sciatic nerve defect. Furthermore, we divided them into three groups as follows: in Group 1, we used 3D nerve guidance conduits (NGCs) and adipose stem cells (ASCs) in seven rats; in Group 2, we used only 3D NGCs for seven rats; and in Group 3, we created only the defect in four rats. We monitored the degree of atrophy at 4, 8, and 12 weeks by measuring the diameter of the tibialis anterior (TA) muscle. At the end of 12 weeks, we took the TA muscle and analyzed it uniaxially at 10% stretch until failure. Results: In the group of animals with 3D NGCs and ASCs, we recorded the lowest degree of atrophy at 4 weeks, 8 weeks, and 12 weeks after nerve reconstruction. At 10% stretch, the control group had the highest Cauchy stress values compared to the 3D NGC group (0.164 MPa vs. 0.141 MPa, p = 0.007) and the 3D NGC + ASC group (0.164 MPa vs. 0.123 MPa, p = 0.007). In addition, we found that the control group (1.763 MPa) had the highest TA muscle stiffness, followed by the 3D NGC group (1.412 MPa), with the best muscle elasticity showing in the group in which we used 3D NGC + ASC (1.147 MPa). At failure, TA muscle samples from the 3D NGC + ASC group demonstrated better compliance and a higher degree of elasticity compared to the other two groups (p = 0.002 and p = 0.008). Conclusions: Our study demonstrates that the combination of 3D NGC and ASC increases the process of nerve regeneration and significantly improves the compliance and mechanical characteristics of muscle tissue distal to the injury site in a PNI murine model. Full article

Therapy with clinical nerve guidance conduits often causes functional incompleteness in patients. With the aim of better therapeutic efficacy, nerve regeneration and gait function were investigated in this study using a novel nerve guidance conduit consisting of glucose/mannose. The glucose/mannose nerve guidance conduits were prepared by filling the conduits with the glucose/mannose aqueous solutions for different kinematic viscosity, which were applied to sciatic nerve defects (6 mm gap) in a rat model. The nerve regeneration effect and the gait function recovery with the fabricated nerve guidance conduits were examined. From the results of the XRD measurement, the glucose/mannose conduits were identified as crystal structures of cellulose type II. Young’s modulus and the maximum tensile strength of the crystalline glucose/mannose conduits demonstrated good strength and softness for the human nerve. Above 4 weeks postoperative, macroscopic observation revealed that the nerve was regenerated in the defective area. In various staining results of the nerve tissue removed at 4 weeks postoperative, myelinated nerves contributing to gait function could not be observed in the proximal and distal sites to the central nerve. At 8–12 weeks postoperative, myelinated nerves were found at the proximal and distal sites in hematoxylin/eosin staining. Glia cells were confirmed by phosphotungstic acid–hematoxylin staining. Continuous nerve fibers were observed clearly in the sections of the regenerated nerves towards the longitudinal direction at 12 weeks postoperative. The angle between the metatarsophalangeal joint and the ground plane was approximately 93° in intact rats. At 4 weeks postoperative, walking was not possible, but at 8 weeks postoperative, the rats were able to walk, with an angle of 53°. At 12 weeks postoperative, the angle increased further, reaching 65°, confirming that the rats were able to walk more quickly than at 8 weeks postoperative. These results demonstrated that gait function in rats treated with glucose/mannose nerve guidance conduits was rapidly recovered after 8 weeks postoperative. The glucose/mannose nerve guidance conduit could be applied as a new promising candidate material for peripheral nerve regeneration. Full article

Traumatic nerve defects result in dysfunctions of sensory and motor nerves and are usually accompanied by pain. Nerve guidance conduits (NGCs) are widely applied to bridge large-gap nerve defects. However, few NGCs can truly replace autologous nerve grafts to achieve comprehensive neural regeneration and function recovery. Herein, a three-dimensional (3D) sponge-filled nanofibrous NGC (sf@NGC) resembling the structure of native peripheral nerves was developed. The conduit was fabricated by electrospinning a poly(L-lactide-co-glycolide) (PLGA) membrane, whereas the intraluminal filler was obtained by freeze-drying a collagen-based matrix (ColM) resembling the extracellular matrix. The effects of the electrospinning process and of the composition of ColM on the physicochemical performance of sf@NGC were investigated in detail. Furthermore, the biocompatibility of the PLGA sheath and ColM were evaluated. The continuous and homogeneous PLGA nanofiber membrane had high porosity and tensile strength. ColM was shown to exhibit an ECM-like architecture characterized by a multistage pore structure and a high porosity level of over 70%. The PLGA sheath and ColM were shown to possess stagewise degradability and good biocompatibility. In conclusion, sf@NGC may have a favorable potential for the treatment of nerve reconstruction. Full article

Peripheral nerve damage that results in lost segments requires surgery, but currently available hollow scaffolds have limitations that could be overcome by adding internal guidance support. A novel solution is to use filaments of absorbable metals to supply physical support and guidance for nerve regeneration that then safely disappear from the body. Previously, we showed that thin filaments of magnesium metal (Mg) would support nerve regeneration. Here, we tested another absorbable metal, zinc (Zn), using a proprietary zinc alloy with 2% iron (Zn-2%Fe) that was designed to overcome the limitations of both Mg and pure Zn metal. Non-critical-sized gaps in adult rat sciatic nerves were repaired with silicone conduits plus single filaments of Zn-2%Fe, Mg, or no metal, with autografts as controls. After seventeen weeks, all groups showed equal recovery of function and axonal density at the distal end of the conduit. The Zn alloy group showed some improvements in early rat health and recovery of function. The alloy had a greater local accumulation of degradation products and inflammatory cells than Mg; however, both metals had an equally thin capsule (no difference in tissue irritation) and no toxicity or inflammation in neighboring nerve tissues. Therefore, Zn-2%Fe, like Mg, is biocompatible and has great potential for use in nervous tissue regeneration and repair. Full article

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

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

Peripheral nerve injuries (PNIs) are detrimental to the quality of life of affected individuals. Patients are often left with life-long ailments that affect them physically and psychologically. Autologous nerve transplant is still the gold standard treatment for PNIs despite limited donor site and partial recovery of nerve functions. Nerve guidance conduits are used as a nerve graft substitute and are efficient for the repair of small nerve gaps but require further improvement for repairs exceeding 30 mm. Freeze-casting is an interesting fabrication method for the conception of scaffolds meant for nerve tissue engineering since the microstructure obtained comprises highly aligned micro-channels. The present work focuses on the fabrication and characterization of large scaffolds (35 mm length, 5 mm diameter) made of collagen/chitosan blends by freeze-casting via thermoelectric effect instead of traditional freezing solvents. As a freeze-casting microstructure reference, scaffolds made from pure collagen were used for comparison. Scaffolds were covalently crosslinked for better performance under load and laminins were further added to enhance cell interactions. Microstructural features of lamellar pores display an average aspect ratio of 0.67 ± 0.2 for all compositions. Longitudinally aligned micro-channels are reported as well as enhanced mechanical properties in traction under physiological-like conditions (37 °C, pH = 7.4) resulting from crosslinking treatment. Cell viability assays using a rat Schwann cell line derived from sciatic nerve (S16) indicate that scaffold cytocompatibility is similar between scaffolds made from collagen only and scaffolds made from collagen/chitosan blend with high collagen content. These results confirm that freeze-casting via thermoelectric effect is a reliable manufacturing strategy for the fabrication of biopolymer scaffolds for future peripheral nerve repair applications. Full article

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals. Full article

Background: Peripheral nerve injuries affect over 2% of trauma patients and can lead to severe functional impairment and permanent disability. Autologous nerve transplantation is still the gold standard in the reconstruction of nerve defects. For small defects, conduits can be considered for bridging. Lately, the combined use of conduits and electrical stimulation has gained attention in the treatment of peripheral nerve injury. This review aimed to present the currently available data on this topic. Methods: PubMed, Embase, Medline and the Cochrane Library were searched for studies on electrical stimulation through nerve conduits for nerve defects in in vivo studies. Results: Fifteen studies fit the inclusion criteria. All of them reported on the application of nerve conduits combined with stimulation for sciatic nerve gaps in rats. Functional, electrophysiological and histological evaluations showed improved nerve regeneration after electrical stimulation. High variation was observed in the treatment protocols. Conclusion: Electrically stimulated conduits could improve peripheral nerve regeneration in rat models. The combined application of nerve guidance conduits and electrical stimulation shows promising results and should be further evaluated under standardized conditions. Full article

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical polymer is used. Our characterisation of the PLA/PHA filament suggest that its tensile properties might be useful to applications such as stents, NGCs, and bone scaffolds. In addition to this, the proof-of-concept work for other applications shows that FDM is very useful for a large variety of other soft tissue applications, however other more elastomeric MCL-PHAs need to be used. Full article