Development Of Nerve Guidance Conduits Research Articles

Biomimetic ECM nerve guidance conduit with dynamic 3D interconnected porous network and sustained IGF-1 delivery for enhanced peripheral nerve regeneration and immune modulation.

Recent advancements in tissue engineering have promoted the development of nerve guidance conduits (NGCs) that significantly enhance peripheral nerve injury treatment, improving outcomes and recovery rates. However, utilising tailored biomimetic three-dimensional (3D) topological porous structures combined with multiple bio-effect neurotrophic factors to create environments similar to neural tissues, regulate local immune responses, and develop a supportive microenvironment to promote peripheral nerve regeneration and repair poses significant challenges. Herein, a biomimetic extracellular matrix (ECM) NGC featuring an interconnected 3D porous network and sustained delivery of insulin-like growth factor-1 (IGF-1) is designed using multi-functional gelatine microcapsules (GMs). Nerve conduits made by blending chitosan (CS) with GMs demonstrate suitable degradation rates, reduced swelling rates, increased suture tensile strength, improved elongation at break, and 50% radial compression performance that meet clinical application requirements. In vitro cytological studies indicate that biomimetic ECM NGCs exhibit good biocompatibility, promote early survival, proliferation, and remyelination potential of Schwann cells (SCs), and support neurite outgrowth. The biomimetic ECM NGCs comprising a 3D interconnected porous network in a 10-mm sciatic nerve defect rat model sustain IGF-1 delivery, promoting early infiltration of macrophages and polarisation towards M2-type macrophages. Furthermore, observations at 12 weeks post-implantation revealed improvements in electrophysiological performance, alleviation of gastrocnemius muscle atrophy, increased peripheral nerve regeneration, and motor function restoration. Thus, biomimetic ECM NGCs offer a therapeutic strategy for peripheral nerve regeneration with promising clinical applications and transformation prospects to regulate immune microenvironments, promoting SC proliferation and differentiation with nerve axon growth.

Micropattern-based nerve guidance conduit with hundreds of microchannels and stem cell recruitment for nerve regeneration

Guiding the regrowth of thousands of nerve fibers within a regeneration-friendly environment enhances the regeneration capacity in the case of peripheral nerve injury (PNI) and spinal cord injury (SCI). Although clinical treatments are available and several studies have been conducted, the development of nerve guidance conduits (NGCs) with desirable properties, including controllable size, hundreds of nerve bundle-sized microchannels, and host stem-cell recruitment, remains challenging. In this study, the micropattern-based fabrication method was combined with stem-cell recruitment factor (substance P, SP) immobilization onto the main material to produce a size-tunable NGC with hundreds of microchannels with stem-cell recruitment capability. The SP-immobilized multiple microchannels aligned the regrowth of nerve fibers and recruited the host stem cells, which enhanced the functional regeneration capacity. This method has wide applicability in the modification and augmentation of NGCs, such as bifurcated morphology or directional topographies on microchannels. Additional improvements in fabrication will advance the regeneration technology and improve the treatment of PNI/SCI.

Preparation and mechanical optimization of a two‐layer silk/magnesium wires braided porous artificial nerve guidance conduit

Peripheral nerve injures have long been a tricky problem in surgery and a feasible treatment is the transplantation of nerve guidance conduits (NGCs). This study presents a two-layer composite NGC with fair mechanical properties and good biocompatibility. The inner layer was made of degummed silk yarns/magnesium wires using braiding technology, and the outer layer was made from mixed solution of silk fibroin/chitosan (SF/CS) using freeze-drying treatment. Orthogonal experimental design was applied to rationally design the braided structural layer and obtain the optimal combination of technical process parameters. Meanwhile, the SF/CS porous outer layer was optimized from three concentrations of SF/CS solution. In vitro and in vivo study suggested that the textile-forming scaffold exhibited good biocompatibility and no toxicity. During 4 weeks' degradation, the skeleton of conduits retained its shape, and magnesium ions released from degraded magnesium wires contributed to sustainable release and uniform dispersion, proliferation and adhesion of Schwann cells, indicating potential approach in the development of NGCs.

The Physicochemical Properties of Decellularized Extracellular Matrix-Coated 3D Printed Poly(ε-caprolactone) Nerve Conduits for Promoting Schwann Cells Proliferation and Differentiation.

Although autologous nerve grafting remains the gold standard treatment for peripheral nerve injuries, alternative methods such as development of nerve guidance conduits have since emerged and evolved to counter the many disadvantages of nerve grafting. However, the efficacy and viability of current nerve conduits remain unclear in clinical trials. Here, we focused on a novel decellularized extracellular matrix (dECM) and polydopamine (PDA)-coated 3D-printed poly(ε-caprolactone) (PCL)-based conduits, whereby the PDA surface modification acts as an attachment platform for further dECM attachment. We demonstrated that dECM/PDA-coated PCL conduits possessed higher mechanical properties when compared to human or animal nerves. Such modifications were proved to affect cell behaviors. Cellular behaviors and neuronal differentiation of Schwann cells were assessed to determine for the efficacies of the conduits. There were some cell-specific neuronal markers, such as Nestin, neuron-specific class III beta-tubulin (TUJ-1), and microtubule-associated protein 2 (MAP2) analyzed by enzyme-linked immunosorbent assay, and Nestin expressions were found to be 0.65-fold up-regulated, while TUJ1 expressions were 2.3-fold up-regulated and MAP2 expressions were 2.5-fold up-regulated when compared to Ctl. The methodology of PDA coating employed in this study can be used as a simple model to immobilize dECM onto PCL conduits, and the results showed that dECM/PDA-coated PCL conduits can as a practical and clinically viable tool for promoting regenerative outcomes in larger peripheral nerve defects.

Strategic Design and Fabrication of Nerve Guidance Conduits for Peripheral Nerve Regeneration.

Nerve guidance conduits (NGCs) have been drawing considerable attention as an aid to promote regeneration of injured axons across damaged peripheral nerves. Ideally, NGCs should include physical and topographic axon guidance cues embedded as part of their composition. Over the past decades, much progress has been made in the development of NGCs that promote directional axonal regrowth so as to repair severed nerves. This paper briefly reviews the recent designs and fabrication techniques of NGCs for peripheral nerve regeneration. Studies associated with versatile design and preparation of NGCs fabricated with either conventional or rapid prototyping (RP) techniques have been examined and reviewed. The effect of topographic features of the filler material as well as porous structure of NGCs on axonal regeneration has also been examined from the previous studies. While such strategies as macroscale channels, lumen size, groove geometry, use of hydrogel/matrix, and unidirectional freeze-dried surface are seen to promote nerve regeneration, shortcomings such as axonal dispersion and wrong target reinnervation still remain unsolved. On this basis, future research directions are identified and discussed.

Evaluating nerve guidance conduits for peripheral nerve injuries: a novel normalization method.

Evaluating nerve guidance conduits for peripheral nerve injuries: a novel normalization method.

Nano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein

The development of nerve guidance conduits is constantly evolving as the need arises for therapies for spinal cord injury. In addition to providing a path for regrowing axons to reconnect with their appropriate targets, the structural and biochemical cues provided by these conduits should be permissive for directional neurite outgrowth and be protective against inhibition in the vicinity of the injury site. Here, we adapted the use of iso-electric focusing to drive the alignment of supramolecular fibrils into self-assembled collagen hydrogels (∼300 µm diameter), and tested those hydrogels for the ability to direct and enhance the migration of neurites. Structural characterization revealed anisotropic alignment of nanofibrillar aggregates (∼20 nm diameter), arranged in micron-scale bundles (∼1 to 2 µm diameter) similar to the hierarchical size scales observed in native tissues. Neurite outgrowth extended bidirectionally along the axes of aligned hydrogels. Furthermore, it was shown that, as opposed to poly-D-lysine, neurite outgrowth on aligned hydrogels is not inhibited in the presence of myelin-associated glycoprotein (p > 0.05). These results highlight for the first time a structural and biochemical role for iso-electrically aligned collagen hydrogels in controlling neuronal growth, and indicate that the short-term signaling associated with these hydrogels can be used in adjunct therapy following injury to the spinal cord.