Scaffolds made of aligned nanofibers are favorable for nerve regeneration due to their superior nerve cell attachment and proliferation. However, it is challenging not only to produce a neat mat or a conduit form with aligned nanofibers but also to use these for surgical applications as a nerve guide conduit due to their insufficient mechanical strength. Furthermore, no studies have been reported on the fabrication of aligned nanofibers and randomly-oriented nanofibers on the same mat. In this study, we have successfully produced a mat with both aligned and randomly-oriented nanofibers by using a novel electrospinning set up. A new conduit with a highly-aligned electrospun mat is produced with this modified electrospinning method, and this proposed conduit with favorable features, such as selective permeability, hydrophilicity and nerve growth directional steering, were fabricated as nerve guide conduits (NGCs). The inner surface of the nerve conduit is covered with highly aligned electrospun nanofibers and is able to enhance the proliferation of neural cells. The central part of the tube is double-coated with randomly-oriented nanofibers over the aligned nanofibers, strengthening the weak mechanical strength of the aligned nanofibers.

/pdf/a-controlled-design-of-aligned-and-random-nanofibers-for-3d-2sningowlv.pdf

A Controlled Design of Aligned and Random Nanofibers for 3D Bi-functionalized Nerve Conduits Fabricated via a Novel Electrospinning Set-up.

Polyhydroxyalkanoates (PHA) are produced by a large number of microbes under stress conditions such as high carbon (C) availability and limitations of nutrients such as nitrogen, potassium, phosphorus, magnesium, and oxygen. Here, microbes store C as granules of PHAs-energy reservoir. PHAs have properties, which are quite similar to those of synthetic plastics. The unique properties, which make them desirable materials for biomedical applications is their biodegradability, biocompatibility, and non-toxicity. PHAs have been found suitable for various medical applications: biocontrol agents, drug carriers, biodegradable implants, tissue engineering, memory enhancers, and anticancer agents.

/pdf/biomedical-applications-of-polyhydroxyalkanoates-ea26m079es.pdf

Biomedical Applications of Polyhydroxyalkanoates.

The only types of polyhydroxyalkanoates (PHAs) that have been explored for use in nerve regeneration are poly(3-hydroxybutyrate), P(3HB), and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(3HB-co-3HHx)). However, nerve regeneration induced by these PHAs is inferior to that of autologous nerve grafting. The aim of this work was to study novel PHA blends as resorbable biomaterials for the manufacture of nerve guidance conduits. PHA blend films with varying ratios of poly(3-hydroxyoctanoate)/P(3HB) (P(3HO)/P(3HB)) were produced using the solvent-casting method. Neat films of P(3HO) and P(3HB), along with 25:75, 50:50, and 75:25 blend films of P(3HO)/P(3HB), were characterized with respect to chemical, material, and biological properties. On surface analysis, the blends exhibited higher values of roughness compared with the neat films. The differential scanning calorimetry characterization of the blends confirmed that P(3HO) and P(3HB) formed immiscible blends. FTIR and XRD analysis of the blends showed a decrease in crystallinity along with an increase of the proportion of P(3HO) . However, an increase in the stiffness of the blends was observed when the proportion of P(3HB) increased. Although all of the blends were biocompatible with NG108-15 neuronal cells, the 25:75 P(3HO)/P(3HB) blend showed significantly better support for growth and differentiation of these cells. The mechanical properties of PHA blends correspond to the reported properties of peripheral nerves. Therefore, they could serve as base material for the manufacture of nerve guidance conduits.

/pdf/nerve-tissue-engineering-using-blends-of-poly-3-38ar0wzywr.pdf

Nerve tissue engineering using blends of poly(3‐hydroxyalkanoates) for peripheral nerve regeneration

Tissue engineering technology aids in the regeneration of new tissue to replace damaged or wounded tissue. Three-dimensional biodegradable and porous scaffolds are often utilized in this area to mimic the structure and function of the extracellular matrix. Scaffold material and design are significant areas of biomaterial research and the most favorable material for seeding of in vitro and in vivo cells. Polyhydroxyalkanoates (PHAs) are biopolyesters (thermoplastic) that are appropriate for this application due to their biodegradability, thermo-processability, enhanced biocompatibility, mechanical properties, non-toxicity, and environmental origin. Additionally, they offer enormous potential for modification through biological, chemical and physical alteration, including blending with various other materials. PHAs are produced by bacterial fermentation under nutrient-limiting circumstances and have been reported to offer new perspectives for devices in biological applications. The present review discusses PHAs in the applications of conventional medical devices, especially for soft tissue (sutures, wound dressings, cardiac patches and blood vessels) and hard tissue (bone and cartilage scaffolds) regeneration applications. The paper also addresses a recent advance highlighting the usage of PHAs in implantable devices, such as heart valves, stents, nerve guidance conduits and nanoparticles, including drug delivery. This review summarizes the in vivo and in vitro biodegradability of PHAs and conducts an overview of current scientific research and achievements in the development of PHAs in the biomedical sector. In the future, PHAs may replace synthetic plastics as the material of choice for medical researchers and practitioners.

/pdf/biomedical-applications-of-polyhydroxyalkanoate-in-tissue-2rdzd9uh.pdf

Biomedical Applications of Polyhydroxyalkanoate in Tissue Engineering

Nerve guidance conduits (NGCs) are used as an alternative to the “gold standard” nerve autografting, preventing the need for surgical intervention required to harvest autologous nerves. However, the regeneration outcomes achieved with the current NGCs are only comparable with autografting when the gap is short (less than 10 mm). In the present study, we have developed NGCs made from a blend of Polyhydroxyalkanoates, a family of natural resorbable polymers. Hollow NGCs made from a 75:25 Poly(3‐hydroxyoctanoate)/Poly(3‐hydroxybutyrate) blend (PHA‐NGCs) were manufactured using dip‐moulding. These PHA‐NGCs showed appropriate flexibility for peripheral nerve regeneration. In vitro cell studies performed using RT4‐D6P2T rat Schwann cell line confirmed that the material is capable of sustaining cell proliferation and adhesion. PHA‐NGCs were then implanted in vivo to repair 10 mm gaps of the median nerve of female Wistar rats for 12 weeks. Functional evaluation of the regenerated nerve using the grasping test showed that PHA‐NGCs displayed similar motor recovery as the autograft, starting from week 7. Additionally, nerve cross‐sectional area, density and number of myelinated cells, as well as axon diameter, fibre diameter, myelin thickness and g‐ratio obtained using the PHA‐NGCs were found comparable to an autograft. This preclinical data confirmed that the PHA‐NGCs are indeed highly promising candidates for peripheral nerve regeneration.

Preclinical study of peripheral nerve regeneration using nerve guidance conduits based on polyhydroxyalkanaotes.

https://www.thieme-connect.com/products/ejournals/pdf/10.1016/S0973-0508(08)80023-8.pdf

Entubulation techniques in peripheral nerve repair

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Entubulation techniques in peripheral nerve repair