Electroconductive PEDOT nanoparticle integrated scaffolds for spinal cord tissue repair.

BACKGROUND: Hostile environment around the lesion site following spinal cord injury (SCI) prevents the re-establishment of neuronal tracks, thus significantly limiting the regenerative capability. Electroconductive scaffolds are emerging as a promising option for SCI repair, though currently available conductive polymers such as polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) present poor biofunctionality and biocompatibility, thus limiting their effective use in SCI tissue engineering (TE) treatment strategies. METHODS: PEDOT NPs were synthesized via chemical oxidation polymerization in miniemulsion. The conductive PEDOT NPs were incorporated with gelatin and hyaluronic acid (HA) to create gel:HA:PEDOT-NPs scaffolds. Morphological analysis of both PEDOT NPs and scaffolds was conducted via SEM. Further characterisation included dielectric constant and permittivity variances mapped against morphological changes after crosslinking, Young's modulus, FTIR, DLS, swelling studies, rheology, in-vitro, and in-vivo biocompatibility studies were also conducted. RESULTS: Incorporation of PEDOT NPs increased the conductivity of scaffolds to 8.3 × 10-4 ± 8.1 × 10-5 S/cm. The compressive modulus of the scaffold was tailored to match the native spinal cord at 1.2 ± 0.2 MPa, along with controlled porosity. Rheological studies of the hydrogel showed excellent 3D shear-thinning printing capabilities and shape fidelity post-printing. In-vitro studies showed the scaffolds are cytocompatible and an in-vivo assessment in a rat SCI lesion model shows glial fibrillary acidic protein (GFAP) upregulation not directly in contact with the lesion/implantation site, with diminished astrocyte reactivity. Decreased levels of macrophage and microglia reactivity at the implant site is also observed. This positively influences the re-establishment of signals and initiation of healing mechanisms. Observation of axon migration towards the scaffold can be attributed to immunomodulatory properties of HA in the scaffold caused by a controlled inflammatory response. HA limits astrocyte activation through its CD44 receptors and therefore limits scar formation. This allows for a superior axonal migration and growth towards the targeted implantation site through the provision of a stimulating microenvironment for regeneration. CONCLUSIONS: Based on these results, the incorporation of PEDOT NPs into Gel:HA biomaterial scaffolds enhances not only the conductive capabilities of the material, but also the provision of a healing environment around lesions in SCI. Hence, gel:HA:PEDOT-NPs scaffolds are a promising TE option for stimulating regeneration for SCI.

The Meniscus in Normal and Osteoarthritic Tissues: Facing the Structure Property Challenges and Current Treatment Trends.

The treatment of meniscus injuries has recently been facing a paradigm shift toward the field of tissue engineering, with the aim of regenerating damaged and diseased menisci as opposed to current treatment techniques. This review focuses on the structure and mechanics associated with the meniscus. The meniscus is defined in terms of its biological structure and composition. Biomechanics of the meniscus are discussed in detail, as an understanding of the mechanics is fundamental for the development of new meniscal treatment strategies. Key meniscal characteristics such as biological function, damage (tears), and disease are critically analyzed. The latest technologies behind meniscal repair and regeneration are assessed.

Regional dependency of bovine meniscus biomechanics on the internal structure and glycosaminoglycan content.

Menisci play a major role in the mechanical function of the knee. They are subjected to large compressive forces and as a result and due to its avascular structure, menisci are prone to irreparable damage. Meniscectomy was once a common procedure for damaged menisci, however alternative approaches involving meniscus regeneration to restore function are of current interest. In order to enable these regenerative strategies, it is of utmost importance to initially establish he structure/property/function relationships of native menisci. Therefore, this study explores the influence of major constituents of the meniscal extracellular matrix; namely the glycosaminoglycan (GAG), and the collagen fibre orientation on the mechanical properties of the bovine meniscus. GAG distribution and mechanical properties are mapped with respect to depth and regional variance within the meniscus. Results show that the inner zone of the meniscus has a significantly larger quantity of GAG compared to the peripheral zone. The tibial and femoral layers contain a higher quantity of GAG than the mid-section and collagen fibre alignment differed depending on region. Overall, it was established that the viscoelastic properties of the meniscus are determined by the co-dependent relationship between the solid and fluid fractions of the meniscus and this varied depending on region. The hydrophilic nature of the GAG molecules play an important role in maintaining the solid/fluid balance while collagen fibre orientation restricts fluid flow within tissue, combined these processes act to support the meniscus under compressive loads.