Bioinspired nanofibers support chondrogenesis for articular cartilage repair

Abstract

Articular cartilage repair remains a significant and growing clinical challenge with the aging population. The native extracellular matrix (ECM) of articular cartilage is a 3D structure composed of proteinaceous fibers and a hydrogel ground substance that together provide the physical and biological cues to instruct cell behavior. Here we present fibrous scaffolds composed of poly(vinyl alcohol) and the biological cue chondroitin sulfate with fiber dimensions on the nanoscale for application to articular cartilage repair. The unique, low-density nature of the described nanofiber scaffolds allows for immediate cell infiltration for optimal tissue repair. The capacity for the scaffolds to facilitate cartilage-like tissue formation was evaluated in vitro. Compared with pellet cultures, the nanofiber scaffolds enhance chondrogenic differentiation of mesenchymal stems cells as indicated by increased ECM production and cartilage specific gene expression while also permitting cell proliferation. When implanted into rat osteochondral defects, acellular nanofiber scaffolds supported enhanced chondrogenesis marked by proteoglycan production minimally apparent in defects left empty. Furthermore, inclusion of chondroitin sulfate into the fibers enhanced cartilage-specific type II collagen synthesis in vitro and in vivo. By mimicking physical and biological cues of native ECM, the nanofiber scaffolds enhanced cartilaginous tissue formation, suggesting their potential utility for articular cartilage repair.

Reinforcement of hydrogels using three-dimensionally printed microfibres

“…Hydrogels have previously been reinforced with solutionelectrospun nonwovens 9,24,25,27 . However, most traditional solution-electrospun meshes have disadvantages from both a mechanical and biological point of view, for example, fibres are not fused and hence slide under loading meshes are usually not thicker than 100 m and have a pore size of less than 5 mm and are, therefore, too dense for cell infiltration 25,27,40 .…”

“…However, most traditional solution-electrospun meshes have disadvantages from both a mechanical and biological point of view, for example, fibres are not fused and hence slide under loading meshes are usually not thicker than 100 m and have a pore size of less than 5 mm and are, therefore, too dense for cell infiltration 25,27,40 . To overcome these issues related to traditional solution electrospinning, fibres have been collected in an earthed ethanol bath, yielding nonwovens with high porosities 9,24 . Hydrogel stiffness was increased fourfold when reinforced with these randomly organized nonwovens, irrespective of the porosity 24,25 .…”

“…The performance of hydrogel implants is expected to be superior when they closely match the mechanical properties of their target tissue 8,9 . This is based on the principle that cells in native tissues are responsive to different types of mechanical stresses, such as compression, tension and shear [10][11][12] .…”

“…The mechanical properties of hydrogels in such composites are less demanding; therefore, they can be processed with a low crosslink density, which is beneficial for cell migration and the formation of neo-tissue 2,3 . Recent composite systems include nonwoven scaffolds manufactured via solution-electrospinning techniques 9,[24][25][26][27] and scaffolds fabricated via 3D-printing [28][29][30][31][32][33] . Owing to the small fibre diameters that can be obtained, electrospun meshes have the potential to mimic native tissue extracellular matrix structures, including its mechanical properties.…”

Protein-based injectable hydrogels towards the regeneration of articular cartilage

“…Coburn et al obtained low-density electrospinning microfiber meshes of polyvinyl alcohol and chitosan that allowed cell infiltration [168], but this type of fibers could not be used in injectable hydrogels. Regev et al obtained serum albumin short electrospun fibers; for this they used a serum albumin solution with a viscosity that enables jet fragmentation during the electrospinning process.…”