Chondroitin sulfate modified 3D porous electrospun nanofiber scaffolds promote cartilage regeneration

Abstract

3D electrospun nanofibrous scaffolds have been developed for cartilage regeneration, however, there is no consensus on the preferable method for biocompatible scaffolds that enhance regeneration and attenuate inflammation. We designed a 3D porous electrospun polylactic acid (PLA) @gelatin-based scaffold by a novel method. Chondroitin sulfate (CS), commonly used in clinical cartilage treatment, is capable of regulating cartilage formation and inhibiting inflammation. Thus we further functionalized the 3D scaffold by crosslinking of CS, assuming that CS-functionalized scaffold (CSS) would promote cartilage regeneration and modulate inflammation. We confirmed that CSS exhibits not only appropriate reversible compressibility and mechanical property, but also appropriate biocompatibility, allowing cell proliferation. In vitro, the potential of CSS for chondrogenic differentiation was improved compared to control and PLA@gelatin scaffold as chondrogenic markers Collagen2 and Aggrecan was significantly increased. Meanwhile, significant reduction in two crucial inflammatory factors (NO and PGE2) in CSS group demonstrated inflammation inhibition. In vivo, rabbit cartilage defects were created and CSS effectively promoted cartilage repair. Additionally, superior anti-inflammation effect of CSS was demonstrated by reduction in iNOS and PGES, enzymes producing NO and PGE2, respectively by immunohistology. Our results indicated the preferable property of CSS for cartilage regeneration and its potential in immunoregulation.

Keywords: 3D scaffolds; Anti-inflammation; Cartilage regeneration; Chondroitin sulfate; Nanofibrous scaffolds.