Dual role of injectable curcumin-loaded microgels for efficient repair of osteoarthritic cartilage injury

Abstract

Curcumin has been widely used for the treatment of age-associated diseases, and showed chondroprotective potential for post-traumatic osteoarthritis (OA). However, due to the irregular-shaped and large-sized defects on joint cartilage in degenerated OA, the <i>in vivo</i> delivery and therapeutic effect of curcumin for effective repair remain challenging. In this study, we first present a PEG-GelMA [Poly(Ethylene Glycol) Dimethacrylate-Gelatin Methacrylate, PGMs] hydrogel microgel-based curcumin delivery system for both improved anti-inflammatory and pro-regenerative effects in treatment for cartilage defects. The curcumin-loaded PGMs were produced by a microfluidic system based on light-induced gelation of gelatin methacrylate (GelMA). This PGMs embedding curcumin at a relative low dosage were demonstrated to promote the proliferation and chondrogenic differentiation of mesenchymal stem cells <i>in vitro</i>. More importantly, the PGMs were shown to attenuate the inflammatory response of chondrocytes under IL-1β stimulation. Lastly, the <i>in vivo</i> application of the injectable PGMs significantly promoted the repair of large-sized cartilage injury. These results confirmed that curcumin-loaded PGMs can not only enhance the chondroprotective efficacy under inflammatory conditions but also induce efficient cartilage regeneration. This study provides an advanced strategy with anti-inflammatory and pro-regenerative dual-role therapeutic for treatment of extensive cartilage injuries.