Improving Mitochondrial Function in Chondrocytes to Improve Cartilage Regeneration
Cartilage is a poorly regenerative tissue, one of the reasons why cartilage damage is a feature of aging and persistent consequences of joint injury. Nonetheless, cartilage is formed during development so in principle there must exist programs of regeneration that might be activated via suitable forms of therapy. Here, researchers use a targeted nanoparticle approach to deliver a therapeutic cargo into chondrocytes in damaged cartilage tissue. This caused an improvement in both mitochondrial function and capacity for regeneration.
Treating osteoarthritis (OA) presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release. Here, amino-modified cationic mesoporous silica nanoparticles were covalently conjugated with cartilage-targeted peptides to form a Trojan horse-like architecture for enveloping the prochondrogenic fucoidan.
The hydrogel microsphere, consisting of photocurable gelatin methacryloyl (GelMA) and chondroitin sulfate methacryloyl (ChSMA), were fabricated using a microfluidic platform for cargo delivery. The cationic targeting nanoparticle-hydrogel microsphere@fucoidan (CTNM@FU) possess three-step programmable characteristics that enable responsive transport toward injured cartilage, effective penetration of the cartilage extracellular matrix and selective entry into chondrocytes, escape from lysosomes, and release of bio-activators.
The impaired cartilage metabolism was significantly reversed upon co-culturing with CTNM@FU. Intra-articular administration of CTNM@FU not only mitigated cartilage degeneration but also expedited de novo cartilage formation. Mechanistically, CTNM@FU protected cartilage by activating SIRT3, enhancing mitochondrial energy and countering aging. Collectively, a spatiotemporally guided strategy enables more precise treatments for degenerative joint disorders.