Abstract
There is no efficient tracking system available for the therapeutic molecules delivered to cartilage. The dense matrix covering the cartilage surface is the main biological barrier that the therapeutic molecules must overcome. In this study, we aimed to establish a system that can dynamically and effectively track the therapeutic molecules delivered to cartilage. To this aim, we adopted bovine and human cartilage explants as ex vivo models for chondrocyte-targeted exosome dispersion. The efficiency of drug delivery was evaluated using frozen sections. The results of this study showed that the penetration and distribution of chondrocyte-targeted exosomes in cartilage explants can be tracked dynamically. Thus, ex vivo cartilage explants provide an effective and economic system to evaluate therapeutic drugs encapsulated in chondrocyte-targeted exosomes in preclinical studies.
Highlights
Production of chondrocyte affinity peptide (CAP)-exosomes The transfection of dendritic cells with the CAP-GFP-lamp2b plasmid and plasmid constructions were performed according to Duan L and Liang Y
Exosomes were diluted to 500 ng/mL and the size distribution was determined with fast video capture and particle-tracking software on a NanoSight NS300 (Malvern Panalytical, UK)
The cartilage affinity peptide CAP was engineered on the Dendritic cells (DCs)-derived exosome membrane. miR-140, a dual-factor that inhibits cartilage degradation and promotes cartilage regeneration, was encapsulated into cartilage-target exosomes (Duan et al, 2020a; Liang et al, 2021a)
Summary
Osteoarthritis (OA) is a mainly cartilage-degenerated joint disease that has become a severe threat to public health and a large financial expenditure burden. No effective strategy is available to stop cartilage degeneration (Abramoff and Caldera, 2020). One of the challenges of nonsurgical treatment is that it barely stops OA inflammation microenvironment-induced cartilage matrix degradation (Liang et al, 2021b). The development of a targeted system that delivers therapeutics to cartilage defects is urgently needed (Maudens et al, 2018). Another obstacle in strategy development is the lack of an ideal tracking and evaluation system. OA animal models are often used in preclinical studies to evaluate the treatment strategy outcomes, which is a time-consuming process and cannot accurately reflect the OA progression of patients (Nganvongpanit et al, 2008; Nganvongpanit et al, 2009).
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