Fibrin-hyaluronic acid hydrogel-based delivery of antisense oligonucleotides for ADAMTS5 inhibition in co-delivered and resident joint cells in osteoarthritis

Fibrin-hyaluronic acid hydrogel-based delivery of antisense oligonucleotides for ADAMTS5 inhibition in co-delivered and resident joint cells in osteoarthritis.

Article specifications

This study published in 2018 in Journal of J Control Release. (IF 2015:6.00) by Israel and Dutch specialists. Here, a gapmer sequence identified from a gapmer screen showed 90% ADAMTS5 silencing in a monolayer culture of human OA chondrocytes. Incorporation of the gapmer in a fibrin-hyaluronic acid hydrogel exhibited a sustained release profile up to 14 days. Gapmers loaded in hydrogels were able to transfect both co-embedded chondrocytes and chondrocytes in a neighboring gapmer-free hydrogel, as demonstrated by flow cytometry and confocal microscopy.

 

Result

In this study, we show proof-of-concept for the combined delivery of cells and ASOs in hydrogel-based scaffold as a potential therapeutic strategy for cartilage re-surfacing and silencing of OA-related genes. The F:HA hydrogel platform displayed a 14-days sustained release of the incorporated ASO, and allowed for ASO uptake by primary human OA chondrocytes after diffusion into the hydrogel. Moreover, efficient ADAMTS5 knockdown was found. Future studies will be focused on ex vivo evaluation of the potential of LNA-based ASOs as new therapeutic agents for modulation of OA-related genes.