Biomaterial-Guided rAAV Delivery from pNaSS-Grafted PCL Films to Target Human Bone Marrow Aspirates
Résumé
Scaffold-guided gene transfer offers strong systems to develop noninvasive convenient therapeutic options for the treatment of articular cartilage defects, especially when targeting bone marrow aspirates from patients containing chondroregenerative mesenchymal stromal cells in a native microenvironment. In this study, we examined the feasibility of delivering reporter (red fluorescent protein [RFP], lacZ) recombinant adeno-associated virus (rAAV) vectors over time to such samples through biocompatible mechanically stable poly(ɛ-caprolactone) (PCL) films grafted with poly(sodium styrene sulfonate) (pNaSS) for improved biological responses as clinically adapted tools for cartilage repair. Effective transgene expression (RFP, lacZ) was noted over time in human bone marrow aspirates using pNaSS-grafted films (up to 90% efficiency for at least 21 days) versus control conditions (ungrafted films, absence of vector coating on the films, free or no vector treatment), without displaying cytotoxic nor detrimental effects on the osteochondrogenic or hypertrophic potential of the samples. These findings demonstrate the potential of directly modifying therapeutic bone marrow from patients by controlled delivery of rAAV using biomaterial-guided procedures as a future noninvasive strategy for clinical cartilage repair.
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