{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:00:00Z","timestamp":1781082000048,"version":"3.54.1"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>\n                    Recombinant AAV vectors are among the most extensively studied vectors for viral gene delivery due to their unique safety profile and their ability to mediate efficient, long-term transgene expression by persisting episomally in the nucleus. These properties make AAV vectors promising not only for the treatment of monogenic diseases but also for tissue regenerative applications. In the context of critical-sized bone defects, current gold-standard treatments are often associated with severe side effects, highlighting the need for alternative therapy strategies. In this study, we therefore developed a gene-activated matrix (GAM) for localized AAV-mediated gene delivery for potential applications in bone regeneration, establishing a workflow that is straightforward and transferable to other therapeutic settings. Following an initial screening of AAV serotypes and transgene DNA formats, reporter gene\u2013expressing AAV2 vectors were associated with chitosan-based scaffolds containing varying amounts of \u03b2-tricalcium phosphate (\u03b2-TCP). Analysis of AAV release revealed that incorporation of \u03b2-TCP significantly reduced AAV release from 15.7% to approximately 6.6%. Furthermore, seeding of primary ovine mesenchymal stromal cells (oMSC) onto AAV-loaded scaffolds demonstrated efficient\n                    <jats:italic>in situ<\/jats:italic>\n                    delivery and expression of the osteogenic and angiogenic growth factors BMP-2 and VEGF\n                    <jats:italic>in vitro<\/jats:italic>\n                    . To further enhance AAV-mediated gene delivery, a panel of poloxamers was screened, leading to the identification of novel transduction enhancer AAVBlast. AAVBlast stabilized AAV particles and increased their bioavailability, resulting in significantly elevated intracellular AAV DNA levels, enhanced transgene mRNA expression, and increased protein production across multiple cell types. Modular application of AAVBlast onto the GAM significantly enhanced transduction of scaffold-released AAV particles but did not significantly affect transduction of oMSC by GAM-retained AAV vectors. In summary, this study demonstrates the identification of novel transduction enhancer AAVBlast and the successful development of a gene-activated matrix enabling efficient, localized AAV-mediated gene delivery\n                    <jats:italic>in vitro<\/jats:italic>\n                    , providing a promising platform for future GAM applications.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2026.1832901","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:20:56Z","timestamp":1781079656000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a gene-activated matrix for enhanced AAV gene delivery in vitro"],"prefix":"10.3389","volume":"14","author":[{"given":"Ahmed","family":"Musoski","sequence":"first","affiliation":[{"name":"Institute of Molecular Immunology, TUM University Hospital Rechts der Isar, School of Medicine and Health, Technical University of 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