20.500.12556/DiRROS-16610 Engineered combinatorial cell device for wound healing and bone regeneration Growth factors are the key regulators that promote tissue regeneration and healing processes. While the effects of individual growth factors are well documented, a combination of multiple secreted growth factors underlies stem cell–mediated regeneration. To avoid the potential dangers and laborintensive individual approach of stem cell therapy while maintaining their regeneration-promoting effects based on multiple secreted growth factors, we engineered a “mix-and-match” combinatorial platform based on a library of cell lines producing growth factors. Treatment with a combination of growth factors secreted by engineered mammalian cells was more efficient than with individual growth factors or even stem cell–conditioned medium in a gap closure assay. Furthermore, we implemented in a mouse model a device for allogenic cell therapy for an in situ production of growth factors, where it improved cutaneous wound healing. Augmented bone regeneration was achieved on calvarial bone defects in rats treated with a cell device secreting IGF, FGF, PDGF, TGF-β, and VEGF. In both in vivo models, the systemic concentration of secreted factors was negligible, demonstrating the local effect of the regeneration device. Finally, we introduced a genetic switch that enables temporal control over combinations of trophic factors released at different stages of regeneration mimicking the maturation of natural wound healing to improve therapy and prevent scar formation. wound healing bone regeneration growth factors celjenje ran regeneracija kosti rastni faktorji true false true Frontiers Editorial Office Frontiers in bioengineering and biotechnology Angleški jezik Slovenski jezik © 2023 Kadunc Polajnar, Lainšček, Gašperšič, Sušjan-Leite, Kovačič, Butinar, Turk, Jerala and Hafner-Bratkovič. Neznano 2023-06-01 12:36:56 2023-06-01 13:31:26 2024-03-21 13:42:16 0000-00-00 00:00:00 2023 0 0 Soavtorji: Duško Lainšček, Rok Gašperšič, Petra Sušjan-Leite, Uroš Kovačič, Miha Butinar, Boris Turk, Roman Jerala and Iva Hafner-Bratkovič; Nasl. z nasl. zaslona; Opis vira z dne 15. 5. 2023; str. 1-16 Vol. 11 2023 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2023-01-01 61 2296-4185 10.3389/fbioe.2023.1168330 152044035 https://www.frontiersin.org/articles/10.3389/fbioe.2023.1168330/full 1 7b090e07-0057-11ee-a314-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=22497 RAZ_Kadunc_Lucija_2023.pdf RAZ_Kadunc_Lucija_2023.pdf 1 D1D6665BE18C9B6BB2B881BAD58A247E 64bd6d59dfc45701d50f611fe840e8e7b3d0871ab811d4ed7976470af1c09c14 d267a2f7-005d-11ee-a314-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=22498 Kemijski inštitut 0 0 0