20.500.12556/RUL-155119 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 labor-intensive 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 cell device engineered cells celjenje ran regeneracija kosti rastni faktorji true false true Angleški jezik Slovenski jezik Članek v reviji 2024-03-20 16:15:37 2024-03-20 16:15:40 2024-03-21 10:42:38 0000-00-00 00:00:00 2023 0 0 16 str. Vol. 11, art. 1168330 2023 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 61 2296-4185 10.3389/fbioe.2023.1168330 152044035 fbioe-11-1168330.pdf fbioe-11-1168330.pdf 1 66F1329D8D3CD43DAD7A1CDEB3253DB7 98040368b5545d7a0877f05593d39f9d4548dc65eddcd62e532127d7a755cf20 14a34716-e6cd-11ee-8d8c-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=181904 https://www.frontiersin.org/articles/10.3389/fbioe.2023.1168330/full 1 b7975ba6-e6cc-11ee-8d8c-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=181903 Medicinska fakulteta 0 0 0