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Title:Engineered combinatorial cell device for wound healing and bone regeneration
Authors:ID Kadunc, Lucija (Author)
ID Lainšček, Duško (Author)
ID Gašperšič, Rok (Author)
ID Sušjan, Petra (Author)
ID Kovačič, Uroš (Author)
ID Butinar, Miha (Author)
ID Turk, Boris (Author)
ID Jerala, Roman (Author)
ID Hafner Bratkovič, Iva (Author)
Files:URL URL - Source URL, visit https://www.frontiersin.org/articles/10.3389/fbioe.2023.1168330/full
 
.pdf PDF - Presentation file, download (2,59 MB)
MD5: D1D6665BE18C9B6BB2B881BAD58A247E
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo KI - National Institute of Chemistry
Abstract: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.
Keywords:wound healing, bone regeneration, growth factors
Publication status:Published
Publication version:Version of Record
Publication date:01.01.2023
Publisher:Frontiers Editorial Office
Year of publishing:2023
Number of pages:str. 1-16
Numbering:Vol. 11
Source:Frontiers in bioengineering and biotechnology
PID:20.500.12556/DiRROS-16610 New window
UDC:61
ISSN on article:2296-4185
DOI:10.3389/fbioe.2023.1168330 New window
COBISS.SI-ID:152044035 New window
Copyright:© 2023 Kadunc Polajnar, Lainšček, Gašperšič, Sušjan-Leite, Kovačič, Butinar, Turk, Jerala and Hafner-Bratkovič.
Note: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;
Publication date in DiRROS:01.06.2023
Views:924
Downloads:395
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Record is a part of a journal

Title:Frontiers in bioengineering and biotechnology
Shortened title:Front. bioeng. biotechnol.
Publisher:Frontiers Editorial Office
ISSN:2296-4185
COBISS.SI-ID:523093017 New window

Document is financed by a project

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:P4-0176
Name:Sintezna biologija in imunologija

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:J1-9173
Name:Načrtovanje hitro odzivne signalne in logične poti na osnovi ortogonalnih proteaz

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:N4-0080
Name:Optimizacija sinteznobioloških genskih vezij in reprogramiranja celic s pomočjo mikrofluidike

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:J3-6791
Name:Sintezno biološki pristop k celjenju ran in nevroregeneraciji

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:J3-1746
Name:Vloga celične smrti v različnih aktivacijskih poteh inflamasoma NLRP3 in njena uporaba za inovativno imunoterapijo raka

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:P1-0140
Name:Proteoliza in njena regulacija pri zdravju in boleznih

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:P3-0293
Name:Parodontalna medicina

Funder:ARRS - Slovenian Research Agency
Funding programme:Javna agencija Republike Slovenije za raziskovalno dejavnost
Project number:P3-0171
Name:Plastičnost živčevja v fizioloških in patofizioloških razmerah

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:10.05.2023
Applies to:Version of Record valid from 2023-05-10

Secondary language

Language:Slovenian
Keywords:celjenje ran, regeneracija kosti, rastni faktorji


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