TY - JOUR
T1 - Biocompatibility of two model elastin-like recombinamer-based hydrogels formed through physical or chemical cross-linking for various applications in tissue engineering and regenerative medicine
AU - Ibáñez-Fonseca, Arturo
AU - Ramos, Teresa L.
AU - González de Torre, Israel
AU - Sánchez-Abarca, Luis Ignacio
AU - Muntión, Sandra
AU - Arias, Francisco Javier
AU - del Cañizo, María Consuelo
AU - Alonso, Matilde
AU - Sánchez-Guijo, Fermín
AU - Rodríguez-Cabello, José Carlos
N1 - Funding Information:
Junta de Castilla y León, Grant/Award Number: VA244U13 and VA313U14; Ministerio de Economía y Competitividad, Grant/Award Number: MAT2012‐38043, MAT2013‐ 41723‐R, MAT2013‐42473‐R, MAT2015‐ 68901‐R, MAT2016‐78903‐R and MAT2016‐ 79435‐R; Instituto de Salud Carlos III, Grant/ Award Number: RD12/0019/0017; Portuguese Fundação para a Ciência e Tecnologia, Grant/Award Number: SFRH/BD/86451/ 2012; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, and Junta de Castilla y León, Grant/ Award Number: VA313U14 and VA244U13; Spanish Government, Grant/Award Number: MAT2012‐38043, MAT2013‐41723‐R, MAT2013‐42473‐R, MAT2016‐79435‐R and MAT2016‐78903‐R; European Commission, Grant/Award Number: HEALTH‐F4‐2011‐ 278557, MSCA‐ITN‐2014‐642687, NMP‐ 2014‐646075 and PITN‐GA‐2012‐317306
Funding Information:
The authors are grateful for funding from the European Commission (NMP-2014-646075, HEALTH-F4-2011-278557, PITN-GA-2012-317306 and MSCA-ITN-2014-642687), MINECO of the Spanish Government (MAT2016-78903-R, MAT2016-79435-R, MAT2015-68901-R, MAT2013-42473-R, MAT2013-41723-R and MAT2012-38043), Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, and Junta de Castilla y León (VA244U13 and VA313U14). Teresa L. Ramos is supported by a fellowship from the Portuguese Fundação para a Ciência e Tecnologia (SFRH/BD/86451/2012). Sandra Muntión is supported by grant RD12/0019/0017 from the Instituto de Salud Carlos III.
Funding Information:
The authors are grateful for funding from the European Commission (NMP‐2014‐646075, HEALTH‐F4‐2011‐278557, PITN‐GA‐2012‐ 317306 and MSCA‐ITN‐2014‐642687), MINECO of the Spanish Government (MAT2016‐78903‐R, MAT2016‐79435‐R, MAT2015‐ 68901‐R, MAT2013‐42473‐R, MAT2013‐41723‐R and MAT2012‐ 38043), Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, and Junta de Castilla y León (VA244U13 and VA313U14). Teresa L. Ramos is supported by a fellowship from the Portuguese Fundação para a Ciência e Tecnologia (SFRH/BD/86451/ 2012). Sandra Muntión is supported by grant RD12/0019/0017 from the Instituto de Salud Carlos III.
Publisher Copyright:
Copyright © 2017 John Wiley & Sons, Ltd.
PY - 2018/3
Y1 - 2018/3
N2 - Biocompatibility studies, especially innate immunity induction, in vitro and in vivo cytotoxicity, and fibrosis, are often lacking for many novel biomaterials including recombinant protein-based ones, such as elastin-like recombinamers (ELRs), and has not been extensively explored in the scientific literature, in contrast to traditional biomaterials. Herein, we present the results from a set of experiments designed to elucidate the preliminary biocompatibility of 2 types of ELRs that are able to form extracellular matrix-like hydrogels through either physical or chemical cross-linking both of which are intended for different applications in tissue engineering and regenerative medicine. Initially, we present in vitro cytocompatibility results obtained upon culturing human umbilical vein endothelial cells on ELR substrates, showing optimal proliferation up to 9 days. Regarding in vivo cytocompatibility, luciferase-expressing hMSCs were viable for at least 4 weeks in terms of bioluminescence emission when embedded in ELR hydrogels and injected subcutaneously into immunosuppressed mice. Furthermore, both types of ELR-based hydrogels were injected subcutaneously in immunocompetent mice and serum TNFα, IL-1β, IL-4, IL-6, and IL-10 concentrations were measured by enzyme-linked immunosorbent assay, confirming the lack of inflammatory response, as also observed upon macroscopic and histological evaluation. All these findings suggest that both types of ELRs possess broad biocompatibility, thus making them very promising for tissue engineering and regenerative medicine-related applications.
AB - Biocompatibility studies, especially innate immunity induction, in vitro and in vivo cytotoxicity, and fibrosis, are often lacking for many novel biomaterials including recombinant protein-based ones, such as elastin-like recombinamers (ELRs), and has not been extensively explored in the scientific literature, in contrast to traditional biomaterials. Herein, we present the results from a set of experiments designed to elucidate the preliminary biocompatibility of 2 types of ELRs that are able to form extracellular matrix-like hydrogels through either physical or chemical cross-linking both of which are intended for different applications in tissue engineering and regenerative medicine. Initially, we present in vitro cytocompatibility results obtained upon culturing human umbilical vein endothelial cells on ELR substrates, showing optimal proliferation up to 9 days. Regarding in vivo cytocompatibility, luciferase-expressing hMSCs were viable for at least 4 weeks in terms of bioluminescence emission when embedded in ELR hydrogels and injected subcutaneously into immunosuppressed mice. Furthermore, both types of ELR-based hydrogels were injected subcutaneously in immunocompetent mice and serum TNFα, IL-1β, IL-4, IL-6, and IL-10 concentrations were measured by enzyme-linked immunosorbent assay, confirming the lack of inflammatory response, as also observed upon macroscopic and histological evaluation. All these findings suggest that both types of ELRs possess broad biocompatibility, thus making them very promising for tissue engineering and regenerative medicine-related applications.
KW - biocompatibility
KW - catalyst-free click gels
KW - cytocompatibility
KW - elastin-like recombinamers
KW - regenerative medicine
KW - silk-elastin multiblock corecombinamers
KW - tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=85043357764&partnerID=8YFLogxK
U2 - 10.1002/term.2562
DO - 10.1002/term.2562
M3 - Article
C2 - 28865091
AN - SCOPUS:85043357764
SN - 1932-6254
VL - 12
SP - e1450-e1460
JO - Journal of Tissue Engineering and Regenerative Medicine
JF - Journal of Tissue Engineering and Regenerative Medicine
IS - 3
ER -