TY - JOUR
T1 - Optimizing Glutaraldehyde-Fixed Tissue Heart Valves with Chondroitin Sulfate Hydrogel for Endothelialization and Shielding against Deterioration
AU - Lopez-Moya, Mario
AU - Melgar-Lesmes, Pedro
AU - Kolandaivelu, Kumaran
AU - De La Torre Hernández, Jose María
AU - Edelman, Elazer R.
AU - Balcells, Mercedes
N1 - Funding Information:
We acknowledge support provided by the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology for providing access to multiphoton microscopy used for this study. M.B. was supported in part by Fundació Empreses IQS, and a grant from Spanish Ministry of Economy, grant no. SAF2013-43302-R. E.R.E. was supported in part by grants (grant no. R01 GM 49039) from the National Institutes of Health. K.K. was supported in part by an American Heart Association Fellow to Faculty Transition Award (grant no. 12FTF12080241). P.M.-L. was supported by the Pla estrateg̀ ic de recerca i innovació en salut (grant no. PERIS SLT002/16/00341) and then by the Beatriu de Pinos Program 2016 (grant no. BP-00236. M.L.-M was supported by European Social Funds. AGAUR, Generalitat de Catalunya (grant no. 2018 FI_B2 00136).
Funding Information:
We acknowledge support provided by the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology for providing access to multiphoton microscopy used for this study. M.B. was supported in part by Fundacio Empreses IQS, and a grant from Spanish Ministry of Economy, grant no. SAF2013-43302-R. E.R.E. was supported in part by grants (grant no. R01 GM 49039) from the National Institutes of Health. K.K. was supported in part by an American Heart Association Fellow to Faculty Transition Award (grant no. 12FTF12080241).
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/4/9
Y1 - 2018/4/9
N2 - Porcine glutaraldehyde-fixed pericardium is widely used to replace human heart valves. Despite the stabilizing effects of glutaraldehyde fixation, the lack of endothelialization and the occurrence of immune reactions contribute to calcification and structural valve deterioration, which is particularly significant in young patients, in whom valve longevity is crucial. This report shows an optimization system with which to enhance endothelialization of fixed pericardium to mimic the biological function of a native heart valve. The glutaraldehyde detoxification, together with the application of a biodegradable methacrylated chondroitin sulfate hydrogel, reduces aldehydes cytotoxicity, increases the migration and proliferation of endothelial cells and the recruitment of endothelial cell progenitors, and confers thromboresistance in fixed pericardium. The combination of glutaraldehyde detoxification and a coating with chondroitin sulfate hydrogel promotes in situ mechanisms of endothelialization in fixed pericardium. We offer a new solution for improving the long life of bioprosthetic valves and exploring the means of making valves suitable to endothelialization.
AB - Porcine glutaraldehyde-fixed pericardium is widely used to replace human heart valves. Despite the stabilizing effects of glutaraldehyde fixation, the lack of endothelialization and the occurrence of immune reactions contribute to calcification and structural valve deterioration, which is particularly significant in young patients, in whom valve longevity is crucial. This report shows an optimization system with which to enhance endothelialization of fixed pericardium to mimic the biological function of a native heart valve. The glutaraldehyde detoxification, together with the application of a biodegradable methacrylated chondroitin sulfate hydrogel, reduces aldehydes cytotoxicity, increases the migration and proliferation of endothelial cells and the recruitment of endothelial cell progenitors, and confers thromboresistance in fixed pericardium. The combination of glutaraldehyde detoxification and a coating with chondroitin sulfate hydrogel promotes in situ mechanisms of endothelialization in fixed pericardium. We offer a new solution for improving the long life of bioprosthetic valves and exploring the means of making valves suitable to endothelialization.
UR - https://www.scopus.com/pages/publications/85045149314
U2 - 10.1021/acs.biomac.8b00077
DO - 10.1021/acs.biomac.8b00077
M3 - Article
C2 - 29539266
AN - SCOPUS:85045149314
SN - 1525-7797
VL - 19
SP - 1234
EP - 1244
JO - Biomacromolecules
JF - Biomacromolecules
IS - 4
ER -