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Non-cytotoxic cross-linking of bioactive porcine matrices

Pamela Somers (UGent) , Filip De Somer (UGent) , Maria Cornelissen (UGent) , Hubert Thierens (UGent) and Guido Van Nooten (UGent)
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Abstract
Objectives: Incubating a porcine aortic valve matrix with a platelet gel (PG) concentrate creates a bioactive matrix which is loaded with growth factors. These matrices can be repopulated with mesenchymal stem cells. However, these recellularized matrices still elicit a host immune response. Therefore, the aim of this study was to evaluate the cytotoxicity and cross-linking effect of naturally organic compounds such as quercetin, tannic acid, caffeic acid and catechin on these matrices and to investigate the effect of these cross-linkers on the in vitro growth factor release rate. Materials and methods: Porcine aortic heart valves were decellularized using a patented detergent/enzymatic treatment. Cytotoxicty of the cross-linkers was evaluated by cell culture media supplementation of 10, 100, 1000, 5000, 10000 and 20000µg/mL These concentrations were also used to cross-link the acellular matrices. Mechanical strength of the leaflets was investigated. Also the effect of these cross-linkers on the growth factor release from the PG loaded scaffolds was evaluated by ELISA. Results: Results showed that proliferation of porcine mesenchymal stem cells increased significantly with increasing concentrations of quercetin, tannic acid, caffeic acid and catechin. All compounds except tannic acid significantly increased mechanical strength of the matrices. Moreover, tensile strength of quercetin cross-linked matrices was comparable to the commercially available 0.625% glutaradehyde fixed valves. Furthermore, cross-linking of the matrices resulted in a decreased burst release of growth factors during the first 4 hours but prolonged the release after 24 hours when compared to non-cross-linked matrices. Conclusion: Natural compounds such as quercetin, caffeic acid and catechin can be used to cross-link porcine aortic valve matrices. Moreover, the in vitro release of growth factors can be prolonged which can be very advantageous in the recellularization of these scaffolds.

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Chicago
Somers, Pamela, Filip De Somer, Maria Cornelissen, Hubert Thierens, and Guido Van Nooten. 2012. “Non-cytotoxic Cross-linking of Bioactive Porcine Matrices.” In QScience Proceedings. Vol. 2012.
APA
Somers, P., De Somer, F., Cornelissen, M., Thierens, H., & Van Nooten, G. (2012). Non-cytotoxic cross-linking of bioactive porcine matrices. QScience Proceedings (Vol. 2012). Presented at the 5th Biennial conference on Heart Valve Biology and Tissue Engineering.
Vancouver
1.
Somers P, De Somer F, Cornelissen M, Thierens H, Van Nooten G. Non-cytotoxic cross-linking of bioactive porcine matrices. QScience Proceedings. 2012.
MLA
Somers, Pamela, Filip De Somer, Maria Cornelissen, et al. “Non-cytotoxic Cross-linking of Bioactive Porcine Matrices.” QScience Proceedings. Vol. 2012. 2012. Print.
@inproceedings{2128525,
  abstract     = {Objectives: Incubating a porcine aortic valve matrix with a platelet gel (PG) concentrate creates a bioactive matrix which is loaded with growth factors. These matrices can be repopulated with mesenchymal stem cells. However, these recellularized matrices still elicit a host immune response. Therefore, the aim of this study was to evaluate the cytotoxicity and cross-linking effect of naturally organic compounds such as quercetin, tannic acid, caffeic acid and catechin on these matrices and to investigate the effect of these cross-linkers on the in vitro growth factor release rate.
Materials and methods: Porcine aortic heart valves were decellularized using a patented detergent/enzymatic treatment. Cytotoxicty of the cross-linkers was evaluated by cell culture media supplementation of 10, 100, 1000, 5000, 10000 and 20000{\textmu}g/mL These concentrations were also used to cross-link the acellular matrices. Mechanical strength of the leaflets was investigated. Also the effect of these cross-linkers on the growth factor release from the PG loaded scaffolds was evaluated by ELISA.
Results: Results showed that proliferation of porcine mesenchymal stem cells increased significantly with increasing concentrations of quercetin, tannic acid, caffeic acid and catechin. All compounds except tannic acid significantly increased mechanical strength of the matrices. Moreover, tensile strength of quercetin cross-linked matrices was comparable to the commercially available 0.625\% glutaradehyde fixed valves.  Furthermore, cross-linking of the matrices resulted in a decreased burst release of growth factors during the first 4 hours but prolonged the release after 24 hours when compared to non-cross-linked matrices.
Conclusion: Natural compounds such as quercetin, caffeic acid and catechin can be used to cross-link porcine aortic valve matrices. Moreover, the in vitro release of growth factors can be prolonged which can be very advantageous in the recellularization of these scaffolds.},
  articleno    = {abstract 35},
  author       = {Somers, Pamela and De Somer, Filip and Cornelissen, Maria and Thierens, Hubert and Van Nooten, Guido},
  booktitle    = {QScience Proceedings},
  language     = {eng},
  location     = {Myconons, Greece},
  title        = {Non-cytotoxic cross-linking of bioactive porcine matrices},
  url          = {http://dx.doi.org/10.5339/qproc.2012.heartvalve.4.35},
  volume       = {2012},
  year         = {2012},
}

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