Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications
A fast re-endothelialization, along with the inhibition of neointima hyperplasia, are crucial to reduce the failure of vascular bypass grafts. Implants modifications with molecules capable of speeding up the re-endothelialization process have been proposed over the last years. However, clinical tria...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2019.00074/full |
| _version_ | 1828383709859938304 |
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| author | Francesco Copes Francesco Copes Pascale Chevallier Caroline Loy Daniele Pezzoli Francesca Boccafoschi Francesca Boccafoschi Diego Mantovani |
| author_facet | Francesco Copes Francesco Copes Pascale Chevallier Caroline Loy Daniele Pezzoli Francesca Boccafoschi Francesca Boccafoschi Diego Mantovani |
| author_sort | Francesco Copes |
| collection | DOAJ |
| description | A fast re-endothelialization, along with the inhibition of neointima hyperplasia, are crucial to reduce the failure of vascular bypass grafts. Implants modifications with molecules capable of speeding up the re-endothelialization process have been proposed over the last years. However, clinical trials of angiogenic factor delivery have been mostly disappointing, underscoring the need to investigate a wider array of angiogenic factors. In this work, a drug release system based on a type I collagen hydrogel has been proposed for the controlled release of Pleiotrophin (PTN), a cytokine known for its pro-angiogenetic effects. Heparin, in virtue of its ability to sequester, protect and release growth factors, has been used to better control the release of PTN. Performances of the PTN drug delivery system on endothelial (ECs) and smooth muscle cells (SMCs) have been investigated. Structural characterization (mechanical tests and immunofluorescent analyses of the collagen fibers) was performed on the gels to assess if heparin caused changes in their mechanical behavior. The release of PTN from the different gel formulations has been analyzed using a PTN-specific ELISA assay. Cell viability was evaluated with the Alamar Blue Cell Viability Assay on cells directly seeded on the gels (direct test) and on cells incubated with supernatant, containing the released PTN, obtained from the gels (indirect test). The effects of the different gels on the migration of both ECs and SMCs have been evaluated using a Transwell migration assay. Hemocompatibility of the gel has been assessed with a clotting/hemolysis test. Structural analyses showed that heparin did not change the structural behavior of the collagen gels. ELISA quantification demonstrated that heparin induced a constant release of PTN over time compared to other conditions. Both direct and indirect viability assays showed an increase in ECs viability while no effects were noted on SMCs. Cell migration results evidenced that the heparin/PTN-modified gels significantly increased ECs migration and decreased the SMCs one. Finally, heparin significantly increased the hemocompatibility of the collagen gels. In conclusion, the PTN-heparin-modified collagen here proposed can represent an added value for vascular medicine, able to ameliorate the biological performance, and integration of vascular grafts. |
| first_indexed | 2024-12-10T04:52:40Z |
| format | Article |
| id | doaj.art-c35e456f6d284dd7baca2067d64f7674 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-10T04:52:40Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-c35e456f6d284dd7baca2067d64f76742022-12-22T02:01:34ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852019-04-01710.3389/fbioe.2019.00074442491Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular ApplicationsFrancesco Copes0Francesco Copes1Pascale Chevallier2Caroline Loy3Daniele Pezzoli4Francesca Boccafoschi5Francesca Boccafoschi6Diego Mantovani7Laboratory of Human Anatomy, Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyLaboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering, CHU de Quebec Research Center, Laval University, Quebec, QC, CanadaLaboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering, CHU de Quebec Research Center, Laval University, Quebec, QC, CanadaLaboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering, CHU de Quebec Research Center, Laval University, Quebec, QC, CanadaLaboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering, CHU de Quebec Research Center, Laval University, Quebec, QC, CanadaLaboratory of Human Anatomy, Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyLaboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering, CHU de Quebec Research Center, Laval University, Quebec, QC, CanadaLaboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering, CHU de Quebec Research Center, Laval University, Quebec, QC, CanadaA fast re-endothelialization, along with the inhibition of neointima hyperplasia, are crucial to reduce the failure of vascular bypass grafts. Implants modifications with molecules capable of speeding up the re-endothelialization process have been proposed over the last years. However, clinical trials of angiogenic factor delivery have been mostly disappointing, underscoring the need to investigate a wider array of angiogenic factors. In this work, a drug release system based on a type I collagen hydrogel has been proposed for the controlled release of Pleiotrophin (PTN), a cytokine known for its pro-angiogenetic effects. Heparin, in virtue of its ability to sequester, protect and release growth factors, has been used to better control the release of PTN. Performances of the PTN drug delivery system on endothelial (ECs) and smooth muscle cells (SMCs) have been investigated. Structural characterization (mechanical tests and immunofluorescent analyses of the collagen fibers) was performed on the gels to assess if heparin caused changes in their mechanical behavior. The release of PTN from the different gel formulations has been analyzed using a PTN-specific ELISA assay. Cell viability was evaluated with the Alamar Blue Cell Viability Assay on cells directly seeded on the gels (direct test) and on cells incubated with supernatant, containing the released PTN, obtained from the gels (indirect test). The effects of the different gels on the migration of both ECs and SMCs have been evaluated using a Transwell migration assay. Hemocompatibility of the gel has been assessed with a clotting/hemolysis test. Structural analyses showed that heparin did not change the structural behavior of the collagen gels. ELISA quantification demonstrated that heparin induced a constant release of PTN over time compared to other conditions. Both direct and indirect viability assays showed an increase in ECs viability while no effects were noted on SMCs. Cell migration results evidenced that the heparin/PTN-modified gels significantly increased ECs migration and decreased the SMCs one. Finally, heparin significantly increased the hemocompatibility of the collagen gels. In conclusion, the PTN-heparin-modified collagen here proposed can represent an added value for vascular medicine, able to ameliorate the biological performance, and integration of vascular grafts.https://www.frontiersin.org/article/10.3389/fbioe.2019.00074/fullcollagenpleiotrophinheparinendothelial cellssmooth muscle cellscontrolled release |
| spellingShingle | Francesco Copes Francesco Copes Pascale Chevallier Caroline Loy Daniele Pezzoli Francesca Boccafoschi Francesca Boccafoschi Diego Mantovani Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications Frontiers in Bioengineering and Biotechnology collagen pleiotrophin heparin endothelial cells smooth muscle cells controlled release |
| title | Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications |
| title_full | Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications |
| title_fullStr | Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications |
| title_full_unstemmed | Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications |
| title_short | Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications |
| title_sort | heparin modified collagen gels for controlled release of pleiotrophin potential for vascular applications |
| topic | collagen pleiotrophin heparin endothelial cells smooth muscle cells controlled release |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2019.00074/full |
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