Proangiogenic Hydrogels Within Macroporous Scaffolds Enhance Islet Engraftment in an Extrahepatic Site
| Autor: | Cherie L. Stabler, Jeffrey A. Hubbell, Mikaël M. Martino, Antonello Pileggi, Ann Christina Brady, Steve Sukert, Eileen Pedraza, Camillo Ricordi |
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| Rok vydání: | 2013 |
| Předmět: |
Scaffold
Platelet-derived growth factor medicine.medical_treatment Becaplermin Islets of Langerhans Transplantation Biomedical Engineering Bioengineering Biochemistry Biomaterials Islets of Langerhans Mice chemistry.chemical_compound medicine Animals Dimethylpolysiloxanes Integrin binding geography geography.geographical_feature_category biology Chemistry Growth factor Hydrogels Proto-Oncogene Proteins c-sis Original Articles Allografts Islet Cell biology Transplantation Fibronectin Nylons Self-healing hydrogels biology.protein Angiogenesis Inducing Agents Porosity Biomedical engineering |
| Zdroj: | Tissue Engineering Part A. 19:2544-2552 |
| ISSN: | 1937-335X 1937-3341 |
| DOI: | 10.1089/ten.tea.2012.0686 |
| Popis: | The transplantation of allogeneic islets in recent clinical trials has shown substantial promise as a therapy for type 1 diabetes; however, long-term insulin independence remains inadequate. This has been largely attributed to the current intravascular, hepatic transplant site, which exposes islets to mechanical and inflammatory stresses. A highly macroporous scaffold, housed within an alternative transplant site, can support an ideal environment for islet transplantation by providing three-dimensional distribution of islets, while permitting the infiltration of host vasculature. In the present study, we sought to evaluate the synergistic effect of a proangiogenic hydrogel loaded within the void space of a macroporous poly(dimethylsiloxane) (PDMS) scaffold on islet engraftment. The fibrin-based proangiogenic hydrogel tested presents platelet derived growth factor (PDGF-BB), via a fibronectin (FN) fragment containing growth factor and major integrin binding sites in close proximity. The combination of the proangiogenic hydrogel with PDMS scaffolds resulted in a significant decrease in the time to normoglycemia for syngeneic mouse islet transplants. This benefit was associated with an observed increase in competent vessel branching, as well as mature intraislet vessels. Overall, the addition of the proangiogenic factor PDGF-BB, delivered via the FN fragment-functionalized hydrogel, positively influenced the efficiency of engraftment. These characteristics, along with its ease of retrieval, make this combination of a biostable macroporous scaffold and a degradable proangiogenic hydrogel a supportive structure for insulin-producing cells implanted in extrahepatic sites. |
| Databáze: | OpenAIRE |
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