Abstract
Type 1 diabetes mellitus (T1DM) is a widespread chronic condition affecting millions of patients globally. While insulin therapy serves as the primary treatment method, it falls short of fully restoring normal glycemic balance, thereby increasing the risk of secondary complications. Beta-cell therapy emerges as a potential cure for T1DM, demonstrating promise in clinical settings. Nevertheless, low retention rates, inadequate cell survival, and limited therapeutic efficacy are ongoing challenges, underscoring the necessity for advanced cell encapsulation devices.
This study aimed to develop a mechanically reinforced drug delivery encapsulation device tailored for beta cell encapsulation and transplantation. Poly(l-lactide-co-E-caprolactone) (PLCL)/gelatin methacryloyl(GelMA)/alginate coaxial nanofibres were produced using electrospinning and embedded in an alginate hydrogel. Physical characterization of porosity, swelling ratio, and mechanical properties revealed the device's suitability for beta cell encapsulation, vascularization, and transplantation. Additionally, the device was found to be biocompatible allowing comparable viability between encapsulated and unencapsulated beta cell clusters. The clusters were likewise found to remain functional after encapsulation, however, they were not entirely comparable to unencapsulated clusters. To enhance beta cell functionality, the glucagon-like peptide-1 (GLP-1) analogue exendin-4 (Ex-4) was incorporated into the device. The peptide was released for 14 days, however, the bioactivity of the peptide could not be confirmed from the presented studies. Lastly, the vascular endothelial growth factor (VEGF) was incorporated into the hydrogel to induce vascularization into the device. The VEGF release kinetics and functional studies revealed a release of bioactive VEGF for at least 14 days. Although VEGF demonstrated good efficacy in vitro, the in vivo effect on vascularization could not be confirmed in this thesis. Despite not confirming all hypotheses, the mechanically reinforced alginate device proved to be a promising candidate for improving the survival of beta cells after transplantation.
This study aimed to develop a mechanically reinforced drug delivery encapsulation device tailored for beta cell encapsulation and transplantation. Poly(l-lactide-co-E-caprolactone) (PLCL)/gelatin methacryloyl(GelMA)/alginate coaxial nanofibres were produced using electrospinning and embedded in an alginate hydrogel. Physical characterization of porosity, swelling ratio, and mechanical properties revealed the device's suitability for beta cell encapsulation, vascularization, and transplantation. Additionally, the device was found to be biocompatible allowing comparable viability between encapsulated and unencapsulated beta cell clusters. The clusters were likewise found to remain functional after encapsulation, however, they were not entirely comparable to unencapsulated clusters. To enhance beta cell functionality, the glucagon-like peptide-1 (GLP-1) analogue exendin-4 (Ex-4) was incorporated into the device. The peptide was released for 14 days, however, the bioactivity of the peptide could not be confirmed from the presented studies. Lastly, the vascular endothelial growth factor (VEGF) was incorporated into the hydrogel to induce vascularization into the device. The VEGF release kinetics and functional studies revealed a release of bioactive VEGF for at least 14 days. Although VEGF demonstrated good efficacy in vitro, the in vivo effect on vascularization could not be confirmed in this thesis. Despite not confirming all hypotheses, the mechanically reinforced alginate device proved to be a promising candidate for improving the survival of beta cells after transplantation.
| Originalsprog | Engelsk |
|---|
| Forlag | Aarhus University |
|---|---|
| Status | Udgivet - mar. 2024 |