Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels

Growth factors are of vital importance for controlling and coordinating blood vessels formation, organization and maturation. Among other important factors, spatiotemporally regulated bioavailability of growth factors is of critical need for controlling vascularization within an engineered tissue. However, conventional approaches for growth factor localization mainly focus on their physical entrapment or chemical coupling within the engineered matrices (hydrogel) via metalloproteinase-sensitive linker. Even though these approaches allow passive release rate and growth factor delivery on demand, they fail to provide spatial or temporal control on growth factor’s release rates which is essential for mimicking native tissue/organ developmental environment. To address this issue, nucleic acid aptamers have emerged as a class of affinity ligands that could be selected from DNA/RNA libraries for binding to growth factors with high affinity and specificity.1,2 This approach provides an alternative system that could allow sequential loading of different growth factors and provide temporal control on their release rate.
To this end, in the present study, aptamer conjugated gelatin methacrylate (GelMA) hydrogels have been developed for programmable release of vascular endothelial growth factor (VEGF). Furthermore, the effect of programmable VEGF release on angiogenic properties of human umbilical vein derived endothelial cells (HUVECs) co-cultured with mesenchymal stem cells (MSCs) have been studied. The results obtained from VEGF ELISA experiments revealed that acrydite functionalized aptamers could sustain a controlled VEGF release up to 10 days, if no complementary sequence (CSs) for these VEGF specific aptamers were provided. However, immediately after adding the CSs, triggered VEGF release was observed. In co-culture experiments, the developed programmable hydrogels supported HUVECs and MSCs in terms of cell viability and vascular network formation over a span of 7 days within the hydrogels (triggered VEGF release was observed on Day 5). Therefore, the results of this study demonstrated a successful programmable VEGF release within a hydrogel and its positive effect on vascular formation in HUVECs/MSCs co-culture.
References
1. B. Soontornworajit, et. al., Affinity hydrogels for controlled protein release using nucleic acid aptamers and complementary oligonucleotides. Biomaterials 32 (2011) 6839-6849.
2. M.R. Battig, et. al., Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization. J. Am. Chem. Soc. 134 (2012) 12410-12413.