Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels

D. Rana, N. Salehi Nik, J. Rouwkema

    Research output: Contribution to conferenceAbstract

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    Abstract

    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.
    Original languageEnglish
    Pages27
    Number of pages1
    Publication statusPublished - 28 Jun 2019
    EventAptamers in Bordeaux 2019: International Conference on Aptamer Biology, Chemistry, Technologies & Therapeutics - La Cité du Vin, Bordeaux, France
    Duration: 28 Jun 201929 Jun 2019
    http://www.aptamers-in-bordeaux.com/

    Conference

    ConferenceAptamers in Bordeaux 2019
    CountryFrance
    CityBordeaux
    Period28/06/1929/06/19
    Internet address

    Fingerprint

    Hydrogels
    Vascular Endothelial Growth Factor A
    Intercellular Signaling Peptides and Proteins
    Human Umbilical Vein Endothelial Cells
    Mesenchymal Stromal Cells
    Blood Vessels
    Hydrogel
    Coculture Techniques
    Nucleic Acids
    Nucleic Acid Hybridization
    Methacrylates
    Biocompatible Materials
    Metalloproteases
    Gelatin
    Gene Library
    Oligonucleotides
    Biological Availability
    Cell Survival
    Proteins
    Cell Culture Techniques

    Keywords

    • Aptamers
    • Vascularization
    • Tissue engineering

    Cite this

    Rana, D., Salehi Nik, N., & Rouwkema, J. (2019). Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels. 27. Abstract from Aptamers in Bordeaux 2019, Bordeaux, France.
    Rana, D. ; Salehi Nik, N. ; Rouwkema, J. / Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels. Abstract from Aptamers in Bordeaux 2019, Bordeaux, France.1 p.
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    Rana, D, Salehi Nik, N & Rouwkema, J 2019, 'Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels' Aptamers in Bordeaux 2019, Bordeaux, France, 28/06/19 - 29/06/19, pp. 27.

    Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels. / Rana, D.; Salehi Nik, N.; Rouwkema, J.

    2019. 27 Abstract from Aptamers in Bordeaux 2019, Bordeaux, France.

    Research output: Contribution to conferenceAbstract

    TY - CONF

    T1 - Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels

    AU - Rana, D.

    AU - Salehi Nik, N.

    AU - Rouwkema, J.

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    N2 - 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.References1. 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.

    AB - 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.References1. 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.

    KW - Aptamers

    KW - Vascularization

    KW - Tissue engineering

    M3 - Abstract

    SP - 27

    ER -

    Rana D, Salehi Nik N, Rouwkema J. Towards Controlling Vascularization within Engineered Tissues via Programmable Hydrogels. 2019. Abstract from Aptamers in Bordeaux 2019, Bordeaux, France.