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Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry
Published on: March 29, 2018
Regulating specific growth factor signaling using immobilized branched ligands.
Michael W Toepke1, Nicholas A Impellitteri, Sheeny K Lan Levengood
1Departments of Biomedical Engineering and Orthopedics & Rehabilitation, University of Wisconsin, 5009 Wisconsin Institutes of Medical Research, 1111 Highland Ave., Madison, WI 53705, USA.
Advanced Healthcare Materials
|November 28, 2012
Summary
Hydrogel microspheres with dimerized VEGF-binding peptide ligands reduce vascular endothelial growth factor (VEGF) levels, inhibiting HUVEC growth and calcium signaling. These reversible spheres show potential as VEGF delivery vehicles.
Area of Science:
- Biomaterials Science
- Vascular Biology
- Drug Delivery Systems
Background:
- Vascular Endothelial Growth Factor (VEGF) is crucial for angiogenesis and vascular homeostasis.
- Controlling free VEGF levels is essential for therapeutic applications in diseases involving aberrant angiogenesis.
- Hydrogel microspheres offer a versatile platform for encapsulating and delivering bioactive molecules.
Purpose of the Study:
- To develop and characterize VEGF-binding peptide ligands incorporated into hydrogel microspheres.
- To investigate the effect of ligand dimerization on VEGF binding affinity.
- To evaluate the efficacy of these microspheres in modulating VEGF-mediated cellular responses and their potential as delivery vehicles.
Main Methods:
- Synthesis and incorporation of VEGF-binding peptide ligands into hydrogel microspheres.
- Characterization of ligand dimerization and its impact on binding affinity.
- In vitro assessment of microsphere capacity to reduce free VEGF concentration.
- Evaluation of VEGF-mediated Human Umbilical Vein Endothelial Cell (HUVEC) proliferation and calcium signaling.
Main Results:
- Incorporation of peptide ligands into hydrogel microspheres effectively reduced soluble VEGF levels.
- Dimerization of peptide ligands significantly enhanced VEGF binding affinity.
- VEGF-mediated HUVEC proliferation and calcium signaling were successfully inhibited by the microspheres.
- The VEGF-binding interaction with the microspheres was demonstrated to be reversible.
Conclusions:
- Hydrogel microspheres functionalized with dimerized VEGF-binding peptide ligands provide an effective method for sequestering VEGF.
- These microspheres demonstrate controlled modulation of VEGF bioactivity, reducing HUVEC growth and signaling.
- The reversible binding nature of the ligands suggests potential for developing sophisticated VEGF delivery systems.
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