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Stimulation of In Vivo Angiogenesis Through Dual Growth Factor Loaded Hyaluronic Acid Hydrogels. Celeste Riley Mentor: Dr. Robert Peattie Department of Chemical Engineering. Importance. Engineered tissues Organ transplants Ischemic Pathologies (Diabetes). Components of the Project.
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Stimulation of In Vivo Angiogenesis Through Dual Growth Factor Loaded Hyaluronic Acid Hydrogels Celeste Riley Mentor: Dr. Robert Peattie Department of Chemical Engineering
Importance • Engineered tissues • Organ transplants • Ischemic Pathologies (Diabetes)
Components of the Project • Preparation of Hydrogels • Surgery on living mouse models • Count formed blood vessels and analyze data
Hydrogel Preparation What is a hydrogel? • Natural or Synthetic • Biocompatible • Crosslinked to form a gel-like substance • Dehydration
Hydrogel Preparation What is Hyaluronic Acid? • Glycosaminoglycan • Complexes H20 molecules • Chief component of extracellular matrix • Contributes to cell proliferation and migration Chemical structure of hyaluronic acid http://www.hyalogic.com/aboutha.htm
Addition of Growth Factors What are growth factors? • Signaling proteins • Bind receptors of target cells • Promote differentiation and maturation Diagram of Growth Factor Binding http://www.grahamstudios.net/medcon.html
Addition of Growth Factors Which Growth Factors? • Vascular Endothelial Growth Factor (VEGF) • Angiopoietin 1 (Ang-1) Model of VEGF http://kerrins.net/ud/proteins.html
Make hydrogel from hyaluronic acid Impregnate hydrogel with growth factors Ang-1 and VEGF Dehydrate and implant hydrogel into mouse ear Determine if implant, loaded with growth factors, stimulates angiogenesis Goal of Project GFs +
Project Setup Conditions to consider • Spontaneous Growth • Original Vessels • Individual combinations: control cases (chart)
Treatment Cases • 6 animals per treatment group
Determining Blood Vessel Growth • Thin-section both surgical and contralateral ear • Count blood vessels under 400X magnification Contralateral Ear
Data Analysis What do we want to measure? Define a statistical index to account for • effect of sham surgery • number of vessels present before surgery How do we measure it? Additional vessels due only to the particular surgical treatment
Neovascularization Index NI = (treatment-CL) – (sham-CL) mean CL • (treatment-CL) = average # of additional blood vessels in the implanted ear of treatment group • (sham-CL) = average # of additional vessels due to the surgical procedure itself • mean CL = average vessel count in all contralateral ears: effectiveness measure
Conclusion • Currently, data collection is still ongoing • When calculated, compare NI of experimental case to NIs of control cases • At this point, no definite conclusion can be drawn about the effect of Ang-1 and VEGF delivered through HA hydrogel on angiogenesis
Acknowledgments Dr. Robert Peattie Dr. Kevin Ahern Howard Hughes Medical Institute Co-researcher Peter Fuegy