Coronary artery disease is the leading cause of mortality and disability in the US. Current treatment methods including autologous artery and vein grafts have considerable limitations despite decades of refinement. Two critical challenges in small artery substitutes are high compliance and nonthrombogenicity. Our long-term goal is to create mechanically competent, nonthrombogenic and vasoresponsive small artery substitutes. The objective of this proposal is to engineer mechanically competent small arteries. The central hypothesis of this application is that a biomimetic culture environment will facilitate the formation of small arteries with structure and properties representative of the native vessels. We will create a culture condition that mimics angiogenesis and vasculogenesis by cultivating vascular progenitor cells in rationally-designed elastomeric scaffolds under dynamic mechanical conditions. This innovative approach may lead to physiological compliance in the near future, and nonthrombogenicity and vasoresponsiveness ultimately. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims.
Under aim 1, we will fabricate tubular scaffolds from elastomeric and stiff biomaterials that will be used in aims 2 and 3 to examine the effects of scaffold properties on the structure and properties of the resultant artificial arteries. The feedbacks from aims 2 and 3 will guide the selection and optimization of the scaffolds.
Under aim 2, we will culture circulating endothelial progenitor cells with smooth muscle cells to engineer closely interacting intima/media composites with compliance matching native arteries.
Aim 3 will focus on increasing the strength and stability of the constructs by adding an adventitia layer while maintaining the high compliance of the intima/media layer. The combined work in aims 1 to 3 is expected to create mechanically competent small arteries that provides a solid foundation for future investigations in antithrombogenicity and vasoresponsiveness. This multidisciplinary proposal combines the complementary expertise of the Principal Investigator in biomaterial and regenerative medicine, and the Collaborators in vascular cell biology, biomechanics, and blood-material interfacial phenomenon. When successfully completed, the proposed research is expected to represent a significant advance in the field of blood vessel substitutes and accelerate the translation of tissue-engineered arteries from benchside promise to bedside benefit. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL089658-01
Application #
7300949
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lundberg, Martha
Project Start
2007-07-25
Project End
2011-06-30
Budget Start
2007-07-25
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$363,581
Indirect Cost
Name
Georgia Institute of Technology
Department
Type
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Lee, Soo Hyon; Lee, Kee-Won; Gade, Piyusha S et al. (2018) Microwave-assisted facile fabrication of porous poly (glycerol sebacate) scaffolds. J Biomater Sci Polym Ed 29:907-916
Ding, Xiaochu; Wu, Yen-Lin; Gao, Jin et al. (2017) Tyramine functionalization of poly(glycerol sebacate) increases the elasticity of the polymer. J Mater Chem B 5:6097-6109
Procter, Nathan Ek; Ball, Jocasta; Ngo, Doan Tm et al. (2016) Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation. J Geriatr Cardiol 13:202-8
Khosravi, Ramak; Best, Cameron A; Allen, Robert A et al. (2016) Long-Term Functional Efficacy of a Novel Electrospun Poly(Glycerol Sebacate)-Based Arterial Graft in Mice. Ann Biomed Eng 44:2402-16
Johnson, Noah R; Wang, Yadong (2015) Coacervate delivery of HB-EGF accelerates healing of type 2 diabetic wounds. Wound Repair Regen 23:591-600
Jeffries, Eric M; Allen, Robert A; Gao, Jin et al. (2015) Highly elastic and suturable electrospun poly(glycerol sebacate) fibrous scaffolds. Acta Biomater 18:30-9
Jeffries, Eric M; Nakamura, Shintaro; Lee, Kee-Won et al. (2014) Micropatterning electrospun scaffolds to create intrinsic vascular networks. Macromol Biosci 14:1514-20
Bae, Hojae; Chu, Hunghao; Edalat, Faramarz et al. (2014) Development of functional biomaterials with micro- and nanoscale technologies for tissue engineering and drug delivery applications. J Tissue Eng Regen Med 8:1-14
Allen, Robert A; Wu, Wei; Yao, Mingyi et al. (2014) Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model. Biomaterials 35:165-73
Johnson, Noah R; Wang, Yadong (2014) Coacervate delivery systems for proteins and small molecule drugs. Expert Opin Drug Deliv 11:1829-32

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