Computational modeling-guided printing of proangiogenic hydrogel for vascular patterning

vascular endothelial growth factor (VEGF);vascular patterning;angiogenesis;computational modeling;hydrogel;inkjet printing

Rich, Max ; Kong ; Hyun Joon

关键词: vascular endothelial growth factor (VEGF);    vascular patterning;    angiogenesis;    computational modeling;    hydrogel;    inkjet printing;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/45659/Max_Rich.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Our living tissue is highly vascularized to facilitate transports of gaseous and bioactive molecules and subsequently ensure development, homeostasis, and remodeling processes. Cardiovascular diseases diminish the ability of vasculature to carry out these tasks and, in severe cases, cause ischemia. Cardiovascular diseases are the leading cause of human deaths worldwide, making a real need to find a way to restore the vascular blood supply where it is damaged. Therefore, revascularization therapy has emerged to enhance treatments of a plethora of tissue defects, ischemic tissue, and acute and chronic wounds.It is common to administer various growth factors known to promote angiogenesis to target sites, often combined with biomaterials processed in the form of microporous constructs, hydrogels, or nano/micro-sized particles.These previous studies reported some impressive results to increase the number of newly formed mature blood vessels.However, revascularization therapies conducted by repeated administration of proangiogenic factors at high dosage often resulted in inadvertent formations of leaky, immature vasculature and aggregated blood vessels, termed hemangioma.It is suggested that these inadvertent results are related to physical deformation of pre-existing blood vessels where sprouting initiates and further damages on vascular wall.However, there is a lack of tools that allows us to control growth direction and spacing of vasculature and address such complications resulting from revascularization.In this study, I hypothesized that an implantable device that can create local increase of proangiogenic growth factors in a pre-defined micropattern would allow us to control growth direction of new blood vessels and further examine their impacts on pre-existing blood vessels.To examine this hypothesis, I printed multiple poly(ethylene glycol) diacrylate (PEGDA) hydrogel strips loaded with vascular endothelial growth factor (VEGF) using an ink-jet printer.The viscosity and surface tension of the pre-gel PEGDA solution were optimized to fabricate the gel with desired pattern.The spacing of PEGDA gel strips computationally optimized to ensure local increase of VEGF concentration in tissue which is in contact with the hydrogel strips.Finally, the printed hydrogel was implanted on a chicken chorioallantoic membrane to examine vascularization in vivo.Specifically, the hydrogel implant was placed between two large pre-existing blood vessels, while making the direction of hydrogel strips in parallel with or perpendicular to the pre-existing blood vessels. I found that the orientation of the implant as well as the spacing between the printed hydrogel bars is critical in promoting the development of healthy vasculature. If the implant is designed with appropriate spacing and implanted parallel to existing vasculature, then nice healthy patterned vasculature develops. However, if the implant is placed perpendicular to existing vasculature, then pathological vasculature develops.This research goes a long way towards developing a high-throughput method to create patterned vasculature at a physiologically relevant length scale which has previously been difficult to impossible to accomplish.