2, National University of Singapore, Singapore, , Singapore
3, Laval University, Quebec City, Quebec, Canada
4, Oregon Health and Science University, Portland, Oregon, United States
5, Singapore Eye Research Institute, Singapore, , Singapore
6, Duke-NUS Graduate Medical School, Singapore, , Singapore
Cells respond to both physical and biochemical changes in their extracellular microenvironment. An ideal scaffold for tissue engineering application should mimic the microenvironment for natural tissue development and present the appropriate biochemical and topographical cues in a spatially controlled manner. Our research group is interested in studying the interfacial interactions of cells with the extracellular substrate and how to apply this knowledge to tissue engineering applications. In this presentation, strategies on engineering cell-materials interface, such as incorporating topographies on implantable device, development of disease model and generating functional cells, for different application for vascular and corneal repair will be discussed.
Small diameter vascular grafts (< 6 mm internal diameter) are used in bypass or replacement of occluded peripheral arteries. However, there is a lack of commercially available synthetic small diameter grafts with acceptable long-term patency. Enhancement of in situ endothelialization of small diameter vascular grafts is needed to improve clinical outcomes. Topographical cues may be used to affect the change by influencing the behavior of endothelial cells, such as increasing their migration and proliferation capacities. Poly(vinyl alcohol) (PVA), a biocompatible and non-thrombogenic hydrogel, is an excellent material for vascular tissue engineering, showing short term patency in a rat abdominal aorta model and in a rabbit model with multi-level peripheral arterial occlusion.
Although PVA has been shown to be inert, the lack of endothelial cell attachment on the luminal surface of the graft would impact the long-term patency. We fabricated PVA small diameter vascular graft with topography on its luminal surface. Implantation of patterned PVA grafts in rat abdominal aorta model exhibited patency and in situ endothelialization after 20 days. Chemical modification such as the incorporation of cyclic-RGD adhesive peptide or N2 plasma treatment could further enhance the endothelial cell adhesion and functional marker expression, while these chemical modifications did not compromise the hemocompatibility. PVA vascular grafts are excellent candidates as a small diameter vascular graft by, preventing thrombosis, stimulating in situ endothelialization and supporting long-term patency.
In addition to incorporating topographical patterns in implantable vascular devices, we investigated the application of topographies to enhance human corneal endothelial cell growth. Cornea endothelium dysfunction is one of the main reasons for corneal transplantation. Tissue engineered cornea endothelium will be highly sought after due to the shortage of donor cornea grafts. Our studies show that micro-pillars enhanced and primary human cornea endothelial cell’s responses. Examples of topography-modulation for corneal tissue-engineering applications and corneal endothelial disease model will be also be discussed.