Review on the topographical effects on vascular cells for the applications in vascular conduits

Cardiovascular diseases are the leading cause of mortality worldwide and represent a pressing clinical need.  Vascular occlusions are the predominant cause of cardiovascular disease and necessitate surgical interventions such as bypass graft surgery to replace the damaged or obstructed blood vessel with a synthetic conduit.  In our review article published in Advanced Healthcare Materials, we discussed and reviewed the application of surface topography in synthetic small-diameter vascular graft and how topography affects vascular cell behaviors.

Refer to Conner A et al. The effect of biomimetic surface topography on vascular cells: implications for vascular conduits.  Advanced Healthcare Materials. 2024, 13, 2400335.  

Fucoidan molecule from seaweed and topography modification improved endothelialization on off-the-self synthetic vascular grafts

We have developed a surface modification strategy using fucoidan, a polysaccharide molecule extracted from seaweeds, and luminal topography to enable fast in situ endothelialization of polyvinyl alcohol (PVA) small diameter vascular graft.  In our work published in Bioactive Materials, using a clinically relevant rabbit model, in situ endothelialization was observed throughout the entire lumen of 1.7 mm inner diameter modified grafts, and the 4-week graft patency was also increased. 

The work has also been reported on CTV News, and recovered in Newsweek and Science Daily.

Please refer to Yao et al. Fucoidan and topography modification improved in situ endothelialization on acellular synthetic vascular grafts, Bioactive Materials, 22, 2023, Pages 535-550.

Our research article on development of corneal endothleial cell therapy is selected as back cover in the latest issue of "Advanced Healthcare Materials"

Our research article "In-vitro Topographical Model of Fuchs Dystrophy for Evaluation of Corneal Endothelial Cell Monolayer Formation" appeared on the  Back cover of Advanced Healthcare Materials latest issue.

Several diseases have been known to be caused by microstructural changes in the extracellular microenvironment. Therefore, the knowledge of the interaction of cells with the altered extracellular micro-structures or surface topography is critical to develop a better understanding of the disease for therapeutic development. One such disease is Fuchs corneal endothelial dystrophy (FED). FED is the primary disease and major reason of corneal endothelial cell death. If left untreated, corneal blindness will be resulted; thus, FED is the leading indication for corneal transplantation. In the USA, 4% of population over the age of 40 is believed to have compromised corneal endothelium due to FED, which will further increase due to increasing life expectancy and rapidly ageing population. A diagnostic clinical hallmark of FED is the development of discrete pillar or dome-like microstructures on the corneal endothelial basement membrane (Descemet membrane). These microstructures are called corneal guttata or guttae. Cell therapies have been proposed as an alternative treatment method for Fuchs dystrophy patients. However, currently, no in-vitro or in-vivo FED disease model is available to study the cell therapies before clinical trials. 

In this study, the pathological changes in the micro-structure of basement membranes resulting from FED disease was analyzed, to identify geometrical dimension to develop an in-vitro disease model of synthetic corneal guttata pillars/domes by using microfabrication techniques. This model was used to study the monolayer formation of donor-derived human corneal endothelial cells to test the effectiveness of the corneal endothelial cell regenerative therapies. The results suggest that the corneal cell therapies may not be equally effective for patients at different stages of disease progression. The pre-existing guttata in patients could interfere with the cells thus hampering monolayer formation within the eye. Surgical removal of the guttata from the diseased Descemet membrane prior to cell regenerative therapy could increase the success rate of monolayer formation, which could potentially increase the chances of cell therapy success. This study also demonstrate how biomaterial design can be employed to mimic the pathological microstructural changes in basement membranes for better understanding of cellular responses in disease conditions.

http://onlinelibrary.wiley.com/doi/10.1002/adhm.201600848/full  

Investigating the mechanobiology of nanotopography-induced cell behaviour, and applying to direct stem cell differentiation and in tissue engineering applications.

Scaffold with Appropriate Cues for Tissue Engineering

Cells are surrounded by various nano-scaled topographical and biochemical cues in their microenvironment during the natural tissue development. An ideal scaffold for tissue engineering application should mimic the natural microenvironment for natural tissue and present the appropriate biochemical and topographical cues in a spatially controlled manner. Recent findings underscore the phenomenon that mammalian cells do respond to nanoscale features on a synthetic surface. Our previous studies show nanotopography can significantly influence cellular behaviours ranging from attachment to proliferation and differentiation. The understanding of how each of these two cues could influence the stem cell behaviour would aid the development of the next generation scaffold for tissue engineering and stem cell applications. We are interested to investigate the underlying mechanobiology of nanotopography-induced cell behaviour and to apply this knowledge to direct stem cell differentiation and in tissue engineering applications.

Research Projects

To investigate how the biophysical and biochemical cues regulate cell behavior, we are pursuing the following research program

1. Interaction of adult and embryonic stem cells with nanotopography
2. Fabrication of nano-structures for biomedical applications
3. Nanotopography-induced differentiation of stem cells for neuronal, cornea and vascular tissue engineering