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Biomaterial Regulation of Diseased vs. Healthy Tissue Function

Research Team: Ana Porras, J. Taylor Stofflet
Funded by: NSF CAREER Award, NIH/NHLBI R01
We are interested in using biomaterials and tissue engineering-based approaches to investigate the mechanisms of heart valve calcification and to develop engineered platforms for testing potential anti-calcific therapeutics. While traditional tissue engineering focuses upon the creation of healthy tissue to be used in tissue repair or replacement, our lab intentionally generates diseased tissue in order to better understand disease etiologies and identify potential treatment targets to prevent or halt disease progression. The projects within this theme include: investigation of how the extracellular matrix regulates valvular interstitial cell (dys)function, development of 3-D models of valvular disease for testing therapeutic drugs such as statins, and characterization of sex-related differences in valve function. Knowledge gained from this work will help us characterize the mechanism of valve calcification as well as identify environmental/biomaterial properties that control the function and phenotype of valvular interstitial cells, which is of use in both our re-creation of disease and more traditional tissue engineering of healthy valves.

Cellular Decision-Making Processes in Wound Healing and Angiogenesis

Research Team: Mary Regier, Yao Fu
Funded by: NIH/NIGMS R01
In both in vivo and in vitro environments, cells are exposed to numerous extracellular stimuli that regulate their function, such as extracellular matrix proteins, growth factors, and mechanical forces. The nature of these cues and their subsequent interpretation by cells is complex; sometimes these cues work in concert to instruct cells to perform a certain function, and other times these cues are conflicting. We aim to better understand how cells “decide” what cues to follow in this complex environment, particularly in the context of dermal wound healing and angiogenesis. This work will also be combined with computational modeling (collaboration with Prof. Pam Kreeger) to predict cell behavior in untested environments. Such efforts to better understand and predict cellular decision-making processes is important in not only informing the construction of environments that allow greater control over cell behavior, but also in understanding native physiological phenomena.

Nylon-3 Copolymers for Tissue Engineering

Research Team: Runhui Liu
Funded by: NIH/NIBIB R21
The creation of biomimetic substrates and scaffolds that support cell attachment, growth, and differentiation is a crucial component in the development of engineered tissues. The use of synthetic materials that encourage cell adhesion avoids many of the limitations associated with natural materials, but such materials often require labor-intensive synthetic protocols. Nylon-3 copolymers are intriguing as prospective biomaterials because these polymers have a protein-mimetic backbone (β-amino acid residues) and can be assembled rapidly in functionally diverse forms. In collaboration with Prof. Sam Gellman, we have identified nylon-3 copolymers that support better cell adhesion and spreading than native peptides (e.g., RGD) and that support cell adhesion in the absence of serum proteins. Moreover, the chemical features of these polymers allow us to gain a better understanding of how discrete, controlled changes in materials chemistry can control cell behavior, thereby yielding information that can be used to construct scaffolds with an optimized composition. Ongoing work in this area focuses upon characterizing the mechanism of cell adhesion to these polymers, creating nylon-3 materials that spontaneously self-assemble into 3-D structures, and using these diverse materials as substrates for stem cell culture.

Development of Hemocompatible Materials for Vascular Applications

Research Team: Amaliris Ruiz
Funded by: W.H. Coulter Translational Research Partnership
Despite several decades of research into hemocompatible biomaterials, there remain surprisingly few materials that can be used in blood-contacting applications. Even materials that are accepted as hemocompatible, such as Teflon and Dacron, are too thrombogenic for use in certain applications, such as small-diameter vascular grafts. Moreover, Teflon and Dacron have mechanical properties that are orders of magnitude different from those of native blood vessels, which leads to further problems in graft healing and performance. Thus, in an effort to create materials that are non-thrombogenic and have appropriate mechanical properties for vascular applications, we have synthesized materials that are copolymers of polyurethane with various glycosaminoglycans. Several of these materials are entirely resistant to platelet adhesion, yet still support endothelial cell adhesion, viability, and proliferation, which makes these materials very attractive for use as vascular grafts. Our current research in this area focuses on in vivo testing of materials and extending their usage to tissue engineering applications.