Biologically Inspired Artificial Organs
Biomolecular engineering to improve the performance of implanted devices
Artificial organs, such as ventricular assist devices, a total artificial heart, implantable respiratory and renal support systems, or synthetic vascular grafts are prone to failure due to the activation of thrombotic cascades and detrimental inflammatory reactions that lead to blood clots. The immobilization of bioactive proteins or carbohydrates on the surfaces of implanted medical devices to limit adverse biological responses have yielded promising results. However, these strategies remain limited by the biodegradation of surface bound bioactive molecules by oxidation, hydrolysis, and proteolysis when exposed over time to a physiological environment over extended timescales. We have sought to improve the activity and stability of bioactive proteins and carbohydrates that limit blood mediated thrombotic and inflammatory reactions through rational molecular design. We are also developing schemes that rapidly and reproducibly regenerate selective molecular constituents after device implantation to extend the lifetime of bioactive films and enhance clinically related performance characteristics.
Team Members
Carolyn Haller, Ph.D.
Oki Ham, Ph.D.
Relevant Publications
Ham HO, Haller CA, Su G, Dai E, Patel MS, Liu DR, Liu J, Chaikof EL. A rechargeable anti-thrombotic coating for blood-contacting devices. Biomaterials 2021;276:121011. https://doi.org/10.1016/j.biomaterials.2021.121011
Varghese M, Rokosh RS, Haller CA, Chin SL, Chen J, Dai E, Xiao R, Chaikof EL, Grinstaff MW. Sulfated poly-amido-saccharides (sulPASs) are anticoagulants in vitro and in vivo. Chem Sci 2021;12:12719–25. https://doi.org/10.1039/d1sc02302k
McNamara SL, Brudno Y, Miller AB, Ham HO, Aizenberg M, Chaikof EL, Mooney DJ. Regenerating Antithrombotic Surfaces through Nucleic Acid Displacement. ACS Biomater Sci Eng 2020;6:2159–66. https://doi.org/10.1021/acsbiomaterials.0c00038
Ham HO, Qu Z, Haller CA, Dorr BM, Dai E, Kim W, Liu DR, Chaikof EL. In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A. Nat Commun 2016;7:11140. https://doi.org/10.1038/ncomms11140