Our laboratory (chaikoflab.org) is focused on the development of biologically inspired materials, devices, and pharmacotherapeutics based upon the principles of molecular engineering and nanofabrication technologies. Ongoing research is directed at the following areas.
Tissue engineering and regenerative medicine
Engineering blood vessels
Synthetic blood vessel substitutes for cardiac or vascular surgery do not exist. Ongoing efforts in our group seek to design new synthetic collagen and elastin analogues and to assemble them along with vascular wall cells derived from stem cells to engineer a living artery.
Materials for soft tissue repair
Current synthetic materials cannot be used for surgical reconstruction in the setting of bacterial contamination or infection. As a test bed, we are investigating the application of new materials, stem cells, and fabrication techniques to design abdominal wall patches to facilitate normal healing and local tissue repair in the setting of bacterial contamination.
A major obstacle in islet transplantation for the treatment of diabetes is the high rate of early islet destruction. Synthetic cell coatings, anti-thrombotic fusion proteins, and carbohydrate mimics that limit inflammatory responses are being explored to enhance the effectiveness of islet transplantation.
Targeted therapies to promote vascular wall healing
Restenosis remains a major cause of failure after angioplasty and stenting for treatment of lower extremity peripheral arterial disease. New approaches are being developed that target thrombotic and inflammatory events at the site of vessel wall injury through antibody directed targeting of activated platelets.
Preventing and treating aortic aneurysms
Medical therapy that prevents the growth or induces the regression of aortic aneurysms does not exist. Current investigations in our laboratory are directed at harnessing the innate immune system to turn off proteolytic or inflammatory events and promote local tissue repair at sites of early aneurysm formation.
Chemical biology and materials science
Design of anti-thrombogenic surfaces
The development of artificial organs remains limited by the propensity of all synthetic surfaces to induce thrombus formation despite systemic anticoagulation. Current studies are designing surfaces that present molecules that resist clotting, along with computational models that describe surface-induced coagulation events under conditions of flow.
Chemoenzymatic synthesis of P-Selectin Glycoprotein-1
Selectins play an important role in the recruitment of leukocytes to inflamed tissue. We are currently synthesizing P-Selectin Glycoprotein-1 (PSGL-1) mimics to block inflammatory responses.
SELECTED RESEARCH SUPPORT
In situ regeneration of bioactive surfaces: Rechargeable anti-thrombogenic films; NIH, 2013-2017; PI: Elliot L. Chaikof, MD, PhD
Site-specific therapies to prevent intimal hyperplasia; NIH, 2011-2016; PI: Elliot L. Chaikof, MD, PhD
Molecularly engineered blockade of islet induced inflammatory responses; NIH,2010-2015; PI: Elliot L. Chaikof, MD, PhD
Engineered fascia for stem cell therapy in hernia repair; Wyss Institute for Biologically Inspired Engineering, 2014-2015; PI: Elliot L. Chaikof, MD, PhD
Hohmann JD, Wang X, Krajewski S, Selan C, Haller CA, Straub A, Chaikof EL, Nandurkar HH, Hagemeyer CE, Peter K. Delayed targeting of CD39 to activated platelet GPIIb/IIIa via a single-chain antibody: Breaking the link between antithrombotic potency and bleeding? Blood 2013;121(16):3067-75.
Kumar VA, Caves JM, Haller CA, Dai E, Li L, Grainger S, Chaikof EL. Acellular vascular grafts generated from collagen and elastin analogues. Acta Biomaterialia 2013;8:8067-8074.
Dorr BM, Ham O, An C, Chaikof EL, Liu DR. Reprogramming the specificity of sortase enzymes by directed evolution. Proc Nat Acad Sci USA 2014;111:13343–13348.
Qu Z, Krishnamurthy V, Haller CA, Dorr BM, Marzec UM, Hurst S, Hinds MT, Hanson SR, Liu DR, Chaikof EL. Immobilization of actively thromboresistant assemblies on sterile blood-contacting surfaces. Adv Healthcare Mater 2014;3(1):30-5.
Angsana J, Chen J, Smith S, Xiao J, Wen J, Liu L, Haller CA, Chaikof EL. Syndecan-1 modulates the motility and resolution responses of macrophages. Arteriosclerosis Thromb Vasc Biol 2014.
Kim W, Haller CA, Dai E, Wang X, Hagemeyer CE, Liu DR, Peter K, Chaikof EL. Targeted anti-thrombotic protein micelles. Angew Chemie 2014.