Mauricio A. Contreras, MD
Instructor in Surgery, Harvard Medical School
Our research has focused on three main areas of vascular biology: 1) Evaluating mechanisms responsible for prosthetic graft failure, 2) preventing intimal hyperplasia (IH) in vein grafts, and 3) developing novel biomaterials as well as surface modification.
In close collaboration with Matthew D. Phaneuf (Biosurfaces, Inc.), we have developed, through electrospinning, a polyester (Dacron) prosthetic vascular graft with unique structural properties. We have the ability to either modify the vascular graft luminal surface with thrombolytic agents, growth factors, or antibiotics, or incorporate them into the prosthetic graft material during the manufacturing process.
Presently we have completed one of our projects, our 4mm ID Dacron prosthetic vascular graft, where the luminal surface was modified with Activated Protein C (APC), a natural anticoagulant and implanted in our common carotid artery (CCA) model. Even though our final histology, immunohistochemistry, and morphometric studies show differences in healing between control and APC treated grafts (APC-TG), the effect of increased patency on the APC-TG was mainly attributed to the clopidogrel (Plavix) effect. Thus, longer implantation time points (6-12 months) are required to help determine if complete graft healing could occur, which would eliminate the need for the use of Plavix beyond this point. We are currently seeking NIH funding to continue our studies. Our results were presented at the annual American Society for Investigative Pathology (ASIP) meeting at the Federation of the American Society for Experimental Biology (FASEB), in San Diego, CA in April 2014. Our manuscript is in progress and will be submitted to the American Society for Artificial Internal Organs Journal.
The second project we are working on is the in vivo (canine) arterio-venous fistula evaluation of our new 6mm ID nanofibrous bioactive hemodialysis access graft (BAG), which was designed with anti-thrombin, anti-proliferative, and anti-microbial properties by incorporating recombinant Hirudin (rHir), paclitaxel (Pac), and moxifloxacin (Moxi) dissolved in an organic solvent prior to electrospinning. Our preliminary results show striking differences in healing between our BAG and ePTFE AV-fistula graft. At the arterial and venous anastomosis, there is no capsule (C) or neointima (NI) formation up to 60 days on our BAG grafts, unlike the control ePTFE grafts.
However, perhaps more striking is the effect through the needle puncture (NP) sites created to mimic dialysis (Figures 1 and 2). There, fibroblasts and smooth muscle cells from the capsule penetrate and migrate through the ePTFE graft’s wall into the lumen, but do not in our BAG, where its self-sealing bioengineered properties (Dacron/Polyurethane) and Pac prevent such migration/proliferation. Our immunohistochemistry and morphometric studies are ongoing. Our preliminary results were presented at the annual American Society for Artificial Internal Organs (ASAIO) meeting in Washington, DC, in June 2014.
Selected Research Support
A nanofibrous bioactive hemodialysis access graft; NIH, 2012-2014; Co-PI: Mauricio A. Contreras, MD (PI: Saif Pathan)
Mechanisms of prosthetic graft failure; NIH, 2010-2014; Co-Investigator: Mauricio A. Contreras, MD (PI: Frank W. LoGerfo, MD)
Genetic engineering of vein bypass grafts in vascular and cardiovascular surgery; NIH, 2013-2017; Co-Investigator: Mauricio A. Contreras, MD (PI: Frank W. LoGerfo, MD)
A bioactive nanofibrous sewing cuff for treatment of cardiac valvular disease; NIH, 2014; Co-PI: Mauricio A. Contreras, MD (PI: Matthew D. Phaneuf)
Vissapragada R, Contreras MA, da Silva CG, Kumar VA, Ochoa A, Vasudevan A, Selim MH, Ferran C, Thomas AJ. Bidirectional crosstalk between periventricular endothelial cells and neural progenitor cells promotes the formation of a neurovascular unit. Brain Res 2014;27;1565:8-17.