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
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.
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.