Mechanocompatible Polymer-Extracellular-Matrix Composites for Vascular Tissue Engineering.
Small-diameter vascular grafts developed from vascular extracellular matrix (ECM) can potentially be used for bypass surgeries and other vascular reconstruction and repair procedures. The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical cross-linking, which increases ECM mechanical stiffness compared to native arteries. Herein, the importance of maintaining ECM mechanocompatibility is demonstrated, and a mechanocompatible strategy to immobilize heparin onto the ECM via a biodegradable elastomer is described. Specifically, poly(1,8-octamethylene citrate)-co-cysteine is hybridized to the ECM, forming a polymer-ECM composite that allows for heparin immobilization via maleimide-thiol "click" chemistry. Heparinized composites reduce platelet adhesion by >60% in vitro, without altering the elastic modulus of the ECM. In a rat abdominal aortic interposition model, intimal hyperplasia in heparinized mechanocompatible grafts is 65% lower when compared to ECM-only control grafts at four weeks. In contrast, grafts that are heparinized with carbodiimide chemistry exhibit increased intimal hyperplasia (4.2-fold) and increased macrophage infiltration (3.5-fold) compared to ECM-only control grafts. All grafts show similar, partial endothelial cell coverage and little to no ECM remodeling. Overall, a mechanocompatible strategy to improve ECM thromboresistance is described and the importance of ECM mechanical properties for proper in vivo graft performance is highlighted.
Biomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USA.|Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.|Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Bin
B
Jiang
Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, 60208, USA.
Rachel
R
Suen
Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.|Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Jiao-Jing
JJ
Wang
Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.|Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Zheng J
ZJ
Zhang
Biomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USA.|Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.|Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.|Department of Surgery, Jesse Brown VA Medical Center, Chicago, IL, 60612, USA.|Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, 60208, USA.|Simpson Querrey Institute, Northwestern University, Chicago, IL, 60611, USA.
Jason A
JA
Wertheim
Biomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USA.|Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.|Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, 60208, USA.|Simpson Querrey Institute, Northwestern University, Chicago, IL, 60611, USA.
Guillermo A
GA
Ameer
D000818:Animals; D001012:Aorta, Abdominal; D001705:Bioprosthesis; D001807:Blood Vessel Prosthesis; D004195:Disease Models, Animal; D020724:Elastomers / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051381:Rats; D017207:Rats, Sprague-Dawley; D014188:Transposition of Great Vessels / Q000378:metabolism / Q000473:pathology / Q000601:surgery
D020724:Elastomers
composite; extracellular matrix (ECM); heparin; poly(1,8-octamethylene citrate) (POC); vascular graft