title: A polymer-extracellular matrix composite with improved thromboresistance and recellularization properties.
abstract: Organ engineering using decellularized scaffolds is a potential long-term solution to donor organ shortage. However, this technology is severely limited by small vessel thrombosis due to incompletely recellularized vessels, resulting in exposure of extracellular matrix (ECM) components to platelets and clotting factors in flowing blood. To address this limitation, we designed a polymer-ECM composite and demonstrated its potential to reduce thrombosis and facilitate re-endothelialization in a vascular graft model. Rat aortas were decellularized using a sequential combination of weak detergents followed by a nuclease treatment that resulted in 96.5±1.3% DNA removal, while ECM components and mechanical properties were well maintained. A biodegradable and biocompatible elastomer poly(1,8 octanediol citrate) (POC, 1wt.%) was infused throughout the ECM at mild conditions (37°C and 45°C) and was functionalized with heparin using carbodiimide chemistry. The polymer-ECM composite significantly reduced platelet adhesion (67.4±8.2% and 82.7±9.6% reduction relative to untreated ECM using one of two processing temperatures, 37°C or 45°C, respectively); inhibited whole blood clotting (85.9±4.3% and 87.0±11.9% reduction relative to untreated ECM at 37°C or 45°C processing temperature, respectively); and supported endothelial cell-and to a lesser extent smooth muscle cell-adhesion in vitro. Taken together, this novel POC composite may provide a solution for thrombosis of small vessel conduits commonly seen in decellularized scaffolds used in tissue engineering applications.
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, IL 60201, United States; Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States.
authors.forename: Berke
authors.initials: B
authors.lastname: Akgun
authors.affiliation: Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, United States.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Lam
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, IL 60201, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60201, United States; Simpson Querrey Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, IL 60611, United States. Electronic address: g-ameer@northwestern.edu.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Ameer
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, IL 60201, United States; Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60201, United States; Simpson Querrey Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Jesse Brown VA Medical Center, Chicago, IL 60612, United States. Electronic address: jason.wertheim@northwestern.edu.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Wertheim
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology*; D002417:Cattle; D002450:Cell Communication / Q000187:drug effects; D002951:Citrates / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000473:pathology*
chemical_list: D002951:Citrates; D011108:Polymers; C513817:poly(1,8-octanediol citrate); D006493:Heparin; D004247:DNA
keywords: Decellularization; Regenerative medicine; Small diameter vascular graft; Tissue engineering