title: Acellular vascular grafts generated from collagen and elastin analogs.
abstract: Tissue-engineered vascular grafts require long fabrication times, in part due to the requirement of cells from a variety of cell sources to produce a robust, load-bearing extracellular matrix. Herein, we propose a design strategy for the fabrication of tubular conduits comprising collagen fiber networks and elastin-like protein polymers to mimic native tissue structure and function. Dense fibrillar collagen networks exhibited an ultimate tensile strength (UTS) of 0.71±0.06 MPa, strain to failure of 37.1±2.2% and Young's modulus of 2.09±0.42 MPa, comparing favorably to a UTS and a Young's modulus for native blood vessels of 1.4-11.1 MPa and 1.5±0.3 MPa, respectively. Resilience, a measure of recovered energy during unloading of matrices, demonstrated that 58.9±4.4% of the energy was recovered during loading-unloading cycles. Rapid fabrication of multilayer tubular conduits with maintenance of native collagen ultrastructure was achieved with internal diameters ranging between 1 and 4mm. Compliance and burst pressures exceeded 2.7±0.3%/100 mmHg and 830±131 mmHg, respectively, with a significant reduction in observed platelet adherence as compared to expanded polytetrafluoroethylene (ePTFE; 6.8±0.05×10(5) vs. 62±0.05×10(5) platelets mm(-2), p<0.01). Using a rat aortic interposition model, early in vivo responses were evaluated at 2 weeks via Doppler ultrasound and CT angiography with immunohistochemistry confirming a limited early inflammatory response (n=8). Engineered collagen-elastin composites represent a promising strategy for fabricating synthetic tissues with defined extracellular matrix content, composition and architecture.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Vivek A
authors.initials: VA
authors.lastname: Kumar
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Caves
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Haller
authors.forename: Erbin
authors.initials: E
authors.lastname: Dai
authors.forename: Liying
authors.initials: L
authors.lastname: Liu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grainger
authors.forename: Elliot L
authors.initials: EL
authors.lastname: Chaikof
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000601:surgery*; D001705:Bioprosthesis; D001807:Blood Vessel Prosthesis; D002474:Cell-Free System; D024042:Collagen Type I / Q000737:chemistry*; D055119:Elastic Modulus; D004549:Elastin / Q000737:chemistry*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000295:instrumentation*
chemical_list: D024042:Collagen Type I; D004549:Elastin
keywords: Biofabrication; Collagen fiber; Elastin-mimetic protein; Vascular graft