Publications by authors named "Jay Reimer"

6 Publications

  • Page 1 of 1

Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs.

Nat Commun 2016 09 27;7:12951. Epub 2016 Sep 27.

Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Treatment of congenital heart defects in children requiring right ventricular outflow tract reconstruction typically involves multiple open-heart surgeries because all existing graft materials have no growth potential. Here we present an 'off-the-shelf' vascular graft grown from donor fibroblasts in a fibrin gel to address this critical unmet need. In a proof-of-concept study, the decellularized grafts are implanted as a pulmonary artery replacement in three young lambs and evaluated to adulthood. Longitudinal ultrasounds document dimensional growth of the grafts. The lambs show normal growth, increasing body weight by 366% and graft diameter and volume by 56% and 216%, respectively. Explanted grafts display physiological strength and stiffness, complete lumen endothelialization and extensive population by mature smooth muscle cells. The grafts also show substantial elastin deposition and a 465% increase in collagen content, without signs of calcification, aneurysm or stenosis. Collectively, our data support somatic growth of this completely biological graft.
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http://dx.doi.org/10.1038/ncomms12951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052664PMC
September 2016

Implantation of a Tissue-Engineered Tubular Heart Valve in Growing Lambs.

Ann Biomed Eng 2017 Feb 11;45(2):439-451. Epub 2016 Apr 11.

Department of Biomedical Engineering, University of Minnesota, 312 Church St SE, Minneapolis, MN, 55455, USA.

Current pediatric heart valve replacement options are suboptimal because they are incapable of somatic growth. Thus, children typically have multiple surgeries to replace outgrown valves. In this study, we present the in vivo function and growth potential of our tissue-engineered pediatric tubular valve. The valves were fabricated by sewing two decellularized engineered tissue tubes together in a prescribed pattern using degradable sutures and subsequently implanted into the main pulmonary artery of growing lambs. Valve function was monitored using periodic ultrasounds after implantation throughout the duration of the study. The valves functioned well up to 8 weeks, 4 weeks beyond the suture strength half-life, after which their insufficiency index worsened. Histology from the explanted valves revealed extensive host cell invasion within the engineered root and commencing from the leaflet surfaces. These cells expressed multiple phenotypes, including endothelial, and deposited elastin and collagen IV. Although the tubes fused together along the degradable suture line as designed, the leaflets shortened compared to their original height. This shortening is hypothesized to result from inadequate fusion at the commissures prior to suture degradation. With appropriate commissure reinforcement, this novel heart valve may provide the somatic growth potential desired for a pediatric valve replacement.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064828PMC
http://dx.doi.org/10.1007/s10439-016-1605-7DOI Listing
February 2017

6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep.

Biomaterials 2015 Dec 11;73:175-84. Epub 2015 Sep 11.

Departments of Biomedical Engineering, University of Minnesota, United States; Department of Chemical Engineering & Material Science, University of Minnesota, United States. Electronic address:

Diseased aortic valves often require replacement, with over 30% of the current aortic valve surgeries performed in patients who will outlive a bioprosthetic valve. While many promising tissue-engineered valves have been created in the lab using the cell-seeded polymeric scaffold paradigm, none have been successfully tested long-term in the aortic position of a pre-clinical model. The high pressure gradients and dynamic flow across the aortic valve leaflets require engineering a tissue that has the strength and compliance to withstand high mechanical demand without compromising normal hemodynamics. A long-term preclinical evaluation of an off-the-shelf tissue-engineered aortic valve in the sheep model is presented here. The valves were made from a tube of decellularized cell-produced matrix mounted on a frame. The engineered matrix is primarily composed of collagen, with strength and organization comparable to native valve leaflets. In vitro testing showed excellent hemodynamic performance with low regurgitation, low systolic pressure gradient, and large orifice area. The implanted valves showed large-scale leaflet motion and maintained effective orifice area throughout the duration of the 6-month implant, with no calcification. After 24 weeks implantation (over 17 million cycles), the valves showed no change in tensile mechanical properties. In addition, histology and DNA quantitation showed repopulation of the engineered matrix with interstitial-like cells and endothelialization. New extracellular matrix deposition, including elastin, further demonstrates positive tissue remodeling in addition to recellularization and valve function. Long-term implantation in the sheep model resulted in functionality, matrix remodeling, and recellularization, unprecedented results for a tissue-engineered aortic valve.
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http://dx.doi.org/10.1016/j.biomaterials.2015.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520964PMC
December 2015

Pediatric tubular pulmonary heart valve from decellularized engineered tissue tubes.

Biomaterials 2015 Sep 16;62:88-94. Epub 2015 May 16.

Department of Biomedical Engineering, University of Minnesota, USA; Department of Chemical Engineering and Material Science, University of Minnesota, USA. Electronic address:

Pediatric patients account for a small portion of the heart valve replacements performed, but a pediatric pulmonary valve replacement with growth potential remains an unmet clinical need. Herein we report the first tubular heart valve made from two decellularized, engineered tissue tubes attached with absorbable sutures, which can meet this need, in principle. Engineered tissue tubes were fabricated by allowing ovine dermal fibroblasts to replace a sacrificial fibrin gel with an aligned, cell-produced collagenous matrix, which was subsequently decellularized. Previously, these engineered tubes became extensively recellularized following implantation into the sheep femoral artery. Thus, a tubular valve made from these tubes may be amenable to recellularization and, ideally, somatic growth. The suture line pattern generated three equi-spaced leaflets in the inner tube, which collapsed inward when exposed to back pressure, per tubular valve design. Valve testing was performed in a pulse duplicator system equipped with a secondary flow loop to allow for root distention. All tissue-engineered valves exhibited full leaflet opening and closing, minimal regurgitation (<5%), and low systolic pressure gradients (<2.5 mmHg) under pulmonary conditions. Valve performance was maintained under various trans-root pressure gradients and no tissue damage was evident after 2 million cycles of fatigue testing.
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http://dx.doi.org/10.1016/j.biomaterials.2015.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490908PMC
September 2015

Tubular heart valves from decellularized engineered tissue.

Ann Biomed Eng 2013 Dec 30;41(12):2645-54. Epub 2013 Jul 30.

Department of Biomedical Engineering, University of Minnesota, 7-114 NHH, 312 Church St SE, Minneapolis, MN, 55455, USA.

A novel tissue-engineered heart valve (TEHV) was fabricated from a decellularized tissue tube mounted on a frame with three struts, which upon back-pressure cause the tube to collapse into three coapting "leaflets." The tissue was completely biological, fabricated from ovine fibroblasts dispersed within a fibrin gel, compacted into a circumferentially aligned tube on a mandrel, and matured using a bioreactor system that applied cyclic distension. Following decellularization, the resulting tissue possessed tensile mechanical properties, mechanical anisotropy, and collagen content that were comparable to native pulmonary valve leaflets. When mounted on a custom frame and tested within a pulse duplicator system, the tubular TEHV displayed excellent function under both aortic and pulmonary conditions, with minimal regurgitant fractions and transvalvular pressure gradients at peak systole, as well as well as effective orifice areas exceeding those of current commercially available valve replacements. Short-term fatigue testing of one million cycles with pulmonary pressure gradients was conducted without significant change in mechanical properties and no observable macroscopic tissue deterioration. This study presents an attractive potential alternative to current tissue valve replacements due to its avoidance of chemical fixation and utilization of a tissue conducive to recellularization by host cell infiltration.
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http://dx.doi.org/10.1007/s10439-013-0872-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847912PMC
December 2013