title: Species-specific effects of aortic valve decellularization.
abstract: Decellularized heart valves have great potential as a stand-alone valve replacement or as a scaffold for tissue engineering heart valves. Before decellularized valves can be widely used clinically, regulatory standards require pre-clinical testing in an animal model, often sheep. Numerous decellularization protocols have been applied to both human and ovine valves; however, the ways in which a specific process may affect valves of these species differently have not been reported. In the current study, the comparative effects of decellularization were evaluated for human and ovine aortic valves by measuring mechanical and biochemical properties. Cell removal was equally effective for both species. The initial cell density of the ovine valve leaflets (2036±673cells/mm2) was almost triple the cell density of human leaflets (760±386cells/mm2; p<0.001). Interestingly, post-decellularization ovine leaflets exhibited significant increases in biaxial areal strain (p<0.001) and circumferential peak stretch (p<0.001); however, this effect was not observed in the human counterparts (p>0.10). This species-dependent difference in the effect of decellularization was likely due to the higher initial cellularity in ovine valves, as well as a significant decrease in collagen crosslinking following the decellularization of ovine leaflets that was not observed in the human leaflet. Decellularization also caused a significant decrease in the circumferential relaxation of ovine leaflets (p<0.05), but not human leaflets (p>0.30), which was credited to a greater reduction of glycosaminoglycans in the ovine tissue post-decellularization. These results indicate that an identical decellularization process can have differing species-specific effects on heart valves.
  
  
  
  The decellularized heart valve offers potential as an improved heart valve substitute and as a scaffold for the tissue engineered heart valve; however, the consequences of processing must be fully characterized. To date, the effects of decellularization on donor valves from different species have not been evaluated in such a way that permits direct comparison between species. In this manuscript, we report species-dependent variation in the biochemical and biomechanical properties of human and ovine aortic heart valve leaflets following decellularization. This is of clinical significance, as current regulatory guidelines required pre-clinical use of the ovine model to evaluate candidate heart valve substitutes.
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, United States; Bioengineering Program, University of Kansas, 3135A Learned Hall, 1530 W. 15th St., Lawrence, KS 66045, United States.
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: VeDepo
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, United States.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Buse
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, United States.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Quinn
authors.affiliation: University of Kansas Mass Spectrometry Laboratory, 3006 Malott Hall, 1251 Wescoe Hall Drive, Lawrence, KS 66045, United States.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Williams
authors.affiliation: Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Detamore
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hopkins
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, United States. Electronic address: glconverse@cmh.edu.
authors.forename: Gabriel L
authors.initials: GL
authors.lastname: Converse
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000737:chemistry*; D006801:Humans; D012756:Sheep; D013045:Species Specificity; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: Collagen crosslinking; Decellularization; Heart valve; Tissue engineering; Tissue mechanics