VeDepo Mitchell C, Buse Eric E, Quinn Rachael W, Williams Todd D, Detamore Michael S, Hopkins Richard A, Converse Gabriel L
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.
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.
Acta Biomater. 2017 Mar 1;50:249-258. doi: 10.1016/j.actbio.2017.01.008. Epub 2017 Jan 6.
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/mm) was almost triple the cell density of human leaflets (760±386cells/mm; 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.
去细胞心脏瓣膜作为独立的瓣膜置换物或作为组织工程心脏瓣膜的支架具有巨大潜力。在去细胞瓣膜能够在临床上广泛应用之前，监管标准要求在动物模型（通常是绵羊）中进行临床前测试。许多去细胞方案已应用于人类和绵羊瓣膜；然而，尚未有报道表明特定过程对这些物种的瓣膜产生不同影响的方式。在当前研究中，通过测量力学和生化特性，评估了去细胞对人类和绵羊主动脉瓣膜的比较效果。两种物种的细胞去除效果相同。绵羊瓣膜小叶的初始细胞密度（2036±673个细胞/mm）几乎是人类小叶细胞密度（760±386个细胞/mm；p<0.001）的三倍。有趣的是，去细胞后绵羊小叶的双轴面积应变（p<0.001）和周向峰值拉伸（p<0.001）显著增加；然而，在人类对应物中未观察到这种效应（p>0.10）。去细胞效果的这种物种依赖性差异可能是由于绵羊瓣膜中较高的初始细胞密度，以及绵羊小叶去细胞后胶原交联显著减少，而人类小叶中未观察到这种情况。去细胞还导致绵羊小叶的周向松弛显著降低（p<0.05），但人类小叶未出现这种情况（p>0.30），这归因于去细胞后绵羊组织中糖胺聚糖的更大减少。这些结果表明相同的去细胞过程对心脏瓣膜可能有不同的物种特异性影响。
去细胞心脏瓣膜作为一种改良的心脏瓣膜替代品和组织工程心脏瓣膜的支架具有潜力；然而，必须充分表征处理的后果。迄今为止，尚未以允许物种间直接比较的方式评估去细胞对不同物种供体瓣膜的影响。在本手稿中，我们报告了去细胞后人类和绵羊主动脉心脏瓣膜小叶的生化和生物力学特性的物种依赖性变化。这具有临床意义，因为当前的监管指南要求在临床前使用绵羊模型来评估候选心脏瓣膜替代品。
