6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep.
6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep.
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DOI：
10.1016/j.biomaterials.2015.09.016
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发表时间：
2015-12
期刊：
影响因子：
14
通讯作者：
Tranquillo RT
中科院分区：
文献类型：
--
作者：
Syedain Z;Reimer J;Schmidt J;Lahti M;Berry J;Bianco R;Tranquillo RT
患病的主动脉瓣经常需要替换，目前超过30%的主动脉瓣手术是在比生物瓣膜存活时间更长的患者身上进行的。虽然许多有希望的组织工程瓣膜已经在实验室中使用细胞种子聚合物支架范例被创造出来，但没有一个在临床前模型的主动脉位置上被成功地测试过。主动脉瓣叶的高压力梯度和动态流动要求设计出一种组织，该组织具有足够的强度和顺应性，能够在不影响正常血流动力学的情况下承受高机械需求。在绵羊模型中，对现成的组织工程化主动脉瓣进行了长期的临床前评估。这些阀门是由安装在框架上的脱细胞细胞产生的基质制成的。工程化组织基质主要由胶原蛋白组成，其强度和组织结构可与天然瓣叶相媲美。体外试验表明，低返流、低收缩压和大的瓣口面积具有良好的血流动力学性能。植入的瓣膜在6个月的植入过程中表现出较大的瓣叶运动，并保持有效的瓣口面积，无钙化。植入24周(超过1700万个循环)后，瓣膜的拉伸机械性能或胶原含量没有变化。此外，组织学和DNA定量显示，工程化基质中可见大量间质样细胞和内皮化。新的细胞外基质沉积，包括弹性蛋白，除了再细胞化和瓣膜功能外，还进一步显示出积极的组织重塑。绵羊模型的长期植入导致了功能性、基质重塑和再细胞化，这对组织工程主动脉瓣来说是前所未有的结果。
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 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 sheep model is presented here. The valves were made from a tube of decellularized cell-produced matrix mounted on a frame. The engineered tissue 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, 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 or collagen content. 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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影响因子：
37.8
作者：
Aikawa, E;Whittaker, P;Schoen, FJ
通讯作者：
Schoen, FJ
影响因子：
4.6
作者：
da Costa, Francisco D. A.;Costa, Ana Claudia B. A.;Lopes, Sergio Veiga
通讯作者：
Lopes, Sergio Veiga
影响因子：
2.9
作者：
KIM, YJ;SAH, RLY;GRODZINSKY, AJ
通讯作者：
GRODZINSKY, AJ
影响因子：
4.1
作者：
Syedain, Zeeshan H.;Meier, Lee A.;Tranquillo, Robert T.
通讯作者：
Tranquillo, Robert T.
影响因子：
4.1
作者：
Syedain, Zeeshan H.;Bradee, Allison R.;Tranquillo, Robert T.
通讯作者：
Tranquillo, Robert T.