3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels.

3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels.
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DOI:
10.1002/jbm.a.34420
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发表时间:
2013-05
影响因子:
4.9
通讯作者:
Butcher, Jonathan T.
Butcher, Jonathan T.
中科院分区:
工程技术3区
文献类型:
--
作者:
Duan, Bin;Hockaday, Laura A.;Kang, Kevin H.;Butcher, Jonathan T.

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心脏瓣膜疾病是一个严重的和日益增长的公共卫生问题,其中人工瓣膜置换术是最常见的指征。目前的假肢装置不适合年轻成人和成长中的儿童。组织工程活主动脉瓣管道具有重塑、再生和生长的潜力,但制造具有细胞异质性的自然解剖复杂性仍然具有挑战性。在目前的研究中,我们实施3D生物打印来制造具有解剖结构的活藻酸盐/明胶水凝胶瓣膜导管,并以区域限制的方式直接掺入双细胞类型。包封的主动脉根窦平滑肌细胞(SMC)和主动脉瓣叶间质细胞(维克)在藻酸盐/明胶水凝胶盘中培养7天以上是有活力的。经过7天的培养,无细胞3D打印水凝胶的模量、极限强度和峰值应变均有所降低,而载有细胞的水凝胶的拉伸生物力学性能则得以保持。成功地生物打印了主动脉瓣管道,瓣膜根部直接包封SMC,瓣叶中直接包封维克。两种细胞类型在3D打印的组织中都是活的(SMC为81.4±3.4%,维克为83.2±4.0%)。当在硬基质中打印时,包封的SMC表达升高的α-平滑肌肌动蛋白,而维克在软基质中表达升高的波形蛋白。这些结果表明,可以用3D生物打印制造解剖学上复杂的、异质包封的主动脉瓣水凝胶导管。
Heart valve disease is a serious and growing public health problem for which prosthetic replacement is most commonly indicated. Current prosthetic devices are inadequate for younger adults and growing children. Tissue engineered living aortic valve conduits have potential for remodeling, regeneration, and growth, but fabricating natural anatomical complexity with cellular heterogeneity remain challenging. In the current study, we implement 3D bioprinting to fabricate living alginate/gelatin hydrogel valve conduits with anatomical architecture and direct incorporation of dual cell types in a regionally constrained manner. Encapsulated aortic root sinus smooth muscle cells (SMC) and aortic valve leaflet interstitial cells (VIC) were viable within alginate/gelatin hydrogel discs over 7 days in culture. Acellular 3D printed hydrogels exhibited reduced modulus, ultimate strength, and peak strain reducing slightly over 7-day culture, while the tensile biomechanics of cell-laden hydrogels were maintained. Aortic valve conduits were successfully bioprinted with direct encapsulation of SMC in the valve root and VIC in the leaflets. Both cell types were viable (81.4±3.4% for SMC and 83.2±4.0% for VIC) within 3D printed tissues. Encapsulated SMC expressed elevated alpha-smooth muscle actin when printed in stiff matrix, while VIC expressed elevated vimentin in soft matrix. These results demonstrate that anatomically complex, heterogeneously encapsulated aortic valve hydrogel conduits can be fabricated with 3D bioprinting.
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