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高度对齐的组织工程构建体的丝状光(FLight)生物制造

Filamented Light (FLight) Biofabrication of Highly Aligned Tissue-Engineered Constructs.

作者信息

Liu Hao, Chansoria Parth, Delrot Paul, Angelidakis Emmanouil, Rizzo Riccardo, Rütsche Dominic, Applegate Lee Ann, Loterie Damien, Zenobi-Wong Marcy

机构信息

Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences & Technology, ETH Zürich, Otto-Stern-Weg 7, Zürich, 8093, Switzerland.

Readily3D SA, EPFL Innovation Park, Lausanne, 1015, Switzerland.

出版信息

Adv Mater. 2022 Nov;34(45):e2204301. doi: 10.1002/adma.202204301. Epub 2022 Oct 9.

Abstract

Cell-laden hydrogels used in tissue engineering generally lack sufficient 3D topographical guidance for cells to mature into aligned tissues. A new strategy called filamented light (FLight) biofabrication rapidly creates hydrogels composed of unidirectional microfilament networks, with diameters on the length scale of single cells. Due to optical modulation instability, a light beam is divided optically into FLight beams. Local polymerization of a photoactive resin is triggered, leading to local increase in refractive index, which itself creates self-focusing waveguides and further polymerization of photoresin into long hydrogel microfilaments. Diameter and spacing of the microfilaments can be tuned from 2 to 30 µm by changing the coherence length of the light beam. Microfilaments show outstanding cell instructive properties with fibroblasts, tenocytes, endothelial cells, and myoblasts, influencing cell alignment, nuclear deformation, and extracellular matrix deposition. FLight is compatible with multiple types of photoresins and allows for biofabrication of centimeter-scale hydrogel constructs with excellent cell viability within seconds (<10 s per construct). Multidirectional microfilaments are achievable within a single hydrogel construct by changing the direction of FLight projection, and complex multimaterial/multicellular tissue-engineered constructs are possible by sequentially exchanging the cell-laden photoresin. FLight offers a transformational approach to developing anisotropic tissues using photo-crosslinkable biomaterials.

摘要

组织工程中使用的载细胞水凝胶通常缺乏足够的三维地形引导,以使细胞成熟为排列整齐的组织。一种名为丝状光(FLight)生物制造的新策略能快速创建由单向微丝网络组成的水凝胶,其直径在单个细胞的长度尺度上。由于光学调制不稳定性,一束光被光学分割成FLight光束。引发光活性树脂的局部聚合,导致局部折射率增加,这本身会产生自聚焦波导,并使光树脂进一步聚合成长的水凝胶微丝。通过改变光束的相干长度,微丝的直径和间距可在2至30微米之间调节。微丝对成纤维细胞、肌腱细胞、内皮细胞和成肌细胞具有出色的细胞指导特性,影响细胞排列、核变形和细胞外基质沉积。FLight与多种类型的光树脂兼容,并能在数秒内(每个构建体<10秒)生物制造出具有出色细胞活力的厘米级水凝胶构建体。通过改变FLight投影方向,可在单个水凝胶构建体内实现多向微丝,通过依次交换载细胞光树脂,可制造复杂的多材料/多细胞组织工程构建体。FLight为使用可光交联生物材料开发各向异性组织提供了一种变革性方法。

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