Cell-Laden Gradient Microgel Suspensions for Spatial Control of Differentiation During Biofabrication.

Cell-Laden Gradient Microgel Suspensions for Spatial Control of Differentiation During Biofabrication.
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载有细胞的梯度微凝胶悬浮液,用于生物制作过程中分化的空间控制。

DOI:
10.1002/adhm.202201122
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发表时间:
2022-12
影响因子:
10
通讯作者:
Kilian, Kristopher A.
Kilian, Kristopher A.
中科院分区:
工程技术1区
文献类型:
--
作者:
Molley, Thomas G.;Hung, Tzong-tyng;Kilian, Kristopher A.

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在组织发育过程中,干细胞和祖细胞形成具有高度细胞多样性和复杂的微观和宏观结构的功能组织。目前的方法试图用材料线索或通过自发的细胞自组织来复制这一过程。然而,细胞定向和材料定向的组织需要同时实现仿生结构和功能。在这里,它显示了如何整合活的脂肪来源的干细胞与梯度微凝胶悬浮液转向不同的分化结果。发现由小颗粒组成的微凝胶基质促进成脂分化,而较大颗粒促进增加的细胞铺展和成骨分化。调整基质配方表明,早期细胞粘附和扩散决定分化结果。将小的和大的微凝胶组合成梯度在空间上指导随时间的增殖和分化。在培养21天后,成骨条件促进单个微凝胶内的显著矿化,从而在梯度多孔支架内提供成分和力学的细胞定向变化。在这些梯度上进行高密度细胞悬液的自由打印,以证明分层组织生物制品的潜力。间质孔隙率影响来自打印的细胞扩增,并且微凝胶尺寸引导空间分化,从而提供了通过整合和打印的细胞群以多个尺度制造组织梯度的范围。颗粒状微凝胶以不同的尺寸合成,并用于形成空间梯度。脂肪来源的干细胞被均匀地整合在微凝胶悬浮液内或打印为具有间质基质的高密度聚集体以将构建体结合在一起。微凝胶和介入基质的性质都有助于引导脂肪生成和骨生成
During tissue development, stem and progenitor cells form functional tissue with high cellular diversity and intricate micro- and macro-architecture. Current approaches have attempted to replicate this process with materials cues or through spontaneous cell self-organization. However, cell-directed and materials-directed organization are required simultaneously to achieve biomimetic structure and function. Here, it is shown how integrating live adipose derived stem cells with gradient microgel suspensions steers divergent differentiation outcomes. Microgel matrices composed of small particles are found to promote adipogenic differentiation, while larger particles fostered increased cell spreading and osteogenic differentiation. Tuning the matrix formulation demonstrates that early cell adhesion and spreading dictate differentiation outcome. Combining small and large microgels into gradients spatially directs proliferation and differentiation over time. After 21 days of culture, osteogenic conditions foster significant mineralization within the individual microgels, thereby providing cell-directed changes in composition and mechanics within the gradient porous scaffold. Freeform printing of high-density cell suspensions is performed across these gradients to demonstrate the potential for hierarchical tissue biofabrication. Interstitial porosity influences cell expansion from the print and microgel size guides spatial differentiation, thereby providing scope to fabricate tissue gradients at multiple scales through integrated and printed cell populations. Granular microgels were synthesised in variable sizes and used to form spatial gradients. Adipose derived stem ells are integrated uniformly within the microgel suspension or printed as high-density aggregates with an interstitial matrix to bind the construct together. The properties of the microgels and the intervening matrix both contribute to guiding adipogenesis and osteogenesis
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