A dentin-derived hydrogel bioink for 3D bioprinting of cell laden scaffolds for regenerative dentistry.

A dentin-derived hydrogel bioink for 3D bioprinting of cell laden scaffolds for regenerative dentistry.
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DOI:
10.1088/1758-5090/aa9b4e
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发表时间:
2018-01-10
期刊:
影响因子:
9
通讯作者:
Bertassoni LE
Bertassoni LE
中科院分区:
工程技术1区
文献类型:
--
作者:
Athirasala A;Tahayeri A;Thrivikraman G;França CM;Monteiro N;Tran V;Ferracane J;Bertassoni LE

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近年来,组织工程的研究已采用细胞外基质(ECM)衍生的支架作为组织再生的天然和细胞相容性微环境。牙本质基质,特别是,已被证明是与主机的可溶性和不溶性的信号分子,可以促进牙发生。在这里,我们开发了一种新型的生物墨水,将可打印的藻酸盐(3% w/v)水凝胶与牙本质基质的可溶性和不溶性部分混合。我们已经优化了打印参数和生物墨水的各个成分的浓度,以实现打印准确性,细胞活力和牙源性潜力。我们发现,虽然在含有较高浓度的藻酸盐的制剂中生物墨水的粘度和因此的可印刷性更大,但较高比例的不溶性牙本质基质蛋白显著提高了细胞活力;其中藻酸盐和牙本质的1:1比例(1:1 Alg-Dent)是最合适的。我们进一步证明了1:1 Alg-Dent水凝胶共混物中可溶性牙本质分子的高保留,证明了这些分子与交联后牙本质基质之间的新相互作用。此外,在100 μg/ml的浓度下,这些可溶性牙本质分子显著增强了包封在生物打印水凝胶中的来自根尖乳头(SCAP)的干细胞的牙源性分化。综上所述,所提出的新型生物墨水具有明显的细胞相容性和天然的牙形成能力,这可以用于可重复地制造具有复杂三维微结构的支架,用于未来的再生牙科。
Recent studies in tissue engineering have adopted extracellular matrix (ECM) derived scaffolds as natural and cytocompatible microenvironments for tissue regeneration. The dentin matrix, specifically, has been shown to be associated with a host of soluble and insoluble signaling molecules that can promote odontogenesis. Here, we have developed a novel bioink, blending printable alginate (3% w/v) hydrogels with the soluble and insoluble fractions of the dentin matrix. We have optimized the printing parameters and the concentrations of the individual components of the bioink for print accuracy, cell viability and odontogenic potential. We find that, while viscosity, and hence printability of the bioinks, was greater in the formulations containing higher concentrations of alginate, a higher proportion of insoluble dentin matrix proteins significantly improved cell viability; where a 1:1 ratio of alginate and dentin (1:1 Alg-Dent) was most suitable. We further demonstrate high retention of the soluble dentin molecules within the 1:1 Alg-Dent hydrogel blends, evidencing renewed interactions between these molecules and the dentin matrix post crosslinking. Moreover, at concentrations of 100 μg/ml, these soluble dentin molecules significantly enhanced odontogenic differentiation of stem cells from the apical papilla (SCAP) encapsulated in bioprinted hydrogels. In summary, the proposed novel bioinks have demonstrable cytocompatibility and natural odontogenic capacity, which can be a used to reproducibly fabricate scaffolds with complex three-dimensional microarchitectures for regenerative dentistry in the future.
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