PDF(Pubmed)
Abstract：
Bioinks play a fundamental role in skin bioprinting, dictating the printing fidelity, cell response, and function of bioprinted 3D constructs. However, the range of bioinks that support skin cells\' function and aid in the bioprinting of 3D skin equivalents with tailorable properties and customized shapes is still limited. In this study, we describe a bioinspired design strategy for bioengineering double crosslinked pectin-based bioinks that recapitulate the mechanical properties and the presentation of cell-adhesive ligands and protease-sensitive domains of the dermal extracellular matrix, supporting the bioprinting of bilayer 3D skin models. Methacrylate-modified pectin was used as a base biomaterial enabling hydrogel formation via either chain-growth or step-growth photopolymerization and providing independent control over bioink rheology, as well as the mechanical and biochemical cues of cell environment. By tuning the concentrations of crosslinker and polymer in bioink formulation, dermal constructs were bioprinted with a physiologically relevant range of stiffnesses that resulted in strikingly site-specific differences in the morphology and spreading of dermal fibroblasts. We also demonstrated that the developed thiol-ene photo-clickable bioinks allow for the bioprinting of skin models of varying shapes that support dermis and epidermis reconstruction. Overall, the engineered bioinks expand the range of printable biomaterials for the extrusion bioprinting of 3D cell-laden hydrogels and provide a versatile platform to study the impact of material cues on cell fate, offering potential for in vitro skin modeling.
摘要：
生物墨水在皮肤生物打印中起着至关重要的作用，决定印刷保真度，细胞反应，和生物打印3D构建体的功能。然而,支持皮肤细胞功能和帮助3D皮肤等效物生物打印的生物墨水的范围仍然有限。在这项研究中,我们描述了一种生物工程双交联果胶基生物墨水的生物启发设计策略，该策略概括了真皮细胞外基质的机械特性和细胞粘附配体和蛋白酶敏感域的呈现。支持双层3D皮肤模型的生物打印。甲基丙烯酸酯改性的果胶被用作基础生物材料，能够通过链增长或逐步增长光聚合形成水凝胶，并提供对生物墨水流变学的独立控制。以及细胞环境的机械和生化线索。通过调整生物墨水配方中交联剂和聚合物的浓度，真皮构建体是生物打印的,具有生理相关的硬度范围,这导致真皮成纤维细胞的形态和扩散的显著位点特异性差异.我们还证明，开发的硫醇-烯光可点击生物墨水允许生物打印支持真皮和表皮重建的不同形状的皮肤模型。总的来说,工程生物墨水扩大了可打印生物材料的范围，用于挤出生物打印3D充满细胞的水凝胶，并提供了一个通用的平台来研究材料线索对细胞命运的影响，提供体外皮肤建模的潜力。
