Guanidinylated/PEGylated chitosan in the bioink promotes the formation of multi-layered keratinocytes in a human skin equivalent.
Guanidinylated/PEGylated chitosan in the bioink promotes the formation of multi-layered keratinocytes in a human skin equivalent.
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DOI：
10.1016/j.carbpol.2023.120964
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发表时间：
2023-04
影响因子：
11.2
通讯作者：
M. Zhu;Tian Hu;W. Song;X. Cui;Ye Tian;B. Yao;Man Wu;Shan Huang;Z. Niu
中科院分区：
文献类型：
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作者：
M. Zhu;Tian Hu;W. Song;X. Cui;Ye Tian;B. Yao;Man Wu;Shan Huang;Z. Niu
由于啮齿类动物和人类皮肤的生物学差异，以及对替代实验动物的强烈需求，导致了与真实人类皮肤结构相似的替代模型的发展。在常规真皮支架中培养的角质形成细胞倾向于形成单层而不是多层上皮组织结构。如何用类似于真实人体表皮的多层角质形成细胞构建人体皮肤或表皮等级物仍然是最大的挑战之一。在此，通过3D生物打印成纤维细胞和随后培养表皮角质形成细胞，构建了具有多层角质形成细胞的人体皮肤等效物。采用生物相容性胍/聚乙二醇化壳聚糖（GPCS）作为生物链的主要成分，制备了3D生物打印组织工程真皮。GPCS促进HaCat细胞增殖和连接的功能在遗传、细胞和组织学水平得到证实。与胶原和明胶单层角质形成细胞的皮肤组织相比，在生物链中添加GPCS可生成具有多层角质形成细胞的组织工程化人体皮肤组织。这种人体皮肤等效物可以作为生物医学、毒理学和药学研究的替代模型。
The biological differences of skin between rodent and human beings and the strong appeal to replace the experimental animals have led to the development of alternative models with structures similar to the real human skin. Keratinocytes culturedin vitroon conventional dermal scaffolds tend to form monolayer rather than multi-layer epithelial tissue architectures. How to construct human skin or epidermal equivalents with multi-layered keratinocytes similar to real human epidermis remains one of the greatest challenges. Herein, a human skin equivalent with multi-layered keratinocytes was constructed by 3D bioprinting fibroblasts and subsequent culturing epidermal keratinocytes. Biocompatible guanidinylated/PEGylated chitosan (GPCS) was used as the main component of bioink to 3D bioprint tissue-engineered dermis. The function of GPCS to promote HaCat cell proliferation and connection was confirmed at the genetic, cellular, and histological levels. Compared with the skin tissues with mono-layered keratinocytes engineered with collagen and gelatin, adding GPCS in the bioink generated tissue-engineered human skin equivalents with multi-layered keratinocytes. Such human skin equivalents could be alternative models for biomedical, toxicological, and pharmaceutical research.