3D bioprinting of a gelatin-alginate hydrogel for tissue-engineered hair follicle regeneration
3D bioprinting of a gelatin-alginate hydrogel for tissue-engineered hair follicle regeneration
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DOI：
10.1016/j.actbio.2022.03.011
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发表时间：
2023-06-13
影响因子：
9.7
通讯作者：
Miao, Yong
中科院分区：
文献类型：
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作者：
Kang, Deni;Liu, Zhen;Miao, Yong
毛囊（HF）再生仍然具有挑战性，主要是由于缺乏一个平台，可以成功地产生头发新生的微环境线索。在这里，我们展示了一种基于明胶/藻酸盐水凝胶（GAH）的3D生物打印技术，以构建模拟体内HF微环境的多层复合支架。将成纤维细胞（FB）、人脐静脉内皮细胞（HUVEC）、毛乳头细胞（DPC）和表皮细胞（EPC）包封在GAH（由明胶和藻酸盐的混合物制备）中，并分别3D生物打印到复合支架的不同层中。随后将具有表皮和真皮样结构的生物打印支架移植到裸鼠的全层伤口中。多层支架具有良好的细胞相容性，可提高DPC的增殖能力（1.2倍; P < 0.05）。它还促进了自聚集DPC球状体的形成，并恢复了与毛发诱导相关的DPC基因（ALP，β-连环蛋白和α-SMA）。真皮和表皮细胞在体外成功地自组装成未成熟的HFs。HF在体内以适当的方向再生，这主要归因于支架的分层网格结构和DPC的点生物打印。我们的3D打印支架为DPC提供了一个合适的微环境来再生整个HFs，并可以在脱发的医疗管理中做出重大贡献。这种方法也可能在皮肤组织（和附件）工程中有更广泛的应用。重要性声明脱发仍然是一个具有挑战性的临床问题，影响生活质量。三维（3D）生物打印已经成为用于制造用于移植和其他生物医学应用的组织构建体的有用工具。在这项研究中，我们使用基于明胶/藻酸盐水凝胶的3D生物打印技术构建具有表皮层和真皮层的多层复合支架，以模拟人体内毛乳头细胞（DPC）的微环境。这种新方法允许在生理相关的细胞外基质中可控地形成DPC的自聚集球体，并启动表皮-间充质相互作用，从而导致体内HF形成。再生整个HFs的能力应该对脱发的医疗管理产生重大影响。COPY; 2022 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Hair follicle (HF) regeneration remains challenging, principally due to the absence of a platform that can successfully generate the microenvironmental cues of hair neogenesis. Here, we demonstrate a 3D bioprinting technique based on a gelatin/alginate hydrogel (GAH) to construct a multilayer composite scaffold simulating the HF microenvironment in vivo . Fibroblasts (FBs), human umbilical vein endothelial cells (HUVECs), dermal papilla cells (DPCs), and epidermal cells (EPCs) were encapsulated in GAH (prepared from a mixture of gelatin and alginate) and respectively 3D-bioprinted into the different layers of a composite scaffold. The bioprinted scaffold with epidermis-and dermis-like structure was subsequently transplanted into full-thickness wounds in nude mice. The multilayer scaffold demonstrated suitable cytocompatibility and increased the proliferation ability of DPCs (1.2-fold; P < 0.05). It also facilitated the formation of self-aggregating DPC spheroids and restored DPC genes associated with hair induction ( ALP, & beta;-catenin, and & alpha;-SMA). The dermal and epidermal cells self-assembled successfully into immature HFs in vitro . HFs were regenerated in the appropriate orientation in vivo , which can mainly be attributed to the hierarchical grid structure of the scaffold and the dot bioprinting of DPCs. Our 3D printed scaffolds provide a suitable microenvironment for DPCs to regenerate entire HFs and could make a significant contribution in the medical management of hair loss. This method may also have broader applications in skin tissue (and appendage) engineering.Statement of significanceHair loss remains a challenging clinical problem that influences quality of life. Three-dimensional (3D) bioprinting has become a useful tool for the fabrication of tissue constructs for transplantation and other biomedical applications. In this study, we used a 3D bioprinting technique based on a gelatin/alginate hydrogel to construct a multi-layer composite scaffold with cuticular and corium layers to simulate the microenvironment of dermal papilla cells (DPCs) in the human body. This new approach permits the controllable formation of self-aggregating spheroids of DPCs in a physiologically relevant extracellular matrix and the initiation of epidermal-mesenchymal interactions, which results in HF formation in vivo . The ability to regenerate entire HFs should have a significant impact on the medical management of hair loss.& COPY; 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.