Tissue engineering ECM-enriched controllable vascularized human microtissue for hair regenerative medicine using a biomimetic developmental approach.
Tissue engineering ECM-enriched controllable vascularized human microtissue for hair regenerative medicine using a biomimetic developmental approach.
复制标题
组织工程富含 ECM 的可控血管化人体微组织，采用仿生发育方法用于毛发再生医学
DOI：
10.1016/j.jare.2021.09.010
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发表时间：
2022-05
影响因子：
10.7
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Chen, Peng;Miao, Yong;Zhang, Feifei;Fan, Zhexiang;Huang, Junfei;Mao, Xiaoyan;Chen, Jian;Hu, Zhiqi;Wang, Jin
关键词：
层层自组装构建纳米仿生ECM。Ca 2+作为交联剂，以制备尺寸可控的真皮乳头（DP）球状体。组织工程可控的富含ECM和血管的人体微组织。血管化防止缺氧引起的坏死和与宿主血管连接的功能。仿生ECM和血管化三倍毛发诱导效率。再生医学是治疗脱发的一种有前途的方法;然而，其主要挑战是人类毛乳头细胞（DPC）的诱导性，这些细胞在2D培养中迅速失去毛发生长诱导特性。尽管广泛的研究努力构建DPC，目前的3D微环境制造恢复头发诱导仍然不足。在这里，我们的目的是制造ECM丰富的可控血管化毛乳头（DP）球体，高度模拟体内DPC微环境，以恢复其毛发诱导性。我们采用层层自组装技术，以明胶和海藻酸钠为原料，以钙离子为交联剂，构建了纳米级的仿生细胞外基质。将DPC与人脐静脉内皮细胞共培养以构建血管化DP球体。免疫荧光染色和血管造影检测血管生成。采用RNA测序和体内植入来研究DPC特征。LbL技术使DPC能够聚集成可控的DP球状体，其大小和细胞数量与原代DP相似。血管化防止缺氧引起的坏死，并在移植后与宿主血管一起发挥作用。与传统的3D培养相比，发现纳米级ECM和血管化在植入后恢复DPC的转录特征和三倍的毛发诱导效率。我们的新型仿生发育组织工程策略是恢复人类DPC毛发诱导性的关键一步，这将使大规模毛发再生平台的快速临床应用成为可能。
Layer-by-layer (LbL) self-assembly to construct nanoscale biomimetic ECM. Ca2+ as a cross-linking agent to make size controllable dermal papilla (DP) spheroids. Tissue engineering controllable human microtissue rich in ECM and vessels. Vascularization prevents hypoxia-induced necrosis and functions in connection with host vessels. Biomimetic ECM and vascularization triple hair induction efficiency. Regenerative medicine is a promising approach for hair loss; however, its primary challenge is the inductivity of human dermal papilla cells (DPCs), which rapidly lose hair growth-inducing properties in 2D culture. Despite extensive research efforts to construct DPCs, current 3D microenvironments fabricated to restore hair inductivity remain insufficient. Here, we aimed to fabricate ECM-enriched controllable vascularized dermal papilla (DP) spheroids that highly mimic in vivo DPCs microenvironments to restore their hair inductivity. We employed layer-by-layer (LbL) self-assembly using gelatin and alginate to construct nanoscale biomimetic ECM for DPCs, with Ca2+ as a cross-linking agent to create controllable DP spheroids. DPCs were also co-cultured with human umbilical vein endothelial cells to construct vascularized DP spheroids. Immunofluorescence staining and angiography was used to detect angiogenesis in vitro and in vivo. RNA sequencing and in vivo implantation were employed to investigate DPCs signature. LbL technology enabled DPCs to aggregate into controllable DP spheroids of size and cell numbers similar to those of primary DP. Vascularization prevented hypoxia-induced necrosis and functioned in association with host vessels post-transplantation. Compared with traditional 3D culture, nanoscale ECM and vascularization were found to restore the transcriptional signature of DPCs and triple hair induction efficiency following engraftment. Our novel biomimetic developmental tissue engineering strategy is a crucial step toward the recovery of human DPC hair inductivity, which would enable the rapid clinical application of large-scale hair regeneration platforms.
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影响因子：
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作者：
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