Tissue engineering ECM-enriched controllable vascularized human microtissue for hair regenerative medicine using a biomimetic developmental approach,Journal of Advanced Research

当前位置： X-MOL 学术 › J. Adv. Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Tissue engineering ECM-enriched controllable vascularized human microtissue for hair regenerative medicine using a biomimetic developmental approach
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2021-10-13 , DOI: 10.1016/j.jare.2021.09.010
Peng Chen ₁ , Yong Miao ₁ , Feifei Zhang ₁ , Zhexiang Fan ₁ , Junfei Huang ₁ , Xiaoyan Mao ₁ , Jian Chen ₁ , Zhiqi Hu ₁ , Jin Wang ₁

Affiliation

Introduction

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

组织工程 ECM 富集的可控血管化人体微组织用于毛发再生医学，采用仿生发展方法

介绍

再生医学是一种很有前途的脱发方法；然而，它的主要挑战是人类真皮乳头细胞 (DPC) 的诱导能力，这种细胞在 2D 培养中会迅速失去诱导毛发生长的特性。尽管为构建 DPC 进行了广泛的研究努力，但目前为恢复头发感应性而制造的 3D 微环境仍然不足。

目标

在这里，我们的目标是制造富含 ECM 的可控血管化真皮乳头 (DP) 球体，该球体高度模拟体内DPC 微环境以恢复其头发的诱导能力。

方法

我们采用明胶和海藻酸盐的逐层 (LbL) 自组装来构建用于 DPC 的纳米级仿生 ECM，以 Ca ²⁺作为交联剂来创建可控的 DP 球体。DPCs 还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用于检测体外和体内的血管生成。采用RNA 测序和体内植入来研究 DPC 的特征。