Constructing epidermal rete ridges using a composite hydrogel to enhance multiple signaling pathways for the maintenance of epidermal stem cell niche

Zhizhong Shen; Zixian Liu; Lei Sun; Meng Li; Lu Han; Jianming Wang; Xunwei Wu; Shengbo Sang

doi:10.1016/j.actbio.2023.07.037

Constructing epidermal rete ridges using a composite hydrogel to enhance multiple signaling pathways for the maintenance of epidermal stem cell niche

Acta Biomater. 2023 Oct 1:169:273-288. doi: 10.1016/j.actbio.2023.07.037. Epub 2023 Jul 28.

Authors

Zhizhong Shen¹, Zixian Liu², Lei Sun², Meng Li³, Lu Han³, Jianming Wang⁴, Xunwei Wu⁵, Shengbo Sang⁶

Affiliations

¹ Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Information and Computer, Taiyuan University of Technology, Taiyuan, 030024, China.
² Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Information and Computer, Taiyuan University of Technology, Taiyuan, 030024, China; Key Lab of Advanced Transducers and Intelligent Control System of the Ministry of Education, Taiyuan University of Technology, Taiyuan, 030024, China.
³ Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Information and Computer, Taiyuan University of Technology, Taiyuan, 030024, China; Shanxi Research Institute of 6D Artificial Intelligence Biomedical Science, Taiyuan, 030031, China.
⁴ General Hospital of TISCO, North Street, Xinghualing District, Taiyuan, 030809, China.
⁵ Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China; Department of Tissue Engineering and Regeneration, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Jinan, Shandong, China.
⁶ Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Information and Computer, Taiyuan University of Technology, Taiyuan, 030024, China; Key Lab of Advanced Transducers and Intelligent Control System of the Ministry of Education, Taiyuan University of Technology, Taiyuan, 030024, China. Electronic address: sunboa-sang@tyut.edu.cn.

PMID: 37516415
DOI: 10.1016/j.actbio.2023.07.037

Abstract

The undulating microstructure rete ridge (RR) located at the junction between the dermis and epidermis plays a crucial role in improving skin mechanical properties and maintaining skin homeostasis. However, the investigation of RR microstructures is usually neglected in current tissue engineering for skin regeneration. Here, to create an epidermal model with RR microstructures, keratinocytes were cultured on a patterned GelMA-PEGDA hydrogel constructed using molding technology. Furthermore, grafting acryloylated Arg-Gly-Asp (RGD) peptides on the hydrogel surface significantly improved cell adhesion, fusion, and development. RT-PCR, Western blot, and immunofluorescence staining confirmed that cells on RR microstructures exhibited higher gene and protein expression associated with epidermal stem cells. RNA sequencing analysis of cells on RR microstructure showed higher gene expression profiles related to stem cell maintenance, basement membrane formation, and epidermal development. Furthermore, RT-PCR analysis of epidermal models of various dimensions demonstrated that smaller microstructures were more conducive to epidermal stem cell marker gene expression, which is analogous to human skin. Overall, we have successfully developed a method for integrating RR microstructures into an epidermal model that mimics natural skin to maintain epidermal stem cell niche, providing a valuable reference for researching skin regeneration within the fields of tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE: This study presents a method for precisely fabricating microstructures of skin rete ridges using composite hydrogels, thereby creating a skin model that mimics natural human skin. The findings reveal that this microstructure provides a stem cell niche that regulates the pathways and promotes the expression of proteins related to epidermal stem cells. This work advances the functional properties of tissue engineered skin and holds promise for improving the therapeutic efficacy of artificial skin grafts for the skin wounds.

Keywords: GelMA-PEGDA hydrogel; Molding technology; Rete ridge; Skin regeneration; Stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cells, Cultured
Epidermis
Humans
Hydrogels* / pharmacology
Signal Transduction
Stem Cell Niche*
Tissue Engineering / methods

Substances

Hydrogels