Engineering of diseased human skin equivalent using 3D cell printing for representing pathophysiological hallmarks of type 2 diabetes in vitro

Byoung Soo Kim, Minjun Ahn, Won Woo Cho, Ge Gao, Jinah Jang, Dong Woo Cho*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

Despite many significant advances in 3D cell printing for skin, a disease model displaying the pathological processes present in the native skin has not been reported yet. Therefore, we were motivated for modeling a 3D diseased skin tissue with pathophysiological hallmarks of type 2 diabetes in vitro based on 3D cell printing technique. By stimulating epidermal-dermal intercellular crosstalk found in the native skin, it was hypothesized that normal keratinocytes would be differentiated as diabetic epidermis when interacting with the diabetic dermal compartment. To prove this, a novel wounded skin model was successfully devised during tissue maturation in vitro. Interestingly, the slow re-epithelization was observed in our diabetic model, which is a representative hallmark of diabetic skin. Using the versatility of 3D cell printing, the structural similarities and diabetic properties of the model were further augmented by addition of perfusable vascularized diabetic hypodermis. Insulin resistance, adipocyte hypertrophy, inflammatory reactions, and vascular dysfunction, as the typical hallmarks in diabetes, were found under hyperglycemia. Finally, the feasibility of this new disease model for drug development was successfully demonstrated through application of test drugs. We trust that this study provides a pioneering step towards 3D cell printing-based in vitro skin disease modeling.

Original languageEnglish
Article number120776
JournalBiomaterials
Volume272
DOIs
Publication statusPublished - May 2021

Keywords

  • 3D cell printing
  • Delayed re-epithelization
  • Diabetic skin
  • In vitro disease modeling
  • Wounded skin model

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Kim, B. S., Ahn, M., Cho, W. W., Gao, G., Jang, J., & Cho, D. W. (2021). Engineering of diseased human skin equivalent using 3D cell printing for representing pathophysiological hallmarks of type 2 diabetes in vitro. Biomaterials, 272, Article 120776. https://doi.org/10.1016/j.biomaterials.2021.120776