期刊
BIOMATERIALS ADVANCES
卷 156, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bioadv.2023.213702
关键词
Radial matrix constraint; In vitro human skin equivalent; Collagen hydrogel; 3D-printed culture system; Tissue organization; Keratinocyte differentiation; Extracellular matrix production; Mechanical stimulus; Finite element simulation
Human skin equivalents (HSEs) play a crucial role in tissue engineering. This study introduces a 3D-printed culture insert to apply a static radial constraint on HSEs and examines its effects on tissue characteristics. The results show that the diameter of the culture insert significantly influences tissue contraction, fibroblast and matrix organization, keratinocyte differentiation, epidermal stratification, and basement membrane formation. This study provides important insights for the design of skin tissue engineering.
Human skin equivalents (HSEs) serve as important tools for mechanistic studies with human skin cells, drug discovery, pre-clinical applications in the field of tissue engineering and for skin transplantation on skin defects. Besides the cellular and extracellular matrix (ECM) components used for HSEs, physical constraints applied on the scaffold during HSEs maturation influence tissue organization, functionality, and homogeneity.In this study, we introduce a 3D-printed culture insert that exposes bi-layered HSEs to a static radial constraint through matrix adhesion. We examine the effect of various diameters of the ring-shaped culture insert on the HSE's characteristics and compare them to state-of-the-art unconstrained and planar constrained HSEs.We show that radial matrix constraint of HSEs regulates tissue contraction, promotes fibroblast and matrix organization that is similar to human skin in vivo and improves keratinocyte differentiation, epidermal stratification, and basement membrane formation depending on the culture insert diameter.Together, these data demonstrate that the degree of HSE's contraction is an important design consideration in skin tissue engineering. Therefore, this study can help to mimic various in vivo skin conditions and to increase the control of relevant tissue properties.
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