In this study, we present a novel 3D perfused skin-on-a-chip model fabricated using micro-precision 3D printing, which offers a streamlined and reproducible approach for incorporating perfusion. Perfused skin models are well-regarded for their advantages, such as improved nutrient supply, enhanced barrier function, and prolonged tissue viability. However, current models often require complex setups, such as self-assembled endothelial cells or sacrificial rods, which are prone to variability and time-consuming. Our model uses projection micro-stereolithography 3D printing to create precise microcapillary-like channels using a biocompatible resin, overcoming the drug-absorbing properties of PDMS. A customized chip holder allows for the simultaneous culture of six perfused chips, enabling high-throughput testing. The engineered skin-on-a-chip features distinct dermis and epidermis layers, confirmed via H&E staining and immunostaining. To evaluate drug screening capabilities, inflammation was induced using TNF-α and treated with dexamethasone, with cytokine levels compared to 2D cultures and human skin biopsies. Our 3D model exhibited drug response trends similar to human skin, while showing reduced cytotoxicity over time compared to biopsies. This perfused skin-on-a-chip provides a reliable, physiologically relevant alternative for drug and cosmetics screening, simplifying perfusion setup while preserving key benefits.
1 February 2024 in Tissue Engineering Part C: Methods
A major obstacle to the implantation of ex vivo engineered tissues is the incorporation of functional vascular supply to support the growth of the new tissue and to minimize ischemic injury. Existing pre-vascularization systems, such as arterio-venous (AV) loop-based systems, require microsurgery, limiting their use to larger animals. We aimed to develop an implantable device that can be pre-vascularized to enable vascularization of tissues in small rodents and test its application on the vascularization of embryonic kidneys. Implanting the chamber between the abdominal aorta and the inferior vena cava, we detected endothelial cells and vascular networks after 48h of implantation. Loading the chamber with collagen I (C), Matrigel (M), or Matrigel + vascular endothelial growth factor (VEGF) (MV) had a strong influence on vascularization speed: Chambers loaded with C took seven days to vascularize, four days for chambers with M, and 2 days for chambers with MV. Implantation of E12.5 mouse embryonic kidneys into pre-vascularized chambers (C, MV) was followed with significant growth and ureteric branching over 22 days. In contrast, the growth of kidneys in non-pre-vascularized chambers was stunted. We concluded that our pre-vascularized chamber is a valuable tool for vascularizing implanted tissues and tissue-engineered constructs. Further optimization will be necessary to control the directional growth of vascular endothelial cells within the chamber and the vascularization grade.