Speaker
Description
The dermal-epidermal junction is critical in maintaining skin homeostasis, providing mechanical support, and facilitating nutrient exchange. One of the key features of this interface is the papillary dermis, which is characterized by a series of undulations that increase surface area for diffusion between dermal and epidermal compartments. During aging, these undulations flatten, resulting in a less effective dermal-epidermal junction. This flattening has been associated with a thinner epidermis, decreased skin elasticity, and impaired wound healing. Despite its importance, the precise contribution of the papillary dermis to epidermal maintenance remains poorly understood.
To address this gap, this study aims to develop a 3D bioprinted model of the papillary dermis using a decellularized extracellular matrix (dECM) derived from porcine skin. Preliminary results have demonstrated the successful production of full-thickness skin equivalents using 5 mg/mL dECM to generate a dermal layer and a keratinocyte suspension seeded to form the epidermal layer. In the next phase, the dECM will be methacrylated to enable light-mediated crosslinking, facilitating the fabrication of structured, villi-like papillary dermis features over a reticular dermis base. Constructs will be fabricated using a digital light processing (DLP) bioprinter (LumenX), aiming for high-resolution features mimicking native papillae in the range of 50–100 μm.
NIH3T3 fibroblasts will be encapsulated within the dECM-based hydrogel to populate the dermal compartment. Following fabrication, dermal constructs will be coated with laminin to promote epidermal attachment. A suspension of immortalized mouse keratinocytes (M4+/+, ABM) will then be seeded on top, and epidermal stratification will be induced by initiating air-liquid interface (ALI) culture with simultaneous supplementation of 1.5 mM calcium to the differentiation medium.
Histological analysis and immunohistochemistry (IHC) will be performed on Day 14 of ALI culture to assess epidermal development. Keratin 14 will be used to visualize basal keratinocytes, while filaggrin will identify cornified layers and terminal differentiation. We hypothesize that constructs with a flat, aged-like papillary dermis will exhibit reduced epidermal thickness and diminished keratinization compared to constructs with a more undulated, youthful papillary dermis, due to decreased surface area for nutrient diffusion.
This study aims to provide novel insights into how age-related changes in the dermal-epidermal interface affect epidermal architecture and homeostasis. A better understanding of these interactions could advance the development of improved skin tissue models for basic research in dermatology and aging biology.
85410410405