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US 2021/0212810 A1Published application
Multi-layer skin constructs and methods of making and using the same
AssigneeWake Forest University Health Sciences
InventorsMathew VARKEY, Anthony ATALA
Life of this patent
Estimating the term…
Abstract
Provided are skin constructs and methods of making and using the same, such as for wound treatment and/or compound testing, including compound testing for efficacy, toxicity, immune response, penetration, irritation and/or metabolism testing of drug candidates or compositions such as cosmetics.
Claims28
An artificial mammalian skin construct, comprising:
- optionally, a first (“hypodermis-like”) layer comprising live mammalian adipocytes (e.g., induced pre-adipocytes) and optionally live mammalian endothelial cells (e.g., dermal microvasculature endothelial cells) in a first hydrogel carrier;
- a second (“dermis-like”) layer on or directly contacting said first layer, when present, said second layer comprising live mammalian fibroblast cells, live mammalian follicle dermal papilla cells, and optionally live mammalian endothelial cells (e.g., dermal microvasculature endothelial cells) in combination in a second hydrogel carrier;
- and
- a third (“epidermis-like”) layer on or directly contacting said second layer, said third layer comprising live mammalian keratinocytes, live mammalian melanocytes, and live mammalian immune cells (e.g., CD14+ monocytes, Langerhans cells, dermal dendritic cells, or a combination of two of more thereof) in combination in a third hydrogel carrier,
- wherein said construct has visible pigmentation (e.g., after 3, 4, 5, 6, 7, or 8 weeks in culture).
2 more elements
A method of making a skin construct, comprising the steps of:
- (a) optionally co-culturing adipocytes and endothelial cells as spheroids;
- incorporating the spheroids into a first hydrogel carrier to form a hypodermal bioink;
- and depositing (e.g., by bioprinting) the hypodermal bioink on a substrate to form a first (hypodermis-like) layer;
- (b) culturing follicle dermal papilla cells as spheroids;
- independently, co-culturing endothelial cells and fibroblasts as spheroids;
- incorporating the spheroids into a second hydrogel carrier to form a dermal bioink;
- and depositing (e.g., by bioprinting) the dermal bioink onto the hypodermis-like layer, when present, or a substrate when not present, to form a second (dermis-like) layer;
- and
- (c) incorporating the keratinocytes, melanocytes and immune cells into a third hydrogel carrier to form an epidermal bioink;
- and depositing (e.g., by bioprinting) the epidermal bioink onto the dermis-like layer to form a third (epidermis-like) layer,
- to thereby make the skin construct.
8 more elements
A method of making a skin construct, comprising the steps of:
- (a) incorporating the keratinocytes, melanocytes and immune cells into a third hydrogel carrier to form an epidermal bioink;
- and depositing (e.g., by bioprinting) the epidermal bioink on a substrate to form a third (epidermis-like) layer;
- (b) culturing follicle dermal papilla cells as spheroids;
- independently, co-culturing endothelial cells and fibroblasts as spheroids;
- incorporating the spheroids into a second hydrogel carrier to form a dermal bioink;
- and depositing (e.g., by bioprinting) the dermal bioink onto the epidermis-like layer to form a second (dermis-like) layer;
- and
- (c) optionally, co-culturing adipocytes and endothelial cells as spheroids;
- incorporating the spheroids into a first hydrogel carrier to form a hypodermal bioink;
- and depositing (e.g., by bioprinting) the hypodermal bioink onto the dermis-like layer to form a first (hypodermis-like) layer,
- to thereby make the skin construct.
8 more elements
Dependencies are inferred from the claim text.