Two-Layer Electrospun Substrate for Skin Equivalent
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Solution Overview
Problem
Current in vitro models for skin tissue reconstruction, such as lattice models, suffer from poor extracellular matrix neosynthesis and mechanical properties due to high water content, and are limited by the need for complete dermal compartment filling, which is challenging with fibroblasts from older donors or those exposed to pollution.
Innovation Solution
A two-layer substrate is developed, comprising a layer of at least 200 nm thickness with porosity ≤5 µm formed by electrospinning or electrowriting, and a layer of at least 20 µm thickness with porosity ≥20 µm also formed by electrowriting. This substrate allows for independent reconstruction of the epidermis without requiring a fully filled dermal compartment, and promotes extracellular matrix neosynthesis and remodeling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional porous substrates are used for dermal compartment reconstruction, then extracellular matrix neosynthesis is enabled, but complete filling of the dermal compartment is difficult when using fibroblasts from older donors or those exposed to pollution
Solution Approach 1:
The substrate is divided into two distinct layers: a first layer with porosity ≤5 µm and a second layer with porosity ≥20 µm. The second layer serves as a highly porous support for fibroblast seeding and extracellular matrix production, while the first layer provides a controlled interface for epidermal reconstruction. This segmentation allows fibroblasts to efficiently populate the high-porosity layer without requiring complete filling of the entire substrate, resolving the contradiction between enabling matrix neosynthesis and achieving complete compartment filling.
Solution Approach 2:
Different regions of the substrate have different porosity characteristics tailored to specific functions. The second layer (≥20 µm porosity) is optimized for fibroblast infiltration and extracellular matrix production, while the first layer (≤5 µm porosity) is optimized for epidermal cell attachment and barrier formation. This local differentiation of substrate properties allows each cell type to thrive in its optimal environment, improving both matrix neosynthesis and reconstruction efficiency.
2Ease of operation
If high porosity substrates are used to enable extracellular matrix neosynthesis, then cell infiltration is improved, but epidermal reconstruction becomes difficult without complete dermal compartment filling
Solution Approach 1:
The substrate is divided into two distinct layers: a first layer with porosity ≤5 µm and a second layer with porosity ≥20 µm. The second layer serves as a highly porous support for fibroblast seeding and extracellular matrix production, while the first layer provides a controlled interface for epidermal reconstruction. This segmentation allows fibroblasts to efficiently populate the high-porosity layer without requiring complete filling of the entire substrate, resolving the contradiction between enabling matrix neosynthesis and achieving complete compartment filling.
Solution Approach 2:
The first layer acts as an intermediary structure between the high-porosity second layer and the epidermal environment. It provides a controlled interface that supports epidermal cell attachment and differentiation while preventing excessive keratinocyte migration into the dermal compartment. This intermediary layer ensures reliable epidermal reconstruction even when the dermal compartment is not completely filled.
3Ease of manufacture
If single-layer porous substrates are used for skin tissue reconstruction, then manufacturing is simpler, but the ability to independently reconstruct epidermis without complete dermal filling is limited
Solution Approach 1:
The substrate is divided into two distinct layers: a first layer with porosity ≤5 µm and a second layer with porosity ≥20 µm. The second layer serves as a highly porous support for fibroblast seeding and extracellular matrix production, while the first layer provides a controlled interface for epidermal reconstruction. This segmentation allows fibroblasts to efficiently populate the high-porosity layer without requiring complete filling of the entire substrate, resolving the contradiction between enabling matrix neosynthesis and achieving complete compartment filling.
Solution Approach 2:
The two-layer substrate serves multiple functions within a single structure: the second layer provides mechanical support and facilitates fibroblast infiltration and matrix production, while the first layer enables epidermal cell attachment, differentiation, and barrier formation. This multi-functionality allows the substrate to support independent epidermal reconstruction without requiring complete dermal compartment filling, enhancing versatility while maintaining manufacturing feasibility.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The two-layer substrate enables effective reconstruction of the epidermis and dermal compartment, supporting cell adhesion, growth, and differentiation, while allowing for the passage of nutrients and preventing keratinocyte invaginations. It also enhances extracellular matrix composition and organization, and improves mechanical properties, making it suitable for various applications including wound dressing and skin grafts.
Implementation Method 1
Electrospinning (ES) is a method for producing fibers which uses electric force to design yarns charged with polymer solutions or molten polymer
Implementation Method 2
Electrowriting is an emerging technology which uses polymers with controlled deposition of the electrospun fiber and has made it possible to construct complex structures in situ or assemble them
Data Source
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AI summary
The present invention relates to a method for producing a dermal or skin or epidermal equivalent on a two-layer substrate comprising a layer of at least 200 nm in thickness and having a porosity less than or equal to 5 μm formed by electrospinning of a composition comprising at least one polymer, and a layer of at least 20 μm in thickness and having a porosity greater than or equal to 20 μm formed by electrowriting of a composition comprising at least one polymer. The application also relates to the skin or dermal or epidermal equivalent that can be obtained with said method, the use of a dermal equivalent or a skin equivalent or an epidermal equivalent for screening compounds and finally the use thereof in wound dressing or for skin grafts.