Endogenous Bioengineered Skin Model via Dynamic Fibroblast Seeding
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Solution Overview
Problem
Current human skin equivalent models are not similar enough to native skin, containing a considerable exogenous portion, which limits their reliability for studies, especially those requiring an endogenous extracellular matrix, such as assessing UV radiation effects on collagen and elastin function.
Innovation Solution
A method to produce a totally endogenous bioengineered skin model with a dermis and epidermis layer using dynamic seeding of fibroblasts on biodegradable porous microbeads, followed by maturation in a specialized chamber, resulting in a skin equivalent with a fully organized endogenous extracellular matrix, mimicking native skin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-human biopolymers (exogenous scaffold) are used to form dermis equivalent, then successful HSE formation is achieved, but the model contains considerable exogenous portion and cannot reproduce native ECM organization
Solution Approach 1:
The patent applies self-service by enabling fibroblasts to autonomously produce their own extracellular matrix components (collagen, elastin, proteoglycans) without requiring exogenous scaffolds. The fibroblasts are cultured in a defined medium that triggers endogenous ECM synthesis, allowing the tissue to build itself from within rather than relying on externally provided structural support.
Solution Approach 2:
The patent extracts and removes the exogenous scaffold component from the HSE model. By eliminating non-human biopolymers and replacing them with fibroblast-derived endogenous ECM, the model achieves a purely human-origin dermis equivalent that closely mimics native skin architecture and composition.
2Ease of operation
If fibroblast sheets are used as dermal equivalent to provide endogenous ECM, then native ECM is present, but cell content is higher than native dermis and only very small thickness can be obtained
Solution Approach 1:
The patent applies local quality by creating a three-dimensional distributed network of fibroblasts embedded within self-produced ECM, rather than using dense fibroblast sheets. This spatial distribution allows different regions to have appropriate cell densities and ECM compositions, enabling the formation of thick dermis equivalents with physiological architecture that mimics native skin.
Solution Approach 2:
The patent transitions from two-dimensional fibroblast sheets to three-dimensional fibroblast-ECM constructs. By culturing fibroblasts in suspension or on porous supports that enable 3D ECM deposition, the model achieves substantial dermis thickness while maintaining physiological cell-to-ECM ratios and native-like organization.
3Ease of manufacture
If exogenous scaffold is used to support fibroblasts, then HSE formation is enabled, but the ECM is not fully endogenous and artificial character increases
Solution Approach 1:
The patent applies preliminary action by pre-conditioning fibroblasts in a defined culture medium that stimulates endogenous ECM synthesis before implantation or further culture. This preparatory step ensures that fibroblasts are primed to produce sufficient collagen, elastin, and other ECM components, eliminating the need for exogenous scaffolds while maintaining HSE formation capability.
Data Source
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AI summary
The present invention relates to a method for producing a totally endogenous bioengineered tissue including a first layer of connective tissue and a second layer of epithelial tissue, to a tissue equivalent obtained thereby and to a method for determining the effect of a chemical substance or an agent on skin employing the tissue equivalent.