3D In Vitro Skin Model With Vascular Flow for Reliable Testing

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Solution Overview

Problem

Existing in vitro skin models lack the complexity to accurately mimic the structure and function of human skin, including essential components such as blood vessels, subcutaneous tissue, and bone, limiting their effectiveness in testing transdermal pharmaceutical and cosmetic preparations and non-invasive sensors.

Innovation Solution

A 3D bioprinted in vitro skin model comprising layers of epidermis with keratinocytes, dermis with fibroblasts, subcutaneous tissue with adipocytes, and a bone simulation, integrated with a vascular system and sensors, using biocompatible materials and 3D printing techniques to simulate physiological conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If simple skin models consisting of only dermis or dermis and epidermis are used, then the model structure is simple and easy to manufacture, but the model complexity is low and cannot accurately mimic real skin in vivo

Engineering Contradiction:
Improvemodel complexityVSAvoidease of manufacture
Core Design Contradiction:
Device complexityVSEase of manufacture

Solution Approach 1:

The skin model is divided into multiple distinct layers (epidermis, dermis, subcutaneous tissue, bone) with each layer containing specific cell types and structures. This segmentation allows each layer to be independently constructed and optimized while maintaining overall model complexity that accurately represents in vivo skin structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The model employs a nested structure where the epidermis layer is positioned on top of the dermis, which in turn contains the subcutaneous tissue and bone layers. This nested arrangement allows the complex multi-layer structure to be built systematically, with each layer nested within the previous one, facilitating both manufacturing and physiological representation.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Reliability

If in vitro models are used to reduce clinical trials, then testing costs and time are reduced, but the models cannot ideally mimic real tissue or organ functions

Engineering Contradiction:
Improvereliability of testingVSAvoidmodel complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Each layer of the skin model is constructed with specific local qualities - the epidermis contains keratinocytes for barrier function, the dermis contains fibroblasts and collagen for structural support, the subcutaneous tissue contains adipocytes for energy storage, and the bone layer provides structural integrity. This local quality differentiation enables the model to reliably mimic real skin functions while maintaining manageable complexity through modular construction.

Inventive Principle:
Principle #3Local quality

3Volume of moving object

If microchips with limited dimensions are used, then the device size is reduced, but it is impossible to ensure reliable simulation of skin events due to lack of suitable mechanical, structural, physiological parameters

Engineering Contradiction:
Improvemodel volumeVSAvoidreliability of simulation
Core Design Contradiction:
Volume of moving objectVSReliability

Solution Approach 1:

The model transitions from two-dimensional microchip structures to a three-dimensional multi-layer configuration. By adding the vertical dimension with distinct epidermis, dermis, subcutaneous tissue, and bone layers, the model achieves both compact volume and the necessary structural complexity to reliably simulate skin physiology, including mechanical properties, vascular networks, and tissue interactions.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Data Source

PatentEP4299719B1A complex in vitro model of human skin, a process for preparation and use thereof
Publication Date: 2025.12.31 UNIVERZA V MARIBORU
  • EP4299719B1 patent drawingFigure 1
  • EP4299719B1 patent drawingFigure 2a~2e
  • EP4299719B1 patent drawingFigure 3

AI summary

Complex in vitro human skin model prepared with 3D printing and electrospinning comprises from the uppermost to the lowest layer:- epidermis with keratinocytes and growth factors that allow cell proliferation,- dermis with fibroblasts with growth factors that allow fibroblast proliferation, and nanofibers that simulate extracellular matrix and thus contribute to improved proliferation of cells,- a subdermal layer comprising:o subcutaneous tissue with adipocytes isolated from human fat tissue, ando hollow structures with endothelial cells simulating blood vessels, wherein flow through said hollow structures is enabled with at least one micropump, and wherein sensors for flow, pressure, temperature and/or saturation are provided in the interior of said hollow structures,- optionally bone simulation, wherein a metal substrate is provided with a 3D printed polysaccharide layer and human osteoblasts.