Acellular Dermis via Enzymatic and Ionizing Radiation Treatment
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Solution Overview
Problem
Current methods for treating dermis for transplantation are laborious, difficult to repeat, and prone to immune and rejection reactions in homologous and heterologous transplantations, especially when using tissues from different species, due to the presence of cells responsible for immune reactions.
Innovation Solution
A method involving enzymatic treatment with trypsin solution followed by ionizing radiation, specifically gamma and beta rays, to selectively remove or necrotize cells like fibroblasts, macrophages, and mast cells, while preserving the extracellular matrix, ensuring the dermis is acellular and immune-reactive cell-free, facilitating easier and repeatable processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cleaning substances or enzymes are used to eliminate cells from dermis, then immune and rejection reactions are reduced, but the process becomes laborious and difficult to repeat with variable dehydration requirements
Solution Approach 1:
The patent applies parameter changes by using ionizing radiation (gamma rays at 25-50 kGy, beta rays at 1-10 MeV) with specific energy ranges and doses to achieve consistent cell elimination. This physical parameter-based approach replaces the chemical/enzymatic methods that required variable dehydration steps, providing a standardized, repeatable process that reliably prevents immune reactions without manual adjustment.
Solution Approach 2:
The patent substitutes mechanical and manual operations (manual dehydration, skill-based handling) with automated physical processes (ionizing radiation treatment). This replacement eliminates the need for operator skill and sensitivity in dehydration, making the process easily repeatable and industrially scalable while maintaining reliable cell elimination.
2Object-generated harmful factors
If polyoxyethylene or sodium deoxycholate are used to eliminate cells, then acellular dermis is obtained, but the process requires skilled manual operation and precise dehydration control
Solution Approach 1:
The patent applies self-service by using ionizing radiation to automatically eliminate cells from dermis without requiring manual intervention for cell removal. The radiation treatment autonomously achieves cell necrosis and elimination, replacing the need for skilled operators to manually control dehydration and apply cleaning substances, while still obtaining acellular dermis that prevents immune responses.
3Reliability
If traditional enzymatic treatment alone is used, then cells are removed, but the extracellular matrix may be compromised and the process lacks standardization
Solution Approach 1:
The patent applies composite materials by combining ionizing radiation treatment with specific preserving solutions (glycerol, sorbitol, or glucose at controlled concentrations). This composite approach uses radiation for cell elimination while the preserving solution simultaneously protects and stabilizes the extracellular matrix, achieving both cell removal and matrix preservation with a single standardized process.
Solution Approach 2:
The patent applies beforehand cushioning by immersing dermis in preserving solutions (glycerol, sorbitol, or glucose) before or during radiation treatment. This pre-protection cushions and protects the extracellular matrix from radiation-induced damage, ensuring matrix preservation while the radiation effectively eliminates cells, with the preserving agent acting as a protective buffer.
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 method effectively prevents immune and rejection reactions by achieving high cell viability of less than 2% and maintaining the integrity of the extracellular matrix, allowing for optimal integration and regrowth of cells during transplantation, reducing post-operative complications and enhancing tissue integration.
Implementation Method 1
The dermis is covered with an enzymatic solution capable of phagocytizing, at least partly, fibroblasts, macrophages, mast cells and other cells responsible for immune and rejection reactions in transplantations
Implementation Method 2
ionizing radiation, specifically gamma and beta rays, to selectively remove or necrotize cells like fibroblasts, macrophages, and mast cells
Data Source
AI summary
A method of treatment of connective tissue includes the steps of providing a biological tissue or organ, coating the tissue or organ with an enzymatic solution capable of phagocytizing at least partly fibroblasts, macrophages, mast cells and other cells responsible for immune and rejection reactions in homologous and heterologous transplantations. The biological tissue or organ, after the treatment with the enzymatic solution is irradiated with ionizing electromagnetic radiations in order to obtain an acellular tissue which maintains its own extracellular matrix unchanged. Preferably, such radiations are gamma radiations having a frequency between 1019 and 1022 Hz, beta radiations or mixtures thereof.