Decellularised Bladder Scaffold via Sequential Buffer Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current biomaterials for urological tissue engineering, such as porcine small intestinal submucosa and decellularised porcine dermis, face challenges with immunogenicity, incomplete decellularisation, and inability to support recellularisation, leading to adverse side effects and limited success in bladder tissue replacement.
Innovation Solution
A method for decellularising whole bladders using a mild alkaline buffer solution with proteolytic inhibitors, distending the tissue to facilitate solution penetration, and replacing solutions to maintain distension during decellularisation, ensuring complete removal of cellular components while retaining biomechanical properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional decellularisation methods are used on whole bladders, then cellular components are removed, but complete decellularisation is not achieved and immunogenicity remains
Solution Approach 1:
The decellularisation process is segmented into multiple sequential treatment steps using different solutions (detergent solution, enzymatic solution, oxidative solution) rather than a single treatment, allowing progressive and complete removal of cellular components from the bladder tissue
Solution Approach 2:
Multiple chemical solutions act as intermediaries to facilitate decellularisation. Each solution (detergent, enzymatic, oxidative) serves as a mediator that targets specific cellular components, enabling complete decellularisation without direct mechanical or harsh chemical intervention on the tissue structure
2Object-affected harmful factors
If aggressive decellularisation methods are used to remove all cellular components, then immunogenicity is reduced, but biomechanical properties of the tissue are compromised
Solution Approach 1:
The method changes the parameters of the decellularisation process by using a sequential approach with progressively milder treatments, adjusting the chemical nature and strength of each solution to achieve complete decellularisation while preserving the structural integrity and biomechanical properties of the extracellular matrix
Solution Approach 2:
The decellularisation process maintains continuous useful action through sequential treatments that build upon each other, with each solution building on the previous one to progressively remove cellular components while the tissue structure remains intact and is gradually prepared for recellularisation
3Adaptability or versatility
If decellularised matrices are used for bladder replacement, then tissue engineering is enabled, but the ability to support recellularisation is lost
Solution Approach 1:
The decellularisation process performs preliminary actions to prepare the matrix for recellularisation by removing cellular debris and creating a clean, biocompatible surface that is pre-conditioned to support cell attachment and proliferation, rather than simply removing cells without considering future cell seeding
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 achieves complete decellularisation of bladder tissue with retained mechanical properties, biocompatibility, and ability to support recellularisation, providing a suitable scaffold for bladder tissue engineering with reduced immunogenicity and improved clinical outcomes.
Implementation Method 1
immersing the distensible membranous sac in a buffer solution at a mild alkaline pH which includes active amounts of a proteolytic inhibitor
Implementation Method 2
immersing the distensible membranous sac in a buffer solution at a mild alkaline pH
Implementation Method 3
distending the distensible membranous sac by introducing a sufficient volume of the same buffer solution into the interior cavity of the sac
Implementation Method 4
continuing decellularisation of the sac by replacing and introducing fresh solutions both around the exterior surface of the sac and into the sac interior itself so as to maintain distension of the sac during decellularisation
Data Source
AI summary
The invention provides an improved method of producing a natural, acellular matrix scaffold for subsequent use in tissue-engineered replacement of tissues such as the bladder. Decellularization is carried out on an expanded or distended bladder and the product retains the strength and compliance of natural material. The invention also provides use of the matrix scaffolds as wound healing material and to investigate tissue structure and function in vitro.