Decellularisation of tissue matrices for bladder implantation
Inventors
Bolland, Fiona • Southgate, Jennifer • Korossis, Sotirios • Ingham, Eileen
Assignees
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Publication Number
US-9180144-B2
Publication Date
2015-11-10
Expiration Date
Abstract
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. Decellularisation 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.
Core Innovation
The invention relates to an improved bladder decellularisation process that produces a biocompatible implant material from bladder tissue. The process immerses a bladder material in a buffer solution at a mild alkaline pH that includes a proteolytic inhibitor, and it is described as supporting decellularisation while addressing preservation of native bladder strength and compliance.
A key aspect of the method is expanding the bladder by introducing a sufficient volume of the same buffer solution into an interior cavity of the bladder to stretch and thin the bladder wall. The process maintains expansion during decellularisation by continuing decellularisation while replacing and introducing fresh solutions both around the exterior surface and into the bladder interior itself, which is described as maintaining histoarchitecture during continued decellularisation.
The produced material is characterised by substantially decellularised bladder and specific biochemical and mechanical outcomes. The patent describes a DNA content of less than 0.2 µg/mg dry weight, and mechanical performance including suture retention strength (Fmax) of 3–6 N, ultimate tensile strength (apex to base) of 1–4 MPa, and failure strength (apex to base) of 70–150%.
It is further described as retaining histoarchitecture, preserving collagen/elastin structure, enabling repopulation with smooth muscle cells, and reducing cytotoxicity/inflammation in vivo. Documented outcomes include retained histoarchitecture and preserved mechanical integrity, with reported shelf life up to about 30 months.
Claims Coverage
The patent contains two independent claims. The first covers producing a biocompatible implant material by decellularising and mechanically expanding bladder tissue in a mild alkaline buffer with a proteolytic inhibitor while maintaining expansion through solution exchange to preserve histoarchitecture; the second covers the resulting decellularised bladder product characterized by specific DNA and mechanical property ranges.
Expanded whole bladder decellularisation in mild alkaline protease-inhibitor buffer
A method comprising immersing a bladder material in a buffer solution at a mild alkaline pH which includes a proteolytic inhibitor.
Mechanical expansion by introducing buffer into the bladder interior cavity
Expanding the bladder by introducing a sufficient volume of the same buffer solution into an interior cavity of the bladder so as to stretch and thin the bladder wall.
Maintaining expansion during decellularisation by interior and exterior solution replacement
Continuing decellularisation of the bladder by replacing and introducing fresh solutions both around the exterior surface of the bladder and into the bladder interior itself so as to maintain expansion of the bladder during decellularisation and to maintain the histoarchitecture of the bladder material.
Decellularised whole bladder, sheet or patch with defined DNA and mechanical property ranges
A product comprising decellularised whole bladder, sheet or patch thereof, characterized by a DNA content of less than 0.2 µg/mg dry weight, a suture retention strength (Fmax) of between 3-6 N, ultimate tensile strength (apex to base) of between 1-4 MPa, and failure strength (apex to base) of between 70-150%.
Overall, claim coverage centers on decellularising bladder tissue in a mild alkaline buffer containing a proteolytic inhibitor while mechanically expanding the bladder by filling its interior cavity, and maintaining that expansion through repeated replacement of fresh solutions both exteriorly and interiorly to preserve histoarchitecture. A separate independent claim is directed to the resulting decellularised whole bladder/sheet/patch product defined by specific DNA content and mechanical strength ranges.
Stated Advantages
Maintains histoarchitecture of the bladder material during decellularisation.
Supports substantially decellularised bladder with DNA content less than 0.2 µg/mg dry weight.
Preserves mechanical performance, including suture retention strength (Fmax) of 3–6 N, ultimate tensile strength of 1–4 MPa, and failure strength of 70–150%.
Retains collagen/elastin structure.
Enables repopulation capability with smooth muscle cells.
Reduced cytotoxicity/inflammation in vivo.
Preserved mechanical integrity with reported shelf life up to about 30 months.
Documented Applications
Bladder implantation/replacement/augmentation.
Wound healing or repair using a sheet/patch.
Cosmetic augmentation.
Tissue-engineering scaffold.
In vitro bladder function modeling.
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