Decellularisation of tissue matrices for bladder implantation
Inventors
Bolland, Fiona • Southgate, Jennifer • Korossis, Sotirios • Ingham, Eileen
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9180143-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. 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.
Core Innovation
The invention provides an improved decellularisation approach for producing an acellular bladder-derived ECM scaffold. A distensible membranous sac or bladder material is immersed in a buffer solution at a mild alkaline pH that includes active amounts of a proteolytic inhibitor, and distension or expansion is maintained by introducing a sufficient volume of the same buffer solution into the interior cavity.
Decellularisation is continued by replacing and introducing fresh solutions around the exterior surface and/or into the sac interior so as to maintain distension or expansion during the decellularisation process. The method maintains the histoarchitecture of the bladder material and yields an acellular scaffold for tissue-engineering.
The resulting whole decellularised distensible sac or a portion thereof is implanted into a donor in bladder reconstruction or replacement surgery. The bladder material or a portion thereof is also described for urological tissue engineering replacement or repair, including cosmetic surgery use cases.
Claims Coverage
The partial content provides two independent claims: clm-00001 and clm-00005. Each claim centers on maintaining distension or expansion of a bladder-derived distensible membranous sac during decellularisation using a mild alkaline buffer containing a proteolytic inhibitor, followed by implantation as an acellular tissue matrix or scaffold.
Mild-alkaline protease-inhibitor buffered decellularisation of a distensible membranous sac with maintained distension
Immersing a distensible membranous sac in a buffer solution at a mild alkaline pH including active amounts of a proteolytic inhibitor, distending the sac by introducing a sufficient volume of the same buffer solution into the interior cavity, and continuing decellularisation by replacing and introducing fresh solutions around the exterior surface and/or into the sac interior to maintain distension during decellularisation.
Implantation of whole decellularised distensible sac or portion into a donor for bladder reconstruction or replacement
Implanting the whole decellularised distensible sac or a portion thereof into a donor as part of bladder reconstruction or replacement surgery.
Expansion of bladder material with mild alkaline protease-inhibitor buffer while maintaining histoarchitecture during decellularisation
Immersing bladder material in a buffer solution at a mild alkaline pH including a proteolytic inhibitor, expanding the bladder by introducing a sufficient volume of the same buffer solution into an interior cavity so as to stretch and thin the bladder wall, and continuing decellularisation by replacing and introducing fresh solutions both around the exterior surface and into the bladder interior to maintain expansion during decellularisation and maintain the histoarchitecture of the bladder material.
Urological tissue engineering replacement or repair
Implanting the bladder material or a portion thereof into a donor, wherein the method of tissue engineering replacement or tissue repair is selected from the group consisting of cosmetic surgery and scaffold for tissue-engineering.
Overall claim coverage centers on decellularising bladder-derived tissue matrix or scaffold using a mild alkaline protease-inhibitor buffer while maintaining distension or expansion by interior and exterior solution replacement, followed by implantation into a donor for bladder reconstruction or urological tissue engineering replacement or repair.
Stated Advantages
Retains native bladder mechanical compliance and strength.
Substantially non-cytotoxic.
Supports smooth muscle cell proliferation and partial infiltration in vitro.
Shows reduced immune or foreign-body response in a mouse subcutaneous model consistent with wound-healing-type integration.
Provides biochemical and mechanical performance including low residual DNA, suturing retention, and tensile properties.
Shelf-life up to about 30 months without significant mechanical degradation.
Documented Applications
Bladder reconstruction or replacement surgery using implantation of the whole decellularised distensible sac or a portion thereof into a donor.
Urological tissue engineering replacement or repair as tissue repair or scaffold, including cosmetic surgery and scaffold for tissue-engineering.
In vitro bladder function model as documented in the provided summary context.
Interested in licensing this patent?