Decellularised cell wall structures from plants and use thereof as scaffold materials
Inventors
Pelling, Andrew Edward • Cuerrier, Charles Michel • Modulevsky, Daniel J. • Hickey, Ryan Joseph
Assignees
Publication Number
US-11167062-B2
Publication Date
2021-11-09
Expiration Date
2037-02-10
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Provided herein are scaffold biomaterials comprising a decellularised plant or fungal tissue from which cellular materials and nucleic acids of the tissue are removed, the decellularised plant or fungal tissue comprising a cellulose- or chitin-based 3-dimensional porous structure. Methods for preparing such scaffold biomaterials, as well as uses thereof as an implantable scaffold for supporting animal cell growth, for promoting tissue regeneration, for promoting angiogenesis, for a tissue replacement procedure, and/or as a structural implant for cosmetic surgery are also provided. Therapeutic treatment and/or cosmetic methods employing such scaffolds are additionally described.
Core Innovation
The invention provides scaffold biomaterials comprising decellularised plant or fungal tissue from which cellular materials and nucleic acids are removed, resulting in a cellulose- or chitin-based three-dimensional porous structure. These scaffolds are generated by decellularising plant or fungal tissue via methods such as thermal shock, detergent treatment (e.g., SDS), osmotic shock, lyophilisation, physical lysing, electrical disruption, enzymatic digestion, or combinations thereof. Residual detergent such as SDS is removed by washing with aqueous divalent salt solutions like CaCl2 or MgCl2. The scaffolds may be further functionalized chemically or structurally to support various cell and tissue engineering applications.
The background underscores the problems with existing biomaterials, which often have complex, costly production processes and are derived from human or animal sources, causing risks like immune rejection, disease transmission, ethical sourcing problems, and environmental impact. Moreover, many commercial biomaterials lose their shape after implantation, diminishing tissue repair success. Resorbable biomaterials often cause tissue collapse upon degradation and adverse immune responses.
This invention addresses the need for alternative biomaterials that are biocompatible, minimally immunogenic, structurally stable, environmentally sustainable, and capable of promoting cell infiltration, angiogenesis, and tissue regeneration. By using decellularised plant or fungal tissues, the invention provides biomaterials with a complex native architecture, thin walls, high porosity, and the ability to maintain shape long-term. Additionally, such biomaterials can be modified chemically to suit particular applications, including incorporation of growth factors, collagen, or drugs.
Claims Coverage
The claims include eleven inventive features extracted from the independent claims related to scaffold biomaterials derived from decellularised plant tissues treated with specific processes and functionalizations.
Scaffold biomaterial comprising decellularised plant tissue with cellulose-based 3D porous structure and SDS decellularization with residual SDS removal
A scaffold biomaterial comprising decellularised plant tissue from which cellular materials and nucleic acids are removed, the tissue having a cellulose-based three-dimensional porous structure. The tissue is decellularised by sodium dodecyl sulphate (SDS) treatment, and residual SDS is removed by an aqueous divalent salt solution that precipitates a salt residue containing SDS micelles out of the scaffold.
Further decellularisation methods
The decellularised plant tissue has optionally been further decellularised by thermal shock, treatment with detergent, osmotic shock, lyophilisation, physical lysing, electrical disruption, enzymatic digestion, or combinations thereof.
Removal of residual salt and SDS micelles
Residual aqueous divalent salt solution, salt residue, and/or SDS micelles have been removed by treatment with dH2O, acetic acid, DMSO, sonication, or combinations of these methods.
Specific divalent salts for SDS removal
The divalent salt in the aqueous divalent salt solution comprises MgCl2 or CaCl2.
Defined SDS and CaCl2 concentrations for decellularisation and washing
The plant tissue is decellularised by treatment with about 0.1% or about 1% SDS in water, and residual SDS is removed using an aqueous CaCl2 solution at about 100 mM concentration followed by incubation in dH2O.
Processing and functionalisation of scaffold
The decellularised plant tissue is processed to introduce additional architecture and/or functionalised at free hydroxyl groups by acylation, alkylation, or other covalent modifications to provide functionalized scaffold biomaterials.
Specific processing and functionalization examples
The decellularised plant tissue is processed to introduce microchannels and/or functionalised with collagen, cell-specificity promoting factors, cell growth factors, or pharmaceutical agents.
Specific plant tissue sources and genetic modification
The plant tissue sources include various species such as apple hypanthium, fern, turnip root tissue, gingko branch, horsetail, kale stem, mushroom tissue, and others, including genetically altered tissues produced via direct genome modification or selective breeding to mimic or promote target tissue effects.
Scaffold biomaterial comprising living animal cells
The scaffold biomaterial further comprises living animal cells adhered to the cellulose-based 3D porous structure.
Inclusion of mammalian living cells
The living animal cells adhered to the scaffold are mammalian cells.
Living human cells adhered to scaffold
The living animal cells adhered to the scaffold are human cells.
The claims define scaffolds derived from decellularised plant tissues treated specifically with SDS and purified by divalent salt solutions, optionally further processed and functionalized chemically or structurally, and optionally comprising living mammalian or human cells. The claims cover a broad range of plant tissue sources and methods to produce functional and biocompatible cellulose-based 3D porous scaffold biomaterials.
Stated Advantages
Relatively low-cost and time efficient production procedures for scaffold biomaterials.
Ability to maintain shape and hold intended geometry over long periods, resisting deformation after implantation.
High biocompatibility with minimal or almost no immunogenic response upon implantation.
Promotion of rapid vascularization and angiogenesis in vivo.
Minimal environmental impact due to plant or fungal origin and potential use of food waste as source material.
Non-resorbable characteristic avoiding tissue collapse and adverse immune responses associated with degradation products of resorbable biomaterials.
Documented Applications
Implantable scaffold for supporting animal cell growth and tissue regeneration.
Structural implants for cosmetic surgery and therapeutic tissue replacement procedures.
Structural implants for repair or regeneration following spinal cord injury.
Structural implants for tissue replacement surgery and skin graft or regeneration surgery.
Structural implants for regeneration of blood vasculature in target tissues or regions.
Bone replacement, bone filling, or bone graft materials, and promotion of bone regeneration.
Tissue replacements for skin, bone, spinal cord, heart, muscle, nerve, blood vessel, or other damaged or malformed tissue.
Vitreous humour replacement in hydrogel form.
Artificial bursae forming sac-like structures containing scaffold biomaterial in hydrogel form.
Interested in licensing this patent?