Decellularised cell wall structures from fungus and use thereof as scaffold materials
Inventors
Pelling, Andrew Edward • Cuerrier, Charles Michel • Modulevsky, Daniel J. • Hickey, Ryan Joseph
Assignees
Publication Number
US-12138364-B2
Publication Date
2024-11-12
Expiration Date
2037-02-10
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Abstract
Provided herein are scaffold biomaterials comprising a decellularised fungal tissue from which cellular materials and nucleic acids of the tissue are removed, the decellularised 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 fungal tissue from which cellular materials and nucleic acids are removed. The decellularised fungal tissue comprises a chitin-based three-dimensional porous structure. These biomaterials are prepared by decellularization processes such as treatment with sodium dodecyl sulphate (SDS) and subsequent removal of residual SDS using an aqueous divalent salt solution to precipitate salt residues containing SDS micelles out of the scaffold.
The problem addressed by the invention arises from limitations in the existing biomaterials industry. Many commercial biomaterials are derived from human or animal origins, causing potential rejection and adverse immune responses, alongside concerns about disease transmission and unethical sourcing. Production methods are often complicated and expensive. Moreover, some commercial biomaterials lose their shape after implantation, leading to reduced tissue repair success. Resorbable biomaterials tend to collapse or deform upon degradation, causing challenges in long-term structural maintenance of regenerated tissues. Therefore, there is a need for non-resorbable, biocompatible scaffolds that maintain shape and support tissue regeneration without adverse immune reactions.
The invention solves these problems by providing biomaterials derived from decellularised plant or fungal tissues, offering a cellulose- or chitin-based 3D porous scaffold. These scaffolds exhibit high porosity with thin wall structures, minimal footprint when invaded by living cells, and non-resorbable characteristics that help maintain shape over time. Production employs efficient decellularization techniques involving SDS treatment and removal by aqueous divalent salt solutions such as calcium chloride. The scaffolds can be further functionalized chemically to promote cell adhesion and tissue regeneration, and can be implanted to support animal cell growth, promote angiogenesis, and facilitate tissue repair in various medical and cosmetic applications.
Claims Coverage
The claims contain one independent claim focused on a scaffold biomaterial comprising decellularised fungal tissue with specific treatment steps for decellularization and removal of residual agents. These claims cover inventive features relating to scaffold composition, processing methods, functionalization, and cell adherence.
Scaffold biomaterial comprising decellularised fungal tissue with chitin-based 3D porous structure
A scaffold biomaterial comprising a decellularised fungal tissue, from which cellular materials and nucleic acids are removed, the tissue having a chitin-based three-dimensional porous structure.
Decellularization by SDS treatment with removal of residual SDS by aqueous divalent salt solution
The fungal tissue is decellularised by treatment with sodium dodecyl sulphate (SDS), and residual SDS is removed by using an aqueous divalent salt solution to precipitate salt residues containing SDS micelles out of the scaffold biomaterial.
Further decellularization methods
The decellularised fungal tissue may be further decellularised by at least one of thermal shock, treatment with detergent, osmotic shock, lyophilization, physical lysing, electrical disruption, enzymatic digestion, or combinations thereof.
Removal of aqueous divalent salt solution residues
Divalent salt solution, salt residue, and SDS micelles may be removed using dH2O, acetic acid, dimethylsulfoxide (DMSO), sonication, or a combination thereof.
Use of specific divalent salts in removal process
The divalent salt of the aqueous divalent salt solution comprises magnesium chloride (MgCl2) or calcium chloride (CaCl2).
Specific SDS solution concentration and removal conditions
Decellularization is performed with SDS solution of about 0.1% or 1% in water, and residual SDS is removed using an aqueous CaCl2 solution at about 100 mM concentration followed by incubation in dH2O.
Functionalization and microarchitecture modification
The decellularised fungal tissue can be processed to introduce further architecture, microchannels, and/or functionalized at free hydroxyl groups through acylation, alkylation, or other covalent modifications, including functionalization with collagen, cell-specific growth factors, or pharmaceutical agents.
Incorporation of specific fungal tissue sources
The fungal tissue may be from mushrooms or genetically altered tissues produced via genome modification or selective breeding to create architectures that mimic or promote target tissue effects.
Adherence of living animal cells
The scaffold biomaterial may include living animal cells adhered to the chitin-based 3D porous structure, including mammalian or human cells.
The claims cover a scaffold biomaterial comprising decellularised fungal tissue with a chitin-based porous structure prepared by SDS treatment and residue removal using aqueous divalent salt solutions, with options for further decellularization methods, functionalization, and incorporation of living animal cells. The invention comprehensively addresses scaffold composition, preparation processes, and functional applications.
Stated Advantages
Relatively low-cost and time-efficient production procedures for scaffold biomaterials.
Ability to maintain shape and integrity over long periods, due to non-resorbable or poorly resorbable characteristics.
High porosity scaffolds with thin wall structure providing minimal footprint and near invisibility in vivo after cell infiltration.
High biocompatibility with minimal or almost non-existent immunogenic response following implantation.
Promotion of rapid vascularization and angiogenesis within the scaffold to support tissue regeneration.
Reduced risk of adverse immune response and disease transmission compared to human/animal-derived biomaterials.
Environmental benefits due to derivation from plants or fungi, including potential use of food waste.
Documented Applications
Use as an implantable scaffold for supporting animal cell growth and promoting tissue regeneration.
Implantation for promoting angiogenesis and blood vasculature regeneration in target tissues.
Use in tissue replacement procedures including skin, bone, spinal cord, heart, muscle, nerve, and blood vessels.
Structural implants for cosmetic surgery, skin grafts, and skin regeneration surgeries.
Structural implants for repair or regeneration following spinal cord injury.
Use as bone replacement, bone filling, or bone graft material for promoting bone regeneration.
Use in hydrogel form as a vitreous humour replacement.
Use as an artificial bursae with sac-like hydrogel scaffolds.
Potential use in veterinary applications and as tools for biomedical research, sensing devices, and pharmaceutical delivery.
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