Compositions and methods for scaffold formation
Inventors
Seliktar, Dror • Gonen-Wadmany, Maya
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9624259-B2
Publication Date
2017-04-18
Expiration Date
Abstract
The present invention relates to scaffolds composed of a protein backbone cross-linked by a synthetic polymer. Specifically, the present invention provides PEGylated-thiolated collagen scaffolds and PEGylated albumin scaffolds and methods of generating and using same for treating disorders requiring tissue engineering.
Core Innovation
The described invention relates to biosynthetic hybrid tissue-engineering scaffolds formed by covalently cross-linking PEGylated polymer-protein precursor molecules. The precursor molecules include thiolated collagen or non-thiolated albumin, and the resulting scaffold and hydrogel comprise albumin molecules and synthetic polymers covalently attached to the albumin molecules.
Each polymer-protein precursor includes at least two synthetic polymer functional groups, such as acrylate or vinyl sulfone, which enable cross-linking with like functional groups on other precursors to form a covalently cross-linked scaffold. Thiolation enables attaching PEG to proteins with low cysteine content, and the described attachment concept includes albumin/thiolated protein precursors and covalent attachment to at least two synthetic polymer groups per albumin molecule.
The scaffold is characterized as a denatured albumin-containing scaffold with cross-linked synthetic polymers attached to albumin molecules. The described functionality includes differing cell behaviors depending on the protein backbone, with PEGylated thiolated collagen supporting cell spreading and invasion, PEGylated albumin showing resistance to cell spreading and invasion as an adhesive concept, and PEGylated fibrinogen described as intermediate.
Claims Coverage
Two independent claims are identified, each directed to a composition comprising a covalently cross-linked scaffold of albumin and synthetic polymers, with albumin denatured. The first independent claim further requires a specified scaffold concentration range, and the dependent claims refine polymer identity, attachment-site detail, and denaturing-agent selection.
Denatured albumin scaffold with cross-linked synthetic polymers
A composition comprising a scaffold comprising a plurality of albumin molecules and a plurality of synthetic polymers covalently attached to said albumin molecules, each albumin molecule being covalently attached to at least two synthetic polymers, wherein the synthetic polymers are cross-linked with each other, and wherein the albumin is denatured.
Covalently cross-linked albumin-synthetic polymer scaffold at defined concentration
A composition comprising a scaffold comprising a plurality of albumin molecules and a plurality of synthetic polymers covalently attached to said albumin molecules, each albumin molecule being covalently attached to at least two of said synthetic polymers, wherein said synthetic polymers are cross-linked with each other, wherein said albumin is denatured, and wherein a concentration of said scaffold in the composition is in a range of 3 mg/ml to 50 mg/ml.
PEG synthetic polymers and cysteine attachment site
A composition wherein said synthetic polymers are PEG and wherein at least two synthetic polymers are covalently attached to a cysteine of said albumin.
Denatured albumin using urea or guanidine chloride
A composition wherein the albumin is denatured and the denaturation is by a denaturing agent selected from urea or guanidine chloride.
Across the independent claims, the core claimed subject matter is a composition with an albumin-containing scaffold where albumin molecules are covalently attached to at least two cross-linked synthetic polymers per albumin molecule, with the albumin in denatured form. Dependent claim refinements specify a scaffold concentration range, PEG as the synthetic polymer, a cysteine attachment site, and denaturing agents selected from urea or guanidine chloride.
Stated Advantages
Supports cell spreading and invasion for PEGylated thiolated collagen.
PEGylated albumin shows resistance to cell spreading and invasion as an adhesive concept.
PEGylated fibrinogen is described as intermediate in the reported cell-behavior context.
Documented Applications
Treating various tissue-damage disorders, including cosmetic tissue repair.
Interested in licensing this patent?