Tissue engineering scaffolds promoting matrix protein production
First Claim
1. A method for making a tissue engineering scaffold for inducing formation of extracellular matrix by cells bound to the scaffold comprising covalently coupling matrix-enhancing molecules are selected from the group consisting of TGF-β
- , angiotensin II, insulin-like growth factor and ascorbic acid to the scaffold in an effective density to elicit production of extracellular matrix without increasing cellular proliferation, wherein when the matrix-enhancing molecules are TGF-β
, the TGF-β
is covalently coupled to the matrix by a polymer tether having a molecular weight between 2000 and 6000 and is in a density between 1 and 100 ng TGF-β
/ml or in a concentration of between about 4×
10−
6 and 4×
10−
3 nmol/ml.
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Accused Products
Abstract
Matrix-enhancing molecules, such as TGF-β, are conjugated to or immobilized on scaffolds to increase ECM production by cells for tissue engineering, tissue regeneration and wound healing applications. The matrix-enhancing molecule is conjugated to a tether, such as polyethylene glycol (PEG) monoacrylate, for attachment to a tissue engineering or cell growth scaffold. The matrix-enhancing molecule retains activity after attachment to the scaffold, and causes cells growing in or on the scaffold to increase extracellular matrix (ECM) production, without substantially increasing proliferation of the cells, even when the scaffold additionally contains cell adhesion ligands. The increased ECM produced by the cells aids in maintaining the integrity of the scaffold, particularly when the scaffold is degradable, either by hydrolysis or by enzymatic degradation.
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Citations
20 Claims
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1. A method for making a tissue engineering scaffold for inducing formation of extracellular matrix by cells bound to the scaffold comprising covalently coupling matrix-enhancing molecules are selected from the group consisting of TGF-β
- , angiotensin II, insulin-like growth factor and ascorbic acid to the scaffold in an effective density to elicit production of extracellular matrix without increasing cellular proliferation, wherein when the matrix-enhancing molecules are TGF-β
, the TGF-β
is covalently coupled to the matrix by a polymer tether having a molecular weight between 2000 and 6000 and is in a density between 1 and 100 ng TGF-β
/ml or in a concentration of between about 4×
10−
6 and 4×
10−
3 nmol/ml. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
- , angiotensin II, insulin-like growth factor and ascorbic acid to the scaffold in an effective density to elicit production of extracellular matrix without increasing cellular proliferation, wherein when the matrix-enhancing molecules are TGF-β
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9. A method for making a tissue engineering scaffold, the method comprising:
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providing a scaffold, a polymer tether, and a matrix-enhancing molecule; covalently coupling the polymer tether to the scaffold; and covalently coupling the matrix-enhancing molecule to the scaffold, wherein the matrix-enhancing molecule is present at a concentration sufficient to elicit production of extracellular matrix by a cell attached to the tissue engineering scaffold without increasing cellular proliferation of the attached cell. - View Dependent Claims (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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Specification