Material and method for producing cell receiving scaffold
Inventors
Xu, Pingyong • Alvarez, Luis • Morris, Derek • Yazdi, Iman
Assignees
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Publication Number
US-11597915-B2
Publication Date
2023-03-07
Expiration Date
Abstract
A printable composition for the manufacture of cell-receiving scaffolds comprising about 0.3 wt % to about 3.0 wt % of one or more collagens; about 5.0 wt % to about 40.0 wt % of one or more monomers; about 0.5 wt % to about 2.0 wt % of a photo initiator; and 0 wt % to about 75 wt % of a vehicle comprising a protic solvent, by weight of the printable composition; wherein the printable composition has a resolution of about 100 microns or less when printed, a photo speed (Dp/Ec) of about 0.1-5 mm (Dp) and about 10-100 mJ/cm2 (Ec) when printed, and a green strength of at least about 5 kPa after drying. The present technology further includes methods of manufacturing a three-dimensional cell-receiving scaffold using the printable composition.
Core Innovation
A printable composition is provided for manufacturing three-dimensional cell-receiving scaffolds. The composition comprises collagen, a monomer, a photo initiator, and a vehicle, where the collagen is present in an amount from about 0.3 percent to about 3.0 percent by weight of the printable composition. The vehicle is a protic-solvent vehicle, optionally including water, and the printable composition is formulated to be printable with a resolution of 100 microns or less and to achieve defined photo curing performance characterized by photo speed (Dp/Ec).
The scaffold is manufactured by depositing a layer of the printable composition to a surface to obtain a deposited layer, irradiating the deposited layer, and repeating the depositing and irradiating steps until the deposited layers form the three-dimensional cell-receiving scaffold. Irradiation includes UV, violet, or blue wavelengths, including an example at 355 nm. The deposited scaffold is contacted with an acidic solution that hydrolyzes ester linkages in the printable composition, and this contacting lowers a green strength of the three-dimensional cell-receiving scaffold.
The manufacturing optionally includes heating the printable composition prior to depositing. The resulting three-dimensional cell-receiving scaffold can be contacted with cells, tissues, growth factors, laminin, elastin, fibronectin, proteoglycans, hyaluronic acid, polysaccharides, or a mixture of two or more thereof. Example results include cell viability associated with a printed scaffold and a printed scaffold formed with less than 100 micron resolution at 355 nm.
Claims Coverage
The independent claim set covers manufacturing a three-dimensional cell-receiving scaffold using a collagen-containing printable composition with layer-by-layer depositing and irradiating, followed by acidic hydrolysis to lower green strength. The independent claim includes 3 main inventive categories: layer-by-layer deposition and irradiation, acidic ester-linkage hydrolysis to reduce green strength, and defining the collagen-based printable composition.
Layer-by-layer depositing and irradiating of a collagen-containing printable composition
Depositing a layer of a printable composition to a surface to obtain a deposited layer; irradiating the deposited layer; and repeating the depositing and irradiating steps until the deposited layers form the three-dimensional cell-receiving scaffold, wherein the printable composition comprises collagen, a monomer, a photo initiator, and a vehicle.
Acidic hydrolysis to lower green strength
Contacting the three-dimensional cell-receiving scaffold with an acidic solution that hydrolyzes ester linkages in the printable composition to lower a green strength of the three-dimensional cell-receiving scaffold.
Collagen wt% in the printable composition
The printable composition comprises collagen present in an amount from about 0.3 percent to about 3.0 percent by weight of the printable composition.
Performance constraints for printing and cured scaffold strength
Providing printed resolution of about 100 microns or less, photo speed (Dp/Ec) of about 0.1-5 mm and photo energy of about 10-100 mJ/cm2, and green strength of at least about 5 kPa after drying.
Monomer, photo initiator, and protic-solvent vehicle ranges
Including about 5.0 wt% to about 40.0 wt% monomer; about 0.5 wt% to about 2.0 wt% photo initiator; and 0.1 wt% to about 75 wt% vehicle comprising a protic solvent.
Overall, the claim coverage centers on a collagen-containing printable composition used in a layer-by-layer depositing and irradiating method, followed by contacting the formed scaffold with an acidic solution that hydrolyzes ester linkages to lower green strength. Dependent claims additionally constrain composition ranges, printing, cure, and strength performance, and optionally include heating prior to deposition and expanded contacting with specified biological factors.
Stated Advantages
Enables manufacturing of three-dimensional cell-receiving scaffolds using a printable collagen-containing composition with defined resolution and photo curing performance.
Acidic hydrolysis lowers a green strength of the three-dimensional cell-receiving scaffold.
Printed scaffolds can be obtained with 100 microns or less resolution and green strength of at least about 5 kPa after drying.
Provides a scaffold that can be used in contacting with cells, tissues, growth factors, and extracellular-matrix-related biomolecules such as laminin, elastin, fibronectin, proteoglycans, hyaluronic acid, and polysaccharides.
Documented Applications
Manufacturing three-dimensional cell-receiving scaffolds and contacting the scaffold with cells, tissues, growth factors, laminin, elastin, fibronectin, proteoglycans, hyaluronic acid, polysaccharides, or mixtures thereof.
Use of the printed scaffold in an example associated with cell viability.
Formation of a printed scaffold with less than 100 micron resolution at 355 nm.
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