Chondroitin sulfate glycosaminoglycan hydrogel matrices for the treatment of traumatic brain injury
Inventors
Karumbaiah, Lohitash • Mao, Leidong • Logun, Meghan T. • Zhao, Wujun
Assignees
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Publication Number
US-12090229-B2
Publication Date
2024-09-17
Expiration Date
Abstract
Disclosed herein are compositions and methods for cellular reconstitution of photopolymerized, lyophilized, bioactive chondroitin sulfate glycosaminoglycan (CS-GAG)-based hydrogel matrices.
Core Innovation
A CS-GAG hydrogel is administered to the site of traumatic brain injury (TBI) in a subject. The CS-GAG hydrogel does not comprise cells and is configured for use in treating TBI by local delivery at the injury site.
The CS-GAG hydrogel is photopolymerized and described as capable of cellular encapsulation/reconstitution and rehydration with a cell suspension, while the TBI method described in the independent claim is cell-free. The hydrogel is also described as lyophilized and sterilized, and can be reconstituted prior to administration by rehydration.
A treatment concept is described in which neural stem cells (NSCs) in CS-GAG hydrogels are delivered to the injury site, with optional inclusion of trophic factors such as FGF-2, BDNF, EGF, and IL-10 and adhesion molecules/receptors such as CXCR4, CXCR7, and FAK. CS-GAG sulfation-dependent interactions are described, including effects associated with CXCL12 binding, haptotaxis, and glioma infiltration.
Claims Coverage
The independent claim coverage includes the core TBI treatment approach using a cell-free CS-GAG hydrogel administered at the injury site. The claim set includes additional inventive refinements, including defined CS-GAG variants, hydrogel chemical modification, lyophilization/rehydration handling, optional inclusion of trophic and adhesion-related components for rehydration, and outcome characterizations tied to inflammation and astroglial scarring.
Cell-free CS-GAG hydrogel administration at the TBI site
A method of treating traumatic brain injury (TBI) in a subject by administering a chondroitin sulfate glycosaminoglycan (CS-GAG) hydrogel to the subject at the site of the TBI, wherein the CS-GAG hydrogel does not comprise cells.
Sulfation state selection of CS-A, CS-C, CS-E variants
The CS-GAG hydrogel is selected from monosulfated chondroitin-4-sulfate (CS-A), chondroitin-6-sulfate (CS-C), disulfated chondroitin-4,6-sulfate (CS-E), or a combination thereof.
AEMA modification of CS-GAG carboxylic acid groups
The CS-GAG hydrogel is formed by adding 2-aminoethyl methacrylate (AEMA) to the carboxylic acid groups on the glucuronic acid residues.
Lyophilization followed by rehydration prior to administration
The method includes lyophilizing the CS-GAG hydrogel and rehydrating the lyophilized CS-GAG hydrogel prior to administration.
Rehydration with trophic factors and adhesion-related components
The method includes rehydrating a CS-GAG hydrogel using a rehydration solution that contains a trophic factor and/or adhesion molecules and/or adhesion molecule receptors.
Reduced inflammation and/or reduced astroglial scarring at the TBI site
The method is characterized by the subject showing reduced inflammation and/or reduced astroglial scarring at the site of the TBI.
Overall, the claim set centers on treating TBI by administering a cell-free CS-GAG hydrogel at the injury site, with further refinements specifying CS-GAG sulfation variants, chemical modification (AEMA), lyophilized/rehydrated handling, possible trophic and adhesion-related components used with rehydration, and outcome characterizations including reduced inflammation and reduced astroglial scarring.
Stated Advantages
Reduced inflammation at the site of the TBI.
Reduced astroglial scarring at the site of the TBI.
Documented Applications
Treating traumatic brain injury (TBI) in a subject by administering a CS-GAG hydrogel at the site of the TBI.
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