Scaffolds formed from polymer-protein conjugates, methods of generating same and uses thereof

Inventors

Seliktar, Dror • Shachaf, Yonatan

Assignees

Regentis Biomaterials Ltd

Abstract

Conjugates are provided herein which comprise a protein attached to at least two polymeric moieties, at least one of which exhibits reverse thermal gelation. The conjugates are suitable for being cross-linked by non-covalent and/or covalent cross-linking. Compositions-of-matter comprising cross-linked conjugates are provided herein, as well as processes for producing same. Methods of controlling a physical property of compositions-of-matter are also provided herein. The conjugates and compositions-of-matter may be used for various applications, such as cell growth, tissue formation, and treatment of disorders characterized by tissue damage or loss, as described herein.

Core Innovation

The invention relates to polymer-protein conjugates in which a polypeptide comprises an extracellular matrix protein or a fragment thereof, and has at least two polymeric moieties attached. Each polymeric moiety exhibits reverse thermal gelation, enabling the conjugate to form a reverse-thermally gelling hydrogel or scaffold composition upon warming.

The disclosed systems emphasize reversible non-covalent physical reverse thermal gelation behavior. The polymeric moieties can also be used to generate hydrogels or scaffold compositions with optional covalent cross-linking through cross-linking moieties that are polymerizable groups, thereby further increasing mechanical properties while maintaining reverse thermal gelation features.

The disclosure describes tuning and control of material performance, including low conjugate concentration gelation, increased shear storage modulus upon warming, reversible gelation across cycles, and tuning of stiffness and swelling by non-covalent versus covalent cross-linking and by covalent cross-linking conditions such as temperature. It also addresses decoupling control over biodegradation from mechanical properties by independently adjusting variables associated with cross-linking and composition.

The hydrogel scaffold compositions are described as supporting cell spreading and invasion or outgrowth, with cell behavior modulated by hydrogel modulus, and examples of fibroblasts and HeLa cells are referenced.

Claims Coverage

The partial document provides one independent claim. It claims a conjugate defined by a polypeptide comprising an extracellular matrix protein or fragment with at least two reverse-thermally gelling polymeric moieties attached, defining the core inventive structure as a composition-of-matter.

Overall, the claimed scope centers on a conjugate composition-of-matter where an extracellular matrix protein or fragment polypeptide is functionalized with at least two polymeric moieties that each exhibit reverse thermal gelation. The provided excerpt further describes covalent and non-covalent cross-linking capabilities and particular extracellular matrix proteins and polymeric moieties.

Stated Advantages

Documented Applications