Neutral multidomain peptide hydrogels and uses thereof
Inventors
HARTGERINK, Jeffrey • Leach, David • LOPEZ-SILVA, Tania
Assignees
Publication Number
US-12383653-B2
Publication Date
2025-08-12
Expiration Date
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Abstract
Provided herein are peptide-based hydrogels, or neutral multidomain peptide hydrogel (NMDP), as well as uses thereof. The uses include encapsulating cells to induce quiescence for long-term storage and administering to a subject to induce collagen deposition and macrophage infiltration. The disclosed hydrogel is useful for the preservation of stem cells, including maintaining their quiescence and differentiation potential.
Core Innovation
Provided here are peptide-based hydrogels, or neutral multidomain peptide hydrogel (NMDP), as well as uses thereof. When NMDP is used as a scaffold for cell encapsulation, it induces a quiescence state in cells and promotes their preservation while maintaining their viability and growing capacity over time. The chemical and physical properties of this material make it useful for the preservation of stem cells by maintaining their quiescence and differentiation potential.
Stem cells can lose their potency and differentiation capacity during manipulation in vitro after isolation, and preservation of stem cells is critical for manufacturing and clinical use because it allows for the development of cell banks, the performance of quality and safety testing, transportation, long-term storage, processing, and better availability. Current methods for stem cell preservation include cryopreservation, freeze-drying, and quiescence maintenance in culture, but these methods, preservatives, and additives used (such as DMSO) can have adverse effects that make cell recovery and protection of cell activity challenging. Therefore, compositions and methods for maintaining stem cells in quiescence, a reversible inactive state demonstrating minimal basal cell activity, are needed to allow for the preservation of these cells for prolonged periods of time.
Claims Coverage
The independent claim defines one composition with five main inventive features.
Multidomain peptide composition
A composition comprising a plurality of peptides; wherein each peptide of the plurality of peptides consists of a first domain, a second domain, and a third domain.
Terminal domains of five hydroxyproline residues
Wherein the first and third domain are each Xm, wherein m is 5 and X is 3′-hydroxyproline or 4′-hydroxyproline.
Domain positioning
Wherein the first domain is positioned at the N-terminal end of the second domain; wherein the third domain is positioned at the C-terminal end of the second domain.
Central (SerLeu)6 domain
Wherein the second domain comprises (SerLeu)6.
N-terminal acetylation
Wherein the peptides are N-terminally acetylated.
The independent claim covers an acetylated neutral multidomain peptide composition in which each peptide has an On-(SerLeu)6-On architecture with n=5 and terminal residues of 3′-hydroxyproline or 4′-hydroxyproline, with specified N- and C-domain positioning.
Stated Advantages
Induces a quiescence state in encapsulated cells to promote long-term storage and cell preservation while maintaining cell viability and growing capacity.
Preserves stem cells by maintaining their quiescence and differentiation potential.
When administered to a subject, induces collagen deposition and macrophage infiltration at a target location.
Hydrogel remains intact across a wide pH range (pH 3-11) and at physiological pH, indicating robustness of the material.
Compliant, shear-thinning material with rapid shear recovery enabling injectable handling and facile delivery.
Biocompatible in vivo behavior with cellular infiltration and degradation over time without evidence of eliciting an adverse inflammatory response.
Documented Applications
Encapsulating cells to induce quiescence for long-term storage and methods for cell preservation.
Preservation of stem cells, including maintaining their quiescence and differentiation potential (e.g., hematopoietic stem cells, mesenchymal stem cells, human embryonic stem cells, induced-pluripotent stem cells).
Administering the hydrogel to a target location in a subject to stimulate collagen deposition and cause macrophage infiltration, including sites comprising damaged tissue or sites in need of collagen deposition.
Use as a scaffold for three-dimensional cell culture and cell encapsulation to support cell viability while limiting proliferation.
Pharmaceutical formulations and methods of treatment, including presentation in unit dosage forms and administration by routes such as parenteral, intraperitoneal, intramuscular, subcutaneous, and intratumoral injection.
Kits comprising peptides or hydrogels of the invention and reagents required for formation or delivery of the hydrogel.
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