IP Library Granted Patent US 12,383,653
Granted Patent B2
US 12,383,653 · App. 17/285,767 · Granted Aug 12, 2025

Neutral multidomain peptide hydrogels and uses thereof

Inventors: Jeffrey Hartgerink (Houston, TX); David Leach (Houston, TX); Tania Lopez-Silva (Houston, TX)
Assignee: William Marsh Rice University
A61L27/22A01N1/128A61K38/00A61L27/52C07K7/06C07K7/08C12N11/04
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Quick Facts
Patent No.
US 12,383,653
App. No.
17/285,767
Granted
Aug 12, 2025
Kind
B2
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.

Claims (7)

1. 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; wherein the first and third domain are each X m , wherein m is 5 and X is 3′-hydroxyproline or 4′-hydroxyproline; 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; wherein the second domain comprises (SerLeu) 6 ; and wherein the peptides are N-terminally acetylated.

2. The composition of claim 1 , wherein the amino acid sequence of each peptide consists of SEQ ID NO: 5.

3. The composition of claim 1 , wherein the peptides further comprise a biologically active peptide mimic.

4. The composition of claim 3 , wherein the biologically active peptide mimic has a sequence selected from the group consisting of one of SEQ ID NOs: 10-20.

5. The composition of claim 1 , wherein the composition is lyophilized.

6. A nanofiber comprising a plurality of peptides according to claim 1 .

7. A hydrogel comprising a plurality of peptides according to claim 1 .

Assignments (2)
CONFIRMATORY LICENSE Recorded Jul 26, 2023
From: RICE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064388/0384 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 16, 2022
From: HARTGERINK, JEFFREY; LEACH, DAVID; LOPEZ-SILVA, TANIA
To: WILLIAM MARSH RICE UNIVERSITY
Reel/Frame 059922/0428 →
Continuity (2)
Provisional Application 62746391 · Oct 16, 2018
Related Publication 20210386907A1 · Dec 16, 2021
References Cited (64)
US 5004681A · Boyse et al. · 1991 [cited by applicant]
US 8099297B2 · Brevnova et al. · 2012 [cited by applicant]
US 9526762B1 · Hartgerink et al. · 2016 [cited by applicant]
US 20050106554A1 · Palecek et al. · 2005 [cited by applicant]
US 20050277107A1 · Toner et al. · 2005 [cited by applicant]
US 20080096809A1 · Shai · 2008 [cited by examiner]
US 20090305325A1 · Kale et al. · 2009 [cited by applicant]
US 20140135472A1 · King et al. · 2014 [cited by applicant]
US 20150274789A1 · Guerette · 2015 [cited by examiner]
US 20170172953A1 · Hartgerink et al. · 2017 [cited by applicant]
US 20170335287A1 · Quarta et al. · 2017 [cited by applicant]
WO WO2014104981 · 2014 [cited by applicant]
WO WO2017009358 · 2017 [cited by examiner]
WO WO2019018572 · 2019 [cited by applicant]
Pepscan website; Available at least by Sep. 2016; Accessed online Dec. 2, 2023 at: https://www.pepscan.com/custom-peptide-synthesis/peptide-modifications/n-terminal-modifications/#:˜:text=Generally%2C%20acetyl%20modific… [cited by examiner]
Snyder, M. Drug Discov. & Devel. (Mar. 2017), Lyophilization: The basics; Accessed online Dec. 2, 2023 at: https://www.drugdiscoverytrends.com/lyophilization-the-basics/#:˜:text=Lyophilization%20enables%20longer%20shelf… [cited by examiner]
Watanabe (Journal of Molecular Catalysis B: Enzymatic, 1998, 4, 167-180) (Year: 1998). [cited by examiner]
Wu (Amino Acids, 2011, 40, 1053-1063) (Year: 2011). [cited by examiner]
Bach (Appl Microbiol Biotechnol, 2013, 97, 6623-6634) (Year: 2013). [cited by examiner]
Aggeli, A. et al., “pH as a Trigger of Peptide β-Sheet Self-Assembly and Reversible Switching between Nematic and Isotropic Phases,” [cited by applicant]
Aulisa, L. et al., “Self-assembly of multidomain peptides: sequence variation allows control over cross-linking and viscoelasticity,” [cited by applicant]
Bakota, E. L. et al., “Self-Assembling Multidomain Peptide Fibers with Aromatic Cores,” [cited by applicant]
Bankwell, E. F. et al., “Rational design and application of responsive alpha-helical peptide hydrogels,” [cited by applicant]
Blau, A., “Cell adhesion promotion strategies for signal transduction enhancement in microelectrode array in vitro electrophysiology: An introductory overview and critical discussion,” [cited by applicant]
Carrejo, N. C. et al., “Multidomain Peptide Hydrogel Accelerates Healing of Full-Thickness Wounds in Diabetic Mice,” [cited by applicant]
Chockalingam, K. et al., “Design and application of stimulus-responsive peptide systems,” [cited by applicant]
Collier, J. H. et al., “Thermally and Photochemically Triggered Self-Assembly of Peptide Hydrogels,” [cited by applicant]
Cormier, A. R. et al., “Molecular Structure of RADA16-I Designer Self-Assembling Peptide Nanofibers,” [cited by applicant]
Dong. H. et al., “Self-Assembly of Multidomain Peptides: Balancing Molecular Frustration Controls Conformation and Nanostructure,” [cited by applicant]
Fischer, D. et al., “In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis,” [cited by applicant]
Habibi, N. et al., “Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery,” [cited by applicant]
Hanna, J. et al., “Preservation of Stem Cells,” [cited by applicant]
Hartgerink, J. et al., “Self-Assembling Peptide Nanotubes,” [cited by applicant]
Hartgerink, J. et al., “Self-Assembly and Mineralization of Peptide-Amphiphile Nanofibers,” [cited by applicant]
Holmes, T. C. et al., “Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds,” [cited by applicant]
Hunt, C. J., “Cryopreservation of Human Stem Cells for Clinical Application: A Review,” [cited by applicant]
Kadlecova, Z. et al., “Comparative Study on the In Vitro Cytotoxicity of Linear, Dendritic, and Hyperbranched Polylysine Analogues,” [cited by applicant]
Leach et al., “STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy,” [cited by applicant]
Li, Y. et al., “Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery,” [cited by applicant]
Li, I-C. et al., “Covalent Capture of Aligned Self-Assembling Nanofibers,” [cited by applicant]
Lopez-Silva, T. L. et al., “Self-Assembling Multidomain Peptides: Design and Characterization of Neutral Peptide-Based Materials with pH and Ionic Strength Independent Self-Assembly,” [cited by applicant]
Lutolf. M. P. et al., “Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering,” [cited by applicant]
Lynn, A. D. et al., “Characterization of the in vitro macrophage response and in vivo host response to poly(ethylene glycol)-based hydrogels,” [cited by applicant]
Mazia, D. et al., “Adhesion of cells to surfaces coated with polylysine. Applications to electron microscopy,” [cited by applicant]
Messam, C. A. et al., “Asynchrony and commitment to die during apoptosis,” [cited by applicant]
Meyers, S. et al., “Biocompatible and bioactive surface modifications for prolonged in vivo efficacy,” [cited by applicant]
Micklitsch, C. M. et al., “Zinc-triggered hydrogelation of a self-assembling β-hairpin peptide,” [cited by applicant]
Moore, A. N, et al., “Nanofibrous peptide hydrogel elicits angiogenesis and neurogenesis without drugs, proteins, or cells,” [cited by applicant]
Moore, A. N., “Self-Assembling Multidomain Peptide Nanofibers for Delivery of Bioactive Molecules and Tissue Regeneration,” [cited by applicant]
Nisbet, D. et al., “Self-assembled peptides: characterisation and in vivo response,” [cited by applicant]
PCT International Preliminary Report on Patentability issued in International Patent Application No. PCT/US2019/056581, dated Apr. 29, 2021. [cited by applicant]
PCT International Search Report and Written Opinion issued in International Patent Application No. PCT/US2019/056581, dated Feb. 24, 2020. [cited by applicant]
Pochan, D. J. et al., “Thermally Reversible Hydrogels via Intramolecular Folding and Consequent Self-Assembly of a de Novo Designed Peptide,” [cited by applicant]
Powers, E. T. et al., “Ordered Langmuir-Blodgett films of amphiphilic β-hairpin peptides imaged by atomic force microscopy,” [cited by applicant]
Rad-Malekshahi, M. et al., “Biomedical Applications of Self-Assembling Peptides,” [cited by applicant]
Saha, K. et al., “Technical challenges in using human induced pluripotent stem cells to model disease,” [cited by applicant]
Saraste A., “Morphologic criteria and detection of apoptosis,” [cited by applicant]
Saraste, A. et al., “Morphologic and biochemical hallmarks of apoptosis,” [cited by applicant]
Schneider, J. P. et al., “Responsive Hydrogels from the Intramolecular Folding and Self-Assembly of a Designed Peptide,” [cited by applicant]
Stathopulos, P. B. et al., “Sonication of proteins causes formation of aggregates that resemble amyloid,” [cited by applicant]
Stupp, S. I. et al., “Supramolecular Materials: Self-Organized Nanostructures,” [cited by applicant]
Veiga, A. S. et al., “Arginine-Rich Self-Assembling Peptides as Potent Antibacterial Gels,” [cited by applicant]
Webber, M. J. et al., “Supramolecular biomaterials,” [cited by applicant]
Zhu, J., “Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering,” [cited by applicant]