Hydrogels for in situ-forming tissue constructs
Inventors
Myung, David • Chen, Fang • Fernandes-Cunha, Gabriella • Hull, Sarah • Heilshorn, Sarah • Lindsay, Christopher • Madl, Christopher • LEE, Hyun Jong
Assignees
United States Government Represented By Departement Of Veterans Affairs AS • Leland Stanford Junior University
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12589188-B2
Publication Date
2026-03-31
Expiration Date
Abstract
Compositions and methods are provided for lamellar and defect reconstruction of corneal stromal tissue using biomaterials that form a defined hydrogel structure in situ, including interpenetrating (IPN) and semi-IPN hydrogels.
Core Innovation
The invention relates to in-situ-forming hydrogels for treating or reconstructing a surgically incised or wounded area in a mammalian subject. The hydrogel is formed on the wounded area in situ by mixing separately functionalized polymer components, thereby forming an interpenetrating polymer network (IPN) or semi-IPN without the need for an external energy source.
In one aspect, the hydrogel is an IPN in which each polymer component is cross-linked with a different modality so that independent networks are formed upon mixing. The approach supports independently cross-linked, functionalized polymer components that form an interpenetrating structure in situ, including collagen- and hyaluronic-acid-containing IPN/semi-IPN hydrogels.
In another aspect, the invention includes a semi-IPN in which the second polymer is not chemically cross-linked, and the mixing of a first polymer bearing reactive groups with the second polymer forms an interpenetrating polymer network in situ without external energy. The disclosed compositions also include network crosslinked with multi-arm PEG and a peptide sequence comprising primary amine groups, where hydrogel formation occurs upon mixing without external energy.
The disclosed constructs are used in corneal tissue contexts, including reconstruction of a corneal stromal defect. The described compositions and networks are characterized for optical transparency and high water content, and they are further characterized with functional outcomes such as epithelial overgrowth, tight junction (ZO-1) formation, and curvature restoration.
Claims Coverage
The provided independent claims cover three distinct in-situ-forming hydrogel compositions for treating surgically incised or wounded areas in a mammalian subject, including an IPN formed from independently cross-linked polymer networks without external energy, a semi-IPN where one polymer is not chemically cross-linked, and a multi-arm PEG plus primary-amine peptide system that forms a hydrogel upon mixing without external energy.
In-situ-forming IPN hydrogel from independently cross-linked functionalized polymers without external energy
An in-situ-forming hydrogel composition for treating or reconstructing a surgically incised or wounded area in a mammalian subject, the hydrogel being an IPN comprising a first polymer functionalized with first reactive groups and a second polymer functionalized with second reactive groups, where each polymer component is cross-linked with a different modality so that independent networks are formed, and where upon mixing the first and second polymers form an interpenetrating polymer network on the wounded area in situ without the need for an external energy source.
In-situ-forming semi-IPN hydrogel with one chemically non-cross-linked polymer without external energy
An in-situ-forming hydrogel composition for treating or reconstructing a surgically incised or wounded area in a mammalian subject, comprising an interpenetrating polymer network (IPN) or semi-IPN of independently associated polymers, where the hydrogel is a semi-IPN comprising a first polymer functionalized with first reactive groups and a second polymer that is not chemically cross-linked, and where upon mixing the first and second polymers form an interpenetrating polymer network on the wounded area in situ without the need for an external energy source.
In-situ-forming multi-arm PEG crosslinked network with primary-amine peptide forming hydrogel upon mixing without external energy
A composition for in-situ-forming hydrogel in treating or reconstructing a surgically incised or wounded area in a mammalian subject, comprised of a network of polymer crosslinked with multi-arm PEG, comprising a peptide sequence comprising primary amine groups and a multi-arm PEG crosslinker functionalized with reactive groups, wherein upon mixing the peptide sequence forms a hydrogel without the need for an external energy source.
Across the independent claims, the core claim coverage focuses on in-situ hydrogel formation on an incised or wounded area without external energy, implemented either as independently cross-linked IPN formation, as semi-IPN formation where one polymer is not chemically cross-linked, or as a multi-arm PEG crosslinked network that forms a hydrogel upon mixing with a primary-amine peptide sequence.
Stated Advantages
High optical transparency/transmittance.
High water content.
Tunable mechanics and degradation.
Cytocompatibility.
Improved epithelialization.
Reduced myofibroblast activity and reduced scarring.
Improved functional outcomes including epithelial overgrowth, tight junction (ZO-1) formation, and curvature restoration.
Documented Applications
Treating or reconstructing surgically incised or wounded areas in a mammalian subject.
Treating or reconstructing a surgically incised or wounded corneal area, including corneal stromal defect/layer and defect reconstruction.
Corneal reconstruction outcomes assessed in rabbit corneal defect models, including epithelial overgrowth, ZO-1 tight junction formation, and curvature restoration.
Interested in licensing this patent?