Year: 2025
Type: article
Abstract: Bioorthogonal covalent crosslinking stabilizes collagen type I hydrogels, improving their structural integrity for tissue engineering applications with encapsulated living cells. The chemical modification required for crosslinking, however, interferes with the fibrillar nature of the collagen, leading instead to an amorphous network without fibers. We demonstrate an approach to perform bioconjugation chemistry on collagen with controlled localization such that the modified collagen retains its ability to self-assemble into a fibrillar network while also displaying functional groups for covalent crosslinking with bioorthogonal click chemistry. The collagen matrix is formed through a sequential crosslinking process, in which the modified collagen first physically assembles into fibers and then is covalently crosslinked. This approach preserves the fibrous architecture of the collagen, guiding the behavior of encapsulated human corneal mesenchymal stromal cells while also reinforcing fibers through covalent crosslinks, strengthening the stability of the cell-laden collagen hydrogel against cell-induced contraction and enzymatic degradation.
Source: Biomacromolecules
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Funders: Advanced Research Projects Agency for Health, National Science Foundation, American Heart Association, Research to Prevent Blindness, Stanford University, Achievement Rewards for College Scientists Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, Advanced Research Projects Agency, Stanford Bio-X, National Heart, Lung, and Blood Institute, National Eye Institute, Division of Materials Research, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: G1444531642, G2645760184, G282007457, 3D bioprinting of a bilayered, tissue engineered cornea, Novel, engineered bio-inks for 3D printing of complex, perfusable structures, Biomaterials for manufacturing of patient-derived organoids and assembloids, G4639222109, Social Interactions, Endogenous Networks, and Production, Bioengineered hydrogel for local delivery of minicircle gene therapy encoding NRG1 for myocardial infarction, G6480808432, G7053121448, G717963492, RECODE: Real-time analysis and environmental feedback for directed differentiation of liver organoids, Liposome-crosslinked hyaluronic acid hydrogels with localized protein delivery for myocardial infarction therapy, G8160389401, Fabrication of conductive, biopolymeric, hydrogel scaffolds with tunable time-dependent mechanical properties to generate brain organoids and progress human brain development models, G9000039399, G9000266758, G9000284758, Stanford Vision Research Core, G910075354
OpenAlex ID: W4411598016