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Dynamic Self-Clickable Decellularized Matrix Hydrogels for Regulating Vascularity and Enhancing Muscle Regeneration
Van Thuy Duong1, Tuba Marjan1, Ngoc Ha Luong1
1Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 20, 2026
Summary
Researchers developed self-clickable hydrogels from decellularized small intestine submucosa (SIS) using natural disulfide bonds. These dynamic SIS-norbornene hydrogels offer tunable properties for tissue engineering and regenerative medicine applications.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Decellularized extracellular matrix (dECM) from small intestine submucosa (SIS) supports cell interactions but hydrogel crosslinking is limited.
- Current crosslinking methods like temperature-induced gelation offer poor tunability for dECM hydrogels.
- Previous work introduced bovine decellularized SIS-norbornene (dSIS-NB) for thiol-norbornene hydrogel formation with angiogenic properties.
Purpose of the Study:
- To analyze the protein composition of bovine SIS and dSIS-NB.
- To develop novel 'self-clickable' hydrogels utilizing intrinsic disulfide bonds in dSIS-NB.
- To demonstrate light-induced spatiotemporal control over hydrogel properties and applications in tissue repair.
Main Methods:
- Proteomic profiling of bovine SIS and dSIS-NB to identify key proteins.
- Fabrication of thiol-norbornene hydrogels using dSIS-NB and leveraging inherent disulfide bonds for crosslinking.
- Utilizing thiol-disulfide exchange for light-induced hydrogel stiffness modulation and ligand conjugation.
- In vitro cell culture studies for vascular compression modeling and in vivo studies for volumetric muscle loss treatment.
Main Results:
- Proteomic analysis revealed significant amounts of fibrillin-I in bovine dSIS, stabilized by disulfide bonds.
- Successful fabrication of 'self-clickable' dSIS-NB hydrogels without external thiol crosslinkers.
- Demonstrated light-induced spatiotemporal control over hydrogel stiffness and bioactive ligand labeling.
- Validated the utility of dynamic dSIS-NB hydrogels in in vitro vascular compression models and in vivo muscle regeneration.
Conclusions:
- Bovine dSIS contains fibrillin-I, enabling the creation of disulfide-crosslinked, 'self-clickable' dSIS-NB hydrogels.
- Thiol-disulfide exchange provides a mechanism for dynamic, light-tunable hydrogel properties.
- These advanced dSIS-NB hydrogels show promise for sophisticated tissue engineering applications, including in vitro modeling and in vivo regenerative therapies.
