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Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications
Published on: February 7, 2021
Injectable Matrix Metalloproteinase-Responsive Nanoparticle Hydrogel Scaffold for Sustained Local Drug Delivery in
Lu Xing1, Zhongyu Liu1, Kaichao Wang1
1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
A novel hydrogel drug delivery system targets fibrous dysplasia lesions by responding to matrix metalloproteinases (MMPs). This localized approach provides sustained release of a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, improving bone structure.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Skeletal Biology
Background:
- Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibition is effective for fibrous dysplasia, but sustained inhibition and disease rebound are clinical challenges.
- Matrix metalloproteinases (MMPs) are implicated in fibrous dysplasia pathogenesis and bone remodeling.
- Localized drug delivery is needed to maintain efficacy while minimizing systemic exposure.
Purpose of the Study:
- To develop a localized, MMP-responsive drug delivery system for fibrous dysplasia treatment.
- To investigate the potential of a hyaluronic acid-based hydrogel loaded with a RANKL inhibitor for sustained, lesion-specific drug release.
Main Methods:
- Development of an injectable hydrogel (HPD/TGMS) incorporating triglycerol monostearate nanoparticles.
- Loading of a small-molecule RANKL inhibitor (AS2676293) into the nanoparticles to create HPD/TGMS@A.
- In vitro assessment of injectability, self-healing, cytocompatibility, and MMP-dependent anti-osteoclastic activity.
- In vivo evaluation in a GNASR201C knock-in mouse model of fibrous dysplasia via perilesional injection.
Main Results:
- HPD/TGMS@A demonstrated favorable material properties and MMP-responsive drug release.
- The system exhibited potent anti-osteoclastic activity in vitro.
- Perilesional injection of HPD/TGMS@A significantly reduced fibrous dysplasia progression and improved bone microarchitecture in vivo.
Conclusions:
- The developed HPD/TGMS hydrogel system offers a promising localized and lesion-responsive drug delivery strategy for fibrous dysplasia.
- This approach addresses the need for sustained therapeutic effects while limiting systemic side effects associated with RANKL inhibition.
