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Valproic Acid-Loaded ZIF-8 Nanoparticles with Antibacterial, Immunomodulatory, and Dentin Regenerative Functions for
Yufan Wei1,2, Jun Li3,4, Xiaojie Zhang1,2
1Department of Stomatology, Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, Jiangsu, China.
ACS Applied Materials & Interfaces
|June 15, 2026
Summary
New valproic acid (VPA)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanocomposites offer a promising integrated strategy for vital pulp therapy. These VPA@ZIF-8 NPs demonstrate antibacterial, immunomodulatory, and dentin regeneration capabilities for pulpitis treatment.
Area of Science:
- Biomaterials Science
- Regenerative Dentistry
- Nanotechnology
Background:
- Vital pulp therapy (VPT) aims to preserve pulp vitality and promote dentin regeneration but faces challenges with conventional materials lacking reparative and immunomodulatory functions.
- Pulpitis treatment requires materials that not only support dentin regeneration but also manage the local immune microenvironment.
Purpose of the Study:
- To design and evaluate valproic acid (VPA)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanocomposites (VPA@ZIF-8 NPs) for enhanced vital pulp therapy.
- To assess the biocompatibility, antimicrobial, immunomodulatory, and dentin-regenerative potential of VPA@ZIF-8 NPs.
Main Methods:
- VPA@ZIF-8 NPs were synthesized for sustained and pH-responsive VPA release.
- In vitro studies utilized stem cells from human exfoliated deciduous teeth (SHEDs) and oral pathogens, along with macrophage polarization assays.
- In vivo studies involved a pulp exposure rat model to evaluate dentin regeneration and pathway activation.
Main Results:
- VPA@ZIF-8 NPs enhanced SHED proliferation, migration, and mineralization while suppressing oral pathogen growth and biofilm formation.
- Nanocomposites promoted M2-like macrophage polarization, indicating anti-inflammatory effects, and activated the BMP2/SMAD1/RUNX2 pathway in SHEDs.
- In vivo application led to significant reparative dentin bridge formation in rats.
Conclusions:
- Multifunctional VPA@ZIF-8 NPs integrate biosafety, antibacterial, immunomodulatory, and dentin-regenerative properties.
- This novel nanocomposite offers a promising and integrated strategy for vital pulp therapy in treating pulpitis.
