DNMTi@ZIF-8 Enhances Biomimetic Pulp Regeneration via Epigenetic Regulation.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Endodontics

Background:

• Regenerating the dentin-pulp complex is a major endodontic challenge.
• Conventional therapies often yield suboptimal tissue regeneration.
• Mimicking developmental processes is a promising regenerative strategy.

Purpose of the Study:

• To develop a biomimetic regenerative therapy for dentin-pulp complex regeneration.
• To integrate DNA methyltransferase inhibitors (DNMTi) with a ZIF-8 nanoplatform and dental pulp stem cell (DPSC) spheroids.
• To leverage developmental signals for enhanced tissue engineering.

Main Methods:

• Identified reduction in 5-methylcytosine as an odontogenic signal.
• Utilized DNMTi to promote odontogenic differentiation and inhibit angiogenesis.
• Engineered a DNMTi@ZIF-8 nanoplatform for controlled drug delivery and enhanced angiogenesis via PI3K-AKT pathway activation.
• Combined DNMTi@ZIF-8 with DPSC spheroids for in vitro and in vivo regeneration studies.

Main Results:

• DNMTi significantly promoted odontogenic differentiation and inhibited angiogenesis.
• The DNMTi@ZIF-8 system enhanced angiogenesis through sustained zinc ion release and PI3K-AKT pathway activation.
• Integration with DPSC spheroids significantly boosted odontogenic differentiation.
• Successful regeneration of the dentin-pulp complex was achieved in an in vivo model.

Conclusions:

• The developed biomimetic therapy effectively regenerates the dentin-pulp complex.
• This approach offers a novel strategy for treating pulp and periapical diseases.
• The study highlights the potential of developmental biomimicry in regenerative medicine.