A Self-Adaptive Programming Strategy Enables Local Microenvironment Modulation and Temporal Immunomodulation for...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Immunology

Background:

• Diabetic bone defects present significant challenges due to impaired immune responses and infection susceptibility.
• Hyperglycemia disrupts the immune microenvironment, hindering the necessary shift from pro-inflammatory to anti-inflammatory states crucial for bone healing.

Purpose of the Study:

• To develop a glucose-responsive hydrogel (PEG-ZnO-sita) for treating diabetic bone defects.
• To investigate the hydrogel's ability to modulate the immune microenvironment and promote osteogenesis in a diabetic context.

Main Methods:

• Fabrication of PEG-ZnO-sita hydrogel using DA-PEG-SG and PBA-Gel, incorporating zinc oxide (ZnO) and sitagliptin.
• Evaluation of hydrogel properties including gelation, injectability, mechanical stability, self-healing, and tissue adhesion.
• In vitro and in vivo assessment of hydrogel performance in modulating macrophage polarization (M1/M2) and promoting bone regeneration in diabetic models.

Main Results:

• The PEG-ZnO-sita hydrogel demonstrated rapid gelation, injectability, mechanical robustness, self-healing, and tissue adhesion.
• The hydrogel exhibited a sequential release of Zn2+ and sitagliptin, initially promoting M1 polarization to combat infection and subsequently M2 polarization for osteogenesis.
• In vitro and in vivo studies confirmed the hydrogel's efficacy in promoting bone regeneration by modulating the hyperglycemic microenvironment and macrophage polarization.

Conclusions:

• The developed PEG-ZnO-sita hydrogel offers a self-adaptive strategy for treating diabetic infected bone defects.
• Temporal immunoregulation of the hyperglycemia-immune-osteogenic cascade via this hydrogel shows promise for enhanced bone repair.