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<p>Targeting inflammation and mineralization responses in a controlled manner for vital pulp therapies is a challenging task. Here, we prepared dexamethasone-β-cyclodextrin (DEX/ICD) inclusion complex-loaded hydrogels for pulp–dentin complex regeneration. The formation of the DEX/ICD inclusion complex was verified using Fourier-transformed infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Pristine dexamethasone (DEX) and DEX/ICD were added to methacrylated gelatin (GelMA) hydrogels at a concentration of 1%. Pristine GelMA serves as the control. Drug-loaded hydrogels were evaluated for mechanical properties (<i>n</i> = 10/group), swelling and enzymatic degradation (<i>n</i> = 5/group), and drug release (<i>n</i> = 3/group). Cell proliferation, cell morphology, and mineralization assays were conducted using SHEDs. Cell proliferation was assessed on days 1, 3, and 7 using the MTS assay (<i>n</i> = 6/group). Cell morphology was analyzed via fluorescence microscopy using phalloidin and DAPI. A mineralization assay was performed using Alizarin Red at 14 and 21&#xa0;days (<i>n</i> = 4/group). One-way ANOVA and Tukey’s (<i>α</i> = 0.05) post-hoc tests were applied for statistical analysis. FTIR and XRD data confirmed the formation of the DEX/ICD complex. No statistical differences were found in mechanical properties, swelling, and degradation after incorporating DEX or DEX/ICD. DEX/ICD-loaded hydrogels consistently released dexamethasone, peaking at day 14, and maintained stability until day 21. DEX-loaded GelMA release decreased after day 7. DEX/ICD-loaded GelMA exhibited higher cell proliferation than DEX-loaded GelMA on day 7 (<i>p</i> &lt; 0.05), with no statistical differences observed for days 1 and 3 (p &gt; 0.05). The hydrogels did not compromise cell morphology. DEX/ICD-loaded GelMA significantly enhanced mineralization potential (<i>p</i> &lt; 0.05). The β-CD inclusion complex optimized dexamethasone delivery, and DEX/ICD-containing GelMA enhances the proliferation and mineralization capacity of dental stem cells. DEX/ICD-loaded GelMA is a promising injectable material for halting inflammation and could potentially induce mineralized tissue formation in pulp capping strategies.</p>

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Dexamethasone/β-cyclodextrin inclusion complex hydrogel for vital pulp therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月9日

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  • Saidah Tootla,
  • Isaac J. de Souza Araújo,
  • Arwa Daghrery,
  • Marco C. Bottino

摘要

Targeting inflammation and mineralization responses in a controlled manner for vital pulp therapies is a challenging task. Here, we prepared dexamethasone-β-cyclodextrin (DEX/ICD) inclusion complex-loaded hydrogels for pulp–dentin complex regeneration. The formation of the DEX/ICD inclusion complex was verified using Fourier-transformed infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Pristine dexamethasone (DEX) and DEX/ICD were added to methacrylated gelatin (GelMA) hydrogels at a concentration of 1%. Pristine GelMA serves as the control. Drug-loaded hydrogels were evaluated for mechanical properties (n = 10/group), swelling and enzymatic degradation (n = 5/group), and drug release (n = 3/group). Cell proliferation, cell morphology, and mineralization assays were conducted using SHEDs. Cell proliferation was assessed on days 1, 3, and 7 using the MTS assay (n = 6/group). Cell morphology was analyzed via fluorescence microscopy using phalloidin and DAPI. A mineralization assay was performed using Alizarin Red at 14 and 21 days (n = 4/group). One-way ANOVA and Tukey’s (α = 0.05) post-hoc tests were applied for statistical analysis. FTIR and XRD data confirmed the formation of the DEX/ICD complex. No statistical differences were found in mechanical properties, swelling, and degradation after incorporating DEX or DEX/ICD. DEX/ICD-loaded hydrogels consistently released dexamethasone, peaking at day 14, and maintained stability until day 21. DEX-loaded GelMA release decreased after day 7. DEX/ICD-loaded GelMA exhibited higher cell proliferation than DEX-loaded GelMA on day 7 (p < 0.05), with no statistical differences observed for days 1 and 3 (p > 0.05). The hydrogels did not compromise cell morphology. DEX/ICD-loaded GelMA significantly enhanced mineralization potential (p < 0.05). The β-CD inclusion complex optimized dexamethasone delivery, and DEX/ICD-containing GelMA enhances the proliferation and mineralization capacity of dental stem cells. DEX/ICD-loaded GelMA is a promising injectable material for halting inflammation and could potentially induce mineralized tissue formation in pulp capping strategies.