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Design of a Microgel System for Dental Pulp Tissue Regeneration

Ahmadi, Hamed | 2025

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 58621 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Abdekhodaie, Mohamad Jafar
  7. Abstract:
  8. Immature teeth results from loss of pulp vitality in children and juveniles and is characterized by incomplete root development. Despite available clinical interventions, none of the current medical approaches are capable of fully regenerating pulp tissue and restoring complete root formation and pulp tissue. Considering the tooth’s unique anatomy, injectable gel systems are particularly advantageous. The aim of the present study was to develop an injectable microgel scaffold based on materials approved by the U.S. Food and Drug Administration (FDA) that, in combination with dental pulp stem cells, could support pulp regeneration and root completion. Hyaluronic acid (HA) and type-I collagen (extracted from bovine Achilles tendon) were selected as the scaffold polymers, divinyl sulfone (DVS) as the crosslinker, and concentrated growth factor (CGF) as a bioactive additive. Two independent Box–Behnken designs (BBD) were employed to investigate and optimize the HA- and collagen-based systems. Following behavioral characterization and optimization, three formulations were prepared: HA microgels, collagen microgels, and a HA/collagen hybrid microgel. Reaction of DVS with the polymers was confirmed by FTIR, ¹H-NMR and EDX analyses. Successful extraction and structural integrity of collagen triple helix were validated by FTIR, circular dichroism (CD) and SDS–PAGE. Modeling results indicated that, for the HA system, only mean particle size was modeled with statistical significance, whereas for the collagen system both mean particle size and size distribution were significant. Optimized formulations (HA 4% w/v and collagen 0.1% w/v) and their hybrid were selected for cellular studies. MTT assays demonstrated that exictance of CGF significantly enhanced cell proliferation (p < 0.01). Microgels exhibited overall biocompatibility in MTT assays, with the hybrid microgels showing the best performance and a statistically significant improvement versus control (p < 0.001). When hybrid microgels were soaked in various CGF concentrations, the swollen hybrids in pure CGF produced the strongest cellular response (p < 0.0001). Live/Dead staining of swollen hybrid samples in pure CGF confirmed absence of cytotoxicity and demonstrated an environment permissive for cell adhesion and growth. These findings support the potential of injectable HA/collagen hybrid microgels, combined with autologous CGF, as a promising strategy for dental pulp regeneration and root maturation
  9. Keywords:
  10. Microgel ; Hyaluronic Acid Gel ; Collagen ; Dental Pulp ; Immature Root Canal ; Dental Pulp Regeneration ; Collagen Type I

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