Self-Assembling Peptide Hydrogel for Endodontic Therapy in Apical Periodontitis

Introduction: : Apical periodontitis (AP) is a prevalent local inflammatory disease commonly initiated by pulp infection from local oral bacteria, affecting about 50% of the global population. AP occurs due to advancement of dental caries, trauma, or operative dental procedures. Clinically, AP can range from asymptomatic cases to severe bone destruction with or without abscess formation. This condition is typically treated by removing the intracanal microbes to prevent re-infection and placing a root canal filling. However, despite major technological advances, the incidence of endodontic failure remains high. In this work, we propose the use of self-assembling peptide hydrogels to keep the root canal clean as well as to allow for pulp regeneration in a rodent model.

Materials and

Methods: : The peptides were synthesized using solid phase peptide synthesis using FMOC chemistry. Purification was performed using high performance liquid chromatography, and identity of the amino acid sequence was performed using MALDI. The peptides were solvated in isotonic phosphate buffered saline. The in vivo study involved rodents which were mechanically drilled to expose the dental pulp and induce infection. The animals were subject to soft food diet for a week post-surgery and the presence of apical periodontitis was verified using MILABs Vector6/CT imaging, enabling visualization and quantification of periapical radiolucency. Following confirmation of infection, animals received injectable peptide hydrogels (experimental treatment) or phosphate-buffered saline (PBS, control). CT scans were performed on days 14, and 28 to monitor periapical bone resorption. Healing was assessed by measuring changes in the periapical radiolucency area. After the final scan, the animals were euthanized, and molars were collected for histological and immunostaining analysis to evaluate tissue response, regeneration, and necrosis.

Results, Conclusions, and Discussions:: In this study, animals underwent treatment with hydrogels and CT scans were used to track the infection volumes pre- and post-treatment. The treatment allowed for apical bone resorption, and regeneration of tissue. The results showed an improvement in the periapical bone resorption, up to 35% after 14 days of treatment on the treated molars. To further validate the translational potential of this approach, our lab is currently conducting studies using a porcine model, which more closely recapitulates human dental pulp anatomy and physiology. These ongoing experiments aim to evaluate the efficacy of SAP hydrogels in a large-animal model, focusing on both radiographic outcomes and detailed histological analysis. These self-assembling peptide hydrogels have dual functionality and have clinical efficacy to facilitate effective antimicrobial action with regeneration properties. These hydrogels offer promising potential in regenerative endodontics by providing a conducive environment for odontogenic differentiation and pulp tissue repair.

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