Formulation and Evaluation of Cysteine-rich Peptide Hydrogel as a Local Drug Delivery Agent in Periodontitis Therapy: An In Vitro Study

therapies to restore redox balance and support periodontal regeneration.L-cysteine, a sulfur-containing amino acid, plays a crucial role in collagen synthesis, antioxidant defense, and modulation of matrix metalloproteinases (MMPs), which are involved in IntroductIonPeriodontal disease is a chronic inflammatory condition characterized by the progressive destruction of the periodontium, resulting in attachment loss, alveolar bone resorption, and, in severe cases, tooth loss.1,2 Conventional treatments, such as scaling and root planing (SRP), antimicrobial agents, and surgical interventions, aim to control bacterial infection and promote tissue regeneration.However, these approaches often have limitations, including rapid drug clearance, inadequate drug penetration, and systemic side effects.3 Localized drug delivery systems have emerged as an effective strategy to enhance therapeutic outcomes by ensuring the sustained and targeted release of bioactive agents at the periodontal site.4 Hydrogels, due to their biocompatibility, mucoadhesiveness, and controlled drug release properties, have gained significant attention as vehicles for periodontal drug delivery.Oxidative stress significantly contributes to periodontal disease by promoting excessive reactive oxygen species (ROS), which damage tissues and enhance inflammation through pathways such as NF-κB.SRP alone has been shown to reduce oxidative stress and restore redox homeostasis at 3 months posttreatment but not at 6 months, indicating a limited capacity of treated tissues to counter sustained ROS activity.5 The imbalance between ROS and antioxidant defenses leads to progressive tissue destruction, highlighting the need for targeted antioxidant 1,