Human ß-defensins and their synthetic analogs: Natural defenders and prospective new drugs of oral health.

As a family of cationic host defense peptides, human ß-defensins (HBDs) are ubiquitous in the oral cavity and are mainly synthesized primarily by epithelial cells, serving as the primary barrier and aiming to prevent microbial invasion, inflammation, and disease while maintaining physiological homeostasis. In recent decades, there has been great interest in their biological functions, structure-activity relationships, mechanisms of action, and therapeutic potential in oral diseases. Meanwhile, researchers are dedicated to improving the properties of HBDs for clinical application. In this review, we first describe the classification, structural characteristics, functions, and mechanisms of HBDs. Next, we cover the role of HBDs and their synthetic analogs in oral diseases, including dental caries and pulp infections, periodontitis, peri-implantitis, fungal/viral infections and oral mucosal diseases, and oral squamous cell carcinoma. Finally, we discuss the limitations and challenges of clinical translation of HBDs and their synthetic analogs, including, but not limited to, stability, bioavailability, antimicrobial activity, resistance, and toxicity. Above all, this review summarizes the biological functions, mechanisms of action, and therapeutic potential of both natural HBDs and their synthetic analogs in oral diseases, as well as the challenges associated with clinical translation, thus providing substantial insights into the laboratory development and clinical application of HBDs in oral diseases.

An injectable photopolymerizable chitosan hydrogel doped anti-inflammatory peptide for long-lasting periodontal pocket delivery and periodontitis therapy.

Periodontitis is a common chronic inflammatory disease caused by plaque that leads to alveolar bone resorption and tooth loss. Inflammation control and achieving better tissue repair are the key to periodontitis treatment. In this study, human ß-Defensin 1 short motif Pep-B with inflammation inhibition and differentiation regulation properties, is firstly used in the treatment of periodontitis, and an injectable photopolymerizable Pep-B/chitosan methacryloyl composite hydrogel (CMSA/Pep-B) is constructed. We confirm that Pep-B improves inflammation, and restores osteogenic behavior and function of injured stem cells. CMSA/Pep-B has good injectability, fluidity and photopolymerizability, and can sustainably release Pep-B to maintain drug concentration in periodontal pockets. Furthermore, animal experiments showed that CMSA/Pep-B significantly ameliorated the inflammation of the periodontium and reduced the alveolar bone loss by decreasing inflammatory infiltration, osteoclast formation and collagen destruction. In conclusion, CMSA/Pep-B is envisaged to be a novel bioactive material or therapeutic drug for treating periodontitis.