Thermosensitive hydrogel doped with osteoconductive fillers for the treatment of periodontitis periapicalis chronica: from synthesis to clinical trial

Abstract

Herein, a chitosan-based thermosensitive hydrogel (CH) containing hydroxyapatite (HAp), poly(lactic acid) (PLDLLA) or their mixture is proposed as an innovative, biomimetic composition with antimicrobial and bone-forming properties for guided bone regeneration. The modified hydrogels were synthesized and characterized to verify their suitability for the treatment of periodontitis periapicalis chronica. Compared to the unmodified hydrogel, both CH_HAp and CH_PLDLLA revealed improved mechanical properties, as evidenced by rotational rheology. FTIR analysis proved that no chemical interplay existed between the components. All the tested samples displayed no cytotoxicity against osteoblast-like cell culture and confirmed antimicrobial features, both crucial from an application perspective. Radiation sterilization dosage was tailored for the tested samples to maintain sterility for a minimum of 8 weeks of storage and limit crosslinking of the samples. Finally, the hydrogel was used in a clinical trial to treat a patient with chronic inflammation of periapical tissues in teeth 26 and 27. The medical procedure proved the safety, nontoxicity, non-allergenicity, and, most importantly, bone-forming properties of the hydrogel formulation. The kinetics of new bone formation was analyzed in-depth using graphical cross-sections of anatomical structures obtained from pre- and post-operative CBCT scans.