Calcium phosphate nanoclusters modify periodontium remodeling and minimize orthodontic relapse

Orthodontic relapse is one of the most prevalent concerns of orthodontic therapy. Relapse results in patients' teeth reverting towards their pretreatment positions, which increases the susceptibility to functional problems, dental disease, and substantially increases the financial burden for retreatment. This phenomenon is thought to be induced by rapid remodeling of the periodontal ligament (PDL) in the early stages and poor bone quality in the later stages. Current therapies including fixed or removable retainers and fiberotomies have limitations with patient compliance and invasiveness. Approaches using biocompatible biomaterials, such as calcium phosphate polymer-induced liquid precursors (PILP), are an ideal translational approach for minimizing orthodontic relapse. Here, post-orthodontic relapse is reduced after a single injection of high concentration PILP (HC-PILP) nanoclusters by altering PDL remodeling in the early stage of relapse and improving trabecular bone quality in the later stage. HC-PILP nanoclusters are achieved by using high molecular weight poly aspartic acid (PASP, 14 kDa) and poly acrylic acid (PAA, 450 kDa), which resulted in a stable solution of high calcium and phosphate concentrations without premature precipitation. In vitro results show that HC-PILP nanoclusters prevented collagen type-I mineralization, which is essential for the tooth-PDL-bone interphase. In vivo experiments show that the HC-PILP nanoclusters minimize relapse and improve the trabecular bone quality in the late stages of relapse. Interestingly, HC-PILP nanoclusters also altered the remodeling of the PDL collagen during the early stages of relapse. Further in vitro experiments showed that HC-PILP nanoclusters alter the fibrillogenesis of collagen type-I by impacting the protein secondary structure and forming aggregates. These findings propose a new approach for treating orthodontic relapse and provide additional insight into the PILP nanocluster's structure and properties on collagenous structure repair.