The intrasulcular application effect of bisphosphonate hydrogel toward osteoclast activity and relapse movement

Abstract

Introduction Orthodontic relapse occurs after orthodontic treatment and shifting of teeth to unfavorable positions. Bisphosphonates’ effects on bone resorption and relapse prevention have been extensively investigated. However, topical administration, which results in local effect, is still a problem. Objective This study aimed to investigate the effect of risedronate with gelatin hydrogel as a carrier to prevent relapse movement by inhibiting osteoclast activity. Methods Lower incisors of 75 guinea pigs were moved distally using an orthodontic appliance until ±3 mm length. Gelatin hydrogel was fabricated to obtain a semisolid controlled release of 250 (Bis-CR250) and 500 mmol/L risedronate (Bis-CR500) and then applied intrasulcularly into the mesial subperiosteal area of 50 guinea pigs (25 in each group) every 3 days; the rest were the control (Bis-CR000). After 14 days of stabilization, the apparatus was removed. The distance decrease between incisors and the osteoclast number with TRAP staining at 0, 3, 7, 14, and 21 days were measured. ANOVA was used to determine the differences among the different time and experimental groups. Results Both treatments showed significantly less relapse movement compared to the control (p < 0.05) at 14 and 21 days. Bis-CR500 more effectively inhibited the relapse movement than Bis-CR250 on day 21, indicating a dose dependency in the inhibition. Both treatments showed less osteoclast numbers than control (p < 0.05). Conclusion Controlled release of bisphosphonate risedronate with a topically administered gelatin hydrogel has shown to be effective in decreasing the tooth relapse movement and osteoclast activity.

Use of Hydrogels to Regulate Orthodontic Tooth Movement in Animal Models: A Systematic Review

“…Eight articles in experimental animal models were included; four studies were conducted on rats [20][21][22][23], two used rabbits [24,25], one study was conducted on mice [26] and one study on guinea pigs [27], as shown in Table 1. A quality assessment was performed according to the ARRIVE guidelines [18].…”

“…All studies used a hydrogel of different polymer-gelatin-based composition [20,[24][25][26][27], chitosan hydrogel [20], polyethylene glycol-polycaprolactone-polyethylene glycol [21], hydroxyethyl cellulose [22], methylcellulose [23] for delivery of active substances: carbonated hydroxyapatite [24,25], curcumin [20], sclerostin [21], a formulation of RANKL [22], risedronate bisphosphonate [27], epigallocatechin [26] and parathyroid hormone [23], to accelerate orthodontic tooth movement or inhibit the post treatment relapse. Tooth movement was measured with a digital vernier or in the tomographic software depending on each article.…”

“…All eight studies were done on animal models: four on rats [20][21][22][23], two on rabbits [24,25], one on mice [26], and the last one on guinea pigs [27]. The number of animals used in the experiments of the studies ranged from 20 to 75.…”

“…In the study with mice, they sought to prevent the recurrence of orthodontic dental movement by inhibiting the activity of the osteoclasts using 7-week-old mice [26]; in the same way as in the study carried out on guinea pigs, they used models weighing between 500 and 600 g [27].…”

Fabrication of physical and chemical crosslinked hydrogels for bone tissue engineering

“…On the other side, pharmacological assets carried by degradable hydrogels could regulate cell activities in situ . For instance, bisphosphonate released by an injectable hydrogel that controlled tooth relapse movement and osteoclasts activity after administration [ 12 ].…”