Local application of osteoprotegerin-chitosan gel in critical-sized defects in a rabbit model

Abstract

BackgroundOsteoprotegerin (OPG) is used for the systemic treatment of bone diseases, although it has many side effects. The aim of this study was to investigate a newly formulated OPG-chitosan gel for local application to repair bone defects. Recent studies have reported that immunodetection of osteopontin (OPN) and osteocalcin (OC) can be used to characterise osteogenesis and new bone formation.MethodsThe osteogenic potential of the OPG-chitosan gel was evaluated in rabbits. Critical-sized defects were created in the calvarial bone, which were either left unfilled (control; group I), or filled with chitosan gel (group II) or OPG-chitosan gel (group III), with rabbits sacrificed at 6 and 12 weeks. Bone samples from the surgical area were decalcified and treated with routine histological and immunohistochemical protocols using OC, OPN, and cathepsin K (osteoclast marker) antibodies. The toxicity of the OPG-chitosan gel was evaluated by biochemical assays (liver and kidney function tests).ResultsThe mean bone growth in defects filled with the OPG-chitosan gel was significantly higher than those filled with the chitosan gel or the unfilled group (p < 0.05). At 6 and 12 weeks, the highest levels of OC and OPN markers were found in the OPG-chitosan gel group, followed by the chitosan gel group. The number of osteoclasts in the OPG-chitosan gel group was lower than the other groups. The results of the liver and kidney functional tests indicated no signs of harmful systemic effects of treatment. In conclusion, the OPG-chitosan gel has many characteristics that make it suitable for bone repair and regeneration, highlighting its potential benefits for tissue engineering applications.

Analysis on Efficacy of Chitosan-Based Gel on Bone Quality and Quantity

“…Furthermore, Seo and Kim (2020) stated that the volume analysis of rabbit calvarial defects and bone grafts using CT can be done after 2 and 8 weeks. In point of fact, the HR-pQCT results were corresponding to the histological results of our published literature in 2007 (Jayash et al, 2017a;Jayash et al, 2017b). Likewise, in the current study, the part-comparison map and histomorphometrical analyses results confirmed the changes in microstructure between the reference bone and the newly formed bone after surgery at 6 and 12 weeks.…”

Osteoprotegerin (OPG) pathways in bone diseases and its application in therapeutic perspectives

“…It was previously reported that OPG-chitosan matrices and gel increase the in vitro proliferation of normal human osteoblasts and fibroblasts cells that used later to treat the critical size defects on parietal bone of rabbit. The results of this studies showed that bioresorbable OPGchitosan material induced the formation of a significant quantity of bone in a critical-sized parietal bone defect in a rabbit model [72][73][74].…”

Enzymatic crosslinked gelatin 3D scaffolds for bone tissue engineering

“…Nowadays, the "gold standard" strategy for the treatments of these pathologies results from autologous bone grafting. Nevertheless, several complications are associated with this method including donor site morbidity, prolonged periods of hospitalization and rehabilitation and increased risk of deep infections (Jayash, et al 2017). As a consequence, an immense effort has been made in order to develop novel therapies that could shed light on this challenge.…”