Enhanced bone regeneration with cerium-doped bioactive glasses: In vitro and in vivo study

Bioactive cerium-doped (Ce-BGs) glasses with proven antioxidant properties, which may reduce post-implant oxidative stress, were studied in vitro and in vivo to evaluate their application in bone regeneration. Based on the Kokubo (K) composition, they contain 3.6 and 5.3 mol% cerium (referred to as K3.6 and K5.3, respectively).

Ce-BGs were synthesized by melting and sieved to produce granules (size range = 200-500 µm). In vitro studies were conducted against MLO-Y4 cells using direct Neutral Red (NR) and indirect Bromo-2-deoxyUridine (BrdU) assays to assess cell viability and proliferation respectively. In vivo studies were carried out using a New Zealand white rabbit model to evaluate bone healing potential.

NR results showed a significant increase in cell viability for Ce-BGs: 77% for K and 79 and 85% for K3.6 and K5.3, after 24 h. After 72 h, cell viability decreased for K to 58% and increased for K3.6 and K5.3 (76% and 116% respectively). Cerium inhibits cell proliferation in BrdU assay as explainable by the increased durability of Ce-BGs. In vivo studies, after 30 and 60 days, revealed a delayed degradation for Ce-BGs that can stimulate the osteo-regeneration without inflammatory or degenerative effects. Moreover, the new bone area (NBA) was higher for Ce-BGs compared to control; after 60 days 32% for K5.3 versus 21% for K.

Ce-BGs granules show improved direct cytocompatibility in vitro and enhance the long-term bone remodeling process in vivo, contributing to a more controlled and effective bone healing compared to the K granules. This improved behavior can be linked to the antioxidant and anti-inflammatory properties of cerium, that can assist bone regeneration and reduce implant-associated inflammation, and to their slower dissolution rate that supports the controlled release of ions. These results suggest Ce-BGs as a promising device for therapeutic applications on hard tissues.