Minocycline hydrochloride as a potential adjuvant to improve osteoconductive and osteoinductive properties of bone substitutes in an extra-skeletal bone augmentation model: Preliminary observations in rats

Aim/Hypothesis: Bone tissue regeneration remains an important challenge in orthopedic and maxillofacial surgery. The present in vivo study was performed to determine if minocycline-hydrochloride (minocycline-HCl) could influence the behavior of Deproteinized Bovine Bone Mineral (DBBM) and bioactive glass particles when used as filler material for extra-skeletal bone generation in a Guided Bone Augmentation (GBA) model.

Material and methods: An occlusive titanium cap was placed on each side of the sagittal cranial suture of the rat calvaria. One was filled with bioactive glass particles, the second with DBBM particles, both previously mixed with blood (control groups). In minocycline-HCl loaded groups (experimental groups), bone grafts were additionally placed into a minocycline solution. For each observation time (4, 8 and 16 weeks) samples were harvested and processed for histology. Half of the samples were embedded in methylmethacrylate for undecalcified histology whereas the other half was fixed, decalcified and embedded in paraffin for classical histologic analysis.

Results: This study highlighted osteoconductive and osteoinductive responses associated to bioactive glass particles. However, the addition of minocycline-HCl had no measurable influence on the result. In the control groups, the major part of the space originally created by the caps was occupied by biomaterial particles surrounded by connective tissue. Only slight new bone formations could be seen in the bottom region close to the native skull bone. In sections of minocycline-HCl loaded DBBM, areas of spontaneous ossification could be observed both, after 8 weeks and 16 weeks.

Conclusions and clinical implications: Our observations suggest osteoconductive and osteoinductive properties of bioactive glass particles within the limitations of the present study. Minocycline-HCl may be considered as a promising complementary treatment approach and may add some osteoinductive properties to DBBM. Further investigations as to the volume of newly generated bone are needed to refine the present results.