Biomimetic trace metals improve bone regenerative properties of calcium phosphate bioceramics.

The bone regenerative capacity of synthetic calcium phosphates (CaPs) can be enhanced through the enrichment with selected metal trace ions. However, defining the optimal elemental composition required for bone formation is challenging due to many possible concentrations and combinations of these elements. We hypothesized that the ideal elemental composition exists in the inorganic phase of the bone extracellular matrix (ECM). To study our hypothesis, we first obtained natural hydroxyapatite through the calcination of bovine bone, which was then investigated its reactivity with acidic phosphates to produce CaP cements. Bioceramic scaffolds fabricated using these cements were assessed for their composition, properties, and in vivo regenerative performance and compared with controls. We found that natural hydroxyapatite could react with phosphoric acid to produce CaP cements with biomimetic trace metals. These cements present significantly superior in vivo bone regenerative performance compared with cements prepared using synthetic apatite. In summary, this study opens new avenues for further advancements in the field of CaP bone biomaterials by introducing a simple approach to develop biomimetic CaPs. This work also sheds light on the role of the inorganic phase of bone and its composition in defining the regenerative properties of natural bone xenografts.

Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model.

Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer's disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing.

The antidepressant drug, sertraline, hinders bone healing and osseointegration in rats' tibiae.

AIM: Selective serotonin reuptake inhibitors (SSRIs) are one of the most common antidepressant drugs. SSRI use is associated with increased risk of bone fracture and titanium implant failure. The aim of this in vivo study was to investigate the effect of SSRIs on osseointegration and bone healing. MATERIALS AND METHODS: On a total of 24 Sprague-Dawley rats, a custom-made titanium implant was placed in the left tibia, while a unicortical defect was created in the right tibia. Rats were assigned randomly into two groups and received a daily dose of either sertraline (5 mg/kg) or saline. After two weeks, they were euthanized and bone healing and osseointegration were assessed by micro-CT and histology. RESULTS: Bone formation in bone defects was significantly lower (p < 0.05) in sertraline-treated rats (BV/TV = 20.67 ± 11.98%) compared to the controls (BV/TV = 37.87 ± 9.56%). Furthermore, the percentage of osseointegration was significantly lower (p < 0.05) in sertraline-treated rats (34.40 ± 7.17%) compared to the controls (54.37 ± 8.58%). CONCLUSION: Sertraline hinders bone healing and implant osseointegration.

Melorheostosis of The Leg: A Case Report.

Melorheostosis is a benign hyperostotic disease of the peripheral skeleton, rarely involving the axial skeleton. This disease is associated with ossified and non-ossified soft tissue masses surrounding the joints. We report the case of a 28-year-old male who presented to an orthopedic clinic with a chronic history of right leg pain. Radiological evaluation using X-ray, computed tomography, and magnetic resonance imaging showed features consistent with that of melorheostosis. Recognition of this entity by clinicians can avoid unnecessary investigations and biopsy.

Propranolol enhances bone healing and implant osseointegration in rats tibiae.

BACKGROUND: Propranolol, a non-selective ß-blocker widely used to treat cardiovascular conditions, favours bone accrual. Accordingly, we hypothesized that propranolol could be useful for improving bone healing and osseointegration. This in vivo study was designed to investigate the effect of propranolol on bone healing and osseointegration in rats' tibiae. METHODS: On 24 Sprague-Dawley rats, a unicortical defect was created in the right tibial metaphysis of each rat and a custom-made titanium implant was placed in the left tibia. Animals were then assigned into two groups (n = 12, each group) and treated daily with either propranolol (5 mg/kg: subcutaneous) or saline, for 2 weeks. Then, after killing, the volume of the cortical defects (mm3) and the percentages of newly formed bone in the defects, were assessed with microcomputed tomography; bone-implant contact percentage and peri-implant bone volume/tissue volume were assessed by histomorphometry. RESULT: Propranolol-treated rats presented smaller cortical defects (1.56 ± 0.28 mm3 versus 2.04 ± 0.29 mm3 , p < 0.001) with more bone volume/tissue volume (60.6 ± 7.9% versus 41.1 ± 10.2%, p < 0.001) compared to saline-treated rats. Propranolol also enhanced osseointegration as propranolol-treated rats presented higher bone-implant-contact (65.0 ± 13.1% versus 42.5 ± 8.8%, p < 0.001) and peri-implant bone volume/Tissue volume (73.8 ± 10.1% versus 56.9 ± 5.7%, p = 0.007) than saline-treated rats. CONCLUSION: Propranolol enhanced bone healing and implant osseointegration.

Two-Dimensional Magnesium Phosphate Nanosheets Form Highly Thixotropic Gels That Up-Regulate Bone Formation.

Hydrogels composed of two-dimensional (2D) nanomaterials have become an important alternative to replace traditional inorganic scaffolds for tissue engineering. Here, we describe a novel nanocrystalline material with 2D morphology that was synthesized by tuning the crystallization of the sodium-magnesium-phosphate system. We discovered that the sodium ion can regulate the precipitation of magnesium phosphate by interacting with the crystal's surface causing a preferential crystal growth that results in 2D morphology. The 2D nanomaterial gave rise to a physical hydrogel that presented extreme thixotropy, injectability, biocompatibility, bioresorption, and long-term stability. The nanocrystalline material was characterized in vitro and in vivo and we discovered that it presented unique biological properties. Magnesium phosphate nanosheets accelerated bone healing and osseointegration by enhancing collagen formation, osteoblasts differentiation, and osteoclasts proliferation through up-regulation of COL1A1, RunX2, ALP, OCN, and OPN. In summary, the 2D magnesium phosphate nanosheets could bring a paradigm shift in the field of minimally invasive orthopedic and craniofacial interventions because it is the only material available that can be injected through high gauge needles into bone defects in order to accelerate bone healing and osseointegration.

Systemic administration of omeprazole interferes with bone healing and implant osseointegration: an in vivo study on rat tibiae.

BACKGROUND: Proton pump inhibitors, over-the-counter drugs taken by millions of patients, diminish bone accrual. Accordingly, we hypothesized that these drugs could impair bone healing and implant osseointegration. This study investigated the effect of post-operative systemic administration of omeprazole on bone healing and implant osseointegration in rat tibiae. METHODS: In 24 Sprague-Dawley rats, a titanium implant was placed in the left tibia, and a bone defect was created in the right tibia. During the 2 weeks following surgery, 12 rats were treated with omeprazole (5 mg/kg, daily) and the other 12 with saline. Then, after euthanasia, the volume (mm(3) ) of the cortical defect and the percentages of newly formed bone in the defect, were assessed using microcomputed tomography; peri-implant bone volume/tissue volume and bone-implant contact percentage were assessed by histomorphometry. RESULTS: Omeprazole-treated rats presented larger cortical defects (2.75 ± 0.59 mm(3) , p = 0.003 versus 2.11 ± 0.36 mm(3) ; p = 0.002) and a lower percentage of newly formed bone in the defects (28.62 ± 13.12; 45.89 ± 9.73; p = 0.003) than controls. Omeprazole-treated rats presented lower peri-implant bone volume/tissue volume (14.3 ± 7.3% versus 30.8 ± 11.0%; p < 0.001) and bone-implant contact (23.3 ± 10.8% versus 41.8 ± 13.3%; p < 0.001) than controls. CONCLUSION: Systemically administered omeprazole impairs bone healing and implant osseointegration.

Donepezil regulates energy metabolism and favors bone mass accrual.

The autonomous nervous system regulates bone mass through the sympathetic and parasympathetic arms. The sympathetic nervous system (SNS) favors bone loss whereas the parasympathetic nervous system (PNS) promotes bone mass accrual. Donepezil, a central-acting cholinergic agonist, has been shown to down-regulate SNS and up-regulate PNS signaling tones. Accordingly, we hypothesize that the use of donepezil could have beneficial effects in regulating bone mass. To test our hypothesis, two groups of healthy female mice were treated either with donepezil or saline. Differences in body metabolism and bone mass of the treated groups were compared. Body and visceral fat weights as well as serum leptin level were increased in donepezil-treated mice compared to control, suggesting that donepezil effects on SNS influenced metabolic activity. Donepezil-treated mice had better bone quality than controls due to a decrease in osteoclasts number. These results indicate that donepezil is able to affect whole body energy metabolism and favors bone mass in young female WT mice.

Anti-VEGFs hinder bone healing and implant osseointegration in rat tibiae.

AIM: To assess the effect of anti-vascular endothelial growth factors (VEGF) on bone healing (defect volume) and implant osseointegration (bone-implant contact per cent) in rat tibia. MATERIALS AND METHODS: In Sprague-Dawley rats (n = 36), a unicortical defect was created in the right tibia and a titanium implant was placed in the left tibia of each rat. Rats were assigned into three groups and received either anti-vascular endothelial growth factor neutralizing antibody, Ranibizumab or saline (control). Two weeks following surgery, rats were euthanized and bone samples were retrieved. Bone healing and osseointegration were assessed using micro-CT and histomorphometry. One-way anova followed by the Tukey's test was used for data analyses. RESULTS: The volume of the bone defects in the anti-VEGF group (2.48 ± 0.33 mm(3) ) was larger (p = 0.026) than in the controls (2.11 ± 0.36 mm(3) ) as measured by µ-CT. Bone-implant contact percent in the anti-VEGF (19.9 ± 9.4%) and Ranibizumab (21.7 ± 9.2%) groups were lower (p < 0.00) than in the control group (41.8 ± 12.4%). CONCLUSIONS: The results of this study suggest that drugs that inhibit the activity of vascular endothelial growth factor (i.e. anti-VEGF) may hinder bone healing and implant osseointegration in rat tibiae.