Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site

Authors

Faleh Tamimi, Jesus Torres, Khadijeh Al-Abedalla, Enrique Lopez-Cabarcos, Mohammad H. Alkhraisat, David C. Bassett, Uwe Gburece, Jake E. Barralet

Abstract

Onlay grafts made of monolithic microporous monetite bioresorbable bioceramics have the capacity to conduct bone augmentation. However, there is heterogeneity in the graft behaviour in vivo that seems to correlate with the host anatomy. In this study, we sought to investigate the metabolic activity of the regenerated bone in monolithic monetite onlays by using positron emission tomography–computed tomography (PET-CT) in rats. This information was used to optimize the design of monetite onlays with different macroporous architecture that were then fabricated using a 3D-printing technique. In vivo, bone augmentation was attempted with these customized onlays in rabbits. PET-CT findings demonstrated that bone metabolism in the calvarial bone showed higher activity in the inferior and lateral areas of the onlays. Histological observations revealed higher bone volume (up to 47%), less heterogeneity and more implant osseointegration (up to 38%) in the augmented bone with the customized monetite onlays. Our results demonstrated for the first time that it is possible to achieve osseointegration of dental implants in bone augmented with 3D-printed synthetic onlays. It was also observed that designing the macropore geometry according to the bone metabolic activity was a key parameter in increasing the volume of bone augmented within monetite onlays.

Link To Article

http://dx.doi.org/10.1016/j.biomaterials.2014.03.050

Anorganic bovine bone (ABB) vs. autologous bone (AB) plus ABB in maxillary sinus grafting. A prospective non-randomized clinical and histomorphometrical trial

Authors

Christian M. Schmitt, Tobias Moest, Rainer Lutz, Friedrich W. Neukam and Karl Andreas Schlegel

Abstract

Objectives This investigation focused on histological characteristics and 5-year implant survival after sinus floor augmentation with anorganic bovine bone (ABB, Bio-Oss®) and ABB plus autologous bone (AB) with a ratio of 1/1.

Material and methods Nineteen consecutive patients with bony atrophy of the posterior edentulous maxilla and a vertical bone height ≤4 mm were prospectively included in this study. In the first surgical stage, the maxillary sinus was non-randomized either augmented with ABB alone (n = 12) or a 1/1 mixture of ABB and AB (n = 7). After a mean healing period of 167 days, biopsies were harvested in the region of the grafted sinus with a trephine burr and implants were placed simultaneously, ABB n = 18 and ABB + AB n = 12. The samples were microradiographically and histomorphometrically analyzed judging the newly formed bone (bone volume, BV), residual bone substitute material volume (BSMV), and intertrabecular volume (soft tissue volume, ITV) in the region of the augmented maxillary sinus. Implant survival was retrospectively evaluated from patient's records.

Results No significant difference in residual bone substitute material (BSMV) in the ABB group (31.21 ± 7.74%) and the group with the mixture of ABB and AB (28.41 ± 8.43%) was histomorphologically determined. Concerning the de novo bone formation, also both groups showed statistically insignificant outcomes; ABB 26.02 ± 5.23% and ABB + AB 27.50 ± 6.31%. In all cases, implants were installed in the augmented sites with sufficient primary stability. After a mean time in function of 5 years and 2 months, implant survival was 93.75% in the ABB and 92.86% in the ABB + AB group with no statistically significant differences.

Conclusion The usage of ABB plus AB to a 1/1 ratio leads to an amount of newly formed bone comparable with the solitary use of ABB after grafting of the maxillary sinus. Considering that ABB is a non-resorbable bone substitute, it can be hypothesized that this leads to stable bone over time and long-term implant success. Importantly, in the sole use of ABB, bone grafting and therefore donor site morbidities can be avoided.

Link To Article

http://dx.doi.org/10.1111/clr.12396

Maximizing bone formation in posterior spine fusion using rhBMP-2 and zoledronic acid in wild type and NF1 deficient mice

Authors

Justin Bobyn, Anton Rasch, Mikulec Kathy, David G. Little, and Aaron Schindeler

Abstract

Spinal pseudarthrosis is a well described complication of spine fusion surgery in NF1 patients. Reduced bone formation and excessive resorption have been described in NF1 and anti-resorptive agents may be advantageous in these individuals. In this study, 16 wild type and 16 Nf1+/− mice were subjected to posterolateral fusion using collagen sponges containing 5 µg rhBMP-2 introduced bilaterally. Mice were dosed twice weekly with 0.02 mg/kg zoledronic acid (ZA) or sterile saline. The fusion mass was assessed for bone volume (BV) and bone mineral density (BMD) by microCT. Co-treatment using rhBMP-2 and ZA produced a significant increase (p < 0.01) in BV of the fusion mass compared to rhBMP-2 alone in both wild type mice (+229%) and Nf1+/− mice (+174%). Co-treatment also produced a significantly higher total BMD of the fusion mass compared to rhBMP-2 alone in both groups (p < 0.01). Despite these gains with anti-resorptive treatment, Nf1+/− deficient mice still generated less bone than wild type controls. TRAP staining on histological sections indicated an increased osteoclast surface/bone surface (Oc.S/BS) in Nf1+/− mice relative to wild type mice, and this was reduced with ZA treatment.

Link To Article

http://dx.doi.org/10.1002/jor.22628

Evidence for the role of connexin 43-mediated intercellular communication in the process of intracortical bone resorption via osteocytic osteolysis

Authors

Shane A Lloyd, Alayna E Loiselle, Yue Zhang and Henry J Donahue

Abstract

Background Connexin 43 (Cx43) is the predominant gap junction protein in bone. Mice with a bone-specific deletion of Cx43 (cKO) have an osteopenic cortical phenotype. In a recent study, we demonstrated that cKO mice are resistant to bone loss induced by hindlimb suspension (HLS), an animal model of skeletal unloading. This protective effect occurred primarily as a result of lower osteoclast-mediated bone resorption. Interestingly, we also documented a significant increase in cortical osteocyte apoptosis and reduced sclerostin production. In the present study, we investigated whether osteocytic osteolysis – bone resorption by osteocytes within lacunae – is induced by HLS and the potential effect of Cx43 deficiency on this process during unloading.

Methods 6-month-old male Cx43 cKO or wild-type (WT) mice were subjected to three weeks of HLS (Suspended) or normal loading conditions (Control) (n = 5/group). Lacunar morphology and tartrate-resistant acid phosphatase (TRACP) staining were assessed on sections of femur cortical bone. Experimental groups were compared via two-way ANOVA.

Results Empty lacunae were 26% larger in cKO-Control vs. WT-Control (p < 0.05), while there was no difference in the size of empty lacunae between Control and Suspended within WT or cKO (p > 0.05). Similarly, there was a trend (p = 0.06) for 11% larger lacunae containing viable osteocytes for cKO-Control vs. WT-Control, with no apparent effect of loading condition. There was no difference in the proportion of TRACP + cells between WT-Control and cKO-Control (p > 0.05); however, WT-Suspended mice had 246% more TRACP + osteocytes compared WT-Control mice (p < 0.05). There was no difference in TRACP staining between cKO-Control and cKO-Suspended (p > 0.05).

Conclusions Prior to undergoing apoptosis, osteocytes in cKO mice may be actively resorbing their respective lacunae via the process of osteocytic osteolysis. Interestingly, the proportion of TRACP + osteocytes increased dramatically following unloading of WT mice, an effect that was not observed in cKO mice subjected to HLS. The results of the present study provide initial evidence that osteocytic osteolysis is occurring in cortical bone in response to mechanical unloading. Furthermore, Cx43 deficiency appears to protect against osteocytic osteolysis in a manner similar to the inhibition of unloading-induced osteoclast activation that we have documented previously.

Link To Article

http://dx.doi.org/10.1186/1471-2474-15-122

Comparison of stainless steel and titanium alloy orthodontic miniscrew implants: A mechanical and histologic analysis

Authors

Ryan N. Brown, Brent E. Sexton, Tien-Min Gabriel Chu,Thomas R. Katona, Kelton T. Stewart, Hee-Moon Kyung, Sean Shih-Yao Liu

Abstract

Introduction

The detailed mechanical and histologic properties of stainless steel miniscrew implants used for temporary orthodontic anchorage have not been assessed. Thus, the purpose of this study was to compare them with identically sized titanium alloy miniscrew implants.

Methods

Forty-eight stainless steel and 48 titanium alloy miniscrew implants were inserted into the tibias of 12 rabbits. Insertion torque and primary stability were recorded. One hundred grams of tensile force was applied between half of the implants in each group, resulting in 4 subgroups of 24 specimens each. Fluorochrome labeling was administered at weeks 4 and 5. When the rabbits were euthanized at 6 weeks, stability and removal torque were measured in half (ie, 12 specimens) of each of the 4 subgroups. Microdamage burden and bone-to-implant contact ratio were quantified in the other 12 specimens in each subgroup. Mixed model analysis of variance was used for statistical analysis.

Results

All implants were stable at insertion and after 6 weeks. The only significant difference was the higher (9%) insertion torque for stainless steel. No significant differences were found between stainless steel and titanium alloy miniscrew implants in microdamage burden and bone-to-implant contact regardless of loading status.

Conclusions

Stainless steel and titanium alloy miniscrew implants provide the same mechanical stability and similar histologic responses, suggesting that both are suitable for immediate orthodontic clinical loads.

Link To Article

http://dx.doi.org/10.1016/j.ajodo.2013.12.022

Enhanced Immunoprotective Effects by Anti-IL17 Antibody Translates to Improved Skeletal Parameters Under Estrogen Deficiency Compared to Anti-RANKL and Anti-TNFα Antibodies

Authors

Abdul M Tyagi, Mohd. N Mansoori, Kamini Srivastava, Mohd. P Khan, Jyoti Kureel, Manisha Dixit, Priyanka Shukla, Ritu Trivedi, Naibedya Chattopadhyay and Divya Singh

Abstract

Activated T cell has a key role in the interaction between bone and immune system. T cells produce pro-inflammatory cytokines including, RANKL, TNF-α and IL-17, all of which augment osteoclastogenesis. RANKL and TNF-α are targeted by inhibitors like denosumab, a human monoclonal RANKL antibody and infliximab, which neutralizes TNF-α. IL-17 is also an important mediator of bone loss and an antibody against IL-17 is undergoing phase II clinical trial for rheumatoid arthritis. Although there are few studies showing suppression of Th17 cell differentiation and induction of regulatory T cells (Tregs) by infliximab, however the effect of denosumab remains poorly understood. In this study, we investigated the effects of anti-TNFα, anti-RANKL or anti-IL17 antibody administration to estrogen deficient mice on CD4 + T cell proliferation, CD28 loss, Th17/Treg balance and B lymphopoesis, and finally, the translation of these immunomodulatory effects on skeletal parameters. Adult Balb/c mice were treated with anti-RANKL/-TNFα/-IL17 subcutaneously, twice a week, post-ovariectomy (Ovx) for four weeks. Animals were then autopsied; bone marrow cells collected for FACS and RNA analysis and serum collected for ELISA. Bones were dissected for static and dynamic histomorphometry studies. We observed that while anti-RANKL and anti-TNFα therapies had no effect on Ovx-induced CD4 + T cell proliferation and B lymphopoesis; anti-IL17 effectively suppressed both events with concomitant reversal of CD28 loss. Anti-IL17 antibody reduced pro-inflammatory cytokine production and induced Tregs. All three antibodies restored trabecular microarchitecture with comparable efficacy; however cortical bone parameters, bone biomechanical properties and histomorphometry were best preserved by anti-IL17 antibody likely due to its inhibitory effect on osteoblast apoptosis and increased number of bone lining cells and Wnt10b expression. Based on the superior immunoprotective effects of anti-IL17 which appears to translate to a better skeletal preservation, we propose beginning clinical trials using a humanized antibody against IL-17 for treatment of post-menopausal osteoporosis.

Link To Article

http://dx.doi.org/10.1002/jbmr.2228