Local Oxygen-Based Therapy (blue®m) for Treatment of Peri-Implant Disease: Clinical Case Presentation and Review of Literature about Conventional Local Adjunct Therapies.

Peri-implant diseases including peri-implant mucositis and peri-implantitis are among the major causes of failure of implant-supported dental restorations. They are characterized by progressive inflammation of the peri-implant mucosa, extending to the surrounding connective tissues and leading to bone loss and implant failure. Although strict oral hygiene practices help in preventing peri-implant diseases, plaque buildup around the implant restoration leads to chronic inflammation, due to the adherent bacterial biofilm. While mechanical debridement and non-surgical therapy to remove inflamed connective tissue (ICT) form the mainstay of treatment, additional local adjunctive therapies enhance clinical outcomes. Topical oxygen therapy is known to reduce inflammation, increase vascularity, and act as a bacteriostatic measure. The use of oxygen-based therapy (blue®m) products as a local adjunctive therapy for peri-implant mucositis and peri-implantitis can result in clinical outcomes similar to that of conventional local adjuncts such as chlorhexidine, antibiotics, and antibacterial agents. This report aims to present the clinical findings of patients with peri-implant mucositis and peri-implantitis, who were managed using local oxygen-based therapy as an adjunct to non-surgical therapy. In addition, a review of the literature about commonly used local adjuncts for peri-implant diseases has been included in the report to provide a means of comparison between conventional local adjunct therapy and topical oxygen-based therapy. Based on the reported findings and reviewed literature, local oxygen-based adjunct therapy was equally effective as conventionally used local adjuncts such as antibiotics, antibacterials, and probiotics, in treating patients with peri-implant diseases.

Visualization of calcium phosphate cement in teeth by zero echo time 1 H MRI at high field.

1 H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high-field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T1 and T2 * values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T2 * relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T2 * values were 273 ± 19, 562 ± 221 and 476 ± 147 µs, respectively, the average T2 values were 1234 ± 27, 963 ± 151 and 577 ± 41 µs, respectively, and the average T1 values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal-to-noise-ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC-filled lesions showed less homogeneous structures, a lower T1 value and T2 * separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed.

Biomarkers as Independent Predictors of Bone Regeneration around Biomaterials: A Systematic Review of Literature.

BACKGROUND: Biomarkers are detected during bone formation and resorption associated with the dynamics of bone metabolism and are gaining importance as preferential indicators of bone healing in comparison with conventional methodologies. Current literature suggests that the usage of bone turnover markers for monitoring bone regeneration in association with biomaterials is limited. AIM: To systematically review literature and evaluate whether bone-biomarkers can independently predict bone regeneration following implantation of various bone biomaterials. MATERIALS AND METHODS: An electronic search was conducted in PubMed (MEDLINE) database from 1980 to January 2017. The articles for systematic review were selected based on formulated inclusion and exclusion criteria Results: Upon database searching, 443 articles were retrieved and thoroughly reviewed based on the inclusion and exclusion criteria. In all, 41 studies were finally included for evaluation out of which 4 were clinical studies and the remaining 37 studies utilized animal models. On further evaluation, 12 studies reported the presence of biomarkers in association with cellular response during bone regeneration around bio-materials. Moreover, biomarkers related to enzyme activity and matrix protein derivatives were enhanced during bone-matrix deposition as reported in 14 studies. Inorganic skeletal matrix biomarkers indicative of bone mineralization showed positive expression in eight studies. CONCLUSION: Several biomarkers appear to be useful for the assessment of bone regeneration around biomaterials. Although biomarkers are capable of independently predicting bone regeneration, lack of substantial evidence in the literature limits their true clinical utility. CLINICAL SIGNIFICANCE: Noninvasive and inexpensive methods of isolating and characterization of biomarkers from cellular and extracellular skeletal matrix during bone regeneration have proven value in evaluating success of bone biomaterials.

In vivo evaluation of bioactive glass-based coatings on dental implants in a dog implantation model.

OBJECTIVES: Although titanium is commonly used as a favorable bone implant material due to its mechanical properties, its bioactive and osteoconductive capacity is relatively low. Calcium phosphate ceramics, predominantly hydroxyapatite (HA), have been frequently used for coating purposes to improve the bioactive properties. In view of the suggested osteopromotive capacity of bioactive glasses (BGs), this study aimed to evaluate the effect of BG incorporation into HA coatings on implant performance in terms of bone contact and bone area. MATERIALS AND METHODS: A total of 48 screw-type titanium implants with magnetron sputter coatings containing different ratios of HA and BG (HA, HABGLow, and HABGHigh; n = 8) were placed into the mandible of 16 Beagle dogs. After 4 and 12 weeks, their performance was evaluated histologically and histomorphometrically. Peri-implant bone area percentage (BA%) was determined in three zones (inner, 0-500 µm; middle, 500-1000 µm; and outer, 1000-1500 µm). Additionally, bone-to-implant contact (BIC%) and first bone-implant contact (1st BIC) were assessed for each sample. RESULTS: After 4 weeks, bone-to-implant contact for the HA- and HABGLow-coated groups was significantly higher (P < 0.05) than for the HABGHigh coatings. Mean values for overall BA% showed comparable values for both the HABGLow (58.3%)- and HABGHigh (56.3%)-coated groups. Data suggest that the relative BA around the HA-coated implants (67.8%) was higher, although this was only significant compared to the HABGHigh group. After 12 weeks, all three groups showed similar bone-to-implant contact and no differences in BA were found. CONCLUSIONS: The incorporation of BG into HA sputter coatings did not enhance the performance of a dental implant in implantations sites with good bone quality and quantity. On the contrary, coatings containing high concentrations of BG resulted in inferior performance during the early postimplantation healing phase.

Effectiveness of Topical Oxygen Therapy in Gingivitis and Periodontitis: Clinical Case Reports and Review of the Literature.

Gingivitis and periodontitis are common oral pathological conditions. Several optional adjunctive local therapies are used clinically. While antibiotics and chlorhexidine are the most common agents of choice, their long-term use is associated with several adverse effects. Some of these include staining of teeth and restorations, cellular cytotoxicity and hypersensitivity. Topical oxygen therapy has been recently introduced and could be clinically capable of inhibiting plaque bacterial biofilm growth. Available as a mouthwash, toothpaste and oral gel, this formulation comprises cellulose, glycerol and sodium peroxoborate, and releases topical oxygen in a controlled manner. Moreover, it releases topical oxygen, in a controlled manner, and lactoferrin, which are capable of antibacterial action and stimulation of bone cells, respectively. The aim of this paper is to report a case of gingivitis and another case of periodontitis, both of which were successfully treated clinically with adjunctive local oxygen therapy (blue®m). Additionally, this paper aims to review the relevant literature in terms of adjunct topical or local therapies used in the treatment of gingivitis and periodontitis, in order to understand how local therapies are helpful and to know if local oxygen therapy is a suitable clinical alternative.

Clinical Presentations and Risk Factors of Gastrointestinal Bleeding in the Emergency Department: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Gastrointestinal bleeding is a major healthcare burden and is associated with significant morbidity and mortality. This study aimed to assess the prevalence, clinical presentation, and risk factors of patients presenting with gastrointestinal bleeding in the emergency department. MATERIALS AND METHODS: This retrospective study was conducted in two tertiary care hospitals in Riyadh, Saudi Arabia. The medical records of patients who presented to the emergency department with gastrointestinal bleeding between January 2010 and January 2020 were reviewed. Patients aged 18 years or older, with gastrointestinal bleeding (upper or lower) regardless of underlying cause, lifestyle, location of bleeding, health status, or medication use, were included. Demographic characteristics, initial vital signs, medical history, physical examination findings, comorbidities, medications, laboratory and radiological investigations, cause and stage of liver disease, management, and complications were recorded. Endoscopic findings and management of the bleeding site were collected according to the presenting symptoms. RESULTS: A total of 760 patients were included. The mean age was 62.7 ± 17.8 years, and 61.4% were males. The most common comorbidities at presentation were hypertension (54.1%), diabetes mellitus (51.2%), and ischemic heart disease (18.2%). The origins of the bleeding were lower gastrointestinal in 52% and upper gastrointestinal in 48% of patients. CONCLUSIONS: Lower gastrointestinal bleeding was found to be more common than upper gastrointestinal bleeding. Hemorrhoids, polyps, diverticular disease, and colonic ulcers were the major risk factors for lower gastrointestinal bleeding. In contrast, upper gastrointestinal bleeding was predominantly caused by esophageal varices, gastritis, and peptic ulcers.

Biological response to titanium implants coated with nanocrystals calcium phosphate or type 1 collagen in a dog model.

OBJECTIVE: The current study aimed to evaluate the osteogenic potential of electrosprayed organic and non-organic surface coatings in a gap-implant model over 4 and 12 weeks of implantation into the dog mandible. MATERIAL AND METHODS: Sixteen Beagle dogs received experimental titanium implants in the mandible 3 months after removal of left premolars (P2, P3 and P4). Three types of implants were installed in each animal: non-coated implant, nano-CaP coated implant and implant with type 1 collagen coating. Both micro-CT and histomorphometry were used to evaluate peri-implant bone response after implantation periods of 4 and 12 weeks. The bone area percentage was assessed histomorphometrically in three different zones (inner: 0-300 µm; middle: 300-600 µm; and outer: 600-1000 µm) around the implant surface. Bone-bridging of the gap was also calculated for each sample. RESULTS: Four weeks after implantation, nano-CaP and collagen-coated implants showed significantly higher bone volume (BV) in the inner zone compared with non-coated implants (P < 0.05 and P < 0.01). After 12 weeks, histomorphometric analysis showed comparable amounts of BV between all experimental groups. Also, no significant difference was found in the BV, as measured using micro-CT, between the implant groups. Absolute bone ingrowth measurements were highest for collagen-coated implants, but these differences were not significant. CONCLUSION: The obtained data failed to provide a consistent favourable effect on bone formation of the collagen coating over 3 months of implantation. It is concluded that the source of the collagen as well as the limited osseous environment overshadowed a possible effect of the applied implant surface modifications. Similarly, the tested nano-apatite surface coating did not improve peri-implant bone ingrowth into a gap-implant model.

Effectiveness of generic sofosbuvir in the treatment of chronic hepatitis C virus infection in Saudi patients.

OBJECTIVES: To assess the effectiveness of generic sofosbuvir (SOF) and branded daclatasvir (DCV) for the treatment of chronic hepatitis C virus (HCV)infected patients. METHODS: This retrospective study, performed in a single center in Saudi Arabia between August 2017 and July 2022, we enrolled 140 consecutive patients with HCV who received generic SOF and branded DCV. The primary outcome was sustained virologic response at week 12 (SVR12). RESULTS: The majority of the patients were female (62.1%), infected with genotype 4 (57.9%), and treatment-naïve in 120 (85.7%) patients with baseline cirrhosis in 55 (39.3%). The mean patient age was 61±13.6 years. In the intention-to-treat analysis, 131 (93.6%) patients achieved SVR12. Moreover, 85.7%, 100%, 100%, 88.9%, and 96.3% of genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. In the per-protocol analysis, 131 (96.3%) patients achieved an SVR of 12. Additionally, 92.3%, 100%, 100%, 88.9%, and 98.7% of the patients with genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. No HCV virologic breakthroughs occurred. In the subgroup analysis, SVR12 rates were comparable regardless of baseline characteristics, such as treatment history, cirrhosis, and hepatocellular carcinoma. Patients achieving SVR12 showed a significant improvement in post-treatment serum liver enzyme and total bilirubin levels. CONCLUSION: The findings of our study confirm the effectiveness of generic sofosbuvir as a treatment option for HCV infection.

Endoscopic extraction of vascular embolization coils that have migrated into the biliary tract in a liver transplant recipient.

Hepatic artery pseudoaneurysm (HAA) is a rare vascular complication of liver transplantation. Minimally invasive radiological interventions are generally considered before seeking surgical treatment of HAA. Coil embolization of the aneurysmal sac and or exclusion of pseudoaneurysm by deploying a stent over the aneurysm are effective interventions to control hemobilia arising from the HAA. Migration of coils inside the bile duct is a rarely reported complication in post-hepatic transplantation. Treatment options remain largely unexplored due to the rarity of its occurrence. Endoscopic retrograde cholangiographic removal of migrated vascular coils in the common bile duct following embolization of HAA has not been described in a liver transplant setting. We report a liver transplant recipient who underwent uneventful and successful endoscopic removal of migrated coils into the bile duct.

Histological evaluation of titanium fiber mesh-coated implants in a rabbit femoral condyle model.

OBJECTIVES: This study was aimed to comparatively evaluate new bone formation into the pores of a flexible titanium fiber mesh (TFM) applied on the surface of implant. METHODS: Twenty-eight custom made cylindrical titanium implants (4 ×10 mm) with and without a layer of two different types of TFM (fiber diameter of 22 µm and 50 µm, volumetric porosity ~70%) were manufactured and installed bilaterally in the femoral condyles of 14 rabbits. The elastic modulus for these two TFM types was ~20 GPa and ~5 GPa respectively, whereas the solid titanium was ~110 GPa. The implants (Control, TFM-22, TFM-50) were retrieved after 14 weeks of healing and prepared for histological assessment. The percentage of the bone area (BA%), the bone-to-implant contact (BIC%) and amount were determined. RESULTS: Newly formed bone into mesh porosity was observed for all three types of implants. Histomorphometric analyses revealed significantly higher (~2.5 fold) BA% values for TFM-22 implants (30.9 ± 9.5%) compared to Control implants (12.7 ± 6.0%), whereas BA% for TMF-50 did not significantly differ compared with Control implants. Furthermore, both TFM-22 and TFM-50 implants showed significantly higher BIC% values (64.9 ± 14.0%, ~2.5 fold; 47.1 ± 14.1%, ~2 fold) compared to Control (23.6 ± 17.4%). Finally, TFM-22 implants showed more and thicker trabeculae in the peri-implant region. SIGNIFICANCE: This in vivo study demonstrated that implants with a flexible coating of TFM improve bone formation within the inter-fiber space and the peri-implant region.

Surface Engineering for Dental Implantology: Favoring Tissue Responses Along the Implant.

Dental implants represent an illustrative example of successful medical devices used in increasing numbers to aid (partly) edentulous patients. Particularly in spite of the percutaneous nature of dental implant systems, their clinical success is remarkable. This clinical success is at least partly related to the effective surface treatment of the artificial dental root, providing appropriate physicochemical properties to achieve osseointegration. The demographic changes in the world, however, with a rapidly increasing life expectancy and an increase in patients suffering from comorbidities that affect wound healing and bone metabolism, make that the performance of dental implants requires continuous improvement. An additional factor endangering the clinical success of dental implants is peri-implantitis, which affects both the soft and hard tissue interactions with dental implants. In this study, we shed light on the optimization of dental implant surfaces through surface engineering. Depending on the region along the artificial dental root, different properties of the surface are required to optimize prevailing tissue response to facilitate osseointegration, improve soft tissue attachment, and exert antibacterial efficacy. As such, surface engineering represents an important tool for assuring the continued future success of dental implants. Impact Statement Dental implants represent a common treatment modality nowadays for the replacement of lost teeth or fixation of prosthetic devices. This review provides a detailed overview of the role of surface engineering for dental implants and their components to optimize tissue responses at the different regions along the artificial dental root. The surface properties steering immunomodulatory processes, facilitating osseointegration, and rendering antibacterial efficacy (at both artificial root and abutment region) are described. The review finally concludes that surface engineering provides a tool to warrant that dental implants will remain future proof in more challenging applications, including an aging patient population and comorbidities that affect bone metabolism and wound healing.

Lower prevalence of hepatic fibrosis in low viremic hepatitis B patients with fluctuating HBV DNA levels.

Background: In chronic hepatitis B virus (HBV) patients, fluctuations in HBV DNA serve as a "gray area" and impede the accurate identification of inactive carriers. We aimed to assess if such fluctuations impact the presence of significant hepatic fibrosis (Metavir F2-4) in chronic HBV patients. Methods: Consecutive, untreated HBeAg-negative carriers (n = 234) with fluctuating HBV DNA (n = 73) above or below a level of 2000 IU/mL were included and compared to those without fluctuations (n = 161). Patients without fluctuating HBV DNA were further analyzed based on those with persistently low (<2,000 IU/mL, n = 137) and higher HBV DNA (2,000-20,000 IU/mL, n = 24). Hepatic fibrosis (assessed by transient elastography) was correlated with virologic and biochemical profiles. Results: The mean age of the overall cohort was 47.8 ± 11.1 years, of whom 107 (45.7%) were male. During a median of 60 months (interquartile range [IQR] 34-82) of follow-up, 73 (31.2%) patients had a mean of 1.6 ± 0.9 fluctuations in HBV DNA. The median time to the first fluctuation was at 14.5 (IQR 5.0-33.7) months. Patients with fluctuating viremia had higher log10 qHBsAg (3.1 ± 0.8 vs. 2.7 ± 1.0, P = 0.022) and HBV DNA (3.4 ± 0.5 vs. 2.7 ± 0.8, P < 0.001) compared to those without fluctuations. Patients with fluctuant viremia were less likely to have F2-4 fibrosis (8.2%) compared to those without fluctuant viremia (18.2%, odds ratio [OR]: 0.407, 95% confidence interval [CI]: 0.161-1.030; P = 0.052). Males tended to have less fluctuation constituting 37.0% of patients with fluctuating HBV DNA (P = 0.071). Fluctuations occurred more frequently in those with predominantly higher HBV DNA levels (26.0%) compared to those without fluctuations (14.9%; P = 0.030). Conclusions: Fluctuating HBV DNA levels occur frequently but are not associated with significant fibrosis. Minor fluctuations in HBV DNA levels are unlikely to be of clinical relevance.

Peri-Implant bone response around porous-surface dental implants: A preclinical meta-analysis.

INTRODUCTION: This meta-analysis of relevant animal studies was conducted to assess whether the use of porous-surface implants improves osseointegration compared to the use of non-porous-surface implants. MATERIAL AND METHODS: An electronic search of PubMed (MEDLINE) resulted in the selection of ten animal studies (out of 865 publications) for characterization and quality assessment. Risk of bias assessment indicated poor reporting for the majority of studies. The results for bone-implant contact (BIC%) and peri-implant bone formation (BF%) were extracted from the eligible studies and used for the meta-analysis. Data for porous-surface implants were compared to those for non-porous-surface implants, which were considered as the controls. RESULTS: The random-effects meta-analysis showed that the use of porous-surface implants did not significantly increase overall BIC% (mean difference or MD: 3.63%; 95% confidence interval or 95% CI: -1.66 to 8.91; p = 0.18), whereas it significantly increased overall BF% (MD: 5.43%; CI: 2.20 to 8.67; p = 0.001), as compared to the controls. CONCLUSION: Porous-surface implants promote osseointegration with increase in BF%. However, their use shows no significant effect on BIC%. Further preclinical and clinical investigations are required to find conclusive evidence on the effect of porous-surface implants.

Histological and Histomorphometric Analyses of Bone Regeneration in Osteoporotic Rats Using a Xenograft Material.

We evaluated the effect of osteoporotic induction after eight weeks of initial healing of bone defects grafted with a xenograft material in a rat model. Bone defects were created in the femoral condyles of 16 female Wistar rats (one defect per rat). The defects were filled with bovine bone (Inter-Oss) granules. After eight weeks of bone healing, rats were randomly ovariectomized (OVX) or sham-operated (SHAM). At 14 weeks of bone healing, all animals were euthanized. Bone specimens were harvested and processed for histological and histomorphometric analyses to assess new bone formation (N-BF%), remaining bone graft (RBG%) and trabecular bone space (Tb.Sp%) within the defect area. After 14 weeks of bone healing, histological evaluation revealed a significant alteration in trabecular bone in OVX rats compared to SHAM rats. There was lower N-BF% in OVX rats (22.5% ± 3.0%) compared to SHAM rats (37.7% ± 7.9%; p < 0.05). Additionally, the RBG% was significantly lower in OVX (23.7% ± 5.8%) compared to SHAM (34.8% ± 9.6%; p < 0.05) rats. Finally, the Tb.Sp% was higher in OVX (53.8% ± 7.7%) compared to SHAM (27.5% ± 14.3%; p < 0.05) rats. In conclusion, within the limitations of this study, inducing an osteoporotic condition in a rat model negatively influenced bone regeneration in the created bone defect and grafted with a xenograft material.

Impact of Single or Combined Drug Therapy on Bone Regeneration in Healthy and Osteoporotic Rats.

Complications in bone regeneration in patients with systemic impaired bone metabolism (e.g., osteoporosis) represent a rapidly increasing clinical challenge. Alendronate and simvastatin are drugs commonly used to promote bone metabolism in osteoporotic conditions. The aim of this study was to evaluate initial bone regeneration within osseous defects grafted with beta-tricalcium phosphate (ß-TCP) in adjunction with systemic coadministrations of alendronate and simvastatin (i.e., daily subcutaneous injection for 3 weeks) in healthy and osteoporotic rats. Eighty Wistar female rats were ovariectomized (OVX; n = 40) or sham operated (n = 40). Six weeks later, osseous defects (a 3-mm critical-sized defect) were created in the left femoral condyles and then grafted with ß-TCP. From the day following graft installation, OVX and sham animals received for 3 weeks a daily subcutaneous injection of alendronate (50 µg/kg of body weight) and simvastatin (5 mg/kg of body weight), alone or in combination. A control group was included, which received subcutaneous saline administration. At the end of the 3 weeks, rats were euthanized and specimens (femoral condyles) were retrieved for histological evaluation and histomorphometric measurements, that is, bone area (BA%) and remaining bone graft (RBG%). In osteoporotic rats, 3 weeks of daily subcutaneous injection of combined therapy (alendronate plus simvastatin) led to a significant (p < 0.05) increase in BA% and a significant decrease in RBG% compared to healthy controls in osseous defects grafted with ß-TCP (BA%: 28.6 ± 12.0 vs. 18.2 ± 7.6, RBG% 61.3 ± 11.1 vs. 70.7 ± 7.3). No significant differences in BA% and RBG% were found in the OVX rats for single treatments. Furthermore, healthy controls showed similar BA% and RBG% upon single or combined therapy compared to nontreated control rats. Daily coinjections (for 3 weeks) of alendronate plus simvastatin result in a significant enhancement of bone regeneration within osseous defects grafted with ß-TCP in osteoporotic rats. Despite the expected effects on osteoporotic bone, our study did not confirm the hypothesized benefit of alendronate and simvastatin on bone regeneration in osseous defects in healthy conditions. The efficacy of the combination drug therapy on bone regeneration demands further investigation to elucidate molecular and cellular aspects underlying this therapy.

The development and future of dental implants.

Since 1970s, a lot of effort has been devoted toward the development of dental implants. Dental implants are nowadays an indispensable part of clinical dentistry. The global dental implant market is expected to reach $13 billion in 2023. Although, the survival rate of dental implants has been reported above 90%, compromised bone conditions promote implant failure and endanger the current high success rates. The main concern is related to the aging population. Diabetes, osteoporosis, obesity and use of drugs are all medical conditions, which can hamper bone healing around dental implants. In view of this, research toward developing better methods of enhancing implant osseointegration have to be continued, especially in the presence of impaired bone condition. In this paper, the current changes and their future perspective are discussed.

Histomorphometric Evaluation of Peri-Implant Bone Response to Intravenous Administration of Zoledronate (Zometa®) in an Osteoporotic Rat Model.

We evaluated the response to peri-implant bone placed in the femoral condyle of osteoporotic rats, following intravenous zoledronate (ZOL) treatment in three settings: pre-implantation (ZOL-Pre), post-implantation (ZOL-Post), and pre- + post-implantation (ZOL-Pre+Post). Twenty-four female Wistar rats were ovariectomized (OVX). After 12 weeks, the rats received titanium implants in the right femoral condyle. ZOL (0.04 mg/kg, weekly) was administered to six rats 4 weeks pre-implantation and was stopped at implant placement. To another six rats, ZOL was given post-implantation and continued for 6 weeks. Additional six rats received ZOL treatment pre- and post-implantation. Control animals received weekly saline intravenous injections. At 6 weeks post-implantation, samples were retrieved for histological evaluation of the percentage of bone area (%BA) and of the percentage of bone-to-implant contact (%BIC). BA% for ZOL-Pre (29.6% ± 9.0%) and ZOL-Post (27.9% ± 5.6%) rats were significantly increased compared to that of the controls (17.3% ± 3.9%, p < 0.05). In contrast, ZOL-Pre+Post rats (20.4% ± 5.0%) showed similar BA% compared to Saline controls (p = 0.731). BIC% revealed a significant increase for ZOL-Post (65.8% ± 16.9%) and ZOL-Pre+Post (68.3% ± 10.0%) rats compared with that of Saline controls (43.3% ± 9.6%, p < 0.05), while ZOL-Pre rats (55.6% ± 19%) showed a BIC% comparable to that of Saline controls (p = 0.408). Our results suggest that receiving intravenous ZOL treatment before or after implant placement enhances peri-implant bone responses in terms of bone area. However, the effect of different ZOL treatment regimens on BIC% was found to be inconclusive.

Antiosteoporotic Drugs to Promote Bone Regeneration Related to Titanium Implants: A Systematic Review and Meta-Analysis.

IMPACT STATEMENT: This meta-analysis was to investigate literature on the administration of antiosteoporotic drugs as an effective adjunct therapy for implant osseointegration using in vivo animal models.

Bone Regeneration Using Antiosteoporotic Drugs in Adjunction with Bone Grafting: A Meta-Analysis.

The aim of this review was to systematically assess bone regeneration by using antiosteoporotic drugs in adjunction with bone grafting compared with controls (bone grafting without the administration of antiosteoporotic drugs). The review also evaluated statistical differences in the effect between systemic and local routes of drugs. Also, the effect of type of drugs (anticatabolic vs. anabolic) was subevaluated. PubMed and EMBASE (via OvidSP) resulted in inclusion of 60 animal studies. The studies were assessed for reporting quality and risk of bias. Outcome data from selected studies were categorized as either experimental (bone grafting with the administration of antiosteoporotic drugs) or control. Meta-analysis of selected studies was done for these outcomes: histomorphometrical bone area (BA%) and micro-CT bone volume (BV%). In this review, several animal models (52 healthy, 6 osteoporotic, and 2 both conditions) were subjected to examine the effect of antiosteoporotic drugs on bone grafting, with a predominant use of rodent species. Assessment indicates poor reporting quality and unclear risk of bias in the majority of studies. Random-effects meta-analysis revealed a significant increase in overall BA% (mean difference [MD]: 2.6, confidence interval [CI]: 2.25 to 2.92) and BV% (MD: 0.12, CI: 0.05 to 0.19) due to osteoporotic drug treatment compared with controls. For subgroups, both routes of antiosteoporotic drug administration showed similar effects on BA%. In contrast, systemic antiosteoporotic drug administration led to significantly higher BV% (MD: 6.75, CI: 5.30 to 8.19) compared with local administration (MD: 0.02, CI: -0.03 to 0.08). Further, administration of anabolic drugs significantly increased BA% (MD: 5.75, CI: 4.62 to 6.87) compared with anticatabolic drugs (MD: 1.86, CI: 1.47 to 2.26). In conclusion, both histomorphometrical and micro-CT scan analysis indicated an overall effect of using the antiosteoporotic drugs toward bone regeneration in adjunction with grafting. However, not all studies showed a positive effect and the present results need to be applied with care, as the included papers showed experimental heterogeneity for animal models. Further (pre)clinical research is warranted to explore whether drug-based strategies can be an effective adjunctive with bone grafting. Impact Statement The aim of this meta-analysis was to assess whether antiosteoporotic drugs can promote bone regeneration in adjunction with bone grafting by using preclinical animal models. Although the majority of included studies indicated poor reporting quality and unclear risk of bias, an overall positive effect of the antiosteoporotic drugs toward bone regeneration related to bone grafts can be highlighted.

Surface modification of pH-responsive poly(2-(tert-butylamino)ethyl methacrylate) brushes grafted on mesoporous silica nanoparticles.

Poly(2­(tert-butylamino)ethyl methacrylate) brushes (PTBAEMA) are grown from mesoporous silica nanoparticles via surface-initiated atom transfer radical polymerization (SI-ATRP). Linear PTBAEMA brushes are protonated and highly swollen at low pH; brushes are collapsed at pH higher than 7.7 due to deprotonation, as determined by dynamic light scattering (DLS). Quaternization of these brushes is conducted using 2-iodoethanol in alkali media. DLS measurement of nanoparticles shows that surface-confined quaternization occurs and produces pH-responsive brushes with a hydrophobic upper surface. Variation of the 2-iodoethanol reaction time enables the mean degree of surface quaternization. The pH-responsive behaviour of quaternized PTBEAMA brushes at 1 h reaction time indicates low degrees of surface quaternization, dictated by the spatial location of 2-iodoethanol. Almost uniformly quaternized brushes prepared when the conducted for 3 h and became less swollen at low pH than brushes that conducted for 1 h. The intensity of the C - C - O component (286.5 eV) in the C1s X-ray photoelectron spectrum increased, suggesting that the reaction with iodoethanol was successful occurred.