A randomized clinical trial of phycogenic materials for sinus grafting with hydroxyapatite versus biphasic calcium phosphate: 2 years clinical outcomes.

OBJECTIVES: To assess in a prospective randomized trial two phycogenic bone substitutes-biphasic calcium phosphate (BCP) versus almost pure hydroxyapatite (HA)-for their volume stability and clinical implications after sinus floor elevation (SFE). MATERIALS AND METHODS: Twenty patients requiring lateral-window SFE 6 months prior to implant surgery were randomized to a BCP or HA group. As primary outcome, the grafts were analyzed for volume stability, using four cone-beam computed tomography scans obtained immediately/6/12/24 months after SFE. Secondary outcomes were implant survivval, success, periotest values, oral-health-related quality of life (OHIP-G14), and pain (VAS). RESULTS: Kolmogorov-Smirnov goodness-of-fit test revealed normal distribution of samples (p = .200). At 6/12/24 months, the augmented volumes decreased to 96/92/90% (HA) or 99/96/96% (BCP). Volume changes were significantly a factor of time (p < .001; generalized linear model with repeated measures) and reached significantly lower values in HA group (p = .018). Significant intergroup difference in volume losses was notable at 24 months (p = .021; t-test for independent samples). Periotest values decreased from -3/-4.1 (HA/BCP) after implant placement to -6.3/-4.5 (HA/BCP) after 6 months. OHIP scores diverged at 2 months (HA: 9.5; BCP: 5.2) and largely resolved by 24 months (HA: 1.3; BCP: 1.9). VAS scores were comparable, 2.2 at 1 week after SFE being their highest mean level. CONCLUSIONS: After 2 years, both groups experienced no biological or technical complications, demonstrating a consistent healing trajectory without notable symptoms. Although no significant differences were observed in implant stability and survival, BCP demonstrated higher volume stability than HA.

Self-propelled bioglass janus nanomotors for dentin hypersensitivity treatment.

Dentin hypersensitivity treatment is not always successful owing to the exfoliation of the blocking layer. Therefore, efficiently delivering a desensitization agent into the dental tubule is critical. Nanomotors are widely used as in vivo drug delivery systems owing to their strong power and good biocompatibility. Herein, we report a kind of self-propelled bioglass Janus nanomotor with a Pt motion unit (nBGs@Pt) for application in dentin hypersensitivity that was prepared via a simple sol-gel method and magnetron sputtering method, with an average size of 290 nm. The Pt layer as the power unit provided the dynamics to deliver the bioglass (desensitization agent). Using hydrogen peroxide as a fuel, the nBGs@Pt could automatically move in different media. In addition, the nBGs@Pt with a mesoporous structure demonstrated good hydroxyapatite formation performance. An in vitro dentin pressure model was used to verify the blocking ability of the nBGs@Pt in dentin tubules. The dynamics of the nBGs@Pt was sufficient to resist the outflow of dentin fluid and movement into the dentin tubules, with a blocking rate of 58.05%. After remineralization, the blocking rate could reach 96.07% and the formation of hydroxyapatite of up to 10 µm or more occurred. It is expected that this study will provide a simple and feasible new strategy for the painless treatment of dentin sensitivity.

Effect of different HA/ß-TCP coated 3D printed bioceramic scaffolds on repairing large bone defects in rabbits.

BACKGROUND: Treatment of large segmental bone defects is still a major clinical challenge, and bone grafting is the main method. The development of novel bone graft substitutes will help solve this problem. METHODS: Porous bioceramics hydroxyapatite (HA) scaffolds coated with different ratios of HA/ß-tricalcium phosphate (ß-TCP) were prepared by 3D printing. The scaffolds were sampled and tested in large segmental bone defect rabbit models. X-ray, micro-computed tomography (CT), hematoxylin and eosin (HE) staining, Van-Gieson staining, and type I collagen staining were performed to find the best scaffolds for large segmental bone defect treatment. RESULTS: The average length, diameter, compressive strength, and porosity of the bioceramics scaffolds were 15.05 ± 0.10 mm, 4.98 ± 0.06 mm, 11.11 ± 0.77 MPa, and 54.26 ± 5.38%, respectively. Postoperative lateral radiographs suggested the scaffold group got better bone healing and stability than the blank group. Micro-CT showed new bones grew into the scaffold from the two ends of the fracture along the scaffold and finally achieved bony union. The new bone volume around the scaffolds suggested the 3:7 HA/ß-TCP-coated bioceramic scaffolds were more favorable for the healing of large segmental bone defects. The results of HE, Van-Gieson, and type I collagen staining also suggested more new bone formation in 3:7 HA/ß-TCP-coated bioceramic scaffolds. CONCLUSION: 3:7 HA/ß-TCP-coated porous bioceramics scaffolds are more conducive to the repair of large bone defects in rabbits. The results of this study can provide some reference and theoretical support in this area.

Treatment of Spinal Aneurysmal Bone Cyst with Percutaneous Injection of Hydroxyapatite Osteoconductive Cement.

PURPOSE: The aim of this study was to evaluate treatment efficacy of percutaneous injection of hydroxyapatite-osteoconductive-cement in patients with spinal aneurysmal bone cysts. MATERIALS AND METHODS: The study was designed as a retrospective observational clinical study. We included patients who were diagnosed with of spinal aneurysmal bone cyst, at our institution between 2013 and 2020, and treated with percutaneous injection of osteoconductive cement: "Cerament"® (BONESUPPORT AB, Lund, Sweden). Typical clinical and radiological features of the ABCs treatment and follow-up were investigated. RESULTS: Our study included nine patients, two children and seven adults. Three different types of approaches were applied: (single pedicle approach in 3 patients; double pedicle approach in 2 patients; while in the remaining cases, a multiple access approach was used. VAS score decreased from 8.5 ± 0.5 before treatment to 4.1 ± 0.9 at 6-months-follow up. All of the patients reacted well to treatment, with none neurological complications, complete loss of pain and achieved osteosclerosis as radiological marker of treatment success. CONCLUSION: Treatment of symptomatic spinal ABC's with hydroxyapatite cement is effective to achieve complete pain reduction and sclerosis.

Molecular Complex of HSIM-loaded Polymeric Nanoparticles: Potential Carriers in Osteoporosis.

BACKGROUND: Statins, especially simvastatin promote bone formation by stimulating the activity of osteoblasts and suppressing osteoclast activity via the BMP-Smad signaling pathway. Statins present the liver first-pass metabolism. This study attempts to fabricate and evaluate simvastatin functionalized hydroxyapatite encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (HSIM-PLGA NPs) administered subcutaneously with sustained release properties for effective management of osteoporosis. METHODS: Simvastatin functionalized hydroxyapatite (HSIM) was prepared by stirring and validated by docking studies, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Further, HSIM-loaded PLGA nanoparticles (HSIM-PLGA NPs) were developed via the solvent emulsification method. The nanoparticles were evaluated for zeta potential, particle size, entrapment efficiency, stability studies, and in vitro drug release studies. in vitro binding affinity of nanoparticles for hydroxyapatite was also measured. Bone morphology and its effect on bone mineral density were examined by using a glucocorticoid-induced osteoporosis rat model. RESULTS: The optimized nanoparticles were found to be amorphous and showed no drug-polymer interaction. The particle size of formulated nanoparticles varied from 196.8 ± 2.27nm to 524.8 ± 5.49 nm and the entrapment efficiency of nanoparticles varied from 41.9 ± 3.44% to 70.8 ± 4.46%, respectively. The nanoparticles showed sustained release behaviour (75% in 24 hr) of the drug followed by non-fickian drug release. The nanoparticles exhibited high binding affinity to bone cell receptors, increasing bone mineral density. A significant difference in calcium and phosphorous levels was observed in disease and treatment rats. Porous bone and significant improvement in porosity were observed in osteoporotic rats and treated rats, respectively (P < 0.05). CONCLUSION: Bone-targeting nanoparticles incorporating functionalized simvastatin can target bone. Thus, in order to distribute simvastatin subcutaneously for the treatment of osteoporosis, the developed nanoparticles may act as a promising approach.

A novel rapidly mineralized biphasic calcium phosphate with high acid-resistance stability for long-term treatment of dentin hypersensitivity.

OBJECTIVES: Treating dental hypersensitivity (DH) rapidly and maintaining long-term effectiveness remains challenging. We aimed to address this problem by fabricating a novel rapidly mineralized biphasic calcium phosphate (RMBCP), which could rapidly elicit mineralization to form hydroxyapatite (HA) and perform excellent acid-resistant stability, thus effectively blocking the exposed dental tubules and protecting them from acid attack. METHODS: RMBCP was firstly synthesized by precisely adjusting the molar ratio of acetic acid and calcium hydroxide and characterized by X-ray diffraction (XRD), X-ray fluorescence microprobe (XRF), Fourier-transform infrared (FTIR) spectrometer, scanning electron microscope (SEM), and transmission electron microscope (TEM). Subsequently, using a commercialized desensitizing agent, 45S5 bioglass (BG), as the control group, the mineralization performance of RMBCP was investigated in simulated body fluid (SBF), Dulbecco's modified eagle medium (DMEM), and even slightly acidic artificial saliva (pH=6.6). Moreover, the biocompatibility of RMBCP was studied. Finally, the tubule occlusion effect and acid-resistant stability of RMBCP were evaluated in vitro and in vivo. RESULTS: The rapid mineralization behavior of RMBCP could easily adhere to the dentin surface and block the dentinal tubules completely in vitro and in vivo within 7days. RMBCP performed high acid-resistant stability to maintain the long-term therapeutic effect of DH treatment. SIGNIFICANCE: Developing novel bioactive calcium phosphate materials with the ability to trigger mineralization for HA formation rapidly will be an effective strategy for the long-term treatment of dentin hypersensitivity.

Aminobisfosfonatos: reconsideración a los 25 años de su aprobación para el tratamiento de la osteoporosis / Aminobisphosphonates: Reconsideration 25 years after their approval for the treatment of osteoporosis

Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis. (AU)

Los aminobisfosfonatos se utilizan ampliamente en el tratamiento de la osteoporosis. Tienen gran afinidad por la hidroxiapatita, uniéndose fundamentalmente a las superficies en resorción, pero también a las superficies en formación y, en cierta medida, a las superficies en reposo. Inhiben a los osteoclastos, con lo que disminuyen las unidades de remodelación. En consecuencia, aumentan la masa ósea y reducen los concentradores de tensión. Ello disminuye el riesgo de fracturas. Si esta disminución es suficiente, pueden retirarse transitoriamente (vacaciones terapéuticas), lo que previene complicaciones graves (fractura atípica de fémur). Probablemente disminuyen la mortalidad. Pueden beneficiarse de ellos prácticamente todos los enfermos con osteoporosis en algún momento de su evolución (al comienzo del tratamiento o tras la administración de anabólicos, moduladores selectivos de los receptores estrogénicos o denosumab). Con buena tolerancia oral son preferibles el alendronato y el risedronato. En caso contrario, lo es el zoledronato. Su relación eficacia frente a coste-seguridad-comodidad los convierte en fármacos de referencia en el campo de la osteoporosis. (AU)

Novel Therapeutic Agents for Rare Diseases of Calcium and Phosphate Metabolism.

The last decade has been revolutionary regarding the management of rare bone diseases caused by impaired calcium and phosphate metabolism. Elucidation of the underlying genetic basis and pathophysiologic alterations has been the determinant factor for the development of new, disease-specific treatment agents. The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) possesses a critical role in the pathogenesis of various hypophosphatemic disorders. Among them, the genetic disorder of X-linked hypophosphatemia and the acquired syndrome of tumor-induced osteomalacia, although very rare, have attracted the scientific community's attention towards designing an FGF23-inhibitor as a potential specific therapy. The monoclonal antibody burosumab was approved for the treatment of children and adult patients with X-linked hypophosphatemia and recently for tumor-induced osteomalacia patients, demonstrating benefits regarding their symptoms, biochemical profile and bone mineralization status. Asfotase alfa is a hydroxyapatite-targeted recombinant alkaline phosphatase, an enzymatic replacement therapy, substituting the defective activity of tissue non-specific alkaline phosphatase, in patients suffering from hypophosphatasia. Promising data regarding its favorable effect on survival rate, bone quality, fracture healing, muscle strength, mobility, respiratory function, and general quality of life have led to the approval of the drug for the treatment of childhood-onset hypophosphatasia. Given the high costs of treatment for both agents and their limited clinical use until now, more data are needed to define patients' characteristics that make them ideal candidates for therapy. Long-term safety issues also need to be clarified.

Evaluation of Remineralization Potential of Remin Pro Forte vs Remin Pro on White Spot Lesions: A Randomized Clinical Trial.

AIM: This study was conducted to evaluate the remineralization potential of Remin Pro Forte vs Remin Pro remineralizing agents on white spot lesions (WSLs) post-orthodontic treatment. MATERIALS AND METHODS: Twenty patients with post-orthodontic WSLs were divided into the following two equal groups based on treatment (n = 10): (1) A 3-month program of hydroxyapatite, fluoride, xylitol, ginger, curcuma-containing cream (Remin Pro Forte) as intervention group; (2) A 3-month cream regimen including hydroxyapatite and fluoride, xylitol (Remin Pro) as control group. The main outcomes including caries regression (assessed by ICDAS II), mineral content (assessed by VistaCam iX camera), and color of WSLs (assessed by digital image analysis by Adobe photoshop) were measured at the time of enrollment and 1, 2, and 3 months afterward. Mann-Whitney test used to compare between tested groups. The statistical significance was set at p <0.05. RESULTS: Both Remin Pro Forte and Remin Pro elicited much better caries regression and significantly higher mineral content in WSLs over a 3-month period (p <0.05). However, the difference in mineral content of WSLs between groups did not reach statistical significance (p = 0.414). In both experimental groups, the appearance of WSLs improved significantly (p <0.05). CONCLUSION: Both Remin Pro Forte and Remin Pro were successful in reducing caries, increasing mineral content, and enhancing the appearance of demineralized enamel, indicating that both products could be suggested for post-orthodontic WSL management. CLINICAL SIGNIFICANCE: Natural herbal products could be employed as remineralizing agents and included into tooth preventive measures. It is a less harmful alternative to traditional chemical remineralization methods.

An engineered dual function peptide to repair fractured bones.

Targeted drug delivery, often referred to as "smart" drug delivery, is a process whereby a therapeutic drug is delivered to specific parts of the body in a manner that increases its concentration at the desired sites relative to others. This approach is poised to revolutionize medicine as exemplified by the recent FDA approval of Cytalux (FDA approves pioneering drug for ovarian cancer surgery - Purdue University News) which is a folate-receptor targeted intraoperative near infrared (NIR) imaging agent that was developed in our laboratories. Fracture-associated morbidities and mortality affect a significant portion of world population. United states, Canada and Europe alone spent $48 billion in treating osteoporosis related fractures although this number doesn't count the economic burden due to loss in productivity. It is estimated that by 2050 ca 21 million hip fractures would occur globally which will be leading cause of premature death and disability. Despite the need for improvement in the treatment for fracture repair, methods for treating fractures have changed little in recent decades. Systemic delivery of fracture-homing bone anabolics holds great promise as a therapeutic strategy in this regard. Here we report the design of a fracture-targeted peptide comprised of a payload that binds and activates the parathyroid hormone receptor (PTHR1) and is linked to a targeting ligand comprised of 20 D-glutamic acids (D-Glu20) that directs accumulation of the payload specifically at fracture sites. This targeted delivery results in reduction of fracture healing times to <1/2 while creating repaired bones that are >2-fold stronger than saline-treated controls in mice. Moreover, this hydroxyapatite-targeted peptide can be administered without detectable toxicity to healthy tissues or modification of healthy bones in dogs. Additionally, since similar results are obtained upon treatment of osteoporotic and diabetic fractures in mice, and pain resolution is simultaneously accelerated by this approach, we conclude that this fracture-targeted anabolic peptide displays significant potential to revolutionize the treatment of bone fractures.

Research progress of bone-targeted drug delivery system on metastatic bone tumors.

Bone metastases are common in malignant tumors and the effect of conventional treatment is limited. How to effectively inhibit tumor bone metastasis and deliver the drug to the bone has become an urgent issue to be solved. While bone targeting drug delivery systems have obvious advantages in the treatment of bone tumors. The research on bone-targeted anti-tumor therapy has made significant progress in recent years. We introduced the related tumor pathways of bone metastases. The tumor microenvironment plays an important role in metastatic bone tumors. We introduce a drug-loading systems based on different environment-responsive nanocomposites for anti-tumor and anti-metastatic research. According to the process of bone metastases and the structure of bone tissue, we summarized the information on bone-targeting molecules. Bisphosphate has become the first choice of bone-targeted drug delivery carrier because of its affinity with hydroxyapatite in bone. Therefore, we sought to summarize the bone-targeting molecule of bisphosphate to identify the modification effect on bone-targeting. And this paper discusses the relationship between bisphosphate bone targeting molecular structure and drug delivery carriers, to provide some new ideas for the research and development of bone-targeting drug delivery carriers. Targeted therapy will make a more outstanding contribution to the treatment of tumors.

Aminobisphosphonates: Reconsideration 25 years after their approval for the treatment of osteoporosis. / Aminobisfosfonatos: reconsideración a los 25 años de su aprobación para el tratamiento de la osteoporosis.

Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis.

Effects of rhBMP-2-loaded hydroxyapatite granules/beta-tricalcium phosphate hydrogel (HA/ß-TCP/hydrogel) composite on a rat model of caudal intervertebral fusion.

The effects and inflammation-related side effects of bone morphogenetic protein (BMP)-2 on posterior lumbar interbody fusion are controversial. One of the potential causes for the inconsistent results is the uncontrolled release of BMP-2 from the collagen carrier. Therefore, BMP delivery systems that support effective bone regeneration while attenuating the side effects are strongly sought for. We developed NOVOSIS putty (NP), a novel composite material of hydroxyapatite (HA), beta-tricalcium phosphate (ß-TCP)/hydrogel, and BMP-2, which can sustainably release BMP-2 over 2 weeks. This study was aimed at comparing the effects and side effects of NP and collagen sponge (CS) containing BMP-2 using a rat caudal intervertebral fusion model. The fusion rates of NP with low and high doses of BMP-2 were significantly higher than those of an iliac bone (IB) graft, but those of CS with low and high doses of BMP-2 were not different from those of the IB graft. Furthermore, the incidences of ectopic bone formation and soft tissue swelling were significantly lower in the NP group than in the CS group. The HA/ß-TCP/hydrogel carrier enabled superior bone induction with low-dose BMP-2 and decreased the incidence of side effects caused by high-dose BMP-2 vis-à-vis the collagen carrier.

In-silico Validation of the Proposed Treatment Strategy of Periodontitis.

OBJECTIVE: The present study aims to assess a proposed treatment approach or therapy for periodontitis by using the in-silico technique. The proposed treatment strategy offers a singular vehicular system consisting of minocycline (antibiotic), celecoxib (selective COX-II inhibitor), doxycycline hyclate (matrix metalloproteinase inhibitor), and hydroxyapatite (osteogenic agent). MATERIAL AND METHODS: Molecular docking studies of drugs were performed using Maestro version 9.4 software Schrödinger, and 3-Dimensional Crystallographic X-ray protein structures of targeted proteins were downloaded from RCSB protein data bank in .pdb file format. These agents were docked, and their affinities towards the receptors/protein/enzyme were calculated. Furthermore, their affinities were compared with the standard drug. RESULTS: The study suggests that minocycline and metronidazole possess equal affinity towards the RGPB and Inlj protein of P.gingivalis. Celecoxib, a well-known inhibitor of the COX-II enzyme, showed very high affinity. Selective inhibitor of MMP-8 possessed higher affinity than doxycycline, whereas CMT-3 showed equal affinity as doxycycline for MMP-13. Similarly, hydroxyapatite and simvastatin also showed a comparatively similar affinity for osteopontin receptor. CONCLUSION: Based upon molecular docking results, it can be concluded that the proposed treatment strategy would be a suitable approach for periodontitis and all the selected therapeutic agents have potential similar to the standard drugs, thereby constituting a reliable system for periodontitis.

Bonding Reactions of Dental Self-Adhesive Cements with Synthetic Hydroxyapatite as a Function of the Polymerization Protocol.

OBJECTIVES: This study evaluated the influence of the cement composition and different polymerization protocols on the bonding chemical interaction of self-adhesive cements with synthetic hydroxyapatite. MATERIALS AND METHODS: Two commercial self-adhesive resin cements (RelyX U200 and Maxcem Elite) were selected, manipulated, mixed with hydroxyapatite dry powder (HAp), dispensed into molds, and distributed into three groups according to polymerization protocols: immediate photoactivation (IP); delayed photoactivation, 10 min self-curing and light-curing (DP); and chemical activation (CA, no light exposure). The detailed chemical information, at atomic scale, on the surface and deeper into the bulk of self-adhesive cement/hydroxyapatite mixtures was evaluated with X-ray photoelectron spectroscopy (XPS). RESULTS: Chemical elements were detected in both cements, such as Na, O, Ca, C, P, and Si. Other elements were detected in minor concentrations. RelyX U200 exhibited the most intense formation of calcium salts products when the cement/HAp mixtures were photoactivated (immediate or delayed). RelyX U200/HAp mixture under delayed photoactivation (DP) also exhibited higher binding energy between calcium moieties of the HAp and methacrylates in the cement. A higher energy difference in the interaction of HAp with the cement comparing the bulk and surface areas was observed when RelyX U200 underwent the delayed photoactivation protocol. Maxcem Elite exhibited an increased chemical reactivity when either chemically activated or immediately photoactivated and a higher binding energy of the carboxyl groups bonded to the calcium of HAp when chemically activated. CONCLUSIONS: The interaction of cements with hydroxyapatite is chemical in nature and leads to the formation of calcium salts, which may favor better integrity and longevity of adhesive restorations. The polymerization protocol affects the chemical interaction in mixtures of self-adhesive cements and hydroxyapatite, influencing the formation of these salts and the establishment of intermolecular interactions between the HAp and the cements.

A novel BMP-2-loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration.

Although bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. Therefore, there is a strong need for BMP delivery systems that maximize osteoinductivity while preventing adverse effects. We evaluated the bone-regenerating potential of NOVOSIS putty (NP), a novel composite combining hydroxyapatite, beta-tricalcium phosphate microsphere/poloxamer 407-based hydrogel, and recombinant human (rh) BMP-2. In vitro assessment of release kinetics by enzyme-linked immunosorbent assay demonstrated sustained release of rhBMP-2 from NP and burst release from collagen sponge (CS), and in vivo assessment of release kinetics by longitudinal tracking of fluorescently labeled rhBMP-2 showed a longer biological half-life of rhBMP-2 with NP than with CS. Furthermore, osteogenic gene expression in MC3T3-E1 cells was significantly higher after co-culture with NP than after co-culture with CS, suggesting that the sustained release of rhBMP-2 from NP effectively contributed to the differentiation of osteoblasts. In a rat spinal fusion model, the volume and quality of newly formed bone was higher in the NP group than in the CS group. Use of NP results in efficient bone regeneration through sustained release of rhBMP-2 and improves the quality of BMP-induced bone.

Osteotome-mediated sinus floor elevation using an in situ hardening biphasic calcium phosphate bone graft substitute compared to xenograft: A randomized controlled clinical trial.

AIM: To assess osteotome-mediated sinus floor elevation (OMSFE) with simultaneous implant placement using an in situ hardening biphasic calcium phosphate (BCP) compared to xenograft as a control. METHODS: Patient in need for sinus floor augmentation in one or both sinuses were selected for this randomised controlled clinical trial. Sites presenting a residual sinus floor height of 3-6 mm and eligible for OMSFE were randomly assigned to receive either BCP (test) or xenograft particles (control). CBCT scans were performed before and at the time of implant loading (180 days). The difference in sinus floor height gain between the two groups was set as the primary endpoint parameter for equivalence testing. The implant insertion torque (ITV) was recorded and Implant stability quotients (ISQ) was assessed upon implant placement, abutment connection (160 days) and implant loading (180 days). RESULTS: A total of 54 sinus lifts were performed in 42 patients including 12 bilateral cases. Four implants failed (two in each group) and a total of six patients were lost to follow-up. Statistical analysis of sinus floor height revealed no significant differences (p < 0.05) between groups at baseline nor at 180 days after augmentation. There was no statistical difference in sinus floor height gain between the two groups as supported by the 90% confidence intervals of the difference between groups. Good primary implant stability was confirmed in both treatment groups by ITV and ISQ measurements. CONCLUSIONS: Within the limits of this study, it can be concluded that OMSFE using in situ hardening BCP particles results in equivalent sinus floor height gain than using xenograft particles but offers an easier application.

In vitro biocompatibility and bioactivity of calcium silicate­based bioceramics in endodontics (Review).

Calcium silicate­based bioceramics have been applied in endodontics as advantageous materials for years. In addition to excellent physical and chemical properties, the biocompatibility and bioactivity of calcium silicate­based bioceramics also serve an important role in endodontics according to previous research reports. Firstly, bioceramics affect cellular behavior of cells such as stem cells, osteoblasts, osteoclasts, fibroblasts and immune cells. On the other hand, cell reaction to bioceramics determines the effect of wound healing and tissue repair following bioceramics implantation. The aim of the present review was to provide an overview of calcium silicate­based bioceramics currently applied in endodontics, including mineral trioxide aggregate, Bioaggregate, Biodentine and iRoot, focusing on their in vitro biocompatibility and bioactivity. Understanding their underlying mechanism may help to ensure these materials are applied appropriately in endodontics.

Impact of Reconstruction With Hydroxyapatite Bone Cement on CSF Leak Rate in Retrosigmoid Approach to Vestibular Schwannoma Resection: A Review of 196 Cases.

OBJECTIVE: To assess the impact of reconstructive technique on the incidence of cerebrospinal fluid (CSF) leak following retrosigmoid approach to acoustic neuroma resection. STUDY DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: A total of 1,200 patients with acoustic neuromas presented to our institution from 2005 to 2018. Of these, 196 patients underwent surgical resection via a retrosigmoid approach. INTERVENTION: At our institution, internal auditory canal (IAC) reconstruction following a retrosigmoid approach was performed with bone wax and muscle plug or Norian hydroxyapatite bone cement from 2005 to 2013. Starting in 2014, a newer model of bone cement, Cranios hydroxyapatite, was used exclusively for reconstruction. MAIN OUTCOME MEASURES: Rates of CSF leak were evaluated across different methods of IAC reconstruction and types of bone cement. Patients whose leaks were attributable to the craniectomy site were excluded from analysis. RESULTS: The postoperative CSF leak rate among patients who did not receive bone cement for IAC reconstruction was 15.6% (n.5). The leak rate amongst patients who received Norian bone cement was 6.3% (n.4). After introduction of Cranios bone cement, the total leak rate decreased to 1% (n.1). Compared with all other types of closure, Cranios had a significantly reduced rate of postoperative CSF leak (p < 0.005). The leak rate following Cranios versus Norian was also significantly reduced (p < 0.05). Leak rate was not affected by tumor size (p.0.30) or age (p.0.43). CONCLUSION: CSF leak rate following acoustic neuroma resection was significantly reduced by introduction of Cranios hydroxyapatite bone cement.

Middle Cranial Fossa Repair of Temporal Bone Spontaneous CSF Leaks With Hydroxyapatite Bone Cement.

OBJECTIVES: To determine the safety and effectiveness of the middle cranial fossa (MCF) approach in repairing spontaneous cerebrospinal fluid (sCSF) leaks. STUDY DESIGN: Retrospective cohort study. METHODS: Patient with sCSF leaks repaired by MCF approach between January 1, 2014 and August 31, 2019 were included. Demographic information, clinical and surgical findings, and postoperative outcomes were recorded. RESULTS: The cohort (n = 45) included 24 tegmen repairs by multilayer reconstruction using hydroxyapatite cement and 21 cases of multilayer repair without hydroxyapatite cement. Ten MCF repairs were performed on patients ≥65 years old. Twenty (53%) ears had multiple tegmen defects (range, 1-9 tegmen defects) and 78% of patients had ≥1 encephaloceles. All sCSF leaks were resolved with one surgical intervention. There were no major intracranial complications. Transient expressive aphasia occurred in 2 patients. Medical complications occurred in four patients. There were no short-term postoperative CSF leaks with bone cement reconstruction and two postoperative leaks without bone cement. One resolved with lumbar drain (LD) and the other resolved without treatment. The average (SD) length of stay (LOS) with bone cement was shorter than in patients without bone cement (2.54 [0.83] days vs. 3.52 [1.99] days, P < .05). There have been no long-term CSF leak recurrences with an average (SD) follow-up of 13.5 (12.9) months (range 0.25-46 months). CONCLUSIONS: MCF approach for sCSF repairs demonstrate efficacious outcomes, particularly with tegmen reconstruction using hydroxyapatite cement. The approach exhibited no serious adverse events and few complications requiring intervention. Therefore, MCF is a safe and effective approach to resolve sCSF leaks. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:624-632, 2021.