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Study Design: A multicenter randomized controlled noninferiority trial with intrapatient comparisons., Objective: The aim of this study was to determine noninferiority of a slowly resorbable biphasic calcium phosphate with submicron microporosity (BCP<μm, MagnetOs Granules) as an alternative for autograft in instrumented posterolateral fusion (PLF)., Summary of Background Data: Successful spinal fusion with a solid bone bridge between the vertebrae is traditionally achieved by grafting with autologous iliac bone. However, the disadvantages of autografts and unsatisfactory fusion rates have prompted the exploration of alternatives, including ceramics. Nevertheless, clinical evidence for the standalone use of these materials is limited., Methods: Adults indicated for instrumented PLF (1 to 6 levels) were enrolled at 5 participating centers. After bilateral instrumentation and fusion-bed preparation, the randomized allocation side (left or right) was disclosed. Per segment 10 cc of BCP<μm granules (1 to 2 mm) were placed in the posterolateral gutter on one side and 10 cc autograft on the contralateral side. Fusion was systematically scored on 1-year follow-up CT scans. The study was powered to detect >15% inferiority with binomial paired comparisons of the fusion performance score per treatment side., Results: Of the 100 patients (57 ± 12.9 y, 62% female), 91 subjects and 128 segments were analyzed. The overall posterolateral fusion rate per segment (left and/or right) was 83%. For the BCP<μm side only the fusion rate was 79% versus 47% for the autograft side (difference of 32 percentage points, 95% CI, 23-41). Analysis of the primary outcome confirmed the noninferiority of BCP<μm with an absolute difference in paired proportions of 39.6% (95% CI, 26.8-51.2; p < 0.001)., Conclusion: This clinical trial demonstrates noninferiority and indicates superiority of MagnetOs Granules as a standalone ceramic when compared to autograft for posterolateral spinal fusion. These results challange the belief that autologous bone is the most optimal graft material., Competing Interests: The authors report no conflicts of interest, (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/β-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction., Methods: The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/β-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements., Results: The mean resorption rate in the HA/β-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/β-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/β-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA., Conclusion: The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/β-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning., (© 2024. The Author(s).)

Background and Objectives: Favorable short- and mid-term results for hydroxyapatite (HA)-tricalcium phosphate (TCP)-coated total hip arthroplasty (THA) (Trilogy/Zimmer) have been reported in the literature; however, the long-term results beyond 15 years have not been documented. Therefore, this study evaluated the long-term postoperative results, radiological bone changes, and implant fixation of the acetabular component of HA-TCP-coated THA. Materials and Methods: This is a retrospective cohort study of 212 patients who underwent primary HA-TCP-coated THA (Trilogy/Zimmer) at our institution between 1 October 2002, and 31 March 2008; 166 who were available for follow-up at least 15 years postoperatively were included (capture rate: 78.3%). All implants were Trilogy/Zimmer. We investigated the survival rate, with aseptic loosening as the endpoint. Clinical evaluations included the presence of dislocation and a modified Harris Hip Score (mHHS) preoperatively and at the final observation. Results: The mean age at surgery and at the follow-up period were 57.7 ± 9.6 and 17.1 ± 1.5 years, respectively. The survival rate was 99.4% (165/166), with aseptic loosening as the endpoint. Dislocation was observed in 4/166 (2.4%) patients. The mHHS improved significantly from 46.1 points preoperatively to 82.2 points during the last survey ( p < 0.05). The results revealed that fixation was favorable in all cases except for one case of aseptic loosening. The Trilogy implant coated with HA-TCP was highly effective in bone induction, and bone ingrowth was considered to have occurred without failure, further indicating its usefulness. The long-term results of cementless THA using an HA-TCP coating (Trilogy/Zimmer), with a mean follow-up period of 17.1 years, revealed a commendable survival rate of 99.4%, considering aseptic loosening as the endpoint. Conclusions: HA-TCP-coated THA (Trilogy/Zimmer) had good long-term results. However, further long-term observation is required in patients who have undergone this surgery, and the stem side should be evaluated and investigated, including comorbidities.

Objective: To compare implant stability and clinical outcome in implant placement between osteotome sinus floor elevation (OSFE) with biphasic calcium phosphate (BCP) which consisted of 30% of hydroxyapatite (HA) and 70% of beta-tricalcium phosphate (β -TCP) grafting material and OSFE without using bone grafting material. The research questions is whether the BCP provides any benefit in OSFE or not., Materials and Methods: Thirty patients (30 implants) with a single edentulous area of upper premolar or molar were randomly separated into OSFE with BCP (n = 15) and OSFE without grafting (n = 15). The patients were reevaluated 3, 6, 9, and 12 months after implant loading. The clinical assessments (implant stability quotient (ISQ), implant survival-failure rate, and surgical complication) were analyzed. Together with radiographic assessments in 2D (endo-sinus bone gain (ESBG), mean marginal bone change (MMBC)) and 3D (endo-sinus bone gain in CBCT (ESBG-CT)) were evaluated, with a mean follow-up time of at least 12 months of functional loading and prosthetic complication., Results: 20 remaining implants (OSFE with BCP, n = 10; OSFE without grafting, n = 10) were analyzed. Mean ISQ was 79.18 ± 3.43 in 1-year follow-up (ISQ; OSFE with BCP = 78.72 ± 3.46, OSFE without grafting = 79.65 ± 3.52). ISQ in both groups increased steadily without significant differences in each follow-up. (p = 0.56). In radiographic evaluation, at 6-, 9-, and 12-month, OSFE without grafting group showed statistically significant lower MMBC (p < 0.05). The 1-year clinical results showed that 2 implants failed in OSFE with BCP, and 1 implant failed in OSFE without grafting., Conclusions: Graft material "BCP" (HA30:TCP70) coupled with OSFE presents no extraordinary benefit in implant stability, clinical and radiographic outcome in 1-year follow-up., Clinical Relevance: Clinically, OSFE with grafting materials provides no additional benefit., Clinical Trial Registration Number: TCTR20210517008 (date of registration: May 17, 2021)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Temozolomide (TMZ) is the first line chemotherapy for glioblastoma (GBM) treatment, but the P-glycoprotein (P-gp) expressed in blood-brain barrier (BBB) will pump out TMZ from the brain leading to decreased TMZ concentration. Tariquidar (TQD), a selective and potent P-gp inhibitor, may be suitable for combination therapy to increase concentration of TMZ in brain. Hydroxyapatite (HAP) is a biodegradable material with sustained release characteristics, and stearic acid surface-modified HAP (SA-HAP) can increase hydrophobicity to facilitate TQD loading. TQD-loaded stearic acid surface-modified HAP (SA-HAP-TQD) was prepared with optimal size and high TQD loading efficiency, and in vitro release and cellular uptake of SA-HAP-TQD showed that SA-HAP-TQD were taken up into lysosome and continuously released TQD from macrophages. In vivo studies have found that over 70 % of SA-HAP was degraded and 80 % of TQD was released from SA-HAP-TQD 28 days after administration. SA-HAP-TQD could increase brain penetration of TMZ, but it would not enhance adverse effects of TMZ in healthy mice. SA-HAP-TQD and TMZ combination had longer median survival than TMZ single therapy in GL261 orthotopic model. These results suggest that SA-HAP-TQD has sustained release characteristics and are potential for improving antitumor effect with TMZ treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2023 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

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.

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., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

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/β-tricalcium phosphate (β-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/β-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/β-TCP-coated bioceramic scaffolds., Conclusion: 3:7 HA/β-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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright © 2022 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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., (Copyright © 2022. Published by Elsevier B.V.)

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-Glu 20 ) 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., Competing Interests: Declaration of Competing Interest P.S.L and S.A.L own stock in Quince Tx. S.A.L, C.M.C, M.T. and J.J.N are employees of Quince Tx., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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 (β-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/β-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., (© 2022. The Author(s).)

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.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study., (Copyright © 2021 Roger Borges et al.)

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., (© 2021. The Author(s).)

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., Competing Interests: Disclosures: The authors of this study have no conflicts of interest to disclose regarding any of the products and materials discussed in this report. The University of Pennsylvania Department of Neurosurgery received financial support from Synthes in return for internal data related to Cranios. Synthes was not involved in this study., (Copyright © 2021, Otology & Neurotology, Inc.)

Calcium silicate‑based 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 silicate‑based 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 silicate‑based 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.

Objectives: Mastoid cortex defects resulting from mastoidectomy surgery can rarely lead to negative sequelae, including unsightly post-auricular depression and discomfort. This study sought to evaluate the use of hydroxyapatite cement (HAC) to reconstruct mastoidectomy cortex defects., Methods: Retrospective chart review was undertaken for all patients that underwent reconstruction of the mastoid cortex using HAC at a single tertiary medical center between 2013 and 2019. Collected data included demographics, indications for mastoidectomy, complications, and associated symptom status., Results: Twenty-nine patients that underwent mastoid cortex repair using HAC were included, and ten of these underwent mastoid revision in a secondary procedure to reconstruct the mastoid cortex with a specific goal to eliminate negative signs and symptoms. There were no associated postoperative complications and no instances of post-auricular depression following repair. All cases of secondary reconstruction resolved the primary signs and symptoms that prompted mastoid revision., Conclusions: HAC mastoid cortex reconstruction may be a safe and effective method to resolve negative sequelae resulting from previous mastoidectomy defects. Also, upfront HAC mastoid cortex reconstruction appears viable in select instances as an option to prevent potential future complications.

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., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

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., Competing Interests: None

Natural or synthetic biomaterials are increasingly being used to support bone tissue repair or substitution. The combination of natural calcium phosphates with biocompatible alloys is an important route towards the development of new biomaterials with bioperformance and mechanical responses to mimic those of human bones. This article evaluated the structural, physical, mechanical and biological properties of a new mechanical improved nanocomposite elaborated by association of fish biphasic calcium phosphate (BCP) and niobium pentoxide (Nb 2 O 5 ). The nanocomposite (Nb-BCP) and the pure BCP, used as a positive control, were obtained by powder metallurgy. The density, porosity and microhardness were measured. The structural analysis was determined by X-ray diffraction (XRD) and the biological properties were studied in histological sections of critical size calvaria defects in rats, 7, 15, 30, 45 and 60 days after implantation of disks of both materials. Morphological description was made after scanning electron microscopy (SEM) and optical microscopy analysis. After sintering, the Nb-BCP nanocomposite presented four crystalline phases: 34.36% calcium niobate (CaNb 2 O 6 ), 21.68% phosphorus niobium oxide (PNb 9 O 25 ), 42.55% β-tricalcium phosphate (Ca 3 (PO 4 ) 2 ) and 1.31% of niobium pentoxide (Nb 2 O 5 ) and exhibited increases of 17% in density, 66% in Vickers microhardness and 180% in compressive strength compared to pure BCP. In vivo study, showed biocompatibility, bioactivity and osteoconductivity similar to pure BCP. SEM showed the formation of globular accretions over the implanted nanocomposites, representing one of the stages of bone mineralization. In conclusion, the BCP and Nb 2 O 5 formed a nanocomposite exhibiting characteristics that are desirable for a biomaterial, such as bioperformance, higher β-TCP percentage and improved physical and mechanical properties compared to pure BCP. These characteristics demonstrate the promise of this material for supporting bone regeneration.

The aim of the study was to assess the efficacy of three methods of enamel remineralization on initial approximal caries: (1) a nano-hydroxyapatite gel, (2) gaseous ozone therapy, (3) combination of a nano-hydroxyapatite gel and ozone. Patients (n = 92, age 20-30 years) with initial approximal enamel lesions on premolar and molar teeth (n = 546) were randomly allocated to three groups subjected to a 6-months treatment: Group I: domestic nano-hydroxyapatite remineralizing gel, group II: in-office ozone therapy, group III: both domestic remineralizing gel and ozone therapy. Caries lesions were assessed on bitewing radiographs at baseline, after 1 year and after 2 years. At one-year follow-up, the smallest rate of lesions with remineralisation (36.5%) was found in group I, and the highest (69.3%)-in group III. In group III a significant remineralisation was noticed in after 1 year and then a demineralisation after 2 years. Thus nano-hydroxyapatite gel and ozone therapy exert some capacities to remineralize approximal enamel and dentine subsurface lesions of premolar and molar teeth. Moreover, the combination of both methods produces the best effect compared to nano-hydroxyapatite or ozone therapy applied alone. However, the treatment should be continued for a long time in order to achieve nonrestorative recovery of caries.

Knowledge about the action of immune system in the recognition of biomaterials has been extremely helpful when it comes about understanding host response and biomaterials' fate in human body. This study aimed to investigate inflammatory response and macrophage polarization during bone healing process of rat's calvaria critical defects using different bone materials in order to evaluate their influence on bone repair and on the quality of the newly formed bone tissue. Eighty male albinus Wistar rats underwent surgical procedure for the confectioning of a 5-mm diameter bone defect in their right parietal bone, and divided in four groups (n = 20 each), according the biomaterial: AG - Control, particulate intramembranous autogenous bone graft, HA/TCP - particulate biphasic calcium phosphate with HA/TCP (60/40), DBB - particulate deproteinized bovine bone, VC - particulate bioactive vitroceramic. After 3, 7, 21, and 45 days, the specimens were removed and prepared for microcomputed tomography (microCT), light and polarized microscopy, immunohistochemical analysis, and histomorphometry. No significant differences were detected considering percentage of leukocytes among the groups and periods, as well as in relation to immunolabeling for inflammatory (M1) and reparative (M2) macrophages. However, immunolabeling for bone marker indicated a delayed osteoblast differentiation in VC group, resulting in a decrease in mineralized bone matrix parameters in this group, revealed by microCT. In addition, AG and HA/TCP presented a satisfactory bone collagenous content. Despite the distinct origins and physicochemical properties of the tested biomaterials, they presented similar immune-inflammatory responses in the present experimental model, influencing bone-related proteins and bone quality, which must be considered according to their use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Engineering of materials consisting of hypertrophic cartilage, as physiological template for de novo bone formation through endochondral ossification (ECO), holds promise as a new class of biological bone substitutes. Here, we assessed the efficiency and reproducibility of bone formation induced by the combination of ceramic granules with fractionated human adipose tissue ("nanofat"), followed by in vitro priming to hypertrophic cartilage. Human nanofat was mixed with different volumetric ratios of ceramic granules (0.2-1 mm) and cultured to sequentially induce proliferation (3 weeks), chondrogenesis (4 weeks), and hypertrophy (2 weeks). The resulting engineered constructs were implanted ectopically in nude mouse. The presence of ceramic granules regulated tissue formation, both in vitro and in vivo. In particular, their dispersion in nanofat at a ratio of 1:16 led to significantly increased cell number and glycosaminoglycan accumulation in vitro, as well as amount and inter-donor reproducibility of bone formation in vivo. Our findings outline a strategy for efficient utilization of nanofat for bone regeneration in an autologous setting, which should now be tested at an orthotopic site. STATEMENT OF SIGNIFICANCE: In this study, we assessed the efficiency and reproducibility of bone formation by a combination of ceramic granules and fractionated human adipose tissue, also known as nanofat, in vitro primed into hypertrophic cartilage. The resulting engineered cartilaginous constructs, when implanted ectopically in nude mouse, resulted in bone and bone marrow formation, more reproducibly and strongly that nanofat alone. This project evaluates the impact of ceramic granules on the functionality and chondrogenic differentiation of mesenchymal progenitors inside their native adipose tissue niche and outlines a novel strategy for an efficient application of nanofat for bone regeneration in an autologous setting., (Copyright © 2019. Published by Elsevier Ltd.)

Aims: While numerous materials are available for sinus floor elevation, plant-based alternatives still hold promise of overcoming concerns about allogeneic or xenogeneic materials. Thus, the present authors designed a randomised clinical trial to histologically compare an almost pure hydroxyapatite (HA) to a biphasic calcium phosphate comprising 80% β-tricalcium phosphate (β-TCP) and 20% hydroxyapatite (β-TCP/HA), all of phycogenic origin. Materials and methods: Twenty patients scheduled for lateral window sinus floor elevation were randomised to either an HA or a β-TCP/HA group. Biopsy specimens were taken 3 months after sinus floor elevation and during implant surgery after 6 months. One ground section per biopsy specimen (N = 40) was stained, scanned and histomorphometrically analysed for new bone, old bone, soft tissue, graft, bone infiltration of graft, bone-to-graft contact and penetration depth. Results: At 6 months, more new bone was seen in the β-TCP/HA group (P = 0.011), whereas more residual graft was present and in more extensive contact with new bone in the HA group. More pronounced alterations, and smaller particle sizes, of graft surrounded and infiltrated by bone were seen in the β-TCP/HA group. The less extensive bone-to-graft contact in the β-TCP/ HA group reflected a more advanced state of resorption, while infiltration of residual graft material by bone was also increased in this group. Conclusions: Proper healing was seen in both groups, with the graft materials guiding the formation of new bone, which grew especially well through the particles of the highly osteoconductive and resorptive β-TCP/HA material. HA was very stable, without significant resorption, but was extensively in contact with new bone after 6 months., Competing Interests: This study was partially supportedby Dentsply Sirona Implants(I-BI-14-077; Mannheim, Germany) and the materials investigated in the study were providedfree of charge for patients’ use; however, this company in no way influenced the direction, results or analysis of this study.

Objective: The main goal of this study was to examine the influence of hydroxyapatite (HAp) macroaggreate concentrations on thermal and mechanical properties of radioactive bone cement and to study the relation of glass transition Tg with its mechanical properties., Methods: The bone cement as (1-x)PMMA-xHAp binary system was prepared in six [x] distinct concentration parameters of 0.0 up to 0.5. The HAp was synthesized using a solgel procedure following calcination by thermal treatment. The composite was prepared in cold based (non-radioactive) mixing polymethyl methacrylate (PMMA) and HAp. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and mechanical compressive strength (CS) were used to measure the thermal and mechanical properties., Results: The DSC and TGA thermal profiles in function to concentration parameter [x] were presented. The CS lies in a range of 3.71-7.37 MPa and the glass transition temperature Tg = 126.27 °C. There was a direct relationship between the PMMA-HAp thermoplastic properties with mechanical and thermal properties in function of HAp concentrations., Conclusion: The specific PMMA-HAp composite, with a concentration ratio of 1:1 and HAp thermal treatment at the Tg, provides a material with a compression strength of 7.37 MPa and a suitable amount of porous similar to a trabecular bone, possible to apply in bone cement implants, regardless of whether they are radioactive or not.

We report two patients presenting with delayed complicationsafter Vibrant SounBridge® middle ear implant surgery: in both cases, a revision surgery was performed and lysis of the long process of the incus was highlighted. A re-assembly of the clip around the remaining long process of the incus was performed, associated with hydroxyapatite bone cement application, on the clip and the incudo-stapedial joint. Both patients had a satisfying result, with a mean follow up of 12 months., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Safety and feasibility of a regenerative strategy based on the use of culture-expanded mesenchymal stromal cells (MSCs) have been investigated in phase 2 trials for the treatment of nonunion and osteonecrosis of the femoral head (ONFH). As part of the clinical study, we aimed to evaluate if bone turnover markers (BTMs) could be useful for predicting the regenerative ability of the cell therapy product., Materials and Methods: The bone defects of 39 patients (nonunion: n = 26; ONFH: n = 13) were treated with bone marrow-derived MSCs, expanded using a clinical-grade protocol and combined with biphasic calcium phosphate before implantation. Bone formation markers, bone-resorption markers and osteoclast regulatory proteins were measured before treatment (baseline) and after 12 and 24 weeks from surgery. At the same time-points, clinical and radiological controls were performed to evaluate the bone-healing progression., Results: We found that C-Propeptide of Type I Procollagen (CICP) and C-terminal telopeptide of type-I collagen (CTX) varied significantly, not only over time, but also according to clinical results. In patients with a good outcome, CICP increased and CTX decreased, and this trend was observed in both nonunion and ONFH. Moreover, collagen biomarkers were able to discriminate healed patients from non-responsive patients with a good diagnostic accuracy., Discussion: CICP and CTX could be valuable biomarkers for monitoring and predicting the regenerative ability of cell products used to stimulate the repair of refractory bone diseases. To be translated in a clinical setting, these results are under validation in a currently ongoing phase 3 clinical trial., (Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Aesthetic dermatology (AD) is a rapidly growing subspecialty of dermatology. The acceptance of AD in scientific community and the society is associated with its competence, efficiency, and seriousness. This review highlights some recent developments toward new tools, techniques, and understanding in the field of AD. Analyzing the specific needs of patients and assessing the effect by objective measurements is important for further progress. For long time ignored, white adipose tissue has gained increasing interest in biology and rejuvenation. Characterization of dermal and subcutaneous white adipose tissue has made progress. The interaction of hyaluronic acid and calcium hydroxyl apatite (CaHA) fillers with adipocytes could be responsible for clinical efficacy. New developments of oral collagen treatment and highly diluted CaHA to contour the body outside the face will be discussed. Submental contouring using purified desoxycholic acid is another new development., (© 2018 Wiley Periodicals, Inc.)

To investigate the osteogenesis of macro-pore sized bone scaffolds, biphasic calcium phosphate scaffolds with accurately controlled macro-pore size (0.8, 1.2, and 1.6 mm) and identical porosity of 70% were fabricated by the 3D printing technology. Eight New Zealand rabbits were selected in the present study, while four 8-mm-diameter calvarial defects were created in each rabbit to place BCP scaffolds with different macro-pore size. The harvested specimens of four and eight weeks were used to evaluate the bone forming ability by micro CT and histological examination. All 3D-printed BCP scaffolds exhibited excellent mechanical properties and had better bone-forming ability than the control at both four and eight weeks. Among them, scaffold with 0.8 mm pore size was superior for initial bone formation and maturation, resulting in the highest value of total bone formation.

Hydroxyapatite (HA) is the main mineral component of bone and teeth. HA is often used as a bone substitute and especially in its granular form it is osteoconductive and osseointegrating as shown by many investigations in animals and humans. HA granules are used for filling bone defects, but they have poor handling qualities and retention at the surgical site, leading to graft voids between the granules and bone tissue and resulting in mechanical instability. Furthermore HA implantation is not constantly followed by favorable results, especially when it is carried out for augmentation of the alveolar ridge. This article offers a protocol for bone reconstruction and predictable implant treatment outcomes. We provide a step-by-step description of both the recipient site and composite graft preparations using coralline HA granules (CHAG) and homologous fibrin glue (HFG). In the present study, 20 randomly selected patients (12 women and 8 men) underwent bone regeneration using CHAG-HFG before a dental implant procedure. Radiographic imaging, physical examination, and histological analysis were performed during a 2-year period. Biopsies were obtained at second-stage surgery before implant insertion using a 2.8-mm trephine bur. A morphological study of 20 bioptic human specimens was performed. Our results demonstrate that this surgical protocol for the preparation of the recipient site associated with a mixture of coralline HA granules with homologous fibrin glue provides reliable bone regeneration, thus reducing failures and minimizing risks of postoperative morbidity.

Biphasic calcium phosphate ceramic granules (0.5-1.0 mm) with a hydroxyapatite and β -tricalcium phosphate ratio of 90/10 were used. Biphasic calcium phosphate ceramic granules produced in the Riga Technical University, Riga Rudolph Cimdins Biomaterials Innovation and Development Centre, were used for filling the bone loss on 18 patients with peri-implantitis. After 5 years at the minimum, clinical and 3D cone-beam computed tomography control was done. Clinical situation confirmed good stability of implants without any signs of inflammation around. Radiodensity of the previous gap and alveolar bone horizontally from middle point of dental implants showed similar radiodensity as in normal alveolar bone. This trial is registered with ISRCTN13514478.

Purpose: Pixel values from cone-beam computed tomography (CBCT) are proportional to bone density. This study aimed to correlate and compare pixel values of healed maxillary sinus grafts and adjacent native bone (NB)., Material and Methods: This study was conducted on CBCT scan patients referred for maxillary sinus floor augmentation with biphasic calcium phosphate (n = 31). Graft height and width measurements were performed. In addition, mean pixel values were calculated in 3 different regions: NB, sinus graft close to NB (CNB), and sinus graft far from NB (FNB). Micro-CT and histological analyses of bone specimens of a representative case were also performed., Results: Significant correlations were found between CNB and graft height (r = 0.41; P < 0.021); and FNB and graft width (r = 0.519, P < 0.003). In addition, pixel values from both graft groups (CNB and FNB) differed significantly (P < 0.001). Finally, histological sections revealed smaller areas with newly formed bone in the FNB area., Conclusions: Within the limitations of this study, the present findings suggest that pixel values of sinus grafted areas are directly correlated with the extension of the grafted area.

Rationale: The purpose of this report is to present a case of peri-implantitis with successful regeneration. The surface of the affected dental implant was decontaminated with an ultrasonic scaler and treated with bovine-derived hydroxyapatite and enamel matrix derivative., Patient Concerns: A 52-year-old male was referred for evaluation of a dental implant placed in the mandibular right second premolar area., Diagnosis: The radiographic evaluation showed the loss of supporting bone around the dental implant. Bleeding upon probing and suppuration were observed, with the deepest probing depth at 6 mm., Interventions: The area was firstly treated with a nonsurgical approach. After re-evaluation, a full-thickness flap was elevated. The area was well debrided using various instruments, including curettes and an ultrasonic scaler. The defect area was grafted with bovine-derived hydroxyapatite and enamel matrix derivative., Outcomes: Histopathologic evaluation revealed chronic inflammation with fibrosis and calcification. The evaluation at 2 years and 3 months after surgery showed that the prosthesis was functioning well. Bleeding upon probing and suppuration was not noted, and reduction of probing depth was seen, with the deepest depth at 4 mm. The area showed maintenance of graft material with increased radiopacity around the dental implant., Lessons: In conclusion, a case of peri-implantitis can be successfully treated with bovine-derived hydroxyapatite and enamel matrix derivative after surface decontamination with an ultrasonic scaler.

Objectives: The aim of this study was to evaluate the effect of a hydrophilic surface on the osseointegration in grafted areas with deproteinized bovine bone (DBB) and with biphasic ceramics of hydroxyapatite/β-tricalcium phosphate (HA/TCP)., Material and Methods: Fifty-six rats were randomly allocated to four groups with 14 animals each: DBB: DBB+Machined surface; HA/TCP: HA/TCP+Machined surface; DBB-H: DBB+Hydrophilic surface; HA/TCP-H: HA/TCP+Hydrophilic surface. The bone defects were performed at the proximal epiphysis of the tibia. Then, the defects were filled with the biomaterials. After 60 days, the implants were placed in the grafted areas. The animals were submitted to euthanasia at periods of 15 and 45 days after the implants' placement. The osseointegration was assessed by biomechanical, microtomographic, and histometric analyses. In addition, the expression of bone morphogenetic protein-2 (BMP-2), alkaline phosphatase (ALP), and osteocalcin (OCN) was evaluated by immunohistochemistry., Results: The HA/TCP-H group presented higher removal torque values and more mineralized tissue in the vicinity of the implants compared with the HA/TCP group. The DBB-H and HA/TCP-H groups presented higher values of bone-implant contact (at 15 and 45 days), of bone between the threads (45 days), and expression of BMP-2 (45 days) than the DBB and HA/TCP groups. Furthermore, the DBB-H group presented a higher expression of ALP than the DBB group (15 days)., Conclusion: In conclusion, implants with a hydrophilic surface improve osseointegration in grafted areas compared to implants with machined surfaces in a rat tibia model., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Study Design: An animal experimental study was designed to investigate the efficacy of combined magnetic fields (CMF) treatment and nano-hydroxyapatite (HA) coating in the biphasic calcium phosphate (BCP) graft in posterolateral lumbar fusion., Objective: To evaluate the effects of CMF treatment and nano-HA/BCP and their combination effect in posterolateral lumbar fusion., Summary of Background Data: Enhancement of artificial bone graft bioeffects could improve spinal fusion outcomes. The bone graft integration is vital in spinal fusion, nano-HA coating, and CMF treatment were reported as effective methods to improve bone graft integration., Methods: A bilateral transverse process fusion model was performed on 32 rabbits. The CMF treatment was performed for 30 minutes per day postoperation. The fusion rate, new bone formation, artificial bone graft-autologous bone fusion interface in x-ray and scanning electron microscopy, biomechanics property of fusion rate, histological fusion condition, artificial bone residual rate, and immunohistochemistry assessment of bone morphogenetic protein 2 (BMP-2) and Transforming growth factor beta 1 (TGF-β1) expression were observed at 9th week after surgery., Results: CMF treatment and nano-HA coating increased the fusion rate, adjusted optical density index, intensity of binding of artificial and autologous bone, bone growth rate, and bending stiffness. CMF treatment also significantly increased BMP-2 and TGF-β1 expression in fusion region while nano-HA coating significantly decreased artificial bone residual rate., Conclusion: Our findings suggest that porous nano-HA/BCP graft could significantly improve spine fusion outcome with excellent bioactivity, biocompatibility and degradability and CMF treatment could significantly improve spine fusion outcome by improving bioactivity and biocompatibility of artificial bone graft in rabbit. Combination of CMF treatment with nano-HA/BCP graft could significantly increase posterolateral lumbar fusion rate in rabbit, which would be a potential strategy for spine fusion preclinical study., Level of Evidence: N/A.

Objectives/hypothesis: The objectives were to discuss the presentation and symptomatology of patients with jugular bulb abnormalities, summarize the literature describing jugular bulb abnormalities, compare methods of treating symptomatic dehiscent jugular bulb, describe a novel surgical technique and pitfalls to repair dehiscent bulbs with hydroxyapatite cement, and present a case series to demonstrate outcomes with this technique STUDY DESIGN: Case series presentation, PubMed literature review, and description of operative technique., Methods: A series of patients presenting with pulsatile tinnitus due to dehiscent jugular bulbs who underwent operative repair with hydroxyapatite cement resurfacing is described. Literature review was conducted via a PubMed database search. Abstracts and references were reviewed to identify relevant sources. Surgical technique of repair and outcomes are reported., Results: Three patients who presented with unilateral, bothersome, pulsatile tinnitus with history and imaging consistent with a diagnosis of high riding, dehiscent jugular bulbs underwent jugular bulb resurfacing with hydroxyapatite cement. Two patients associated the onset of their symptoms with trauma. All patients reported complete resolution of their tinnitus at an average follow-up of 15 months. No hearing, vestibular, or intracranial complications were encountered., Conclusions: Compressive, obliterative, and endovascular interventions have been attempted to treat pulsatile tinnitus due to high-riding dehiscent jugular bulbs. Reconstruction of the middle ear floor with autologous tissue grafts has also been described. These techniques have been associated with variable results and with the risk of increased intracranial pressure. Hydroxyapatite cement resurfacing may be considered as an alternative for the treatment of this pathology., Level of Evidence: 4. Laryngoscope, 128:1186-1190, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Bone grafting materials are frequently utilized in oral surgery and periodontology to fill bone defects and augment lost or missing bone. The purpose of this study was to compare new bone formation in bone defects created in both normal and osteoporotic animals loaded with three types of bone grafts from different origins., Materials and Methods: Forty-eight female Wistar rats were equally divided into control normal and ovariectomized animals. Bilateral 2.5-mm femur defects were created and filled with an equal weight of (1) natural bone mineral (NBM, BioOss) of bovine origin, (2) demineralized freeze-dried bone allograft (DFDBA, LifeNet), or (3) biphasic calcium phosphate (BCP, Vivoss). Following 3 and 6 weeks of healing, hematoxylin and eosin and TRAP staining was performed to determine new bone formation, material degradation, and osteoclast activity., Results: All bone substitutes demonstrated osteoconductive potential at 3 and 6 weeks with higher osteoclast numbers observed in all ovariectomized animals. NBM displayed continual new bone formation with little to no sign of particle degradation, even in osteoporotic animals. DFDBA particles showed similar levels of new bone formation but rapid particle degradation rates with lower levels of mineralized tissue. BCP bone grafts demonstrated significantly higher new bone formation when compared with both NBM and DFDBA particles; however, the material was associated with higher osteoclast activity and particle degradation. Interestingly, in osteoporotic animals, BCP displayed synergistically and markedly more rapid rates of particle degradation., Conclusion: Recent modifications to synthetically fabricated materials were shown to be equally or more osteopromotive than NBM and DFDBA. However, the current BCP utilized demonstrated much faster resorption properties in osteoporotic animals associated with a decrease in total bone volume when compared with the slowly/nonresorbing NBM. The results from this study point to the clinical relevance of minimizing fast-resorbing bone grafting materials in osteoporotic phenotypes due to the higher osteoclastic activity and greater material resorption.

A variety of synthetic materials are currently in use as bone substitutes, among them a new calcium phosphate-based multichannel, cylindrical, granular bone substitute that is showing satisfactory biocompatibility and osteoconductivity in clinical applications. These cylindrical granules differ in their mechanical and morphological characteristics such as size, diameter, surface area, pore size, and porosity. The aim of this study is to investigate whether the sizes of these synthetic granules and the resultant inter-granular spaces formed by their filling critical-sized bone defects affect new bone formation characteristics and to determine the best formulations from these individual types by combining the granules in different proportions to optimize the bone tissue regeneration. We evaluated two types of multichanneled cylindrical granules, 1 mm and 3 mm in diameter, combined the granules in two different proportions (wt%), and compared their different mechanical, morphological, and in vitro and in vivo biocompatibility characteristics. We assessed in vitro biocompatibility and cytotoxicity using MC3T3-E1 osteoblast-like cells using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal imaging. In vivo investigation in a rabbit model indicated that all four samples formed significantly better bone than the control after four weeks and eight weeks of implantation. Micro-computed tomography analysis showed more bone formation by the 1 mm cylindrical granules with 160 ± 10 µm channeled pore and 50% porosity than the other three samples ( p<.05), which we confirmed by histological analysis.

Objectives: Synthetic biphasic calcium phosphate (BCP) with a hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) ratio of 60/40 (BCP60/40) is successfully used as alternative for autologous bone in patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement. A high percentage of HA in BCP60/40 may hamper efficient scaffold remodeling. Osteogenesis and neovascularization are pivotal in effective bone regeneration. We aimed to investigate whether differences exist in osteogenic and/or vasculogenic potential of BCP60/40 and BCP20/80 in patients undergoing MSFE., Materials and Methods: Twenty patients undergoing MSFE were treated with BCP60/40 (n = 10) or BCP20/80 (n = 10). Bone and graft volumes were determined by micro-computed tomography and histomorphometrical analysis of biopsies of the augmented region. Osteoid volumes, number of osteoclasts, and blood vessels were determined by histomorphometrical analysis. The biopsies were taken 6.5 months (26 weeks) postoperatively prior to dental implant placement., Results: Bone and osteoid volumes were 9.7% and 0.8% higher at the most cranial side of the BCP20/80 biopsies compared to the BCP60/40 biopsies. Graft volumes, number of osteoclasts, and blood vessels were similar in both groups., Conclusions: BCP20/80 showed enhanced osteogenic potential in patients undergoing MSFE compared to BCP60/40, due to either a faster bone remodeling rate or an earlier start of bone formation in BCP20/80-treated patients, suggesting that a higher TCP content positively contributes to the bone remodeling rate. Therefore, BCP20/80 might perform better, at least in the short term, as a scaffold for bone augmentation in the MSFE model than BCP60/40 as more bone is formed, and more osteoid is deposited at the cranial side in BCP20/80-treated patients compared to BCP60/40-treated patients. However, catch-up of BCP60/40 in the long term cannot be ruled out., (© 2018 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.)

Objectives: To evaluate whether the subperiosteal injection of simvastatin (SIM) with a novel in situ gel-forming system, SrHA/Alg (strontium hydroxyapatite/alginate), can stimulate vertical bone augmentation in a rat calvarial model., Material and Methods: The SrHA/Alg solution was synthesized and combined with different doses of SIM (0.01, 0.02, 0.1, and 0.2 mg) to form the following groups: (1) SrHA/Alg only, (2) SrHA/Alg/0.01, (3) SrHA/Alg/0.02, (4) SrHA/Alg/0.1, and (5) SrHA/Alg/0.2. The SIM release pattern was analyzed, and rat primary periosteum-derived cell (PDC) responses were investigated. Twenty male Wistar rats were enrolled in the calvarial subperiosteal injection experiment with each animal receiving a 200-μl single subperiosteal injection of SrHA/Alg with different amounts of SIM (0, 0.01, 0.02, and 0.1 mg) incorporated (n = 5). The 0.2 mg dose group was not tested in vivo due to the severe toxicity found in vitro. The new bone formation was assessed histologically and radiologically at 8 weeks., Results: The slow release of SIM was confirmed, and PDC viability decreased in the SrHA/Alg/0.2 group. Alkaline phosphatase positive areas and mineralization areas were significantly greater in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups (p < .05). The mRNA expression level of Runx2 significantly increased in the SrHA/Alg/SIM-0.02 group by day 7 (p < .05) and significantly higher levels of VEGF were found in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups at different time points (p < .05). In vivo, no prominent clinical sign of inflammation was observed, and the most significant bone gain was shown in the SrHA/Alg/0.02 group (p < .05). The osteoclast formation within the newly formed bone area was reduced in the SrHA/Alg/0.1 group (p < .05)., Conclusions: When combined with SrHA/Alg system, the 0.02 mg SIM seemed to be the optimal dose to stimulate subperiosteal bone formation without inducing inflammation. This combination may hold potential therapeutic benefits for clinical bone augmentation in a minimally invasive manner., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to evaluate the osteoconductive potential of BoneCeramic™ on bone healing in rat calvaria 5-mm defects., Material and Methods: A 5-mm calvaria bone defect was induced in three groups and the defect was not filled with biomaterial [Clot Group (CG)], autogenous bone (AG), or Bone Ceramic Group (BCG). Animals were euthanized after 14 or 28 days and the bone tissue within the central area of the bone defect was evaluated. Results were compared using ANOVA and Tukey test (p<0.05). Immunohistochemistry was performed using primary antibodies against osteocalcin, RUNX-2, TRAP, VEGF proteins, and 3-dimensional images of the defects in μCT were obtained to calculate bone mineral density (BMD)., Results: In BCG, the defect was completely filled with biomaterial and new bone formation, which was statistically superior to that in the GC group, at both time-points (p<0.001 for 14 days; p=0.002 for 28 days). TRAP protein showed weak, RUNX-2 showed a greater immunolabeling when compared with other groups, VEGF showed moderate immunostaining, while osteocalcin was present at all time-points analyzed. The μCT images showed filling defect by BCG (BMD= 1337 HU at 28 days)., Conclusion: Therefore, the biomaterial tested was found to be favorable to fill bone defects for the reporting period analyzed.