Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges

Introduction: The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO₂ nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization.

Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity.

Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.     

Dibucaine in Ionic-Gradient Liposomes: Biophysical,Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.     

Investigation of an increase in large local reactions following vaccine schedule change to include DTaP-HB-IPV-Hib (Infanrix-hexa®) and MMRV (ProQuad®) at 18 months of age

ContextIn 2015 in Quebec, Canada, the passive vaccine adverse event reporting system detected an increase in large local reactions associated with vaccines recommended at the 18-month visit. This followed changes to the pediatric vaccine schedule to include hexavalent diphtheria-tetanus-acellular-pertusis-inactivated polio-Haemophilus influenzae type b-hepatitis B vaccine (DTaP-IPV-Hib-HB, Infanrix-hexa®, GSK) and quadrivalent measles-mumps-rubella-varicella vaccine (MMRV, ProQuad®, Merck) as 18-month booster doses.ObjectivesTo determine if the excess of large local reactions was caused by a specific vaccine or their co-administration in the same limb or during the same visit.MethodsA case-control study was conducted among cases born between January 2012 and April 2015 with a large local reaction following MMR ± V or DTaP-IPV-Hib ± HB vaccines administered between 16 and 23 months of age. Controls were randomly selected from the provincial medicare database among children born during the same period.ResultsOur analysis included 96 cases and 494 controls vaccinated with MMRV or DTaP-IPV-Hib ± HB vaccines. Among the 96 cases, 46% had a cellulitis and 54% had an injection site reaction extending beyond the nearest joint and/or lasting ≥ 4 days. Among the 39 cases who were immunized in different limbs, 77% of the large local reactions were located at the Infanrix-hexa® site, 5% at the DTaP-IPV-Hib site and 18% at the ProQuad® site. Large local reactions were significantly more frequent with Infanrix-hexa® than with DTaP-IPV-Hib vaccine (OR 5.9 95% CI: 1.4–25.7). Administration of ProQuad® and Infanrix-hexa® in the same limb did not increase the risk of large local reactions.ConclusionThis investigation suggested that most large local reactions were causally associated with the Infanrix-hexa® vaccine and that the risk was not greater when ProQuad® and Infanrix-hexa® were administered in the same limb. Given the improved vaccine coverage for hepatitis B, benefit-risk analysis likely still favours ongoing use of Infanrix-hexa® with informed parental consent.     

Metal Articulations as a Source of Total Hip Arthroplasty Pain

The consensus systematic risk stratification algorithm from the American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons, and The Hip Society summarizes clinical challenges in evaluation and treatment of metal-on-polyethylene total hip arthroplasty (THA) patients with adverse local tissue reaction (ALTR) due to mechanically assisted crevice corrosion (MACC), reviews up-to-date evidence, and identifies the areas for future research in order to provide a useful resource for orthopedic surgeons providing care to these patients. A painful THA has various intrinsic and extrinsic causes. ALTR is one of the intrinsic causes in patients with painful THA. The occurrence of ALTR due to MACC at modular junctions is likely to be multifactorial, including implant, surgical, and patient factors. Therefore, a systematic evaluation needs to involve a focused clinical history, detailed physical examination, laboratory tests, and imaging in order to identify potential differential diagnoses. There should be a low threshold to perform a systematic evaluation of patients with painful non–metal-on-metal THA, including patients with metal-on-polyethylene THA, and modular dual-mobility THA with the CoCr metal acetabular insert, as early recognition and diagnosis of ALTR due to MACC will facilitate initiation of appropriate treatment prior to significant adverse biological reactions. Specialized tests such as blood metal analysis and metal artifact reduction sequence magnetic resonance imaging are important modalities in evaluation and management of ALTR in patients with painful THA.     

毫米波局部照射的远位效应

目的探讨毫米波局部照射后,除局部效应外。对动物神经系统、内分泌器官、免疫及其他内脏、生殖器官、胚胎发育及子代有无远位效应。方法选用不同频率、不同功率密度的毫米波辐照小鼠、大鼠、豚鼠,并于照后不同时间,应用先进的技术方法,(光镜、电镜、DNA定量分析、组化、免疫组化、细胞培养、高效液相(HPLC)、RIA、RBA、TAS、畸形学分析、精神行为学分析等)从功能、形态、代谢等不同角度对实验动物进行观察分析。结果系列实验研究证明,在毫米波局部照射后确可引起远位组织、器官发生许多变化(骨髓中多核巨细胞核固缩,睾丸精管中出现多核巨细胞,肝细胞中糖原含量有变化,肝中cAMP、cGMP有起伏,G-6-P酶活性有变化,血液细胞成分有变化)。小鼠孕早期(1～2d)局部受照射,可见胚卵细胞表面一些酶活性有改变,导致胚卵着床减少;小鼠孕后期(5～15d)局部皮肤受照射,其胚胎虽未发生畸形,但其生下之后一代,学习记忆能力有所降低。结论毫米波局部照射确有远位效应。本项研究为临床毫米波的应用和防护标准的制定奠定了理论基础。