Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat.

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.

Bioresorbable zinc hydroxyapatite guided bone regeneration membrane for bone regeneration.

OBJECTIVES: The aim of this study was to investigate the bone regenerative properties of a heat treated cross-linked GBR membrane with zinc hydroxyapatite powders in the rat calvarial defect model over a 6-week period. MATERIAL AND METHODS: In vitro physio-chemical characterization involved X-ray diffraction analysis, surface topology by scanning electron microscopy, and zinc release studies in physiological buffers. Bilateral rat calvarial defects were used to compare the Zn-HAp membranes against the commercially available collagen membranes and the unfilled defect group through radiological and histological evaluation. RESULTS: The synthesized Zn-MEM (100 µm thick) showed no zinc ions released in the phosphate buffer solution (PBS) buffer, but zinc was observed under acidic conditions. At 6 weeks, both the micro-CT and histological analyses revealed that the Zn-MEM group yielded significantly greater bone formation with 80 ± 2% of bone filled, as compared with 60 ± 5% in the collagen membrane and 40 ± 2% in the unfilled control group. CONCLUSION: This study demonstrated the use of heat treatment as an alternative method to cross-linking the Zn-MEM to be applied as a GBR membrane. Its synthesis and production are relatively simple to fabricate, and the membrane had rough surface features on one side, which might be beneficial for cellular activities. In a rat calvarial defect model, it was shown that new bone formation was accelerated in comparison with the collagen membrane and the unfilled defect groups. These results would suggest that Zn-MEM has the potential for further development in dental applications.

Coral exoskeletons as a precursor material for the development of a calcium phosphate drug delivery system for bone tissue engineering.

With the global rise in aging of populations, the occurrence of osteoporosis will continue to increase. Biomaterial and pharmaceutical scientists continue to develop innovative strategies and materials to address this disease. In this article, we describe a new perspective and approach into the use of coral exoskeletons as a precursor material to synthesize a calcium phosphate-based drug delivery system. Studies detailing the methodology of the conversion methods and the strategies and approach for the development of these novel drug delivery systems are described. Furthermore, in vivo studies in osteoporotic mice using a drug loaded and chemically modified version of the biomimetic delivery system showed significant cortical and cancellous bone increases. These studies support the notion and the rationale for future research and development of the use of coral exoskeletons as materials for drug delivery applications.

Bone regeneration of rat tibial defect by zinc-tricalcium phosphate (Zn-TCP) synthesized from porous Foraminifera carbonate macrospheres.

Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP) as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair.

In vitro testing and efficacy of poly-lactic acid coating incorporating antibiotic loaded coralline bioceramic on Ti6Al4V implant against Staphylococcus aureus.

Biofilm formation on an implant surface is most commonly caused by the human pathogenic bacteria Staphylococcus aureus, which can lead to implant related infections and failure. It is a major problem for both implantable orthopedic and maxillofacial devices. The current antibiotic treatments are typically delivered orally or in an injectable form. They are not highly effective in preventing or removing biofilms, and they increase the risk of antibiotic resistance of bacteria and have a dose-dependent negative biological effect on human cells. Our aim was to improve current treatments via a localized and controlled antibiotic delivery-based implant coating system to deliver the antibiotic, gentamicin (Gm). The coating contains coral skeleton derived hydroxyapatite powders (HAp) that act as antibiotic carrier particles and have a biodegradable poly-lactic acid (PLA) thin film matrix. The system is designed to prevent implant related infections while avoiding the deleterious effects of high concentration antibiotics in implants on local cells including primary human adipose derived stem cells (ADSCs). Testing undertaken in this study measured the rate of S. aureus biofilm formation and determined the growth rate and proliferation of ADSCs. After 24 h, S. aureus biofilm formation and the percentage of live cells found on the surfaces of all 5%-30% (w/w) PLA-Gm-(HAp-Gm) coated Ti6Al4V implants was lower than the control samples. Furthermore, Ti6Al4V implants coated with up to 10% (w/w) PLA-Gm-(HAp-Gm) did not have noticeable Gm related adverse effect on ADSCs, as assessed by morphological and surface attachment analyses. These results support the use and application of the antibacterial PLA-Gm-(HAp-Gm) thin film coating design for implants, as an antibiotic release control mechanism to prevent implant-related infections.

Supramolecular-based nanofibers.

Supramolecular-based nanofibers, which successfully combine the unique properties of supramolecular interactions with the advantages of nanofibrous structure, are widely used in a variety of biomedical applications such as controlled drug delivery. Compared with traditional polymer nanofibers, supramolecular-based nanofibers can overcome the bottleneck of sensitivity because of the non-covalent binding modes, and therefore match the requirements of rapid and reversible response to the external stimuli. In addition, supramolecular-based nanofibers can achieve extra controllable and dynamic responsive (e.g. pH, temperature) functions in different environments. In this review, we retrospected and summarized the recent development of supramolecular-based nanofibers, focusing particularly on electrospun supramolecular nanofibers, while also touching on the advances of directly self-assembled supramolecular nanofibers without the use of electrospinning. Furthermore, we discussed the potential biomedical applications of supramolecular nanofibers. Finally, this review was concluded by elaborating upon individual reflection on the current situation, forecasting the future trend of this promising material.

Mechanical testing of antimicrobial biocomposite coating on metallic medical implants as drug delivery system.

Post-operative infection often occurs following orthopedic and dental implant placement requiring systemically administered antibiotics. However, this does not provide long-term protection. Over the last few decades, alternative methods involving slow drug delivery systems based on biodegradable poly-lactic acid and antibiotic loaded hydroxyapatite microspheres were developed to prevent post-operative infection. In this study, thermally anodised and untreated Ti6Al4V discs were coated with Poly-Lactic Acid (PLA) containing Gentamicin (Gm) antibiotic-loaded coralline Hydroxyapatite (HAp) are investigated. Following chemical characterization, mechanical properties of the coated samples were measured using nanoindentation and scratch tests to determine the elastic modulus, hardness and bonding adhesion between film and substrate. It was found that PLA biocomposite multilayered films were around 400nm thick and the influence and effect of the substrate were clearly observed during the nanoindentation studies with heavier loads. Scratch tests of PLA coated samples conducted at ~160nm depth showed the minimal difference in the measured friction between Gm and non Gm containing films. It is also observed that the hardness values of PLA film coated anodised samples ranged from 0.45 to 1.9GPa (dependent on the applied loads) against untreated coated samples which ranged from 0.28 to 0.8GPa.

Roadside drug testing: An evaluation of the Alere DDS® 2 mobile test system.

The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action.

Vertical bone augmentation induced by ultrathin hydroxyapatite sputtered coated mini titanium implants in a rabbit calvaria model.

BACKGROUND: The purpose of this study was to evaluate the vertical new bone formation induced by sputtered HA-coated titanium implants (HA-coated) compared with sandblasted acid-etched titanium implants (noncoated) in a rabbit calvarial model. MATERIALS AND METHOD: Twenty HA-coated and 20 noncoated titanium implants were divided equally into four groups as HA-coated implant (HA); noncoated implant (NC); HA-coated implant with membrane (HA/M); noncoated implant with membrane (NC/M). All implants were placed 5 mm above the original bone (OB). Collagen membranes were placed over the implants in HA/M and NC/M groups. The animals were sacrificed at 4 weeks (n = 5) and 8 weeks (n = 5). Vertical bone height above OB (VBH, mm) and augmented bone area (ABA, mm(2) ) were analyzed histologically and radiographically. RESULTS: At 4 weeks, VBH reached significantly higher level in HA/M group compared with other three groups (p < 0.05). At 8 weeks, significant difference was detected between HA/M and NC groups (p < 0.05). At 4 and 8 weeks, ABA in HA/M group was significantly larger compared with other three groups (p < 0.05). CONCLUSION: The present results indicated that sputtered HA-coated titanium implant together with collagen membrane could be a novel and effective approach for vertical bone augmentation.