Control Implants Research Articles

Surface characteristics of titanium dental implants with improved microdesigns: An in vivo study of their osseointegration performance in goat mandible.

Current trends in endosseous implant research are focused on the modification of microdesign of implants to achieve early and strong osseointegration. This study compares the influence of zinc doped hydroxyapatite (ZnHAp) coated, hydrothermally treated (HT) and machined Ti6Al4V (control) implants on osseointegration. The surface characterisation and microbial affinity test for implants were performed. Twenty seven (27) cylinders (3 types in each animal) were placed in the mandible of 9 black Bengal goats. Bone-implant interface was examined with histological, radiological parameters and scanning electron microscopy at 6, 12, and 24 weeks post-implantation. Surface roughness alterations of bone-separated implants were analysed by non-contact profilometer with time. The ZnHAp coated implants revealed direct and early bone-implant contact but high bacterial adherence and coating cracks. Low bacterial affinity and early strong bony integration was observed with HT implants. Poor bacterial affinity and delayed but strong fixation was evident with control implants. Based on the results of laboratory and animal experiments, we conclude that the hydrothermal modification of titanium implant is the more suitable way to achieve safe and effective osseointegration than the other two implant types for endosseous application.

Photofunctionalization as a suitable approach to improve the osseointegration of implants in animal models-A systematic review and meta-analysis.

To determine whether photofunctionalization influences dental implant osseointegration. Data on osseointegration rates were extracted from 8 databases, based on bone-to-implant contact (BIC) and pushout tests. Internal validity was accessed through the SYRCLE risk of bias tool for animal experimental studies. Meta-analyses were performed for investigation of the influence of photofunctionalization on implant osseointegration, with a random effect and a confidence interval of 95%. The certainty of evidence was accessed through the GRADE approach. Thirty-four records were identified, and 10 were included in the meta-analysis. Photofunctionalized implants showed higher mean values for BIC in rabbits (MD 6.92 [1.01, 12.82], p=.02), dogs (MD 23.70 [10.23, 37.16], p=.001), rats (MD 20.93 [12.91, 28.95], p<.0001), and in the pooled BIC analyses (MD 14.23 [7.80, 20.66], p<.0001) compared to those in control implants in the overall assay. Conversely, at late healing periods, the pooled BIC meta-analyses showed no statistically significant differences (p>.05) for photofunctionalized and control implants at 12weeks of follow-up. For pushout analysis, photofunctionalized implants presented greater bone strength integration (MD 19.92 [13.88, 25.96], p<.0001) compared to that of control implants. The heterogeneity between studies ranged from "not important" to "moderate" for rabbits I2 =24%, dogs I2 =0%, rats I2 =0%, and pooled BIC (I2 =49%), while considerable heterogeneity was observed for pushouts (I2 =90%). Photofunctionalization improves osseointegration in the initial healing period of implants, as summarized from available data from rabbit, dog, and rat in vivo models.

In vitro and in vivo study on the osseointegration of BCP-coated versus uncoated nondegradable thermoplastic polyurethane focal knee resurfacing implants.

Focal knee resurfacing implants (FKRIs) are intended to treat cartilage defects in middle‐aged patients. Most FKRIs are metal‐based, which hampers follow‐up of the joint using magnetic resonance imaging and potentially leads to damage of the opposing cartilage. The purpose of this study was to develop a nondegradable thermoplastic polyurethane (TPU) FKRI and investigate its osseointegration. Different surface roughness modifications and biphasic calcium phosphate (BCP) coating densities were first tested in vitro on TPU discs. The in vivo osseointegration of BCP‐coated TPU implants was subsequently compared to uncoated TPU implants and the titanium bottom layer of metal control implants in a caprine model. Implants were implanted bilaterally in stifle joints and animals were followed for 12 weeks, after which the bone‐to‐implant contact area (BIC) was assessed. Additionally, 18F‐sodium‐fluoride (18F‐NaF) positron emission tomography PET/CT‐scans were obtained at 3 and 12 weeks to visualize the bone metabolism over time. The BIC was significantly higher for the BCP‐coated TPU implants compared to the uncoated TPU implants (p = .03), and did not significantly differ from titanium (p = .68). Similar 18F‐NaF tracer uptake patterns were observed between 3 and 12 weeks for the BCP‐coated TPU and titanium implants, but not for the uncoated implants. TPU FKRIs with surface modifications could provide the answer to the drawbacks of metal FKRIs.

Effect of catgut implantation at "Yingxiang"(LI20) on lower airway remodeling in allergic rhinitis rats

To observe the effect of catgut implantation at "Yingxiang"(LI20) on lower airway remodeling and levels of osteopon-tin (OPN) protein in allergic rhinitis (AR) rats, so as to reveal its mechanisms underlying improvement of AR. Male SD rats were randomly divided into control, model and catgut implantation groups, with 10 rats in each group. The AR model was established by intraperitoneal injection and nasal drip of ovalbumin. The catgut implantation was applied to bilateral "Yingxiang"(LI20) for 28 days in rats of the catgut implantation group. The total score of allergic symptoms of rats in each group were observed. The histopathological changes of lower airway were observed under light microscope after Hematoxylineosin, Periodic acid-Schiff and Masson staining. The expression of OPN protein was detected by immunohistochemistry and Western blot, separately. The total score of allergic symptoms of nose-wiping, running nose and sneezing, count of lung goblet cells, lung fiber content, and immunoactivity and expression levels of OPN protein were significantly increased in the model group in contrast to the control group (P<0.05). After the intervention, the total score of allergic symptoms, count of lung goblet cells, immunoactivity and expression levels of OPN protein were considerably down-regulated in the catgut implantation group relevant to the model group (P<0.05). H．E. stain showed thickening of partial airway wall, narrowing of lumen, increase of mucus section, widened alveolar septum, infiltration of inflammatory cells, lymphocytes and eosinophil around the bronchus and in the lung interstitium in AR rats, which was milder in the catgut implantation group. The immunoactivity and expression levels of OPN protein were positively related with the lung goblet cells count and lung fiber content (P<0.05，P<0.01). Acupoint implantation of catgut can improve pathological changes of lower airway remodeling, which may be related to its effect in down-regulating the expression of OPN protein in the lung tissue.

UV-Pre-Treated and Protein-Adsorbed Titanium Implants Exhibit Enhanced Osteoconductivity.

Titanium materials are essential treatment modalities in the medical field and serve as a tissue engineering scaffold and coating material for medical devices. Thus, there is a significant demand to improve the bioactivity of titanium for therapeutic and experimental purposes. We showed that ultraviolet light (UV)-pre-treatment changed the protein-adsorption ability and subsequent osteoconductivity of titanium. Fibronectin (FN) adsorption on UV-treated titanium was 20% and 30% greater after 1-min and 1-h incubation, respectively, than that of control titanium. After 3-h incubation, FN adsorption on UV-treated titanium remained 30% higher than that on the control. Osteoblasts were cultured on titanium disks after 1-h FN adsorption with or without UV-pre-treatment and on titanium disks without FN adsorption. The number of attached osteoblasts during the early stage of culture was 80% greater on UV-treated and FN-adsorbed (UV/FN) titanium than on FN-adsorbed (FN) titanium; osteoblasts attachment on UV/FN titanium was 2.6- and 2.1-fold greater than that on control- and UV-treated titanium, respectively. The alkaline phosphatase activity of osteoblasts on UV/FN titanium was increased 1.8-, 1.8-, and 2.4-fold compared with that on FN-adsorbed, UV-treated, and control titanium, respectively. The UV/FN implants exhibited 25% and 150% greater in vivo biomechanical strength of bone integration than the FN- and control implants, respectively. Bone morphogenetic protein-2 (BMP-2) adsorption on UV-treated titanium was 4.5-fold greater than that on control titanium after 1-min incubation, resulting in a 4-fold increase in osteoblast attachment. Thus, UV-pre-treatment of titanium accelerated its protein adsorptivity and osteoconductivity, providing a novel strategy for enhancing its bioactivity.

Donald T. Nicolaisen: An Internationalist SEC Chief Accountant (1944–2019)

ABSTRACT Donald T. Nicolaisen (1944–2019) was an internationalist, a progressive thinker, and a leader of the U.S. accounting profession. This memorial article traces Nicolaisen's early education and career in the Milwaukee office of Price Waterhouse &amp; Co. in the 1960s, his rise to partner and eventual transfer to the firm's national office in New York City in the 1970s, and his appointment and tenure as the Chief Accountant of the Securities and Exchange Commission in the early 2000s. During his time as the Chief Accountant, Nicolaisen laid the groundwork for the lifting of the reconciliation requirement for foreign private issuers traded on American stock exchanges; the implantation of Sarbanes-Oxley's internal control reporting requirements; and the introduction of XBRL for companies' annual filings with the Commission. Through these initiatives, Nicolaisen leaves behind a legacy of improving both the quality of financial reporting and the efficiency of U.S. capital markets. JEL Classifications: M41; M42; M48.

Osseodensification Drilling vs. Standard Protocol of Implant Site Preparation: An In Vitro Study on Polyurethane Foam Sheets

(1) Background: The aim of the present in vitro investigation was to evaluate, on polyurethane sheets, two different drilling techniques for dental implant positioning using osteocondensing burs compared to a standard type protocol. (2) Methods: Three different implant designs (Implacil De Bortoli UN III 4 × 10 mm, Restore RBM 4 (HEX) × 10 mm; Implacil De Bortoli UN II 4 × 10 mm) were evaluated (test implant (osteocondensing drills) and control implant (standard drills)). The insertion torque (IT), the removal torque (RT) and the resonance frequency analysis (RFA) values of test and control implants inserted in different size and different density polyurethane foam models were compared for 120 experimental sites. Accordingly, 120 experimental holes were produced in different PCF polyurethane foams: 60 sites were produced in 10 PCF sheets and 60 sites in 10 PCF sheets with an additional 1 mm layer of 30 PCF. (3) Results: The IT, removal torque and RFA values were significantly higher for both of the evaluated implants, in the sites prepared with the osteocondenser drills when compared to sites prepared with standard drills (p &lt; 0.05). The UNII and UN III showed significantly higher stability compared to the HEX implant; these differences increased drastically in the 10 PCF Polyurethane Block with the additional 1 mm cortical layer (p &lt; 0.05). (4) Conclusions: The outcome of this investigation suggested a possible clinical application of osteocondensing burs in case of reduced bone quality and quantity in the posterior maxilla.

Biofilm Formation on Dental Implant Surface Treated by Implantoplasty: An In Situ Study.

Peri-implantitis is a biofilm-related disease whose characteristics are peri-implant tissues inflammation and bone resorption. Some clinical trials report beneficial effects after implantoplasty, namely the surgical smoothening of the implant surface, but there is a lack of data about the development of the bacterial biofilm on those smoothened surfaces. The aim of this study is to evaluate how implantoplasty influences biofilm formation. Three implants with moderately rough surfaces (control) and three implants treated with implantoplasty (test) were set on a tray reproducing the supra- and sub-gingival environment. One volunteer wore this tray for five days. Every 24 h, plaque coverage was measured and, at the end of the period of observartion, the implant surfaces were analyzed using scanning electron microscopy and confocal laser scanning microscopy. The proportion of implant surface covered with plaque was 65% (SD = 7.07) of the control implants and 16% (SD = 0) of the test implants. Untreated surfaces showed mature, complex biofilm structures with wide morphological diversity, and treated surfaces did not show the formation of mature biofilm structures. This study supports the efficacy of implantoplasty in reducing plaque adhesion and influencing biofilm formation. These results can be considered a preliminary proof of concept, but they may encourage further studies about the effects of implantoplasty on biofilm formation.

Effects of Different Divalent Cation Hydrothermal Treatments of Titanium Implant Surfaces for Epithelial Tissue Sealing.

The improvement of peri-implant epithelium (PIE) adhesion to titanium (Ti) may promote Ti dental implant stability. This study aims to investigate whether there is a positive effect of Ti hydrothermally treated (HT) with calcium chloride (CaCl2), zinc chloride (ZnCl2), and strontium chloride (SrCl2) on promoting PIE sealing. We analyzed the response of a rat oral epithelial cell (OEC) culture and performed an in vivo study in which the maxillary right first molars of rats were extracted and replaced with calcium (Ca)-HT, zinc (Zn)-HT, strontium (Sr)-HT, or non-treated control (Cont) implants. The OEC adhesion on Ca-HT and Zn-HT Ti plates had a higher expression of adhesion proteins than cells on the Cont and Sr-HT Ti plates. Additionally, the implant PIE of the Ca-HT and Zn-HT groups revealed better expression of immunoreactive laminin-332 (Ln-322) at 2 weeks after implantation. The Ca-HT and Zn-HT groups also showed better attachment at the implant–PIE interface, which inhibited horseradish peroxidase penetration. These results demonstrated that the divalent cations of Ca (Ca2+) and Zn (Zn2+)-HT improve the integration of epithelium around the implant, which may facilitate the creation of a soft barrier around the implant to protect it from foreign body penetration.

Mechanical Effects of Bone Substitute and Far-Cortical Locking Techniques in 2-Part Proximal Humerus Fracture Reconstruction: A Cadaveric Study.

To make direct comparisons of the biomechanical properties of a control (CTL) group and implants that were augmented with far cortical locking (FCL), bone substitute material (BSM), and a combination of both (ALL) to determine which fixation is most effective in reducing implant failure. The constructs were tested with osteopenic cadaveric specimens in a two-part fracture model. Specimens were subjected to a battery of nondestructive torsion and axial compression tests, followed by a cyclic test. Construct stiffness and cycles to failure were documented, pre- and post-test fluoroscopy was performed, and implant and bone kinematics were quantified. During nondestructive testing, the BSM group exhibited significantly increased torsional and axial stiffness compared with the FCL (P = 0.006, P < 0.001) group and ALL group (P < 0.001, P = 0.006). There were no significant differences in resistance to cyclic loading between groups. Fluoroscopic analysis indicated significant differences in the motions of nonlocked cannulated screws (used in BSM and ALL) versus locked screws (used in CTL and FCL). Patients with poor bone quality and proximal humerus fracture may necessitate added compliance or rigidity to achieve fixation. Both have exhibited favorable biomechanical characteristics in this cadaveric 2-part proximal humerus fracture model.

Stability of screw-retention in two-piece zirconia implants: An in vitro study.

To compare the stability of a screw-retained connection in a novel two-piece zirconia implant to a conventional titanium-based connection in an in vitro chewing simulation including artificial ageing. Incisor (I) and molar (M) shaped monolithic zirconia crowns were screw-retained on either two-piece zirconia (test) or two-piece titanium (control) implants resulting in 4 groups of 8 samples (titanium implants with incisor-shaped crowns (T-I), titanium implants with molar-shaped crowns (T-M), zirconia implants with incisor-shaped crowns (Z-I) and zirconia implants with molar-shaped crowns (Z-M). These were subjected to artificial ageing by thermal cycling (TC: 2×3000×5°C/55°C cycles of 2min) and mechanical loading (ML: 1.2×106 cycles of 50N, f=1Hz). Surviving samples additionally underwent a fracture force test. Kaplan-Meier plots were drawn, and two-way ANOVA was calculated taking anatomical localisation and material variables as factors. The mean corresponding survival times were lower for T-M (0.86×106 ±0.31×106 cycles) and Z-I (0.84×106 ±0.21×106 cycles) compared to T-I (1.14×106 ±0.10×106 cycles) and Z-M (1.20×106 ±0.10×106 cycles). In one-way ANOVAs for survival time dependent on either location or material, no statistically significant differences could be found (location: p=.31; material: p=.62) in one-way ANOVAs. The interaction of location and material showed significant differences (F=21.3, p<.001). The connection of the tested screw-retained zirconia crowns in two-piece zirconia implants is comparable to standard titanium implants in the specific in vitro testing.

Multifunctional Properties of Quercitrin-Coated Porous Ti-6Al-4V Implants for Orthopaedic Applications Assessed In Vitro.

(1) One strategy to improve the outcome of orthopedic implants is to use porous implants with the addition of a coating with an antibacterial biomolecule. In this study, we aimed to produce and test the biocompatibility, the osteopromotive (both under normal conditions and under a bacterial challenge with lipopolysaccharide (LPS)) and antibacterial activities of a porous Ti-6Al-4V implant coated with the flavonoid quercitrin in vitro. (2) Porous Ti-6Al-4V implants were produced by 3D printing and further functionalized with quercitrin by wet chemistry. Implants were characterized in terms of porosity and mechanical testing, and the coating with quercitrin by fluorescence staining. Implant biocompatibility and bioactivity was tested using MC3T3-E1 preosteoblasts by analyzing cytotoxicity, cell adhesion, osteocalcin production, and alkaline phosphatase (ALP) activity under control and under bacterial challenging conditions using lipopolysaccharide (LPS). Finally, the antibacterial properties of the implants were studied using Staphylococcus epidermidis by measuring bacterial viability and adhesion. (3) Porous implants showed pore size of about 500 µm and a porosity of 52%. The coating was homogeneous over all the 3D surface and did not alter the mechanical properties of the Young modulus. Quercitrin-coated implants showed higher biocompatibility, cell adhesion, and osteocalcin production compared with control implants. Moreover, higher ALP activity was observed for the quercitrin group under both normal and bacterial challenging conditions. Finally, S. epidermidis live/dead ratio and adhesion after 4 h of incubation was lower on quercitrin implants compared with the control. (4) Quercitrin-functionalized porous Ti-6Al-4V implants present a great potential as an orthopedic porous implant that decreases bacterial adhesion and viability while promoting bone cell growth and differentiation.

Low Energy Implantation into Transition-Metal Dichalcogenide Monolayers to Form Janus Structures.

Atomically thin two-dimensional (2D) materials face significant energy barriers for synthesis and processing into functional metastable phases such as Janus structures. Here, the controllable implantation of hyperthermal species from pulsed laser deposition (PLD) plasmas is introduced as a top-down method to compositionally engineer 2D monolayers. The kinetic energies of Se clusters impinging on suspended monolayer WS2 crystals were controlled in the <10 eV/atom range with in situ plasma diagnostics to determine the thresholds for selective top layer replacement of sulfur by selenium for the formation of high quality WSSe Janus monolayers at low (300 °C) temperatures and bottom layer replacement for complete conversion to WSe2. Atomic-resolution electron microscopy and spectroscopy in tilted geometry confirm the WSSe Janus monolayer. Molecular dynamics simulations reveal that Se clusters implant to form disordered metastable alloy regions, which then recrystallize to form highly ordered structures, demonstrating low-energy implantation by PLD for the synthesis of 2D Janus layers and alloys of variable composition.

Zn2+-dependent suppression of vascular smooth muscle intimal hyperplasia from biodegradable zinc implants.

Biodegradable arterial implants based on zinc have been found to suppress neointimal hyperplasia, suggesting that biodegradable materials containing zinc may be used to construct vascular implants with a reduced rate of restenosis. However, the molecular mechanism has remained unclear. In this report, we show that zinc-containing materials can be used to prevent neointimal formation when implanted into the rat aorta. Indeed, neointimal cells were significantly more TUNEL positive and alpha-actin negative at the interface of biodegradable zinc vs. biostable platinum implants, in association with greater caspase-3 activity. Although zinc stimulated extensive neointimal smooth muscle cell (SMC) death, macrophage and proinflammatory markers CD68 and iNOS were not increased in neointimal tissue relative to biostable platinum control implants. Using arterial explants, ionic zinc was confirmed to promote SMC apoptosis by activating the caspase apoptotic signaling pathway. These observations suggest that zinc-containing materials can be used to construct vascular implants such as stents with reduced neointimal hyperplasia.

Biocompatibility and osseointegration of nanostructured titanium dental implants in minipigs.

It is well known that surface treatments of dental implants have a great impact on their rate of osseointegration. The aim of this study was to compare the biocompatibility and the bone-implant contact (BIC) of titanium dental implants with different surface treatments. Test implants (Biotech Dental) had a nanostructured surface and control implants (Anthogyr) were grit-blasted with biphasic calcium phosphate and acid-etched surface. Both titanium implants were inserted in mandible and maxillary bones of 6 Yucatan minipigs for 4 and 12weeks (n=10 implants/group). Biocompatibility and osseointegration were evaluated by non-decalcified histology and back-scattered electron microscopy images. The reading of histology sections by an antomo-pathologist indicated that the test implants were considered non-irritating to the surrounding tissues and thus biocompatible compared with control implants. The BIC values were higher for test than for control dental implants at both 4 and 12weeks. In summary, the new nanostructured titanium dental implant is considered biocompatible and showed a better osseointegration than the control implant at both 4 and 12weeks.

UV-Photofunctionalization of Titanium Promotes Mechanical Anchorage in A Rat Osteoporosis Model.

Effects of UV-photofunctionalization on bone-to-titanium integration under challenging systemic conditions remain unclear. We examined the behavior and response of osteoblasts from sham-operated and ovariectomized (OVX) rats on titanium surfaces with or without UV light pre-treatment and the strength of bone-implant integration. Osteoblasts from OVX rats showed significantly lower alkaline phosphatase, osteogenic gene expression, and mineralization activities than those from sham rats. Bone density variables in the spine were consistently lower in OVX rats. UV-treated titanium was superhydrophilic and the contact angle of ddH2O was ≤5°. Titanium without UV treatment was hydrophobic with a contact angle of ≥80°. Initial attachment to titanium, proliferation, alkaline phosphatase activity, and gene expression were significantly increased on UV-treated titanium compared to that on control titanium in osteoblasts from sham and OVX rats. Osteoblastic functions compromised by OVX were elevated to levels equivalent to or higher than those of sham-operated osteoblasts following culture on UV-treated titanium. The strength of in vivo bone-implant integration for UV-treated titanium was 80% higher than that of control titanium in OVX rats and even higher than that of control implants in sham-operated rats. Thus, UV-photofunctionalization effectively enhanced bone-implant integration in OVX rats to overcome post-menopausal osteoporosis-like conditions.

Clinical, host-derived immune biomarkers and microbiological outcomes with adjunctive photochemotherapy compared with local antimicrobial therapy in the treatment of peri-implantitis in cigarette smokers.

The aim of this study was designed to assess the peri-implant oral hygiene parameters, clinical, radiographic, host-derived immune biomarkers and microbiological levels after photochemotherapy (PCT) and local antibiotic therapy (LAT) in peri-implantitis lesions among cigarette smokers. Fifty current cigarette smokers with peri-implantitis were divided into two groups: PCT and LAT. Test implants received PCT that consisted of toluidine blue photosensitizer and application of 660 nm diode laser with a total of 100 mW power and 124.3 W/cm2 energy using continuous mode of irrigation for 60 s. Control implants received one-unit subgingival application of metronidazole gel in viscous consistency. Clinical measurements included the assessment of plaque scores (PS), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL). Intraoral standardized digital peri-apical radiographs were taken at baseline and at 12 months. Interleukin (IL)-1β and matrix metalloproteinase (MMP)-1 in the PICF were determined using the manufacturers guide from one-step enzyme-linked immunosorbent assay. Real-time polymerase chain reaction (PCR) for Parvimonas micra, Porphyromonas gingivalis and Tannerella forsythia was performed and counts evaluated at baseline, 3, 6 and 12-months. Plaque scores reduced in both groups (p < 0.05). Mean BOP percentage significantly increased in both the groups at 1-month follow-up compared to baseline. Following this period, BOP showed reduction from 1-month to consecutive follow-up periods. The PD significantly reduced in both the groups with no statistically significant difference when compared between PCT and LAT groups at follow-up (p > 0.05). CAL did not change over the period and between both groups (p > 0.05). The differences from baseline to 12 months and between the groups for mesial and distal crestal bone levels did not show any statistical significance (p > 0.05). The levels of IL-1β significantly dropped from baseline to 12 months in the LAT group (p < 0.05). However, for PCT groups, the levels of IL-1β significantly reduced only at 12-month visit follow-up (p < 0.05). MMP-1 showed statistically significant reduction at 9 and 12-months compared with baseline for LAT group. Both P. gingivalis and T. forsythia showed statistically significant reduction in both the groups when values were compared from baseline to 3-, 6- and 12-months follow-up (p < 0.05). However, these differences were not significant when compared between the groups (p > 0.05). Both PCT and LAT showed equal efficacies in improving clinical, host-derived immune biomarkers and microbiological parameters in peri-implant infection in cigarette smokers.

Local delivery of minocycline-loaded PLGA nanoparticles from gelatin-coated neural implants attenuates acute brain tissue responses in mice

BackgroundNeural interfaces often elicit inflammatory responses and neuronal loss in the surrounding tissue which adversely affect the function and longevity of the implanted device. Minocycline, an anti-inflammatory pharmaceutics with neuroprotective properties, may be used for reducing the acute brain tissue responses after implantation. However, conventional administration routes require high doses which can cause adverse systemic side effects. Therefore, the aim of this study was to develop and evaluate a new drug-delivery-system for local and sustained administration of minocycline in the brain.MethodsStainless steel needles insulated with Parylene-C were dip-coated with non-crosslinked gelatin and minocycline-loaded PLGA nanoparticles (MC-NPs) were incorporated into the gelatin-coatings by an absorption method and subsequently trapped by drying the gelatin. Parylene-C insulated needles coated only with gelatin were used as controls. The expression of markers for activated microglia (CD68), all microglia (CX3CR1-GFP), reactive astrocytes (GFAP), neurons (NeuN) and all cell nuclei (DAPI) surrounding the implantation sites were quantified at 3 and 7 days after implantation in mice.ResultsMC-NPs were successfully incorporated into gelatin-coatings of neural implants by an absorption method suitable for thermosensitive drug-loads. Immunohistochemical analysis of the in vivo brain tissue responses, showed that MC-NPs significantly attenuate the activation of microglial cells without effecting the overall population of microglial cells around the implantation sites. A delayed but significant reduction of the astrocytic response was also found in comparison to control implants. No effect on neurons or total cell count was found which may suggest that the MC-NPs are non-toxic to the central nervous system.ConclusionsA novel drug-nanoparticle-delivery-system was developed for neural interfaces and thermosensitive drug-loads. The local delivery of MC-NPs was shown to attenuate the acute brain tissue responses nearby an implant and therefore may be useful for improving biocompatibility of implanted neuro-electronic interfaces. The developed drug-delivery-system may potentially also be used for other pharmaceutics to provide highly localized and therefore more specific effects as compared to systemic administration.

Clinical and radiographic changes at tissue level implants with either a machined or a modified transmucosal neck surface: A 3-year multicentre randomized controlled proof-of-concept study.

Surface modification may yield enhanced soft tissue adhesion to transmucosal titanium implant necks. To evaluate and compare changes in soft tissues around implants with a modified hydrophilic sandblasted and acid-etched neck (mSLA; test) to those with a machined neck (M; control). Implants with a diameter of 4.1mm and a neck height of 1.8mm were randomly inserted in healed sites with pristine bone of the posterior maxilla or mandible. The modified Sulcus Bleeding Index (mSBI) (primary outcome) was assessed at baseline (BL) and 6, 12 and 36months. Secondary outcomes included the assessment of pocket probing depth (PPD), mucosal recession (REC) and clinical attachment level (CAL). Standardized radiographs were taken at time of implant placement, at BL and after 12 and 36months. Of the 43 randomized subjects, 38 (19 test and 19 controls) completed the 36-month follow-up. Implant survival rates amounted to 95.5% (test) and 100% (control) (p>.05). At 36months, 77.6% of test implants and 78.9% of control implants were without any bleeding sites (mSBI=0; p>.05). The 36-month success rate was 86.4% in the test and 85.7% in the control group, respectively (p>.05). At 36months, the mean radiographic bone level change from BL was 0.33±0.69mm at test implants and 0.12±0.3mm at control implants (p>.05). Tissue level implants with a hydrophilic mSLA transmucosal neck failed to yield clinical and radiographic benefits compared with implants with a machined neck up to 3years.

Evaluation of a Novel Spun Polytetrafluoroethylene Stent Graft in an Ovine External Iliac Artery Model.

To evaluate the patency, cellular response, and thrombogenicity of a novel vascular stent graft. Test stent grafts, incorporating luminal spun polytetrafluoroethylene and a nonpermeable fluoropolymer layer, and control stent grafts, constructed of permeable expanded polytetrafluoroethylene, were implanted in the external iliac arteries of 14 adult sheep with a median weight of 73.4 kg ranging from 60.6-86.8 kg for 30 (n= 4), 90 (n= 4), and 180 (n= 6) days. Angiographic patency and percent diameter stenosis (%DS) were assessed at termination. Excised stent grafts were fixed and stained for histopathologic analysis, including neointimal coverage (NC) assessment. Test and control device migration occurred in 1 animal, resulting in test device thrombosis. Both devices were excluded from analysis. Mean %DS in test and control implants was 4.6% and 8.2% (P= .563), 2.0% and 10.9% (P= .363), and 2.1% and 10.3% (P= .009) at 30, 90, and 180 days, respectively. Median NC scores at 30, 90, and 180 days were significantly lower in middle test device sections (P < .05). Proximal and distal test and control sections exhibited similar median NC scores at all time periods (P > .05). When present, test and control devices exhibited no neointimal detachment from the graft surface. Except for the migrated test device, no thrombus was observed. Transgraft cellular migration was absent in test devices but present in control devices with tissue accumulation around the stent struts. Test and control devices demonstrated excellent patency in an ovine model. Compared to the control, test devices exhibited significantly lower %DS values at 180 days and significantly lower mid-device NC scores at 30, 90, and 180 days.