Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol) diacrylate Implants for Sustained Ocular Drug Delivery.

PubMed

McAvoy, Kathryn; Jones, David; Thakur, Raghu Raj Singh

2018-01-16

To investigate the sustained ocular delivery of small and large drug molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants with varying pore forming agents. Triamcinolone acetonide and ovalbumin loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were fabricated and characterised for chemical, mechanical, swelling, network parameters, as well as drug release and biocompatibility. HPLC-based analytical methods were employed for analysis of two molecules; ELISA was used to demonstrate bioactivity of ovalbumin. Regardless of PEGDA molecular weight or pore former composition all implants loaded with triamcinolone acetonide released significantly faster than those loaded with ovalbumin. Higher molecular weight PEGDA systems (700 Da) resulted in faster drug release of triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released over the 56-day time period was found to be bioactive. Increasing PEGDA molecular weight resulted in increased system swelling, decreased crosslink density (Ve), increased polymer-water interaction parameter (χ), increased average molecular weight between crosslinks (Mc) and increased mesh size (ε). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were non-toxic when exposed to retinal epithelial cells over a 7-day period. Photocrosslinked PEGDA implant based systems are capable of controlled drug release of both small and large drug molecules through adaptations in the polymer system network. We are currently continuing evaluation of these systems as potential sustained drug delivery devices.

Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy.

PubMed

Li, Dan; Li, Litao; Ma, Yunlong; Zhuang, Yaping; Li, Dawei; Shen, Hong; Wang, Xing; Yang, Fei; Ma, Yuanzheng; Wu, Decheng

2017-03-28

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

PLA/PEG-PPG-PEG/dexamethasone implant prepared by hot-melt extrusion for controlled release of immunosuppressive drug to implantable medical devices, Part 2: in vivo evaluation.

PubMed

Li, DeXia; Guo, Gang; Deng, Xin; Fan, RangRang; Guo, QingFa; Fan, Min; Liang, Jian; Luo, Feng; Qian, ZhiYong

2013-01-01

Hot-melt extrusion (HME) plays an important role in preparing implants as local drug delivery systems in pharmaceutical fields. Here, a new PLA/PEG-PPG-PEG/Dexamethasone (PLA/F68/Dex) implant prepared by HME has been developed. Importantly, the implant was successfully achieved to control release of immunosuppressive drug to an implanted device. In particular, this implant has not been reported previously in pharmaceutical fields. FTIR and XRD were adopted to investigate the properties of the samples. The in vivo release study showed that the maximum value of Dex release from the implants was approximately 50% at 1 month. The in vivo degradation behavior was determined by UV spectrophotometer and scanning electron microscopy studies, and the weight loss rate of the implants were up to 25% at 1 month. Furthermore, complete blood count (CBC) test, serum chemistry and major organs were performed, and there is no significant lesion and side effects observed in these results. Therefore, the results elucidated that the new PLA/F68/Dex implant prepared by HME could deliver an immunosuppressive drug to control the inflammatory reaction at the implant site.

76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... INFORMATION: Bayer HealthCare LLC, Animal Health Division, P.O. Box 390, Shawnee Mission, KS 66201, filed a...

75 FR 13225 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Flunixin AGENCY: Food and... amending the animal drug regulations to reflect approval of an original abbreviated new animal drug... copy of BANAMINE-S, sponsored by Schering-Plough Animal Health Corp. under NADA 101-479. The ANADA is...

Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays.

PubMed

Aw, Moom Sinn; Losic, Dusan

2013-02-25

A non-invasive and external stimulus-driven local drug delivery system (DDS) based on titania nanotube (TNT) arrays loaded with drug encapsulated polymeric micelles as drug carriers and ultrasound generator is described. Ultrasound waves (USW) generated by a pulsating sonication probe (Sonotrode) in phosphate buffered saline (PBS) at pH 7.2 as the medium for transmitting pressure waves, were used to release drug-loaded nano-carriers from the TNT arrays. It was demonstrated that a very rapid release in pulsatile mode can be achieved, controlled by several parameters on the ultrasonic generator. This includes pulse length, time, amplitude and power intensity. By optimization of these parameters, an immediate drug-micelles release of 100% that spans a desirable time of 5-50 min was achieved. It was shown that stimulated release can be generated and reproduced at any time throughout the TNT-Ti implant life, suggesting considerable potential of this approach as a feasible and tunable ultrasound-mediated drug delivery system in situ via drug-releasing implants. It is expected that this concept can be translated from an in vitro to in vivo regime for therapeutic applications using drug-releasing implants in orthopedic and coronary stents. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

In situ forming implants for the delivery of metronidazole to periodontal pockets: formulation and drug release studies.

PubMed

Kilicarslan, Muge; Koerber, Martin; Bodmeier, Roland

2014-05-01

This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.

Biocompatible medical implant materials with binding sites for a biodegradable drug-delivery system

PubMed Central

Al-Dubai, Haifa; Pittner, Gisela; Pittner, Fritz; Gabor, Franz

2011-01-01

Feasibility studies have been carried out for development of a biocompatible coating of medical implant materials allowing the binding of biodegradable drug-delivery systems in a way that their reloading might be possible. These novel coatings, able to bind biodegradable nanoparticles, may serve in the long run as drug carriers to mediate local pharmacological activity. After biodegradation of the nanoparticles, the binding sites could be reloaded with fresh drug-delivering particles. As a suitable receptor system for the nanoparticles, antibodies are anchored. The design of the receptor is of great importance as any bio- or chemorecognitive interaction with other components circulating in the blood has to be avoided. Furthermore, the binding between receptor and the particles has to be strong enough to keep them tightly bound during their lifetime, but on the other hand allow reloading after final degradation of the particles. The nanoparticles suggested as a drug-delivery system for medical implants can be loaded with different pharmaceuticals such as antibiotics, growth factors, or immunosuppressives. This concept may enable the changing of medication, even after implantation of the medical device, if afforded by patients’ needs. PMID:24198488

[Prolonged-release drug formulations for parenteral administration. Part II. Microspheres and implants for injection].

PubMed

Płaczek, Margin; Jacyna, Julia; Sznitowska, Małgorzata

2014-01-01

Microspheres and implants are injectable drug forms, which by special design and selection of appropriate excipients, provide for a long time constant release rate of an active substance in the body. Development of both would not be possible without advances in polymer technology and invention of safe and biocompatible polymers such as: polyesters, vinyl acetate derivatives or silicones. Polymeric matrices provide retardation of drug release--for some implants up to a few years. In addition, this paper presents examples of all commercially available medicinal products containing microspheres and implants, currently registered in Poland, together with their characteristics: composition, time course and frequency of administration. Comments are also enclosed on frequently occurring inconsistent terminology in pharmaceutical forms.

A Review of the Development of a Vehicle for Localized and Controlled Drug Delivery for Implantable Biosensors

PubMed Central

Bhardwaj, Upkar; Papadimitrakopoulos, Fotios; Burgess, Diane J.

2008-01-01

A major obstacle to the development of implantable biosensors is the foreign body response (FBR) that results from tissue trauma during implantation and the continuous presence of the implant in the body. The in vivo stability and functionality of biosensors are compromised by damage to sensor components and decreased analyte transport to the sensor. This paper summarizes research undertaken by our group since 2001 to control the FBR toward implanted sensors. Localized and sustained delivery of the anti-inflammatory drug, dexamethasone, and the angiogenic growth factor, vascular endothelial growth factor (VEGF), was utilized to inhibit inflammation as well as fibrosis and provide a stable tissue–device interface without producing systemic adverse effects. The drug-loaded polylactic-co-glycolic acid (PLGA) microspheres were embedded in a polyvinyl alcohol (PVA) hydrogel composite to fabricate a drug-eluting, permeable external coating for implantable devices. The composites were fabricated using the freeze–thaw cycle method and had mechanical properties similar to soft body tissue. Dexamethasone-loaded microsphere/hydrogel composites were able to provide anti-inflammatory protection, preventing the FBR. Moreover, concurrent release of dexamethasone with VEGF induced neoangiogenesis in addition to providing anti-inflammatory protection. Sustained release of dexamethasone is required for the entire sensor lifetime, as a delayed inflammatory response developed after depletion of the drug from the composites. These studies have shown the potential of PLGA microsphere/PVA hydrogel-based composites as drug-eluting external coatings for implantable biosensors. PMID:19885291

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

PubMed

Gulati, Karan; Ivanovski, Sašo

2017-08-01

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 TiO 2 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.

Near-infrared fluorescence imaging platform for quantifying in vivo nanoparticle diffusion from drug loaded implants.

PubMed

Markovic, Stacey; Belz, Jodi; Kumar, Rajiv; Cormack, Robert A; Sridhar, Srinivas; Niedre, Mark

2016-01-01

Drug loaded implants are a new, versatile technology platform to deliver a localized payload of drugs for various disease models. One example is the implantable nanoplatform for chemo-radiation therapy where inert brachytherapy spacers are replaced by spacers doped with nanoparticles (NPs) loaded with chemotherapeutics and placed directly at the disease site for long-term localized drug delivery. However, it is difficult to directly validate and optimize the diffusion of these doped NPs in in vivo systems. To better study this drug release and diffusion, we developed a custom macroscopic fluorescence imaging system to visualize and quantify fluorescent NP diffusion from spacers in vivo. To validate the platform, we studied the release of free fluorophores, and 30 nm and 200 nm NPs conjugated with the same fluorophores as a model drug, in agar gel phantoms in vitro and in mice in vivo. Our data verified that the diffusion volume was NP size-dependent in all cases. Our near-infrared imaging system provides a method by which NP diffusion from implantable nanoplatform for chemo-radiation therapy spacers can be systematically optimized (eg, particle size or charge) thereby improving treatment efficacy of the platform.

A bioactive implant in situ and long-term releases combined drugs for treatment of osteoarticular tuberculosis.

PubMed

Zhou, Chao-Xi; Li, Litao; Ma, Yi-Guang; Li, Bing-Nan; Li, Guang; Zhou, Zhihang; Shi, Feng; Weng, Jie; Zhang, Cong; Wang, Fenghua; Cui, Xu; Wang, Lei; Wang, Hao

2018-05-24

Anti-tuberculosis chemotherapy with a long duration and adequate dosing is the mainstay for treatment of osteoarticular tuberculosis (TB). However, it is difficult for systemic administration to reach adequate local drug concentrations and achieve effective treatment. Herein, a hydroxyapatite (HA) scaffold implant combined with a drug-releasing system was designed to achieve in situ and long-term anti-TB drug release and highly efficient therapeutic activity in vitro and in vivo. The clinical anti-TB drugs hydrophilic isoniazid (INH) and hydrophobic rifampicin (RFP) were molecularly dispersed into polyvinyl alcohol (PVA) through immersion-curing techniques and were steadily adhered onto the surfaces of HA scaffolds (HA-drug@PVA). The HA-drug@PVA scaffolds showed a long-term, sustained drug release profile and killed proliferating Mycobacteriumin vitro. In vivo experimental results revealed that the HA-drug@PVA scaffolds provided over 10- and 100-fold higher concentrations in muscles and bones, respectively, as well as a much lower concentration (<0.025) in blood. Furthermore, the HA-drug@PVA scaffold implanted in an osteoarticular TB rabbit model showed obvious bone regeneration and fusion due to the inhibition of TB-associated inflammatory changes. The excellent therapeutic effects indicate that in situ implant materials combined with a long-term drug release system are promising for the treatment of osteoarticular TB and other osteoarticular infections. Copyright © 2018. Published by Elsevier Ltd.

76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin... combination drug injectable solution containing oxytetracycline and flunixin meglumine in cattle. [[Page 3489... veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine) Injection for the treatment...

A Wireless Implantable Micropump for Chronic Drug Infusion Against Cancer

PubMed Central

Cobo, Angelica; Sheybani, Roya; Tu, Heidi; Meng, Ellis

2016-01-01

We present an implantable micropump with a miniature form factor and completely wireless operation that enables chronic drug administration intended for evaluation and development of cancer therapies in freely moving small research animals such as rodents. The low power electrolysis actuator avoids the need for heavy implantable batteries. The infusion system features a class E inductive powering system that provides on-demand activation of the pump as well as remote adjustment of the delivery regimen without animal handling. Micropump performance was demonstrated using a model anti-cancer application in which daily doses of 30 μL were supplied for several weeks with less than 6% variation in flow rate within a single pump and less than 8% variation across different pumps. Pumping under different back pressure, viscosity, and temperature conditions were investigated; parameters were chosen so as to mimic in vivo conditions. In benchtop tests under simulated in vivo conditions, micropumps provided consistent and reliable performance over a period of 30 days with less than 4% flow rate variation. The demonstrated prototype has potential to provide a practical solution for remote chronic administration of drugs to ambulatory small animals for research as well as drug discovery and development applications. PMID:26855476

Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability.

PubMed

Gulati, Karan; Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M; Atkins, Gerald J; Losic, Dusan

2016-12-01

There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements. Copyright © 2016 Elsevier B.V. All rights reserved.

Concomitant monitoring of implant formation and drug release of in situ forming poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the subcutis using UV-vis imaging.

PubMed

Sun, Yu; Jensen, Henrik; Petersen, Nickolaj J; Larsen, Susan W; Østergaard, Jesper

2018-02-20

For poly (lactide-co-glycolide acid) (PLGA)-based in situ forming implants, the rate of implant formation plays an important role in determining the overall drug release kinetics. Currently, in vitro techniques capable of characterizing the processes of drug release and implant formation at the same time are not available. A hydrogel-based in vitro experimental setup was recently developed requiring only microliter of formulation and forming a closed system potentially suitable for interfacing with various spectroscopic techniques. The aim of the present proof-of-concept study was to investigate the feasibility of concomitant UV imaging, Vis imaging and light microscopy for detailed characterization of the behavior of in situ forming PLGA implants in the hydrogel matrix mimicking the subcutis. The model compounds, piroxicam and α-lactalbumin were added to PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin solutions. Upon bringing the PLGA-solvent-compound pre-formulation in contact with the hydrogel, Vis imaging and light microscopy were applied to visualize the depot formation and UV imaging was used to quantify drug transport in the hydrogel. As compared to piroxicam, the α-lactalbumin invoked an acceleration of phase separation and an increase of implant size. α-Lactalbumin was released faster from the PLGA-1-methyl-2-pyrrolidinone system than the PLGA-triacetin system opposite to the piroxicam release pattern. A linear relationship between the rate of implant formation and initial compound release within the first 4h was established for the PLGA-NMP systems. This implies that phase separation may be one of the controlling factors in drug release. The rate of implant formation may be an important parameter for predicting and tailoring drug release. The approach combining UV imaging, Vis imaging and light microscopy may facilitate understanding of release processes and holds potential for becoming a useful tool in formulation development of in situ forming

Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone.

PubMed

Trajkovski, Branko; Petersen, Ansgar; Strube, Patrick; Mehta, Manav; Duda, Georg N

2012-09-01

Bone is one of the few tissues in the human body with high endogenous healing capacity. However, failure of the healing process presents a significant clinical challenge; it is a tremendous burden for the individual and has related health and economic consequences. To overcome such healing deficits, various concepts for a local drug delivery to bone have been developed during the last decades. However, in many cases these concepts do not meet the specific requirements of either surgeons who must use these strategies or individual patients who might benefit from them. We describe currently available methods for local drug delivery and their limitations in therapy. Various solutions for drug delivery to bone focusing on clinical applications and intra-operative constraints are discussed and drug delivery by implant coating is highlighted. Finally, a new set of design and performance requirements for intra-operatively customized implant coatings for controlled drug delivery is proposed. In the future, these requirements may improve approaches for local and intra-operative treatment of patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Implementation of wireless power transfer and communications for an implantable ocular drug delivery system.

PubMed

Tang, T B; Smith, S; Flynn, B W; Stevenson, J T M; Gundlach, A M; Reekie, H M; Murray, A F; Renshaw, D; Dhillon, B; Ohtori, A; Inoue, Y; Terry, J G; Walton, A J

2008-09-01

A wireless power transfer and communication system based on near-field inductive coupling has been designed and implemented. The feasibility of using such a system to remotely control drug release from an implantable drug delivery system is addressed. The architecture of the wireless system is described and the signal attenuation over distance in both water and phosphate buffered saline is studied. Additionally, the health risk due to exposure to radio frequency (RF) radiation is examined using a biological model. The experimental results demonstrate that the system can trigger the release of drug within 5 s, and that such short exposure to RF radiation does not produce any significant (implantable system, eliminating the risks associated with battery failure and leakage and also allowing more compact designs for applications such as drug delivery.

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro.

PubMed

Wu, Gui; Wu, Weigang; Zheng, Qixin; Li, Jingfeng; Zhou, Jianbo; Hu, Zhilei

2014-07-19

Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants' surfaces were observed with electron microscope. The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a "nest-shaped" way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day's release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was

In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery.

PubMed

Maulvi, Furqan A; Lakdawala, Dhara H; Shaikh, Anjum A; Desai, Ankita R; Choksi, Harsh H; Vaidya, Rutvi J; Ranch, Ketan M; Koli, Akshay R; Vyas, Bhavin A; Shah, Dinesh O

2016-03-28

Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168h (NP 1:3 batch) with 150μg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Hybrid nanocomposite coatings from metal (Mg alloy)-drug deposited onto medical implant by laser adaptive ablation deposition technique

NASA Astrophysics Data System (ADS)

Serbezov, Valery; Sotirov, Sotir; Serbezov, Svetlin

2013-03-01

Drug-eluting medical implants are active implants whose function is to create healing effects. The current requirements for active medical coatings for Drug-eluting medical implants are to be biocompatible, biodegradable, polymer free, mechanically stable and enable a controlled release of one or more drugs and defined degradation. This brings hybrid nanocomposite coatings into focus especially in the field of cardiovascular implants. We studied the properties of Metal (Mg alloy)-Paclitaxel coatings obtained by novel Laser Adaptive Ablation Deposition Technique (LAAD) onto cardiovascular stents from 316 LVM stainless steel material. The morphology and topology of coatings were studied by Bright field / Fluorescence optical microscope and Scanning Electron Microscope (SEM). Comparative measurements were made of the morphology and topology of hybrid, polymer free nanocomposite coatings deposited by LAAD and polymerdrug coatings deposited by classical spray technique. The coatings obtained by LAAD are homogeneous without damages and cracks. Metal nanoparticles with sizes from 40 nm to 230 nm were obtained in drug matrixes. Energy Dispersive X-ray Spectroscopy (EDX) was used for identification of metal nanoparticles presence in hybrid nanocomposites coatings. The new technology opens up possibilities to obtain new hybrid nanocomposite coatings with applications in medicine, pharmacy and biochemistry.

Clinical Outcomes of Drug-Coated Balloons in Coronary Artery Disease Unsuitable for Drug-Eluting Stent Implantation.

PubMed

Iijima, Raisuke; Kougame, Norihiro; Hara, Hidehiko; Moroi, Masao; Nakamura, Masato

2018-06-12

The aim of this study was to investigate whether drug-coated balloon (DCB) treatment is effective for de novo coronary lesions that are unsuitable for drug-eluting stent (DES) implantation.Methods and Results:This retrospective study included 118 de novo lesions that were not suitable for DES implantation. Of the lesions, 40% was treated because of very small vessel disease. Patients with planned non-cardiac surgery and at high bleeding risk were 3% and 19%, respectively, and lesions that easily develop stent fracture comprised 26%. Clinically driven target lesion revascularization (TLR) was the primary endpoint. The rate of suboptimal lesion preparation before DCB treatment was set as the secondary endpoint. Optimal lesion preparation was defined as acquisition of Thrombolysis in Myocardial Infarction flow grade 3, minor coronary dissection, and residual stenosis ≤30%. The rate of suboptimal lesion preparation was 2.5% and 3 patients needed bail-out stenting. Accordingly, 115 patients were treated with a DCB. Clinically driven TLR had occurred in 8 patients (7.0%) at the 8-month follow-up. The presence of chronic total occlusion was identified as an independent predictor for TLR (odds 11.57; 95% confidence interval, 1.38-135.54; P=0.02). For lesions that are unsuitable for stent implantation, stent-less intervention using a DCB should be considered initially. The present study also highlighted that lesion preparation is key to a successful DCB strategy.

Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

NASA Astrophysics Data System (ADS)

Milne, Peter J.; Gautier, Sandrine; Parel, Jean-Marie A.; Jallet, Valerie

1997-05-01

The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

PubMed Central

2014-01-01

Background Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Methods Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants’ surfaces were observed with electron microscope. Results The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a “nest-shaped” way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day’s release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Conclusions Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was

75 FR 9333 - Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin AGENCY: Food and... dose range for use of an injectable solution of tilmicosin phosphate for treatment of respiratory... 300 (tilmicosin injection, USP) Injection, available by veterinary prescription for use in the...

78 FR 38994 - Implanted Blood Access Devices for Hemodialysis; Draft Guidance for Industry and Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0749] Implanted Blood Access Devices for Hemodialysis; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...

Transdermal power transfer for recharging implanted drug delivery devices via the refill port.

PubMed

Evans, Allan T; Chiravuri, Srinivas; Gianchandani, Yogesh B

2010-04-01

This paper describes a system for transferring power across a transdermal needle into a smart refill port for recharging implantable drug delivery systems. The device uses a modified 26 gauge (0.46 mm outer diameter) Huber needle with multiple conductive elements designed to couple with mechanical springs in the septum of the refill port of a drug delivery device to form an electrical connection that can sustain the current required to recharge a battery during a reservoir refill session. The needle is fabricated from stainless steel coated with Parylene, and the refill port septum is made from micromachined stainless steel contact springs and polydimethylsiloxane. The device properties were characterized with dry and wet ambient conditions. The needle and port pair had an average contact resistance of less than 2 Omega when mated in either environment. Electrical isolation between the system, the liquid in the needle lumen, and surrounding material has been demonstrated. The device was used to recharge a NiMH battery with currents up to 500 mA with less than 15 degrees C of resistive heating. The system was punctured 100 times to provide preliminary information with regard to device longevity, and exhibited about 1 Omega variation in contact resistance. The results suggest that this needle and refill port system can be used in an implant to enable battery recharging. This allows for smaller batteries to be used and ultimately increases the volume efficiency of an implantable drug delivery device.

Wireless implantable chip with integrated nitinol-based pump for radio-controlled local drug delivery.

PubMed

Fong, Jeffrey; Xiao, Zhiming; Takahata, Kenichi

2015-02-21

We demonstrate an active, implantable drug delivery device embedded with a microfluidic pump that is driven by a radio-controlled actuator for temporal drug delivery. The polyimide-packaged 10 × 10 × 2 mm(3) chip contains a micromachined pump chamber and check valves of Parylene C to force the release of the drug from a 76 μL reservoir by wirelessly activating the actuator using external radio-frequency (RF) electromagnetic fields. The rectangular-shaped spiral-coil actuator based on nitinol, a biocompatible shape-memory alloy, is developed to perform cantilever-like actuation for pumping operation. The nitinol-coil actuator itself forms a passive 185 MHz resonant circuit that serves as a self-heat source activated via RF power transfer to enable frequency-selective actuation and pumping. Experimental wireless operation of fabricated prototypes shows successful release of test agents from the devices placed in liquid and excited by radiating tuned RF fields with an output power of 1.1 W. These tests reveal a single release volume of 219 nL, suggesting a device's capacity of ~350 individual ejections of drug from its reservoir. The thermal behavior of the activated device is also reported in detail. This proof-of-concept prototype validates the effectiveness of wireless RF pumping for fully controlled, long-lasting drug delivery, a key step towards enabling patient-tailored, targeted local drug delivery through highly miniaturized implants.

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

PubMed

Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

2016-02-01

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a p

A novel injectable in situ forming poly-DL-lactide and DL-lactide/glycolide implant containing lipospheres for controlled drug delivery.

PubMed

Yehia, Soad A; Elshafeey, Ahmed H; Elsayed, Ibrahim

2012-06-01

One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1-24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96 Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40 mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI.

An implantable thermoresponsive drug delivery system based on Peltier device.

PubMed

Yang, Rongbing; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Rochev, Yury

2013-04-15

Locally dropping the temperature in vivo is the main obstacle to the clinical use of a thermoresponsive drug delivery system. In this paper, a Peltier electronic element is incorporated with a thermoresponsive thin film based drug delivery system to form a new drug delivery device which can regulate the release of rhodamine B in a water environment at 37 °C. Various current signals are used to control the temperature of the cold side of the Peltier device and the volume of water on top of the Peltier device affects the change in temperature. The pulsatile on-demand release profile of the model drug is obtained by turning the current signal on and off. The work has shown that the 2600 mAh power source is enough to power this device for 1.3 h. Furthermore, the excessive heat will not cause thermal damage in the body as it will be dissipated by the thermoregulation of the human body. Therefore, this simple novel device can be implanted and should work well in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

An Implantable MEMS Drug Delivery Device for Rapid Delivery in Ambulatory Emergency Care

DTIC Science & Technology

2009-06-01

controlled devices provide advantages over passive release devices, as the drug delivery process can be controlled actively after implantation and...mm, 5 μm, 100 Å, Alltech Associates, USA), with methanol and 0.1% trifluoroacetic acid (TFA) in water. The gradient used was 2 % TFA/min, starting

Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging.

PubMed

Kim, Hyuncheol; Lizak, Martin J; Tansey, Ginger; Csaky, Karl G; Robinson, Michael R; Yuan, Peng; Wang, Nam Sun; Lutz, Robert J

2005-02-01

Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist) released from a polymer-based implant in rabbit vitreous using T1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm2 s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroidsclera membrane) of 6.0 x 10(-8) cm2 s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.

Systemic opioid elimination after implantation of an intrathecal drug delivery system significantly reduced health-care expenditures.

PubMed

Hatheway, John A; Caraway, David; David, Guy; Gunnarsson, Candace; Hinnenthal, Jennifer; Ernst, Amanda R; Saulino, Michael

2015-04-01

To compare health-care expenditures over a 12-month horizon for chronic pain patients with implanted intrathecal drug delivery systems (IDDS) who eliminated or continued systemic opioids postimplant. Claims data from commercial and Medicare databases were searched for patients who had an IDDS, used systemic opioids before implant, and had 12 months pre- and 13 months postimplant continuous medical and pharmacy coverage. The number and characteristics of patients who eliminated or continued systemic opioids were determined at four times postimplant: 30 days (allowing a systemic opioid washout period), 120 days, 150 days, and 210 days. Multivariable models evaluated the effect of eliminating opioids on health-care expenditures at each of those times. Three hundred eighty-nine patients met inclusion criteria, and 51% completely eliminated systemic opioids (12% within the 30-day washout and an additional 39% by the end of the one-year horizon). Systemic opioid elimination within 120 to 210 days postimplant was associated with a reduction of $3,388 to $4,465 in inpatient and outpatient expenditures, and $4,689 to $5,571 in inpatient, outpatient, and drug expenditures. Fifty-one percent of patients completely eliminated systemic opioids in the year after IDDS implant. This elimination resulted in a 10% to 17% reduction in yearly inpatient, outpatient, and drug expenditures. © 2015 International Neuromodulation Society.

When microchip implants do more than drug delivery: blending, blurring, and bundling of protected health information and patient monitoring.

PubMed

Bramstedt, Katrina A

2005-01-01

Although currently in the research stage, scientists argue that drug-releasing microchip implants are on the horizon for future patients. This paper presents ethical reflection on these implants and identifies specific areas of concern; namely, patient monitoring and tracking, and patient privacy and confidentiality. It is foreseeable that drug delivery chips could be multifunctional with the overt or covert addition of sensors that monitor more than just the bloodstream concentrations of prescribed drugs (e.g., cotinine and alcohol in non-compliant patients, patient location via radio frequency or global positioning satellite). Similarly, it is foreseeable that these chips could be embedded with a patient's protected health information that could potentially be accessed and used by unauthorized persons. While drug delivery microchips are theoretically convenient and accurate for dosing, and might offer faster drug delivery with fewer side effects, ethical issues loom and should be contemplated now, while the technology is still under development.

Controlled diffusional release of dispersed solute drugs from biodegradable implants of various geometries.

PubMed

Collins, R; Paul, Z; Reynolds, D B; Short, R F; Wasuwanich, S

1997-01-01

Chronic diseases and pathological medical conditions requiring the administration of longterm pharmaceutical dosages have in the past been treated by oral administrations of tablets, pills and capsules or through the use of creams and ointments, suppositories, aerosols, and injectables. Such forms of drug delivery, which are still currently used today, provide a prompt release of the drug, but with significant fluctuations in the drug levels within various regions of the body. Repeated administrations of the drug are often needed, at rather precise intervals of time, in order to maintain these levels within a relatively narrow therapeutic range as a means of assuring effectiveness at the low end and of minimizing adverse effects at the higher end of the fluctuation spectrum. Recent technical advances now permit one to control the rate of drug delivery. The required therapeutic levels may thus be maintained over long periods of months and years through implanted rate-controlled drug release capsules. Two such novel drug delivery systems currently employed are implanted erodible polymeric and ceramic capsules. Mathematical modeling and computer simulations can be very effective in improving and optimizing the performance of the self-regulating release of therapeutic drugs into specific regions of the body. Further development is needed for the optimal design of such capsules. It is in this area, in particular, that a review will be presented of the mathematical modeling techniques susceptible to refine the development of a reliable tool for designing and predicting the resulting pharmaceutical dosages as a function of time and space. Of primary importance in such models are the time-varying effective permeability of the capsule to the various molecules composing the drug, the effective solubility and diffusion coefficients of the drug and its metabolites in the surrounding tissues and fluids and, finally, the uptake of the drug at the target organ. Mathematical

Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation

PubMed Central

Zhang, Hao; Tian, Yong; Zhu, Zhenshu; Xu, Huae; Li, Xiaolin; Zheng, Donghui; Sun, Weihao

2016-01-01

Tetrandrine (Tet) could enhance the antitumor effect of Paclitaxel (Ptx) by increasing intracellular Reactive Oxygen Species (ROS) levels, which leads to the possibility of co-delivery of both drugs for synergistic antitumor effect. In the current study, we reported an efficient, local therapeutic strategy employing effective Tet and Ptx delivery with a nanoparticle-loaded gelatin system. Tet- and Ptx co-loaded mPEG-PCL nanoparticles (P/T-NPs) were encapsulated into the physically cross-linked gelatin hydrogel and then implanted on the tumor site for continuous drug release. The drug-loaded gelatin hydrogel underwent a phase change when the temperature slowly increased. In vitro study showed that Tet/Ptx-loaded PEG-b-PCL nanoparticles encapsulated within a gelatin hydrogel (P/T-NPs-Gelatin) inhibited the growth and invasive ability of BGC-823 cells more effectively than the combination of free drugs or P/T-NPs. In vivo study validated the therapeutic potential of P/T-NPs-Gelatin. P/T-NPs-Gelatin significantly inhibited the activation of p-Akt and the downstream anti-apoptotic Bcl-2 protein and also inducing the activation of pro-apoptotic Bax protein. Moreover, the molecular-modulating effect of P/T-NPs-Gelatin on related proteins varied slightly under the influence of NAC, which was supported by the observations of the tumor volumes and weights. Based on these findings, local implantation of P/T-NPs-Gelatin may be a promising therapeutic strategy for the treatment of gastric cancer. PMID:27226240

21 CFR 522.1350 - Melatonin implant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Melatonin implant. 522.1350 Section 522.1350 Food... Melatonin implant. (a) Specifications. The drug is a silicone rubber elastomer implant containing 2.7 milligrams of melatonin. (b) Sponsor. See No. 053923 in § 510.600(c) of this chapter. (c) Conditions of use...

21 CFR 522.1350 - Melatonin implant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Melatonin implant. 522.1350 Section 522.1350 Food... Melatonin implant. (a) Specifications. The drug is a silicone rubber elastomer implant containing 2.7 milligrams of melatonin. (b) Sponsor. See No. 053923 in § 510.600(c) of this chapter. (c) Conditions of use...

21 CFR 522.1350 - Melatonin implant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Melatonin implant. 522.1350 Section 522.1350 Food... Melatonin implant. (a) Specifications. The drug is a silicone rubber elastomer implant containing 2.7 milligrams of melatonin. (b) Sponsor. See No. 053923 in § 510.600(c) of this chapter. (c) Conditions of use...

21 CFR 522.1350 - Melatonin implant.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Melatonin implant. 522.1350 Section 522.1350 Food... Melatonin implant. (a) Specifications. The drug is a silicone rubber elastomer implant containing 2.7 milligrams of melatonin. (b) Sponsor. See No. 053923 in § 510.600(c) of this chapter. (c) Conditions of use...

21 CFR 522.1350 - Melatonin implant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Melatonin implant. 522.1350 Section 522.1350 Food... Melatonin implant. (a) Specifications. The drug is a silicone rubber elastomer implant containing 2.7 milligrams of melatonin. (b) Sponsor. See No. 053923 in § 510.600(c) of this chapter. (c) Conditions of use...

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

PubMed

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

21 CFR 878.4750 - Implantable staple.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implantable staple. 878.4750 Section 878.4750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4750 Implantable staple. (a...

21 CFR 878.4750 - Implantable staple.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implantable staple. 878.4750 Section 878.4750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4750 Implantable staple. (a...

21 CFR 878.4750 - Implantable staple.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implantable staple. 878.4750 Section 878.4750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4750 Implantable staple. (a...

21 CFR 878.4300 - Implantable clip.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implantable clip. 878.4300 Section 878.4300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4300 Implantable clip. (a...

21 CFR 878.4300 - Implantable clip.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implantable clip. 878.4300 Section 878.4300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4300 Implantable clip. (a...

21 CFR 878.4300 - Implantable clip.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implantable clip. 878.4300 Section 878.4300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4300 Implantable clip. (a...

21 CFR 878.4300 - Implantable clip.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implantable clip. 878.4300 Section 878.4300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4300 Implantable clip. (a...

21 CFR 878.4300 - Implantable clip.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implantable clip. 878.4300 Section 878.4300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4300 Implantable clip. (a...

21 CFR 878.4750 - Implantable staple.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implantable staple. 878.4750 Section 878.4750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4750 Implantable staple. (a...

21 CFR 878.4750 - Implantable staple.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implantable staple. 878.4750 Section 878.4750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4750 Implantable staple. (a...

Release and velocity of micronized dexamethasone implants with an intravitreal drug delivery system: kinematic analysis with a high-speed camera.

PubMed

Meyer, Carsten H; Klein, Adrian; Alten, Florian; Liu, Zengping; Stanzel, Boris V; Helb, Hans M; Brinkmann, Christian K

2012-01-01

Ozurdex, a novel dexamethasone (DEX) implant, is released by a drug delivery system into the vitreous cavity. We analyzed the mechanical release aperture of the novel applicator, obtained real-time recordings using a high-speed camera system and performed kinematic analysis of the DEX application. Experimental study. : The application of intravitreal DEX implants (6 mm length, 0.46 mm diameter; 700 μg DEX mass, 0.0012 g total implant mass) was recorded by a high-speed camera (500 frames per second) in water (Group A: n = 7) or vitreous (Group B: n = 7) filled tanks. Kinematic analysis calculated the initial muzzle velocity as well as the impact on the retinal surface at approximately 15 mm of the injected drug delivery system implant in both groups. A series of drug delivery system implant positions was obtained and graphically plotted over time. High-speed real-time recordings revealed that the entire movement of the DEX implant lasted between 28 milliseconds and 55 milliseconds in Group A and 1 millisecond and 7 milliseconds in Group B. The implants moved with a mean muzzle velocity of 820 ± 350 mm/s (±SD, range, 326-1,349 mm/s) in Group A and 817 ± 307 mm/s (±SD, range, 373-1,185 mm/s) in Group B. In both groups, the implant gradually decelerated because of drag force. With greater distances, the velocity of the DEX implant decreased exponentially to a complete stop at 13.9 mm to 24.7 mm in Group A and at 6.4 mm to 8.0 mm in Group B. Five DEX implants in Group A reached a total distance of more than 15 mm, and their calculated mean velocity at a retinal impact of 15 mm was 408 ± 145 mm/s (±SD, range, 322-667 mm/s), and the consecutive normalized energy was 0.55 ± 0.44 J/m (±SD). In Group B, none of the DEX implants reached a total distance of 6 mm or more. An accidental application at an angle of 30 grade and consecutively reduced distance of approximately 6 mm may result in a mean velocity of 844 and mean normalized energy of 0.15 J/m (SD ± 0.47) in a

About Implantable Contraception

MedlinePlus

... Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español About Implantable Contraception KidsHealth / For Parents / About Implantable Contraception Print What ...

21 CFR 882.5820 - Implanted cerebellar stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted...

21 CFR 882.5820 - Implanted cerebellar stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted...

21 CFR 882.5225 - Implanted malleable clip.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted malleable clip. 882.5225 Section 882.5225 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5225 Implanted malleable clip...

21 CFR 882.5225 - Implanted malleable clip.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted malleable clip. 882.5225 Section 882.5225 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5225 Implanted malleable clip...

21 CFR 876.3630 - Penile rigidity implant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Penile rigidity implant. 876.3630 Section 876.3630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Prosthetic Devices § 876.3630 Penile rigidity implant. (a...

Distribution of angiographic measures of restenosis after drug-eluting stent implantation.

PubMed

Byrne, R A; Eberle, S; Kastrati, A; Dibra, A; Ndrepepa, G; Iijima, R; Mehilli, J; Schömig, A

2009-10-01

A bimodal distribution of measures of restenosis has been demonstrated at 6-8 months after bare metal stent implantation. Drug-eluting stent (DES) treatment has attenuated the impact of certain factors (eg, diabetes) on restenosis but its effect on the distribution of indices of restenosis is not known. To perform a detailed analysis of the metrics of restenosis indices after DES implantation. Design, settings, Prospective observational study of patients undergoing DES implantation (Cypher, sirolimus-eluting stent; or Taxus, paclitaxel-eluting stent) at two German centres, with repeat angiography scheduled at 6-8 months after coronary stenting. In-stent late luminal loss (LLL) and in-segment percentage diameter stenosis (%DS) as determined by quantitative coronary angiography at recatheterisation. Paired cineangiograms were available for 2057 patients. Overall mean (SD) LLL was 0.31 (0.50) mm; mean (SD) %DS was 30.3 (15.7)%. Distribution of both LLL and %DS differed significantly from normal (Kolmogorov-Smirnov test; p<0.001 for each). For both parameters a mixed distribution model better described the data (likelihood ratio test with 3df; p<0.001 for each). This consisted of two normally distributed subpopulations with means (SD) of 0.10 (0.25) mm and 0.69 (0.60) mm for LLL, and means (SD) of 22.2 (8.6)% and 40.1 (16.6)% for %DS. The results were consistent across subgroups of DES type, "on-label" versus "off-label" indication, and presence or absence of diabetes. LLL and %DS at follow-up angiography after DES implantation have a complex mixed distribution that may be accurately represented by a bimodal distribution model. The introduction of DES treatment has not resulted in elimination of a variable propensity to restenosis among subpopulations of patients with stented lesions.

21 CFR 886.3320 - Eye sphere implant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Eye sphere implant. 886.3320 Section 886.3320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Prosthetic Devices § 886.3320 Eye sphere implant. (a) Identification. An eye...

21 CFR 886.3320 - Eye sphere implant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Eye sphere implant. 886.3320 Section 886.3320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Prosthetic Devices § 886.3320 Eye sphere implant. (a) Identification. An eye...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... asynchronous devices implanted in the human body. (b) Classification. Class III (premarket approval). (c) Date... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implantable pacemaker pulse generator. 870.3610 Section 870.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... asynchronous devices implanted in the human body. (b) Classification. Class III (premarket approval). (c) Date... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implantable pacemaker pulse generator. 870.3610 Section 870.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implantable pacemaker pulse generator. 870.3610 Section 870.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has...

Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

NASA Astrophysics Data System (ADS)

Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

2016-04-01

Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

21 CFR 874.3695 - Mandibular implant facial prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Mandibular implant facial prosthesis. 874.3695 Section 874.3695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... intended to be implanted for use in the functional reconstruction of mandibular deficits. The device is...

21 CFR 874.3695 - Mandibular implant facial prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Mandibular implant facial prosthesis. 874.3695 Section 874.3695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... intended to be implanted for use in the functional reconstruction of mandibular deficits. The device is...

Influence of the test method on in vitro drug release from intravitreal model implants containing dexamethasone or fluorescein sodium in poly (d,l-lactide-co-glycolide) or polycaprolactone.

PubMed

Stein, Sandra; Auel, Tobias; Kempin, Wiebke; Bogdahn, Malte; Weitschies, Werner; Seidlitz, Anne

2018-06-01

Sustained intravitreal dexamethasone (DX) administration with the FDA and EMA approved Ozurdex® implant is indicated for the treatment of macular edema and non-infectious uveitis. Since drug release after intravitreal application cannot be determined in vivo in human eyes, the characterization of drug release in vitro in addition to animal models is of great importance. The aim of this study was to provide information about the influence of the test method on the in vitro drug release from intravitreal model implants. The following test methods were used: a shaking incubator experiment in reagent tubes, the small volume USP apparatus 7, the Vitreous Model (VM) and a system simulating the impact of movement on the VM (Eye Movement System, EyeMoS). Cylindrical model implants composed of DX and PLGA (poly (d,l-lactide-co-glycolide)) and additional polycaprolactone (PCL) implants containing fluorescein sodium (FS) as a model substance were produced by hot melt extrusion and were cut to a length of approximately 6 mm. Drug release was studied in ringer buffer pH 7.4 and in a modified polyacrylamide gel (PAAG) as vitreous substitute. In combination with the VM, the shape, the gel structure and a partial liquefaction (50%) were simulated in vitro. Swelling, disintegration, fragmentation, surface enlargement and changes in shape of the PLGA model implants were observed during the drug release study. We experienced that not each of the test methods and media were suitable for drug release studies of the PLGA implants. Marked differences in the release profiles were observed depending on the employed test method. These results emphasize the necessity to understand the underlying in vivo processes and to transfer the knowledge about the release determining factors into reliable in vitro test systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Towards an implantable bio-sensor platform for continuous real-time monitoring of anti-epileptic drugs.

PubMed

Hammoud, Abbas; Chamseddine, Ahmad; Nguyen, Dang K; Sawan, Mohamad

2016-08-01

The need of continuous real-time monitoring device for in-vivo drug level detection has been widely articulated lately. Such monitoring could guide drug posology and timing of intake, detect low or high drug levels, in order to take adequate measures, and give clinicians a valuable window into patients' health and their response to therapeutics. This paper presents a novel implantable bio-sensor based on impedance measurement capable of continuously monitoring various antiepileptic drug levels. This portable point-of-care microsystem replaces large and stationary conventional macrosystems, and is a one of a kind system designed with an array of electrodes to monitor various anti-epileptic drugs rather than one drug. The micro-system consists of (i) the front-end circuit including an inductive coil to receive energy from an external base station, and to exchange data with the latter; (ii) the power management block; (iii) the readout and control block; and (iv) the biosensor array. The electrical circuitry was designed using the 0.18-um CMOS process technology intended to be miniature and consume ultra-low power.

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for pain relief. 882.5880 Section 882.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator...

Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology.

PubMed

Gollwitzer, Hans; Ibrahim, Karim; Meyer, Henriette; Mittelmeier, Wolfram; Busch, Raymonde; Stemberger, Axel

2003-03-01

Biomaterial-associated bacterial infections present common and challenging complications with medical implants. The purpose of this study was to determine the antibacterial properties of a low molecular weight biodegradable poly(D,L-lactic acid) coating with integrated antibiotics gentamicin and teicoplanin. Coating of Kirschner-wires was carried out by a solvent casting technique under aseptic conditions with and without incorporated antibiotics. Release kinetics of gentamicin and teicoplanin were studied in phosphate-buffered saline. Initial bacterial adhesion of Staphylococcus epidermidis on coated and bare implants was determined by radiolabelling and counts of detached viable organisms. The incorporated antibiotics showed a continuous release over a period of at least 96 h with an initial peak of release in the first 6 h. Attachment of non-viable microorganisms, detected by radiolabelled bacteria, was increased significantly by the polymer coatings (P < 0.05). In contrast, the number of viable bacteria was reduced by the pure polymer (P < 0.01) and further by the polymer-antibiotic combinations (P < 0.05). Poly(D,L-lactic acid) coating of implants could offer new perspectives in preventing biomaterial-associated infections. Combinations with other drugs to formulate custom-tailored implant surfaces are feasible.

Microfabricated injectable drug delivery system

DOEpatents

Krulevitch, Peter A.; Wang, Amy W.

2002-01-01

A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

21 CFR 872.3970 - Interarticular disc prosthesis (interpositional implant).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Interarticular disc prosthesis (interpositional implant). 872.3970 Section 872.3970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... (interpositional implant) is a device that is intended to be an interface between the natural articulating surface...

21 CFR 878.3500 - Polytetrafluoroethylene with carbon fibers composite implant material.

Code of Federal Regulations, 2010 CFR

2010-04-01

... composite implant material. 878.3500 Section 878.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION... Prosthetic Devices § 878.3500 Polytetrafluoroethylene with carbon fibers composite implant material. (a) Identification. A polytetrafluoroethylene with carbon fibers composite implant material is a porous device...

Free radicals generated by tantalum implants antagonize the cytotoxic effect of doxorubicin.

PubMed

Chen, Muwan; Hein, San; Le, Dang Q S; Feng, Wenzhou; Foss, Morten; Kjems, Jørgen; Besenbacher, Flemming; Zou, Xuenong; Bünger, Cody

2013-05-01

Little is known about the interaction between antineoplastic drugs and implants in bone cancer patients. We investigated the interaction between commercially available porous tantalum (Ta) implants and the chemotherapeutic drug, Doxorubicin (DOX). DOX solutions were prepared in the presence of Ta implant. The changes in fluorescence intensity of the DOX chromophore were measured by spectrofluorometry and the efficacy of DOX was evaluated by viability of rabbit rectal tumor cells (VX2). After 5 min interaction of the DOX solution (5 μg/ml) with the Ta implant, the fluorescent intensity of the DOX solution was 85% degraded, and only 20% the drug efficacy to kill VX2 cells was retained. However, after adding a reducing agent, Dithiothreitol (DTT, 10 μg/ml), 80% of the original fluorescence and 50% of the drug efficacy were restored while UV irradiation enhanced drug degradation in the presence of Ta implant. The action of DTT and UV irradiation indicated that reactive oxygen species (ROS) were involved in the drug degradation mechanism. We detected that Ta implants in aqueous medium produced hydroxyl radicals. Cells showed higher intracellular ROS activity when culture medium was incubated with the Ta implant prior to cell culture. It is concluded that the porous Ta implant antagonizes the cytotoxicity of DOX via ROS generation of the porous Ta implant. Copyright © 2013 Elsevier B.V. All rights reserved.

Meta-analysis of long-term outcomes of drug-eluting stent implantations for chronic total coronary occlusions.

PubMed

Ma, Jian; Yang, Weiwei; Singh, Manpreet; Peng, Tianqing; Fang, Ningyuan; Wei, Meng

2011-01-01

In the treatment of chronic total occlusions (CTOs), some uncertainty exists regarding the effect of drug-eluting stents (DESs) compared with the effects of bare mental stents (BMSs). We reviewed outcomes of DES vs. BMS implantation for CTO lesions, to evaluate the risk-benefit ratio of DES implantation. Relevant studies of long-term clinical outcomes or angiographic outcomes of both BMS and DES implantation were examined. The primary endpoint comprised major adverse cardiovascular events (MACEs), including all-cause deaths, myocardial infarctions (MIs), and target lesion revascularizations (TLRs). A fixed-effect model and random-effect model were used to analyze the pooling results. Ten studies were included according to the selection criteria. Eight were nonrandomized controlled trials, and two consisted of a randomized controlled comparison between DES and BMS implantation. No significant difference was evident for in-hospital MACE rates between the two groups (odds ratio [OR], 1.07; 95% confidence interval [CI], .53 to 2.13), but the long-term MACE rates in the DES group were significantly lower than in the BMS group (OR, .22; 95% CI, .13 to .38; P < .00001). The rates of stent restenosis and reocclusions were also significantly lower in the DES group (OR, .14; 95% CI, .09 to .20; and OR, .23; 95% CI, .12 to .41, respectively). Implantation of the DES improves long-term angiographic and clinical outcomes compared with BMS in the treatment of CTO lesions. Copyright © 2011 Elsevier Inc. All rights reserved.

A review of implantable biosensors for closed-loop glucose control and other drug delivery applications.

PubMed

Scholten, Kee; Meng, Ellis

2018-06-15

Closed-loop drug delivery promises autonomous control of pharmacotherapy through the continuous monitoring of biomarker levels. For decades, researchers have strived for portable closed-loop systems capable of treating ambulatory patients with chronic conditions such as diabetes mellitus. After years of development, the first of these systems have left the laboratory and entered commercial use. This long-awaited advance reflects recent development of chronically stable implantable biosensors able to accurately measure biomarker levels in vivo. This review discusses the role of implantable biosensors in closed-loop drug delivery applications, with the intent to provide a resource for engineers and researchers studying such systems. We provide an overview of common biosensor designs and review the principle challenges in implementing long indwelling sensors: namely device sensitivity, selectivity, and lifetime. This review examines novel advances in transducer design, biological interface, and material biocompatibility, with a focus on recent academic and commercial work which provide successful strategies to overcome perennial challenges. This review focuses primarily on the topics of closed-loop glucose control and continuous glucose monitoring biosensors, which make up the overwhelming majority of published research in this area. We conclude with an overview of recent advances in closed-loop systems targeting applications outside blood glucose management. Copyright © 2018 Elsevier B.V. All rights reserved.

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

The safety of magnetic resonance imaging in patients with programmable implanted intrathecal drug delivery systems: a 3-year prospective study.

PubMed

De Andres, Jose; Villanueva, Vicente; Palmisani, Stefano; Cerda-Olmedo, German; Lopez-Alarcon, Maria Dolores; Monsalve, Vicente; Minguez, Ana; Martinez-Sanjuan, Vicente

2011-05-01

It is common clinical practice to perform magnetic resonance imaging (MRI) in patients with indwelling programmable intrathecal drug delivery (IDD) systems, although the safety of the procedure has never been documented. We performed a single-center, 3-year, prospective evaluation in patients with a programmable implanted IDD to assess patient discomfort, IDD technical failures, and adverse effects during and after exposure to MRI. Forty-three consecutive patients with an implanted programmable IDD system (SynchroMed® EL Implantable Infusion Pump, Model 8626L-18, and SynchroMed® II Model 8637-20, 8637-40; Medtronic, Inc., Minneapolis, MN) requiring a scheduled MRI evaluation were studied during a 3-year period. All MRI scans were performed with a 1.5-tesla clinical use magnet and a specific absorption rate of no more than 0.9 W/kg. Radiograph control was used to confirm postexposure pump rotor movement and detect system dislocations. IDD system failures, patient satisfaction, and discomfort were recorded. None of the patients experienced signs of drug overinfusion that could lead to hemodynamic, respiratory, or neurologic alterations. Radiologic evaluation after MRI revealed no spatial displacements of the intrathecal catheter tip or body pump, and programmer telemetry confirmed the infusion recovery. Patients' satisfaction after the procedure was high. Performing an MRI scan with the proposed protocol in patients with an implanted Medtronic programmable IDD system resulted in virtually no technical or medical complications. © 2011 International Anesthesia Research Society

Implantable drug therapy device: A concept

NASA Technical Reports Server (NTRS)

Feldstein, C.

1972-01-01

Design is described of small, rechargeable, implantable infusor which contains fluid medicament stored under pressure and which dispenses fluid continuously through catheter. Body of infusor is covered by pliable silicone rubber sheath attached to suture pad for securing device.

Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice.

PubMed

DeTolla, L; Sanchez, R; Khan, E; Tyler, B; Guarnieri, M

2014-01-01

Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine.

Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

PubMed Central

DeTolla, L.; Sanchez, R.; Khan, E.; Tyler, B.; Guarnieri, M.

2014-01-01

Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine. PMID:26464927

21 CFR 876.5270 - Implanted electrical urinary continence device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted electrical urinary continence device... Implanted electrical urinary continence device. (a) Identification. An implanted electrical urinary device is a device intended for treatment of urinary incontinence that consists of a receiver implanted in...

21 CFR 876.5270 - Implanted electrical urinary continence device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted electrical urinary continence device... Implanted electrical urinary continence device. (a) Identification. An implanted electrical urinary device is a device intended for treatment of urinary incontinence that consists of a receiver implanted in...

21 CFR 876.5270 - Implanted electrical urinary continence device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted electrical urinary continence device... Implanted electrical urinary continence device. (a) Identification. An implanted electrical urinary device is a device intended for treatment of urinary incontinence that consists of a receiver implanted in...

21 CFR 876.5270 - Implanted electrical urinary continence device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted electrical urinary continence device... Implanted electrical urinary continence device. (a) Identification. An implanted electrical urinary device is a device intended for treatment of urinary incontinence that consists of a receiver implanted in...

21 CFR 876.5270 - Implanted electrical urinary continence device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Implanted electrical urinary continence device. (a) Identification. An implanted electrical urinary device is a device intended for treatment of urinary incontinence that consists of a receiver implanted in... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted electrical urinary continence device...

21 CFR 872.3640 - Endosseous dental implant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endosseous dental implant. 872.3640 Section 872...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3640 Endosseous dental implant. (a) Identification. An endosseous dental implant is a device made of a material such as titanium or titanium alloy, that...

21 CFR 872.3640 - Endosseous dental implant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endosseous dental implant. 872.3640 Section 872...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3640 Endosseous dental implant. (a) Identification. An endosseous dental implant is a device made of a material such as titanium or titanium alloy, that...

21 CFR 872.3640 - Endosseous dental implant.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endosseous dental implant. 872.3640 Section 872...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3640 Endosseous dental implant. (a) Identification. An endosseous dental implant is a device made of a material such as titanium or titanium alloy, that...

21 CFR 872.3640 - Endosseous dental implant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endosseous dental implant. 872.3640 Section 872...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3640 Endosseous dental implant. (a) Identification. An endosseous dental implant is a device made of a material such as titanium or titanium alloy, that...

21 CFR 872.3640 - Endosseous dental implant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endosseous dental implant. 872.3640 Section 872...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3640 Endosseous dental implant. (a) Identification. An endosseous dental implant is a device made of a material such as titanium or titanium alloy, that...

21 CFR 872.3980 - Endosseous dental implant accessories.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

21 CFR 872.3980 - Endosseous dental implant accessories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

21 CFR 872.3980 - Endosseous dental implant accessories.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

21 CFR 872.3980 - Endosseous dental implant accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

21 CFR 872.3980 - Endosseous dental implant accessories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

21 CFR 870.2855 - Implantable Intra-aneurysm Pressure Measurement System.

Code of Federal Regulations, 2012 CFR

2012-04-01

... System. 870.2855 Section 870.2855 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices § 870.2855 Implantable Intra-aneurysm Pressure Measurement System. (a) Identification. Implantable intra...

21 CFR 870.2855 - Implantable Intra-aneurysm Pressure Measurement System.

Code of Federal Regulations, 2013 CFR

2013-04-01

... System. 870.2855 Section 870.2855 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices § 870.2855 Implantable Intra-aneurysm Pressure Measurement System. (a) Identification. Implantable intra...

21 CFR 870.2855 - Implantable Intra-aneurysm Pressure Measurement System.

Code of Federal Regulations, 2014 CFR

2014-04-01

... System. 870.2855 Section 870.2855 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices § 870.2855 Implantable Intra-aneurysm Pressure Measurement System. (a) Identification. Implantable intra...

Current manufacturing processes of drug-eluting sutures.

PubMed

Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine

2017-11-01

Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.

21 CFR 872.3630 - Endosseous dental implant abutment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endosseous dental implant abutment. 872.3630... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3630 Endosseous dental implant abutment. (a) Identification. An endosseous dental implant abutment is a premanufactured prosthetic component...

21 CFR 872.3630 - Endosseous dental implant abutment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endosseous dental implant abutment. 872.3630... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3630 Endosseous dental implant abutment. (a) Identification. An endosseous dental implant abutment is a premanufactured prosthetic component...

21 CFR 872.3630 - Endosseous dental implant abutment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endosseous dental implant abutment. 872.3630... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3630 Endosseous dental implant abutment. (a) Identification. An endosseous dental implant abutment is a premanufactured prosthetic component...

21 CFR 872.3630 - Endosseous dental implant abutment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endosseous dental implant abutment. 872.3630... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3630 Endosseous dental implant abutment. (a) Identification. An endosseous dental implant abutment is a premanufactured prosthetic component...

21 CFR 872.3630 - Endosseous dental implant abutment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endosseous dental implant abutment. 872.3630... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3630 Endosseous dental implant abutment. (a) Identification. An endosseous dental implant abutment is a premanufactured prosthetic component...

Biodegradable implants from poly-(alpha-hydroxy acid) polymers for isoniazid delivery.

PubMed

Hurley, L; Andersen, B R

1999-11-01

In vitro and in vivo study of an isoniazid (INH) drug delivery system. To develop a system for the treatment of tuberculosis using a subcutaneous polymer implant with a large drug load released slowly over a long period. INH delivery by biodegradable poly-(alpha-hydroxy acid) polymers was evaluated using ground polymer and compression molded implants. Rate of drug release and structural stability of the implant in an aqueous environment were measured, as were in vivo evaluations of the duration of measurable levels of INH in serum and urine. Factors that influenced the suitability of an implant in an in vitro system included polymer molecular weight and crystallinity, polymer and drug particle size, drug loading dose, and press temperature and pressure. The implant characteristics that most closely approached optimal conditions include a polymer of 100% L-lactide with low intrinsic viscosity, polymer particle size <75 micron, and INH particle = 126-180 micron, INH loading dose not to exceed 46%, and press conditions of 70 degrees C and 345000 kPa. Studies of subcutaneous implants in rabbits and baboons show that INH is released from the implant for 15 to 26 weeks. An INH-containing polymer was developed that was structurally stable in an aqueous environment and that released INH over a period of at least 15 weeks. Studies with infected animals will be necessary to determine the dose required for prophylaxis and treatment of active disease.

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implantable pacemaker pulse generator. 870.3610... pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has... implantable pacemaker pulse generator device that was in commercial distribution before May 28, 1976, or that...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implantable pacemaker pulse generator. 870.3610... pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has... implantable pacemaker pulse generator device that was in commercial distribution before May 28, 1976, or that...

Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model

PubMed Central

Koskimäki, Janne; Tarkia, Miikka; Ahtola-Sätilä, Tuula; Saloranta, Lasse; Laakso, Aki; Frantzén, Janek

2015-01-01

Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant. PMID:25685803

Use of the Etonogestrel Implant and Levonorgestrel Intrauterine Device Beyond the U.S. Food and Drug Administration–Approved Duration

PubMed Central

McNicholas, Colleen; Maddipati, Ragini; Zhao, Qiuhong; Swor, Erin; Peipert, Jeffrey F.

2014-01-01

Objective To evaluate the effectiveness of the contraceptive implant and the 52mg hormonal intrauterine device (IUD) in women using the method beyond the current U.S. Food and Drug Administration–approved duration of 3 and 5 years respectively. Methods Women willing to continue using their implant or 52mg levonorgestrel IUD (LNG-IUD) beyond the FDA-approved duration were followed prospectively for contraceptive effectiveness. Unintended pregnancy rate per 100 women-years was calculated. Implant users are offered periodic venipuncture for analysis of serum etonogestrel levels. The Kruskal-Wallis test was used to compare the etonogestrel levels across BMI groups. Results Implant users (n=237) have contributed 229.4 women-years of follow-up, with 123 using the etonogestrel implant for 4 years, and 34 using it for 5 years. Zero pregnancies have been documented, for a failure rate of 0 (one-sided 97.5% CI: 0, 1.61) per 100 women-years. Among 263 LNG-IUD users, 197.7 women-years of follow-up have been completed. One pregnancy was confirmed, for a failure rate of 0.51 (95% CI: 0.01, 2.82) per 100 women-years. Among implant users with serum etonogestrel results, the median and range of etonogestrel level at 3 years of use was 188.8 pg/mL (range 63.8, 802.6) and 177.0 pg/mL (67.9, 470.5) at 4 years of use. Etonogestrel levels did not differ by BMI at either time point (3 years: p=0.79; 4 years: p=0.47). Conclusion Preliminary findings indicate the contraceptive implant and 52mg hormonal IUD continue to be highly-effective for an additional year, beyond the FDA approved 3 and 5 years.. Serum etonogestrel levels indicate the implant contains adequate hormone for ovulation suppression at the end of both 3 and 4 years of use. PMID:25730221

Stent implantation into the tracheo-bronchial system in rabbits: histopathologic sequelae in bare metal vs. drug-eluting stents.

PubMed

Sigler, Matthias; Klötzer, Julia; Quentin, Thomas; Paul, Thomas; Möller, Oliver

2015-12-01

Stent implantation into the tracheo-bronchial system may be life-saving in selected pediatric patients with otherwise intractable stenosis of the upper airways. Following implantation, significant tissue proliferation may occur, requiring re-interventions. We sought to evaluate the effect of immunosuppressive coating of the stents on the extent of tissue proliferation in an animal model. Bare metal and sirolimus-coated stents (Bx Sonic and Cypher Select, Johnson & Johnson, Cordis) were implanted into non-stenotic lower airways of New Zealand white rabbits (weight 3.1 to 4.8 kg). Three stents with sirolimus coating and six bare metal stents could be analyzed by means of histology and immunohistochemistry 12 months after implantation. On a macroscopic evaluation, all stents were partially covered with a considerable amount of whitish tissue. Histologically, these proliferations contained fiber-rich connective tissue and some fibromuscular cells without significant differences between both stent types. The superficial tissue layer was formed by typical respiratory epithelium and polygonal cells. Abundant lymphocyte infiltrations and moderate granulocyte infiltrations were found in both groups correspondingly, whereas foreign-body reaction was more pronounced around sirolimus-eluting stents. After stent implantation in the tracheo-bronchial system of rabbits, we found tissue reactions comparable to those seen after stent implantation into the vascular system. There was no difference between coated and uncoated stents with regard to quality and quantity of tissue proliferation. We found, however, a significantly different inflammatory reaction with a more pronounced foreign-body reaction in sirolimus-coated stents. In our small series, drug-eluting stents did not exhibit any benefit over bare metal stents in an experimental setting.

Implantable and transdermal polymeric drug delivery technologies for the treatment of central nervous system disorders.

PubMed

Govender, Thiresen; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

2017-06-01

The complexity of the brain and the membranous blood-brain barrier (BBB) has proved to be a significant limitation to the systemic delivery of pharmaceuticals to the brain rendering them sub-therapeutic and ineffective in the treatment of neurological diseases. Apart from this, lack of innovation in product development to counteract the problem is also a major contributing factor to a poor therapeutic outcome. Various innovative strategies show potential in treating some of the neurological disorders; however, drug delivery remains the most popular. To attain therapeutic drug levels in the central nervous system, large, intolerable systemic doses are generally administered. The major factors responsible for the success maintenance therapy of neurological diseases included controlled and sustained release of neurotherapeutics, reduced frequency of administration, higher bioavailability, and patient compliances. Conventional oral or injectable formulations cannot satisfy all the requirements in many circumstances. This article reviews the therapeutic implantable polymeric and transdermal devices employed in an attempt to effectively achieve therapeutic quantities of drug across the BBB over a prolonged period, to improve patient disease prognosis.

Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

PubMed Central

Hsu, Yung-Heng; Chen, Dave Wei-Chih; Tai, Chun-Der; Chou, Ying-Chao; Liu, Shih-Jung; Ueng, Steve Wen-Neng; Chan, Err-Cheng

2014-01-01

We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. PMID:25246790

Pore structures in an implantable sol gel titania ceramic device used in controlled drug release applications: A modeling study

NASA Astrophysics Data System (ADS)

Peterson, Aaron; Lopez, Tessy; Islas, Emma Ortiz; Gonzalez, Richard D.

2007-04-01

Several process variables, which may be helpful in optimizing the rate at which drugs are released from implantable, sol-gel titania devices have been identified in this study. The controlled rate of drug release is compared for two different anticonvulsant drugs, valproic acid and sodic phenytoin. Contrary to what one might expect, when the concentration is increased in the titania reservoir the rate of initial drug delivery decreases. This is a desirable result, because it may reduce the danger of a high initial discharge, which may harm the epileptic rat. The structure of the porous structure within the titania network has been studied using a generalized form of the BET equation which considers only n layers. In general, following an initial discharge, the rate at which the drug is released will increase with the increasing concentration. Pore mouth blocking can present a problem. However, this problem tends to disappear following the initial discharge. The extent of drug loading is a useful variable parameter, which can be adjusted in order to deliver the amount of drug required in a given application.

COMMUNICATION: Drug loading of nanoporous TiO2 films

NASA Astrophysics Data System (ADS)

Ayon, Arturo A.; Cantu, Michael; Chava, Kalpana; Mauli Agrawal, C.; Feldman, Marc D.; Johnson, Dave; Patel, Devang; Marton, Denes; Shi, Emily

2006-12-01

The loading of therapeutic amounts of drug on a nanoporous TiO2 surface is described. This novel drug-loading scheme on a biocompatible surface, when employed on medical implants, will benefit patients who require the deployment of drug-eluting implants. Anticoagulants, analgesics and antibiotics can be considered on the associated implants for drug delivery during the time of maximal pain or risk for patients undergoing orthopedic procedures. Therefore, this scheme will maximize the chances of patient recovery.

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

Hydrodynamically-driven drug release during interstitial flow through hollow fibers implanted near lymphatics

PubMed Central

Dukhin, Stanislav S.; Labib, Mohamed E.

2016-01-01

Current drug delivery devices (DDD) are mainly based on the use of diffusion as the main transport process. Diffusion-driven processes can only achieve low release rate because diffusion is a slow process. This represents a serious obstacle in the realization of recent successes in the suppression of lymphatic metastasis and in the prevention of limb and organ transplant rejection. Surprisingly, it was overlooked that there is a more favorable drug release mode which can be achieved when a special DDD is implanted near lymphatics. This opportunity can be realized when the interstitial fluid flow penetrates a drug delivery device of proper design and allows such fluid to flow out of it. This design is based on hollow fibers loaded with drug and whose hydrodynamic permeability is much higher than that of the surrounding tissue. The latter is referred to as hollow fiber of high hydrodynamic permeability (HFHP). The interstitial flow easily penetrates the hollow fiber membrane as well as its lumen with a higher velocity than that in the adjacent tissue. The interstitial liquid stream entering the lumen becomes almost saturated with drug as it flows out of the HFHP. This is due to the drug powder dissolution in the lumens of HFHP which forms a strip of drug solution that crosses the interstitium and finally enters the lymphatics. This hydrodynamically-driven release (HDR) may exceed the concomitant diffusion-driven release (DDR) by one or even two orders of magnitude. The hydrodynamics of the two-compartment media is sufficient for developing the HDR theory which is detailed in this paper. Convective diffusion theory for two compartments (membrane of hollow fiber and adjacent tissue) is required for exact quantification when a small contribution of DDR to predominating HDR is present. Hence, modeling is important for HDR which would lead to establishing a new branch in physico-chemical hydrodynamics. The release rate achieved with the use of HFHP increases proportional

21 CFR 876.5280 - Implanted mechanical/hydraulic urinary continence device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted mechanical/hydraulic urinary continence....5280 Implanted mechanical/hydraulic urinary continence device. (a) Identification. An implanted mechanical/hydraulic urinary continence device is a device used to treat urinary incontinence by the...

21 CFR 876.5280 - Implanted mechanical/hydraulic urinary continence device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted mechanical/hydraulic urinary continence....5280 Implanted mechanical/hydraulic urinary continence device. (a) Identification. An implanted mechanical/hydraulic urinary continence device is a device used to treat urinary incontinence by the...

21 CFR 876.5280 - Implanted mechanical/hydraulic urinary continence device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted mechanical/hydraulic urinary continence....5280 Implanted mechanical/hydraulic urinary continence device. (a) Identification. An implanted mechanical/hydraulic urinary continence device is a device used to treat urinary incontinence by the...

21 CFR 876.5280 - Implanted mechanical/hydraulic urinary continence device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted mechanical/hydraulic urinary continence....5280 Implanted mechanical/hydraulic urinary continence device. (a) Identification. An implanted mechanical/hydraulic urinary continence device is a device used to treat urinary incontinence by the...

21 CFR 876.5280 - Implanted mechanical/hydraulic urinary continence device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted mechanical/hydraulic urinary continence....5280 Implanted mechanical/hydraulic urinary continence device. (a) Identification. An implanted mechanical/hydraulic urinary continence device is a device used to treat urinary incontinence by the...

'Breath figure' PLGA films as implant coatings for controlled drug release

NASA Astrophysics Data System (ADS)

Ponnusamy, Thiruselvam

The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 microm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected

Magnetic resonance imaging of breast implants.

PubMed

Shah, Mala; Tanna, Neil; Margolies, Laurie

2014-12-01

Silicone breast implants have significantly evolved since their introduction half a century ago, yet implant rupture remains a common and expected complication, especially in patients with earlier-generation implants. Magnetic resonance imaging is the primary modality for assessing the integrity of silicone implants and has excellent sensitivity and specificity, and the Food and Drug Administration currently recommends periodic magnetic resonance imaging screening for silent silicone breast implant rupture. Familiarity with the types of silicone implants and potential complications is essential for the radiologist. Signs of intracapsular rupture include the noose, droplet, subcapsular line, and linguine signs. Signs of extracapsular rupture include herniation of silicone with a capsular defect and extruded silicone material. Specific sequences including water and silicone suppression are essential for distinguishing rupture from other pathologies and artifacts. Magnetic resonance imaging provides valuable information about the integrity of silicone implants and associated complications.

21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are expressly...

21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are expressly...

21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are expressly...

21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are expressly...

21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are expressly...

21 CFR 882.5860 - Implanted neuromuscular stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted neuromuscular stimulator. 882.5860... neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that provides electrical stimulation to a patient's peroneal or femoral nerve to cause muscles in the leg to contract, thus...

Tardive Dyskinesia, Oral Parafunction, and Implant-Supported Rehabilitation.

PubMed

Lumetti, S; Ghiacci, G; Macaluso, G M; Amore, M; Galli, C; Calciolari, E; Manfredi, E

2016-01-01

Oral movement disorders may lead to prosthesis and implant failure due to excessive loading. We report on an edentulous patient suffering from drug-induced tardive dyskinesia (TD) and oral parafunction (OP) rehabilitated with implant-supported screw-retained prostheses. The frequency and intensity of the movements were high, and no pharmacological intervention was possible. Moreover, the patient refused night-time splint therapy. A series of implant and prosthetic failures were experienced. Implant failures were all in the maxilla and stopped when a rigid titanium structure was placed to connect implants. Ad hoc designed studies are desirable to elucidate the mutual influence between oral movement disorders and implant-supported rehabilitation.

Tardive Dyskinesia, Oral Parafunction, and Implant-Supported Rehabilitation

PubMed Central

Amore, M.

2016-01-01

Oral movement disorders may lead to prosthesis and implant failure due to excessive loading. We report on an edentulous patient suffering from drug-induced tardive dyskinesia (TD) and oral parafunction (OP) rehabilitated with implant-supported screw-retained prostheses. The frequency and intensity of the movements were high, and no pharmacological intervention was possible. Moreover, the patient refused night-time splint therapy. A series of implant and prosthetic failures were experienced. Implant failures were all in the maxilla and stopped when a rigid titanium structure was placed to connect implants. Ad hoc designed studies are desirable to elucidate the mutual influence between oral movement disorders and implant-supported rehabilitation. PMID:28050290

Osteoinductive implants: the mise-en-scène for drug-bearing biomimetic coatings.

PubMed

Liu, Y; de Groot, K; Hunziker, E B

2004-03-01

In orthopaedic and dental implantology, novel tools and techniques are being sought to improve the regeneration of bone tissue. Numerous attempts have been made to enhance the osteoconductivity of titanium prostheses, including modifications in their surface properties and coating with layers of calcium phosphate. The technique whereby such layers are produced has recently undergone a revolutionary change, which has had profound consequences for their potential to serve as drug-carrier systems. Hitherto, calcium phosphate layers were deposited upon the surfaces of metal implants under highly unphysiological physical conditions, which precluded the incorporation of proteinaceous osteoinductive drugs. These agents could only be adsorbed, superficially, upon preformed layers. Such superficially adsorbed molecules are released too rapidly within a biological milieu to be effective in their osteoinductive capacity. Now, it is possible to deposit calcium phosphate layers under physiological conditions of temperature and pH by the so-called biomimetic process, during which bioactive agents can be coprecipitated. Since these molecules are integrated into the inorganic latticework, they are released gradually in vivo as the layer undergoes degradation. This feature enhances the capacity of these coatings to act as a carrier system for osteogenic agents.

Safely re-integrating silicone breast implants into the plastic surgery practice.

PubMed

Gladfelter, Joanne

2006-01-01

In the early 1990s, it was reported that silicone breast implants were possibly responsible for serious damage to women's health. In January 1992, the Food and Drug Administration issued a voluntary breast implant moratorium and, in April, issued a ban on the use of silicone gel-filled implants for cosmetic breast augmentation. Since that time, silicone gel-filled breast implants have been available to women only for select cases: women seeking breast reconstruction or revision of an existing breast implant, women who have had breast cancer surgery, a severe injury to the breast, a birth defect that affects the breast, or a medical condition causing a severe breast deformity. Since the ban on the use of silicone gel-filled breast implants for cosmetic breast augmentation, numerous scientific studies have been conducted. To ensure patient safety, the American Board of Plastic Surgery believes that these scientific studies and the Food and Drug Administration's scrutiny of silicone gel-filled breast implants have been appropriate and necessary.

21 CFR 880.5965 - Subcutaneous, implanted, intravascular infusion port and catheter.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Subcutaneous, implanted, intravascular infusion... Hospital and Personal Use Therapeutic Devices § 880.5965 Subcutaneous, implanted, intravascular infusion port and catheter. (a) Identification. A subcutaneous, implanted, intravascular infusion port and...

21 CFR 880.5965 - Subcutaneous, implanted, intravascular infusion port and catheter.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Subcutaneous, implanted, intravascular infusion... Hospital and Personal Use Therapeutic Devices § 880.5965 Subcutaneous, implanted, intravascular infusion port and catheter. (a) Identification. A subcutaneous, implanted, intravascular infusion port and...

Failure of Urological Implants in Spinal Cord Injury Patients due to Infection, Malfunction, and Implants Becoming Obsolete due to Medical Progress and Age-Related Changes in Human Body Making Implant Futile: Report of Three Cases.

PubMed

Vaidyanathan, Subramanian; Soni, Bakul; Singh, Gurpreet; Hughes, Peter; Selmi, Fahed; Mansour, Paul

2013-01-01

Any new clinical data, whether positive or negative, generated about a medical device should be published because health professionals should know which devices do not work, as well as those which do. We report three spinal cord injury patients in whom urological implants failed to work. In the first, paraplegic, patient, a sacral anterior root stimulator failed to produce erection, and a drug delivery system for intracavernosal administration of vasoactive drugs was therefore implanted; however, this implant never functioned (and, furthermore, such penile drug delivery systems to produce erection had effectively become obsolete following the advent of phosphodiesterase type 5 inhibitors). Subsequently, the sacral anterior root stimulator developed a malfunction and the patient therefore learned to perform self-catheterisation. In the second patient, also paraplegic, an artificial urinary sphincter was implanted but the patient developed a postoperative sacral pressure sore. Eight months later, a suprapubic cystostomy was performed as urethral catheterisation was very difficult. The pressure sore had not healed completely even after five years. In the third case, a sacral anterior root stimulator was implanted in a tetraplegic patient in whom, after five years, a penile sheath could not be fitted because of penile retraction. This patient was therefore established on urethral catheter drainage. Later, infection with Staphylococcus aureus around the receiver block necessitated its removal. In conclusion, spinal cord injury patients are at risk of developing pressure sores, wound infections, malfunction of implants, and the inability to use implants because of age-related changes, as well as running the risk of their implants becoming obsolete due to advances in medicine. Some surgical procedures such as dorsal rhizotomy are irreversible. Alternative treatments such as intermittent catheterisations may be less damaging than bladder stimulator in the long term.

Microchips and controlled-release drug reservoirs.

PubMed

Staples, Mark

2010-01-01

This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. Copyright (c) 2010 John Wiley & Sons, Inc.

Pacemakers and implantable cardioverter defibrillators--general and anesthetic considerations.

PubMed

Rapsang, Amy G; Bhattacharyya, Prithwis

2014-01-01

A pacemaking system consists of an impulse generator and lead or leads to carry the electrical impulse to the patient's heart. Pacemaker and implantable cardioverter defibrillator codes were made to describe the type of pacemaker or implantable cardioverter defibrillator implanted. Indications for pacing and implantable cardioverter defibrillator implantation were given by the American College of Cardiologists. Certain pacemakers have magnet-operated reed switches incorporated; however, magnet application can have serious adverse effects; hence, devices should be considered programmable unless known otherwise. When a device patient undergoes any procedure (with or without anesthesia), special precautions have to be observed including a focused history/physical examination, interrogation of pacemaker before and after the procedure, emergency drugs/temporary pacing and defibrillation, reprogramming of pacemaker and disabling certain pacemaker functions if required, monitoring of electrolyte and metabolic disturbance and avoiding certain drugs and equipments that can interfere with pacemaker function. If unanticipated device interactions are found, consider discontinuation of the procedure until the source of interference can be eliminated or managed and all corrective measures should be taken to ensure proper pacemaker function should be done. Post procedure, the cardiac rate and rhythm should be monitored continuously and emergency drugs and equipments should be kept ready and consultation with a cardiologist or a pacemaker-implantable cardioverter defibrillator service may be necessary. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

21 CFR 882.4545 - Shunt system implantation instrument.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Shunt system implantation instrument. 882.4545 Section 882.4545 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Surgical Devices § 882.4545 Shunt system...

21 CFR 882.4545 - Shunt system implantation instrument.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Shunt system implantation instrument. 882.4545 Section 882.4545 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Surgical Devices § 882.4545 Shunt system...

Kinetics and mechanism of release from glyceryl monostearate-based implants: evaluation of release in a gel simulating in vivo implantation.

PubMed

Allababidi, S; Shah, J C

1998-06-01

The overall objective of the study was to design an implantable delivery system based on glyceryl monostearate (GMS) for the site-specific delivery of antibiotics for the prevention of surgical wound infection. To design the implant, a release method had to be developed that simulate the in vivo implantation conditions to be able to predict the release characteristics from the implants when they are actually used in vivo. Also, identifying the release kinetics and mechanism and evaluating the factors that influence the release of drugs from the GMS-based matrix were necessary to allow further design of implants that could yield a desired release rate. The release of cefazolin was monitored from GMS matrixes implanted into agar gel, simulating subcutaneous tissues with respect to viscosity and water content. The gel method resulted in observation of spatial and temporal concentration profiles in the immediate vicinity of the implants, indicating the benefits of local drug delivery; however, there was no significant difference between the cumulative release profiles by the gel method or the vial release method. The release of cefazolin from the GMS-based matrix with the vial method followed Higuchi's square root of time kinetics. The release rate was found to be directly proportional to cefazolin load (A) and the surface area (SA) of the matrix as expressed by the following equation: = 0.24ASA. On the basis of this equation, one can design a variety of GMS matrixes that would result in a desired release rate or release duration. This also indicated that cefazolin release followed the release kinetics of a freely soluble drug from an insoluble matrix and hence it is a diffusion-controlled process. The effect of drug solubility on the release kinetics was determined by comparing the release kinetics of the poorly water soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer

Cardiac Valve Noise Reduction by Non-Drug Interventions Improves the Sleep Quality of Patients after Mechanical Cardiac Valve Implantation.

PubMed

Lin, Yanjuan; Xu, Le; Huang, Xizhen; Jiang, Fei; Lin, Fen; Ye, Qingyang; Lin, Jianling

2016-01-01

To investigate the effects of non-drug interventions on the sleep quality of patients after mechanical cardiac valve implantation. In this prospective, randomized, controlled trial, 64 patients scheduled for mechanical mitral valve replacement were recruited. Patients underwent cognitive behavioral therapy and wore noise cancelling earplugs and eye mask. Sleep quality was evaluated on the 4th after admission and the 5th days after operation. The primary outcome was the total sleep quality score differences between the 4th day after admission and the 5th day after operation. All patients had been suffering from poor sleep quality for a month before admission. There was no difference between both groups on the 4th day after admission. Overall sleep quality in the intervention group was better than in the control group on the 5th day after operation. The subjective sleep quality of the patients in each group was significantly lower on the 5th day after the operation than on the 4th day after admission (P <0.05). Non-drug intervention could improve the sleep quality of patients after mechanical cardiac valve implantation and help the postoperative recovery of the patients. ( ChiCTR-TRC-14004405, 21 March 2014.).

Dual Antiplatelet Therapy for 6 Months vs 12 Months After New-generation Drug-eluting Stent Implantation: Matched Analysis of ESTROFA-DAPT and ESTROFA-2.

PubMed

de la Torre Hernández, José M; Oteo Domínguez, Juan F; Hernández, Felipe; García Camarero, Tamara; Abdul-Jawad Altisent, Omar; Rivero Crespo, Fernando; Cascón, José D; Zavala, Germán; Gimeno, Federico; Arrebola Moreno, Antonio L; Andraka, Leire; Gómez Menchero, Antonio; Bosa, Francisco; Carrillo, Xavier; Sánchez Recalde, Ángel; Alfonso, Fernando; Pérez de Prado, Armando; López Palop, Ramón; Sanchis, Juan; Diarte de Miguel, José A; Jiménez Navarro, Manuel; Muñoz, Luz; Ramírez Moreno, Antonio; Tizón Marcos, Helena

2015-10-01

The recommendation for dual antiplatelet therapy following drug-eluting stent implantation ranges from 6 months to 12 months or beyond. Recent trials have suggested the safety of a 6-month dual antiplatelet therapy regimen, yet certain caveats to these studies limit the applicability of this shorter duration dual antiplatelet therapy strategy in real world settings. A registry was constructed with consecutive recruitment of patients undergoing new-generation drug-eluting stent implantation and prescribed 6 months of dual antiplatelet therapy. Propensity score matching was undertaken with a historical cohort of patients treated with second-generation drug-eluting stents who received 12 months of dual antiplatelet therapy from the ESTROFA-2 registry. The sample size was calculated using a noninferiority basis and the primary endpoint was the combination of cardiac death, myocardial infarction, revascularization, or major bleeding at 12 months. The analysis included 1286 patients in each group, with no significant differences in baseline characteristics. The primary endpoint occurred in 5.0% and 6.6% in the 6-month and 12-month groups, respectively (P = .001 for noninferiority). The incidence of definite or probable stent thrombosis was 0.5% and 0.7% in the 6-month and 12-month groups, respectively (P = .4). Major bleeding events were lower in the 6-month group than in the 12-month group (0.8% vs 1.4%; P = .2) CONCLUSIONS: In selected patients in this large multicenter study, the safety and efficacy of a 6-month dual antiplatelet therapy regimen after implantation of new-generation drug-eluting stents appeared to be noninferior to those of a 12-month dual antiplatelet therapy regimen. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted peripheral nerve stimulator for pain....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral nerve...

Theranostic 3-Dimensional nano brain-implant for prolonged and localized treatment of recurrent glioma

NASA Astrophysics Data System (ADS)

Ramachandran, Ranjith; Junnuthula, Vijayabhaskar Reddy; Gowd, G. Siddaramana; Ashokan, Anusha; Thomas, John; Peethambaran, Reshmi; Thomas, Anoop; Unni, Ayalur Kodakara Kochugovindan; Panikar, Dilip; Nair, Shantikumar V.; Koyakutty, Manzoor

2017-03-01

Localized and controlled delivery of chemotherapeutics directly in brain-tumor for prolonged periods may radically improve the prognosis of recurrent glioblastoma. Here, we report a unique method of nanofiber by fiber controlled delivery of anti-cancer drug, Temozolomide, in orthotopic brain-tumor for one month using flexible polymeric nano-implant. A library of drug loaded (20 wt%) electrospun nanofiber of PLGA-PLA-PCL blends with distinct in vivo brain-release kinetics (hours to months) were numerically selected and a single nano-implant was formed by co-electrospinning of nano-fiber such that different set of fibres releases the drug for a specific periods from days to months by fiber-by-fiber switching. Orthotopic rat glioma implanted wafers showed constant drug release (116.6 μg/day) with negligible leakage into the peripheral blood (<100 ng) rendering ~1000 fold differential drug dosage in tumor versus peripheral blood. Most importantly, implant with one month release profile resulted in long-term (>4 month) survival of 85.7% animals whereas 07 day releasing implant showed tumor recurrence in 54.6% animals, rendering a median survival of only 74 days. In effect, we show that highly controlled drug delivery is possible for prolonged periods in orthotopic brain-tumor using combinatorial nanofibre libraries of bulk-eroding polymers, thereby controlling glioma recurrence.

Antibiotic use during the intracoelomic implantation of electronic tags into fish

USGS Publications Warehouse

Mulcahy, D.M.

2011-01-01

The use of antibiotics, in particular, the use of a single dose of antibiotics during electronic tag implantation is of unproven value, and carries with it the potential for the development of antibiotic resistance in bacteria and the alteration of the immune response of the fish. Antibiotic use during electronic tag implantation must conform to relevant drug laws and regulations in the country where work is being done, including the requirements for withdrawal times before human consumption is a possibility. Currently, the choice of antibiotics (most often tetracycline or oxytetracycline) and the use of a single dose of the drug are decisions made without knowledge of the basic need for antibiotic usage and of the bacteria involved in infections that occur following electronic tag implantation. Correct perioperative use of an antibiotic is to apply the drug to the animal before surgery begins, to assure serum and tissue levels of the drug are adequate before the incision is made. However, the most common perioperative application of antibiotics during implantation of an electronic tag is to delay the administration of the drug, injecting it into the coelom after the electronic tag is inserted, just prior to closure of the incision. There is little empirical evidence that the present application of antibiotics in fish being implanted with electronic tags is of value. Improvements should first be made to surgical techniques, especially the use of aseptic techniques and sterilized instruments and electronic tags, before resorting to antibiotics. ?? 2010 Springer Science+Business Media B.V.(outside the USA).

Sex differences in the outcomes of stent implantation in mini-swine model.

PubMed

Kunio, Mie; Wong, Gee; Markham, Peter M; Edelman, Elazer R

2018-01-01

Sex-related differences have been noted in cardiovascular anatomy, pathophysiology, and treatment responses, yet we continued to drive evaluation of vascular device development in animal models without consideration of animal sex. We aimed to understand sex-related differences in the vascular responses to stent implantation by analyzing the pooled data of endovascular interventions in 164 Yucatan mini-swine (87 female, 77 male). Bare metal stents (BMS) or drug-eluting stents (DES) were implanted in 212 coronary arteries (63 single BMS implantation, 68 single DES implantation, 33 overlapped BMS implantation, and 48 overlapped DES implantation). Histomorphological parameters were evaluated from vascular specimens at 3-365 days after stent implantation and evaluated values were compared between female and male groups. While neointima formation at all times after implantation was invariant to sex, statistically significant differences between female and male groups were observed in injury, inflammation, adventitial fibrosis, and neointimal fibrin deposition. These differences were observed independently, i.e., for different procedure types and at different follow-up timings. Only subtle temporal sex-related differences were observed in extent and timing of resolution of inflammation and fibrin clearance. These subtle sex-related differences may be increasingly important as interventional devices meld novel materials that erode and innovations in drug delivery. Erodible materials may act differently if inflammation has a different temporal sequence with sex, and drug distribution after balloon or stent delivery might be different if the fibrin clearance speaks to different modes of pharmacokinetics in male and female swine.

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

PubMed Central

Belz, Jodi E.; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S.; Royce, Darlene B.; Zhang, Di; van de Ven, Anne L.; Liby, Karen T.; Sridhar, Srinivas

2017-01-01

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1-deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1Co/Co;MMTV-Cre;p53+/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro. Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors. PMID:29158830

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer.

PubMed

Belz, Jodi E; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S; Royce, Darlene B; Zhang, Di; van de Ven, Anne L; Liby, Karen T; Sridhar, Srinivas

2017-01-01

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1 -deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1 -deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1 Co/Co ;MMTV-Cre;p53 +/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro . Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

Long-term venous access using a subcutaneous implantable drug delivery system.

PubMed Central

Soo, K. C.; Davidson, T. I.; Selby, P.; Westbury, G.

1985-01-01

To facilitate long-term venous access in patients receiving chemotherapy, a subcutaneous totally implantable system (Port-a-Cath, Phamacia) has been used in 14 patients. The method of implantation and the advantages over conventional central venous catheters are discussed. The expense of the system necessitates careful patient selection. PMID:4037644

Association Between Helicobacter Pylori Infection and Long-term Outcome in Patients with Drug-eluting Stent Implantation

NASA Astrophysics Data System (ADS)

Wang, Rui; Chen, Lei-Lei; Wang, De-Zhao; Chen, Bu-Xing

2017-07-01

To investigate the relationship between Helicobacter pylori (Hp) infection and the long-term outcome in acute coronary syndrome (ACS) patients with drug-eluting stent (DES) implantation and so as to explore the significance of Hp eradication therapy in preventing major adverse cardiac events (MACE) and upper gastrointestinal bleeding (UGIB). 539 ACS patients with DES implantation from January 1, 2010 to December 31, 2012 were analyzed. All the patients were divided into two groups according to the result of 13C urea breath test. 253 patients with Hp infection were put into group A (Hp+), and 286 cases without Hp infection were put into group B (Hp-). Demographic data was collected and all patients went through biochemical indicators and other routine blood examinations. We explored the correlations of Hp infection with MACE and UGIB after 3 to 5 years of follow-up using survival analysis. Survival analysis showed that Hp infection was a predictor of MACE and UGI. Sub-group analysis showed that patients with Hp eradication therapy had no relationship with MACE but had a lower rate of UGIB than those without Hp eradication therapy.

21 CFR 882.5830 - Implanted diaphragmatic/phrenic nerve stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted diaphragmatic/phrenic nerve stimulator. 882.5830 Section 882.5830 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5830...

21 CFR 882.5830 - Implanted diaphragmatic/phrenic nerve stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted diaphragmatic/phrenic nerve stimulator. 882.5830 Section 882.5830 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5830...

21 CFR 872.3970 - Interarticular disc prosthesis (interpositional implant).

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Interarticular disc prosthesis (interpositional implant). 872.3970 Section 872.3970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3970 Interarticular...

Three-dimensional printing and nanotechnology for enhanced implantable materials

NASA Astrophysics Data System (ADS)

Tappa, Karthik Kumar

Orthopedic and oro-maxillofacial implants have revolutionized treatment of bone diseases and fractures. Currently available metallic implants have been in clinical use for more than 40 years and have proved medically efficacious. However, several drawbacks remain, such as excessive stiffness, accumulation of metal ions in surrounding tissue, growth restriction, required removal/revision surgery, inability to carry drugs, and susceptibility to infection. The need for additional revision surgery increases financial costs and prolongs recovery time for patients. These metallic implants are bulk manufactured and often do not meet patient's requirements. A surgeon must machine (cut, weld, trim or drill holes) them in order to best suit the patient specifications. Over the past few decades, attempts have been made to replace these metallic implants with suitable biodegradable materials to prevent secondary/revision surgery. Recent advances in biomaterials have shown multiple uses for lactic acid polymers in bone implant technology. However, a targeted/localized drug delivery system needs to be incorporated in these polymers, and they need to be customized to treat orthopedic implant-related infections and other bone diseases such as osteomyelitis, osteosarcoma and osteoporosis. Rapid Prototyping (RP) using additive manufacturing (AM) or 3D printing could allow customization of constructs for personalized medicine. The goal of this study was to engineer customizable and biodegradable implant materials that can elute bioactive compounds for personalized medicine and targeted drug delivery. Post-operative infections are the most common complications following dental, orthopedic and bone implant surgeries. Preventing post-surgical infections is therefore a critical need that current polymethylmethacrylate (PMMA) bone cements fail to address. Calcium Phosphate Cements (CPCs) are unique in their ability to crystallize calcium and phosphate salts into hydroxyapatite (HA) and

Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

PubMed

McNicholas, Colleen; Swor, Erin; Wan, Leping; Peipert, Jeffrey F

2017-06-01

The subdermal contraceptive implant and the 52-mg levonorgestrel intrauterine device are currently Food and Drug Administration approved for 3 and 5 years of use, respectively. Limited available data suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. We sought to evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device in women using the method for 2 years beyond the current Food and Drug Administration-approved duration. We initiated this ongoing prospective cohort study in January 2012. We are enrolling women using the contraceptive implant or 52-mg levonorgestrel intrauterine device for a minimum of 3 and 5 years, respectively (started intrauterine device in ≥2007 or implant in ≥2009). Demographic and reproductive health histories, as well as objective body mass index, were collected. Implant users were offered periodic venipuncture for analysis of serum etonogestrel levels. The primary outcome, unintended pregnancy rate, was calculated per 100 woman-years. We analyzed baseline demographic characteristics using χ 2 test and Fisher exact test, and compared serum etonogestrel levels stratified by body mass index using the Kruskal-Wallis test. Implant users (n = 291) have contributed 444.0 woman-years of follow-up. There have been no documented pregnancies in implant users during the 2 years of postexpiration follow-up. Calculated failure rates in the fourth and fifth years for the implant are calculated as 0 (1-sided 97.5% confidence interval, 0-1.48) per 100 woman-years at 4 years and 0 (1-sided 97.5% confidence interval, 0-2.65) per 100 woman-years at 5 years. Among 496 levonorgestrel intrauterine device users, 696.9 woman-years of follow-up have been completed. Two pregnancies have been reported. The failure rate in the sixth year of use of the

Nanobiotechnology Perspectives on Prevention and Treatment of Ortho-paedic Implant Associated Infection.

PubMed

Borse, Vivek; Pawar, Vaishali; Shetty, Gautam; Mullaji, Arun; Srivastava, Rohit

2016-01-01

Implants are an inevitable part of orthopaedic surgery. However, implant associated infection remains a major challenge for orthopaedic surgeons and researchers. This review focuses on current options available for prevention of implant associated infection, their drawbacks and future promising applications of nanotechnology-based approaches. Nanobiotechnology has shown remarkable progress in recent years especially in biomaterials, diagnostics, and drug delivery system. Although several applications of nanobiotechnology in orthopaedics have been described, few have elaborated their role in the prevention of implant related infection in orthopaedics. Novel "smart" drug delivery systems that release antibiotics locally in response to stimuli such as pH, temperature, enzymes or antigens; implant surface modification on a nanoscale to inhibit bacterial adhesion and propagation at the surgical site and biological approaches such as gene therapy to neutralize bacterial virulence and biomolecules to inhibit the quorum sensing adhesion of bacteria and disruption of biofilms can be used effectively to prevent orthopaedic implant related bacterial infection.

In-stent neoatherosclerosis and tissue characteristics of restenotic lesions following implantation of second generation drug-eluting stents in unrestricted coronary lesions: Optical frequency domain imaging study.

PubMed

Sabbah, Mahmoud; Kadota, Kazushige; El-Eraky, Azza; Kamal, Hanan M; Abdellah, Ahmed-Tageldien; El Hawary, Ahmed

2017-06-01

Differences in stent platform, polymer coatings, and antirestenotic drugs among the current in use second-generation drug-eluting stents (G2-DESs) may induce significant variations in neointimal response and vascular healing, which may impact the prevalence of neoatherosclerosis (NA) and morphological appearance of the restenotic tissue. Utilizing Optical frequency domain imaging, two independent reviewers, retrospectively compared the prevalence of neoatherosclerosis (NA), and the morphological differences, and tissue characteristics of 50 G2-DESs in-stent restenosis (ISR) lesions (35 everolimus-eluting stent [22 cobalt-chromium (CoCr), 13 platinum-chromium (PtCr)], and 15 biolimus-eluting stent [BES]) implanted liberally in unrestricted coronary lesions. More than half of the stents were implanted in type C lesions, while 40% of the stents were implanted primarily in lesions with recanalized chronic total occlusion. NA, defined as a neointima formation with the presence of lipids or calcification, was observed in fewer than half (24/50) of all ISR lesions with no significant in-between group differences (41%, 69%, and 40% in CoCr, PtCr, and BES respectively, P = 0.22), nor were there any significant differences in the morphological appearance or tissue characteristics between all G2-DESs subtypes. Acknowledging some limitations, our results may suggest that the prevalence of NA and the morphological appearance of restenotic lesions might not differ when G2-DESs are implanted in unrestricted, rather complex, coronary lesions. © 2017, Wiley Periodicals, Inc.

Educational Interpreters: Meeting the Communication Needs of Children with Cochlear Implants

ERIC Educational Resources Information Center

Melton, Julie; Higbee, Renee

2013-01-01

Since the early 1990s, when the U.S. Food and Drug Administration approved cochlear implants for deaf and hard of hearing children, the number of children who have cochlear implants has increased in mainstream settings. Recent research suggests that these students, like their deaf and hard of hearing peers without implants who use sign language,…

Bolus intrathecal injection of ziconotide (Prialt®) to evaluate the option of continuous administration via an implanted intrathecal drug delivery (ITDD) system: a pilot study.

PubMed

Mohammed, Salma I; Eldabe, Sam; Simpson, Karen H; Brookes, Morag; Madzinga, Grace; Gulve, Ashish; Baranidharan, Ganesan; Radford, Helen; Crowther, Tracey; Buchser, Eric; Perruchoud, Christophe; Batterham, Alan Mark

2013-01-01

This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system. Twenty adults with severe chronic pain who were under consideration for intrathecal (IT) therapy were enrolled in this open label, nonrandomized, pilot study. Informed consent was obtained. Demographics, medical/pain history, pain scores, and concomitant medications were recorded. A physical examination was performed. Creatine kinase was measured. Initial visual analog scale (VAS), blood pressure, heart rate, and respiratory rate were recorded. All patients received an initial bolus dose of 2.5 mcg ziconotide; the dose in the subsequent visits was modified according to response. Subsequent doses were 2.5 mcg, 1.2 mcg, or 3.75 mcg as per protocol. A good response (≥30% reduction in baseline pain VAS) with no side-effects on two occasions was considered a successful trial. Data were analyzed using a generalized estimating equations model, with pain VAS as the outcome and time (seven time points; preinjection and one to six hours postinjection) as the predictor. Generalized estimating equations analysis of summary measures showed a mean reduction of pain VAS of approximately 25% at the group level; of 11 responders, seven underwent pump implantation procedure, two withdrew because of adverse effects, one refused an implant, and one could not have an implant (lack of funding from the Primary Care Trust). Our data demonstrated that mean VAS was reduced by approximately 25% at the group level after IT ziconotide bolus. Treatment efficacy did not vary with sex, center, age, or pain etiology. Ziconotide bolus was generally well tolerated. Larger studies are needed to determine if bolus dosing with ziconotide is a good predictor of response to continuous IT ziconotide via an intrathecal drug delivery system. © 2012 International

21 CFR 870.2855 - Implantable Intra-aneurysm Pressure Measurement System.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implantable Intra-aneurysm Pressure Measurement System. 870.2855 Section 870.2855 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices...

21 CFR 870.2855 - Implantable Intra-aneurysm Pressure Measurement System.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implantable Intra-aneurysm Pressure Measurement System. 870.2855 Section 870.2855 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices...

The active modulation of drug release by an ionic field effect transistor for an ultra-low power implantable nanofluidic system.

PubMed

Bruno, Giacomo; Canavese, Giancarlo; Liu, Xuewu; Filgueira, Carly S; Sacco, Adriano; Demarchi, Danilo; Ferrari, Mauro; Grattoni, Alessandro

2016-11-10

We report an electro-nanofluidic membrane for tunable, ultra-low power drug delivery employing an ionic field effect transistor. Therapeutic release from a drug reservoir was successfully modulated, with high energy efficiency, by actively adjusting the surface charge of slit-nanochannels 50, 110, and 160 nm in size, by the polarization of a buried gate electrode and the consequent variation of the electrical double layer in the nanochannel. We demonstrated control over the transport of ionic species, including two relevant hypertension drugs, atenolol and perindopril, that could benefit from such modulation. By leveraging concentration-driven diffusion, we achieve a 2 to 3 order of magnitude reduction in power consumption as compared to other electrokinetic phenomena. The application of a small gate potential (±5 V) in close proximity (150 nm) of 50 nm nanochannels generated a sufficiently strong electric field, which doubled or blocked the ionic flux depending on the polarity of the voltage applied. These compelling findings can lead to next generation, more reliable, smaller, and longer lasting drug delivery implants with ultra-low power consumption.

Buprenorphine implants in medical treatment of opioid addiction.

PubMed

Chavoustie, Steven; Frost, Michael; Snyder, Ole; Owen, Joel; Darwish, Mona; Dammerman, Ryan; Sanjurjo, Victoria

2017-08-01

Opioid use disorder is a chronic, relapsing disease that encompasses use of both prescription opioids and heroin and is associated with a high annual rate of overdose deaths. Medical treatment has proven more successful than placebo treatment or psychosocial intervention, and the partial µ-opioid receptor agonist and κ-opioid receptor antagonist buprenorphine is similar in efficacy to methadone while offering lower risk of respiratory depression. However, frequent dosing requirements and potential for misuse and drug diversion contribute to significant complications with treatment adherence for available formulations. Areas covered: This review describes the development of and preliminary data from clinical trials of an implantable buprenorphine formulation. Efficacy and safety data from comparative studies with other administrations of buprenorphine, including tablets and sublingual film, will be described. Key premises of the Risk Evaluation and Mitigation Strategy program for safely administering buprenorphine implants, which all prescribing physicians must complete, are also discussed. Expert commentary: Long-acting implantable drug formulations that offer consistent drug delivery and lower risk of misuse, diversion, or accidental pediatric exposure over traditional formulations represent a promising development for the effective treatment of opioid use disorder.

TiO2 nanotube platforms for smart drug delivery: a review.

PubMed

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Chen, Zhong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Al-Deyab, Salem S; Lai, Yue-Kun

Titania nanotube (TNT) arrays are recognized as promising materials for localized drug delivery implants because of their excellent properties and facile preparation process. This review highlights the concept of localized drug delivery systems based on TNTs, considering their outstanding biocompatibility in a series of ex vivo and in vivo studies. Considering the safety of TNT implants in the host body, studies of the biocompatibility present significant importance for the clinical application of TNT implants. Toward smart TNT platforms for sustainable drug delivery, several advanced approaches were presented in this review, including controlled release triggered by temperature, light, radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used in medical therapy have been demonstrated by various examples including dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a future perspective of TNTs for clinical applications is provided.

21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person seeking...

21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person seeking...

21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person seeking...

21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person seeking...

21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person seeking...

21 CFR 880.5970 - Percutaneous, implanted, long-term intravascular catheter.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Percutaneous, implanted, long-term intravascular catheter. 880.5970 Section 880.5970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital...

21 CFR 880.5970 - Percutaneous, implanted, long-term intravascular catheter.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Percutaneous, implanted, long-term intravascular catheter. 880.5970 Section 880.5970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital...

21 CFR 880.5970 - Percutaneous, implanted, long-term intravascular catheter.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Percutaneous, implanted, long-term intravascular catheter. 880.5970 Section 880.5970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital...

21 CFR 880.5970 - Percutaneous, implanted, long-term intravascular catheter.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Percutaneous, implanted, long-term intravascular catheter. 880.5970 Section 880.5970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital...

21 CFR 880.5970 - Percutaneous, implanted, long-term intravascular catheter.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Percutaneous, implanted, long-term intravascular catheter. 880.5970 Section 880.5970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital...

A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.

PubMed

Gilger, Brian C; Salmon, Jacklyn H; Wilkie, David A; Cruysberg, Lars P J; Kim, Jonghyeon; Hayat, Matt; Kim, Hyuncheol; Kim, Stephanie; Yuan, Peng; Lee, Susan S; Harrington, Susan M; Murray, Patrick R; Edelhauser, Henry F; Csaky, Karl G; Robinson, Michael R

2006-06-01

To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

Prevalence, Features, and Prognostic Importance of Edge Dissection After Drug-Eluting Stent Implantation: An ADAPT-DES Intravascular Ultrasound Substudy.

PubMed

Kobayashi, Nobuaki; Mintz, Gary S; Witzenbichler, Bernhard; Metzger, D Christopher; Rinaldi, Michael J; Duffy, Peter L; Weisz, Giora; Stuckey, Thomas D; Brodie, Bruce R; Parvataneni, Rupa; Kirtane, Ajay J; Stone, Gregg W; Maehara, Akiko

2016-07-01

Intravascular ultrasound detects stent edge dissections after percutaneous coronary intervention that are not seen angiographically. This study investigated the association between stent edge dissections and clinical outcomes. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a large-scale, prospective, multicenter study of patients undergoing drug-eluting stent implantation. In this prospective substudy, 2062 patients (2433 lesions) were evaluated with intravascular ultrasound to characterize the morphological features and clinical outcomes of stent edge dissection after percutaneous coronary intervention. The prevalence of post-percutaneous coronary intervention stent edge dissection was 6.6% per lesion (161 of 2433). Calcified plaque at the proximal stent edge (relative risk [RR]=1.72; P=0.04) and proximal stent edge expansion (RR=1.18; P=0.004) were predictors for proximal dissection; attenuated plaque at the distal stent edge (RR=3.52; P=0.004), distal reference plaque burden (RR=1.56; P<0.0001), and distal edge stent expansion (RR=1.11; P=0.02) were predictors for distal dissection. At 1-year follow-up, target lesion revascularization was more common in lesions with versus without dissection (5.2% versus 2.7%; P=0.04). Multivariable analysis indicated that residual dissection was associated with target lesion revascularization at 1-year follow-up (RR=2.67; P=0.02). Among lesions with dissection, smaller effective lumen area increased the risk of target lesion revascularization at 1-year follow-up (cutoff value of 5.1 mm(2); P=0.05). Greater stent expansion and the presence of large, calcified, and/or attenuated plaques were independent predictors of stent edge dissection. Residual stent edge dissection, especially with a smaller effective lumen area, was associated with target lesion revascularization during 1-year follow-up after drug-eluting stent implantation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794

Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

PubMed Central

Hunter, Rebecca S; Lobo, Ann-Marie

2011-01-01

Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide.

PubMed

Sheshala, Ravi; Hong, Gan Chew; Yee, Wong Pui; Meka, Venkata Srikanth; Thakur, Raghu Raj Singh

2018-02-26

The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.

TiO2 nanotube platforms for smart drug delivery: a review

PubMed Central

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Chen, Zhong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Al-Deyab, Salem S; Lai, Yue-Kun

2016-01-01

Titania nanotube (TNT) arrays are recognized as promising materials for localized drug delivery implants because of their excellent properties and facile preparation process. This review highlights the concept of localized drug delivery systems based on TNTs, considering their outstanding biocompatibility in a series of ex vivo and in vivo studies. Considering the safety of TNT implants in the host body, studies of the biocompatibility present significant importance for the clinical application of TNT implants. Toward smart TNT platforms for sustainable drug delivery, several advanced approaches were presented in this review, including controlled release triggered by temperature, light, radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used in medical therapy have been demonstrated by various examples including dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a future perspective of TNTs for clinical applications is provided. PMID:27703349

21 CFR 878.3500 - Polytetrafluoroethylene with carbon fibers composite implant material.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Polytetrafluoroethylene with carbon fibers... Prosthetic Devices § 878.3500 Polytetrafluoroethylene with carbon fibers composite implant material. (a) Identification. A polytetrafluoroethylene with carbon fibers composite implant material is a porous device...

Five-Year Safety Data for More than 55,000 Subjects following Breast Implantation: Comparison of Rare Adverse Event Rates with Silicone Implants versus National Norms and Saline Implants.

PubMed

Singh, Navin; Picha, George J; Hardas, Bhushan; Schumacher, Andrew; Murphy, Diane K

2017-10-01

The U.S. Food and Drug Administration has required postapproval studies of silicone breast implants to evaluate the incidence of rare adverse events over 10 years after implantation. The Breast Implant Follow-Up Study is a large 10-year study (>1000 U.S. sites) evaluating long-term safety following primary augmentation, revision-augmentation, primary reconstruction, or revision-reconstruction with Natrelle round silicone breast implants compared with national norms and outcomes with saline implants. Targeted adverse events in subjects followed for 5 to 8 years included connective tissue diseases, neurologic diseases, cancer, and suicide. The safety population comprised 55,279 women (primary augmentation, n = 42,873; revision-augmentation, n = 6837; primary reconstruction, n = 4828; and revision-reconstruction, n = 741). No targeted adverse events occurred at significantly greater rates in silicone implant groups versus national norms across all indications. The standardized incidence rate (observed/national norm) for all indications combined was 1.4 for cervical/vulvar cancer, 0.8 for brain cancer, 0.3 for multiple sclerosis, and 0.1 for lupus/lupus-like syndrome. Silicone implants did not significantly increase the risk for any targeted adverse events compared with saline implants. The risk of death was similar with silicone versus saline implants across all indications. The suicide rate (10.6 events per 100,000 person-years) was not significantly higher than the national norm. No implant-related deaths occurred. Results from 5 to 8 years of follow-up for a large number of subjects confirmed the safety of Natrelle round silicone implants, with no increased risk of systemic disease or suicide versus national norms or saline implants. Therapeutic, II.

Technical tips during implantation of selective upper airway stimulation.

PubMed

Heiser, Clemens; Thaler, Erica; Soose, Ryan J; Woodson, B Tucker; Boon, Maurits

2018-03-01

Selective upper airway stimulation is now well-established in the United States and in several European countries, with more than 1,000 patients implanted since U.S. Food and Drug Administration approval in April 2014. The authors herein, all head and neck surgeons, account for approximately one of every five implants completed to date. Several of the authors also provide comprehensive longitudinal care of their patients as dual-specialty sleep medicine physicians. Multi-center, retrospective clinical analysis. More than 300 implants have been evaluated and reviewed in five different implant centers (Germany, United States). This analysis shares tips and techniques from the collective experiences with more than 300 implants, which can help newer implanters learn vicariously both for standard practices in executing routine implants through activation and, importantly, for working through more challenging encounters with anatomy, special patient phenotypes, system testing, and troubleshooting. These tips should help new implanters handle most of the situations arising during implantation and avoid common pitfalls. Laryngoscope, 128:756-762, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

A comparison of two brands of clopidogrel in patients with drug-eluting stent implantation.

PubMed

Park, Yae Min; Ahn, Taehoon; Lee, Kyounghoon; Shin, Kwen-Chul; Jung, Eul Sik; Shin, Dong Su; Kim, Myeong Gun; Kang, Woong Chol; Han, Seung Hwan; Choi, In Suck; Shin, Eak Kyun

2012-07-01

Although generic clopidogrel is widely used, clinical efficacy and safety between generic and original clopidogrel had not been well evaluated. The aim of this study was to evaluate the clinical outcomes of 2 oral formulations of clopidogrel 75 mg tablets in patients with coronary artery disease (CAD) undergoing drug-eluting stent (DES) implantation. Between July 2006 and February 2009, 428 patients that underwent implantation with DES for CAD and completed >1 year of clinical follow-up were enrolled in this study. Patients were divided into the following 2 groups based on treatment formulation, Platless® (test formulation, n=211) or Plavix® (reference formulation, n=217). The incidence of 1-year major adverse cardiovascular and cerebrovascular event (MACCE) and stent thrombosis (ST) were retrospectively reviewed. The baseline demographic and procedural characteristics were not significantly different between two treatment groups. The incidence of 1-year MACCEs was 8.5% {19/211, 2 deaths, 4 myocardial infarctions (MIs), 2 strokes, and 11 target vessel revascularizations (TVRs)} in Platless® group vs. 7.4% (16/217, 4 deaths, 1 MI, 2 strokes, and 9 TVRs) in Plavix® group (p=0.66). The incidence of 1-year ST was 0.5% (1 definite and subacute ST) in Platless® group vs. 0% in Plavix® group (p=0.49). In this study, the 2 tablet preparations of clopidogrel showed similar rates of MACCEs, but additional prospective randomized studies with pharmacodynamics and platelet reactivity are needed to conclude whether generic clopidgrel may replace original clopidogrel.

Evaluation of an injectable thermosensitive hydrogel as drug delivery implant for ocular glaucoma surgery.

PubMed

Xi, Lei; Wang, Tao; Zhao, Feng; Zheng, Qiongjuan; Li, Xiaoning; Luo, Jing; Liu, Ji; Quan, Daping; Ge, Jian

2014-01-01

In this study, a biodegradable thermo-sensitive hydrogel from poly(trimethylene carbonate)15-F127-poly(trimethylene carbonate)15 (PTMC15-F127-PTMC15) was designed and evaluated as an injectable implant during ocular glaucoma filtration surgery in vivo and in vitro. Mitomycin C (MMC) was loaded into this hydrogel for controlled released to prolong the efficacy and to reduce the long-term toxicity. The properties of the hydrogel were confirmed using 1H NMR and gel permeation chromatography (GPC). Compared to the Pluronic F127 hydrogel, the PTMC15-F127-PTMC15 hydrogel showed a good solution-gel transition temperature at 37°C, a lower work concentration of 5% w/v and a longer mass loss time of more than 2 weeks. The in vitro study showed that the drug could be released from PTMC15-F127-PTMC15 (5% w/v) hydrogel for up to 16 days with only 57% of drug released in the first day. Moreover, the cell toxicity, which was tested via LDH and ANNEXIN V/PI, decreased within 72 h in human tenon's fibroblast cells (HTFs). The in vivo behavior in a rabbit glaucoma filtration surgery model indicated that this hydrogel loaded with 0.1 mg/ml MMC led to a better functional bleb with a prolonged mean bleb survival time (25.5±2.9 days). The scar tissue formation, new collagen deposition and myofibroblast generation appeared to be reduced upon histological and immunohistochemistry examinations, with no obvious side effects and inflammatory reactions. The in vitro and in vivo results demonstrated that this novel hydrogel is a safe and effective drug delivery candidate in ocular glaucoma surgery.

Efficacy and safety of low-dose clopidogrel after 12-month dual antiplatelet therapy for patients having drug-eluting stent implantation.

PubMed

Zhuang, Xiao-Dong; Long, Ming; Li, Cui-Ling; Hu, Cheng-Heng; Du, Zhi-Ming; Liao, Xin-Xue

2014-05-01

To prevent stent thrombosis (ST) after implantation of drug-eluting stents (DESs) in patients with coronary heart disease, 12-month dual antiplatelet therapy (DAPT) is recommended. However, the optimal long-term antiplatelet regimen is not clear for the patients who have completed the 12-month DAPT. We reviewed the data of 755 consecutive patients who had undergone percutaneous coronary intervention (PCI) three years ago and completed 12-month DAPT. They were divided into three groups according to the antiplatelet medication they had used for two years after 12-month DAPT [low-dose clopidogrel (Talcom(®), 25mg/d), clopidogrel (Plavix(®), 75mg/d) and aspirin (100 mg/d)]. The efficacy (a composite incidence of cardiac death, myocardial infarction and target vessel revascularization) and safety (incidences of bleeding, gastrointestinal trouble and drug discontinuation) were compared among the three groups. The rates of multi-vessel lesions, prior MI, hemoglobin A1C (HbA1c) and low-density lipoprotein cholesterol were significantly higher in the clopidogrel (75 mg/day) group than in the other two groups (P>0.05 for both comparisons). There was no significant difference in the overall composite incidence of cardiac death, myocardial infarction and target vessel revascularization in the three groups at three years after PCI. The rates of bleeding (especially minor bleeding), gastrointestinal trouble, drug discontinuation and any blood transfusion were markedly lower in the low-dose clopidogrel (25 mg/d) group than in the other two treatment groups (P<0.05). The 25-mg maintenance dose of clopidogrel after 12-month DAPT may be more preferable to Chinese patients who have undergone DES implantation, because of its lower cost but no less efficacy and safety.

Titanium wire implants with nanotube arrays: A study model for localized cancer treatment.

PubMed

Kaur, Gagandeep; Willsmore, Tamsyn; Gulati, Karan; Zinonos, Irene; Wang, Ye; Kurian, Mima; Hay, Shelley; Losic, Dusan; Evdokiou, Andreas

2016-09-01

Adverse complications associated with systemic administration of anti-cancer drugs are a major problem in cancer therapy in current clinical practice. To increase effectiveness and reduce side effects, localized drug delivery to tumour sites requiring therapy is essential. Direct delivery of potent anti-cancer drugs locally to the cancer site based on nanotechnology has been recognised as a promising alternative approach. Previously, we reported the design and fabrication of nano-engineered 3D titanium wire based implants with titania (TiO2) nanotube arrays (Ti-TNTs) for applications such as bone integration by using in-vitro culture systems. The aim of present study is to demonstrate the feasibility of using such Ti-TNTs loaded with anti-cancer agent for localized cancer therapy using pre-clinical cancer models and to test local drug delivery efficiency and anti-tumour efficacy within the tumour environment. TNF-related apoptosis-inducing ligand (TRAIL) which has proven anti-cancer properties was selected as the model drug for therapeutic delivery by Ti-TNTs. Our in-vitro 2D and 3D cell culture studies demonstrated a significant decrease in breast cancer cell viability upon incubation with TRAIL loaded Ti-TNT implants (TRAIL-TNTs). Subcutaneous tumour xenografts were established to test TRAIL-TNTs implant performance in the tumour environment by monitoring the changes in tumour burden over a selected time course. TRAIL-TNTs showed a significant regression in tumour burden within the first three days of implant insertion at the tumour site. Based on current experimental findings these Ti-TNTs wire implants have shown promising capacity to load and deliver anti-cancer agents maintaining their efficacy for cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Triple antithrombotic therapy versus dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation.

PubMed

Kang, Dong Oh; Yu, Cheol Woong; Kim, Hee Dong; Cho, Jae Young; Joo, Hyung Joon; Choi, Rak Kyong; Park, Jin Sik; Lee, Hyun Jong; Kim, Je Sang; Park, Jae Hyung; Hong, Soon Jun; Lim, Do-Sun

2015-08-01

The optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation. A total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs. The 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate analysis, TAT was an independent predictor of worse net clinical outcomes (odds ratio 1.63, 95% confidence interval 1.06-2.50) and major bleeding (odds ratio 3.54, 95% confidence interval 1.65-7.58). After propensity score matching, the TAT group still had worse net clinical outcomes and a higher incidence of major bleeding compared with the DAPT group. In AF patients undergoing DES implantation, prolonged administration of TAT may be harmful due to the substantial increase in the risk for major bleeding without any reduction in MACCE.

pH dependent silver nanoparticles releasing titanium implant: A novel therapeutic approach to control peri-implant infection.

PubMed

Dong, Yiwen; Ye, Hui; Liu, Yi; Xu, Lihua; Wu, Zuosu; Hu, Xiaohui; Ma, Jianfeng; Pathak, Janak L; Liu, Jinsong; Wu, Gang

2017-10-01

Peri-implant infection control is crucial for implant fixation and durability. Antimicrobial administration approaches to control peri-implant infection are far from satisfactory. During bacterial infection, pH level around the peri-implant surface decreases as low as pH 5.5. This change of pH can be used as a switch to control antimicrobial drug release from the implant surface. Silver nanoparticles (AgNPs) have broad-spectrum antimicrobial properties. In this study, we aimed to design a pH-dependent AgNPs releasing titania nanotube arrays (TNT) implant for peri-implant infection control. The nanotube arrays were fabricated on the surface of titanium implant as containers; AgNPs were grafted on TNT implant surface via a low pH-sensitive acetal linker (TNT-AL-AgNPs). SEM, TEM, AFM, FTIR as well as XPS data showed that AgNPs have been successfully linked to TNT via acetal linker without affecting the physicochemical characteristics of TNT. The pH 5.5 enhanced AgNPs release from TNT-AL-AgNPs implant compared with pH 7.4. AgNPs released at pH 5.5 robustly increased antimicrobial activities against gram-positive and gram-negative bacteria compared with AgNPs released at pH 7.4. TNT-AL-AgNPs implant enhanced osteoblast proliferation, differentiation, and did not affect osteoblast morphology in vitro. In conclusion, incorporation of AgNPs in TNT via acetal linker maintained the surface characteristics of TNT. TNT-AL-AgNPs implant was biocompatible to osteoblasts and showed osteoinductive properties. AgNPs were released from TNT-AL-AgNPs implant in high dose at pH 5.5, and this release showed strong antimicrobial properties in vitro. Therefore, this novel design of low pH-triggered AgNPs releasing TNT-AL-AgNPs could be an infection-triggered antimicrobial releasing implant model to control peri-implant infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of different antithrombotic regimens for patients with atrial fibrillation undergoing drug-eluting stent implantation.

PubMed

Gao, Fei; Zhou, Yu Jie; Wang, Zhi Jian; Shen, Hua; Liu, Xiao Li; Nie, Bin; Yan, Zhen Xian; Yang, Shi Wei; Jia, De An; Yu, Miao

2010-04-01

The optimal antithrombotic strategy for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation is unknown. The 622 consecutive AF patients undergoing DES implantation were prospectively enrolled. Among them, 142 patients (TT group) continued triple antithrombotic therapy comprising aspirin, clopidogrel and warfarin after discharge; 355 patients (DT group) had dual antiplatelet therapy; 125 patients (WS group) were discharged with warfarin and a single antiplatelet agent. Target INR was set as 1.8-2.5 and was regularly monitored after discharge. The TT group had a significant reduction in stroke and major adverse cardiac and cerebral events (MACCE) (8.8% vs 20.1% vs 14.9%, P=0.010) as compared with either the DT or WS group. In the Cox regression analysis, administration with warfarin (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.31-0.77; P=0.002) and baseline CHADS(2) score >or=2 (HR 2.09; 95%CI 1.27-3.45; P=0.004) were independent predictors of MACCE. Importantly, the incidence of major bleeding was comparable among 3 groups (2.9% vs 1.8% vs 2.5%, P=0.725), although the overall bleeding rate was increased in the TT group. Kaplan-Meier analysis indicated that the TT group was associated with the best net clinical outcome. The cardiovascular benefits of triple antithrombotic therapy were confirmed by reducing the MACCE rate, and its major bleeding risk might be acceptable if the INR is closely monitored.

Clinical Outcomes of Patients Undergoing Rotational Atherectomy Followed by Drug-eluting Stent Implantation: A Single-center Real-world Experience

PubMed Central

Cuenza, Lucky R.; Jayme, Ada Cherryl; Khe Sui, James Ho

2017-01-01

Background: Rotational atherectomy (RA) is used to improve procedural success of percutaneous catheter interventions (PCIs) of complex and heavily calcified coronary lesions. We report the clinical experience and outcomes in our institution with the use of RA, followed by drug-eluting stent implantation. Materials and Methods: Data of 81 patients treated with PCI and adjunctive RA were analyzed. Clinical follow-up for the occurrence of major adverse events (MAEs) was obtained in all patients and correlated with significant variables using multivariate Cox proportional hazards analysis. Results: Mean age was 67.9 ± 9.2 years, 61.7% had diabetes, 20.9% had chronic kidney disease, and 48.1% had previous acute coronary syndrome (ACS). Mean SYNTAX score was 29.8 ± 12.2, with a 92.5% angiographic success rate achieved. In-hospital MAEs rate was 7.4% while mortality rate was 8.6%. On median follow-up of 12.2 months, incidence of MAEs of 13.5% with a 75% free incidence from MAEs at 34 months. Multivariate analysis revealed that a history of previous ACS, ejection fraction, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, SYNTAX score, burr to artery ratio, and attainment of angiographic success were significant predictors of MAEs. Conclusion: RA followed by drug-eluting stent implantation is a safe and effective method in improving procedural success as well as short- and long-term outcomes of PCI in our center. A combination of clinical and procedural factors is predictive for the occurrence of MAEs and should be taken into account in the application of this technique. PMID:29326773

Perilymph pharmacokinetics of marker applied through a cochlear implant in guinea pigs

PubMed Central

Hartsock, Jared; Gill, Ruth; Smyth, Daniel; Kirk, Jonathon; Verhoeven, Kristien

2017-01-01

Patients undergoing cochlear implantation could benefit from a simultaneous application of drugs into the ear, helping preserve residual low-frequency hearing and afferent nerve fiber populations. One way to apply drugs is to incorporate a cannula into the implant, through which drug solution is driven. For such an approach, perilymph concentrations achieved and the distribution in the ear over time have not previously been documented. We used FITC-labeled dextran as a marker, delivering it into perilymph of guinea pigs at 10 or 100 nL/min though a cannula incorporated into a cochlear implant with the outlet in the mid basal turn. After injections of varying duration (2 hours, 1 day or 7 days) perilymph was collected from the cochlear apex using a sequential sampling technique, allowing dextran levels and gradients along scala tympani to be quantified. Data were interpreted quantitatively using computer simulations of the experiments. For injections of 2 hours duration, dextran levels were critically influenced by the presence or absence of fluid leakage at the cochleostomy site. When the cochleostomy was fluid-tight, substantially higher perilymph levels were achieved at the injection site, with concentration declining along scala tympani towards the apex. Contrary to expectations, large dextran gradients along scala tympani persisted after 24 hours of sustained injection and were still present in some animals after 7 days injection. Functional changes associated with implantation and dextran delivery, and the histological state of the implant and cannula were also documented. The persistent longitudinal gradients of dextan along the ear were not readily explained by computer simulations of the experiments based on prior pharmacokinetic data. One explanation is that inner ear pharmacokinetics are altered in the period after cochlear implantation, possibly by a permeabilization of the blood-labyrinth barrier as part of the immune response to the implant. PMID

Evaluation of an Injectable Thermosensitive Hydrogel As Drug Delivery Implant for Ocular Glaucoma Surgery

PubMed Central

Zhao, Feng; Zheng, Qiongjuan; Li, Xiaoning; Luo, Jing; Liu, Ji; Quan, Daping; Ge, Jian

2014-01-01

In this study, a biodegradable thermo-sensitive hydrogel from poly(trimethylene carbonate)15-F127-poly(trimethylene carbonate)15 (PTMC15-F127-PTMC15) was designed and evaluated as an injectable implant during ocular glaucoma filtration surgery in vivo and in vitro. Mitomycin C (MMC) was loaded into this hydrogel for controlled released to prolong the efficacy and to reduce the long-term toxicity. The properties of the hydrogel were confirmed using 1H NMR and gel permeation chromatography (GPC). Compared to the Pluronic F127 hydrogel, the PTMC15-F127-PTMC15 hydrogel showed a good solution-gel transition temperature at 37°C, a lower work concentration of 5% w/v and a longer mass loss time of more than 2 weeks. The in vitro study showed that the drug could be released from PTMC15-F127-PTMC15 (5% w/v) hydrogel for up to 16 days with only 57% of drug released in the first day. Moreover, the cell toxicity, which was tested via LDH and ANNEXIN V/PI, decreased within 72 h in human tenon's fibroblast cells (HTFs). The in vivo behavior in a rabbit glaucoma filtration surgery model indicated that this hydrogel loaded with 0.1 mg/ml MMC led to a better functional bleb with a prolonged mean bleb survival time (25.5±2.9 days). The scar tissue formation, new collagen deposition and myofibroblast generation appeared to be reduced upon histological and immunohistochemistry examinations, with no obvious side effects and inflammatory reactions. The in vitro and in vivo results demonstrated that this novel hydrogel is a safe and effective drug delivery candidate in ocular glaucoma surgery. PMID:24950176

TOPICAL REVIEW: Microsystem technologies for implantable applications

NASA Astrophysics Data System (ADS)

Receveur, Rogier A. M.; Lindemans, Fred W.; de Rooij, Nicolaas F.

2007-05-01

Microsystem technologies (MST) have become the basis of a large industry. The advantages of MST compared to other technologies provide opportunities for application in implantable biomedical devices. This paper presents a general and broad literature review of MST for implantable applications focused on the technical domain. A classification scheme is introduced to order the examples, basic technological building blocks relevant for implantable applications are described and finally a case study on the role of microsystems for one clinical condition is presented. We observe that the microfabricated parts span a wide range for implantable applications in various clinical areas. There are 94 active and 67 commercial 'end items' out of a total of 142. End item refers to the total concept, of which the microsystem may only be a part. From the 105 active end items 18 (13% of total number of end items) are classified as products. From these 18 products, there are only two for chronic use. The number of active end items in clinical, animal and proto phase for chronic use is 17, 13 and 20, respectively. The average year of first publication of chronic end items that are still in the animal or clinical phase is 1994 (n = 7) and 1993 (n = 11), respectively. The major technology market combinations are sensors for cardiovascular, drug delivery for drug delivery and electrodes for neurology and ophthalmology. Together these form 51% of all end items. Pressure sensors form the majority of sensors and there is just one product (considered to be an implantable microsystem) in the neurological area. Micro-machined ceramic packages, glass sealed packages and polymer encapsulations are used. Glass to metal seals are used for feedthroughs. Interconnection techniques such as flip chip, wirebonding or conductive epoxy as used in the semiconductor packaging and assembly industry are also used for manufacturing of implantable devices. Coatings are polymers or metal. As an alternative to

Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution.

PubMed

Chen, Yu; Xiong, Yan; Jiang, Wentao; Yan, Fei; Guo, Meng; Wang, Qingyuan; Fan, Yubo

2015-01-01

The changes of hemodynamics and drug concentration distribution caused by the implantation of drug eluting stents (DESs) in curved vessels have significant effects on In-Stent Restenosis. A 3D virtual stent with 90° curvature was modelled and the distribution of wall shear stress (WSS) and drug concentration in this model were numerically studied at Reynolds numbers of 200, 400, 600, 800. The results showed that (1) the intensity of secondary flow at the 45° cross-section was stronger than that at the 90° cross-section; (2) As the Reynolds number increases, the WSS decreases. When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of the total area. (3) The effects of Reynolds number on drug concentration in the vascular wall decreases in proportionally and then the blood velocity increased 4 times, the drug concentration in the vascular wall decreased by about 30%. (4) The size of the high drug concentration region is inversely proportional to the Reynolds number. As the blood velocity increases, the drug concentration in the DES decreases, especially at the outer bend. It is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of the stent implantation, because a substantial amount of the drug is released in the first two months of stent implantation, thus a calm status is conducive to drug release and absorption; Subsequently, appropriate exercise which increases the blood velocity is helpful in decreasing regions of low-WSS.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

2012-01-01

This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

An implantable blood pressure and flow transmitter.

NASA Technical Reports Server (NTRS)

Rader, R. D.; Meehan, J. P.; Henriksen, J. K. C.

1973-01-01

A miniature totally implantable FM/FM telemetry system has been developed to simultaneously measure blood pressure and blood flow, thus providing an appreciation of the hemodynamics of the circulation to the entire body or to a particular organ. Developed for work with animal subjects, the telemetry system's transmission time is controlled by an RF signal that permits an operating life of several months. Pressure is detected by a miniature intravascular transducer and flow is detected by an extravascular interferometric ultrasonic technique. Both pressure and flow are calibrated prior to implanting. The pressure calibration can be checked after the implanting by cannulation; flow calibration can be verified only at the end of the experiment by determining the voltage output from the implanted sensing system as a function of several measured flow rates. The utility of this device has been established by its use in investigating canine renal circulation during exercise, emotional encounters, administration of drugs, and application of accelerative forces.

In vivo biocompatibility of three potential intraperitoneal implants.

PubMed

Defrère, Sylvie; Mestagdt, Mélanie; Riva, Raphaël; Krier, Fabrice; Van Langendonckt, Anne; Drion, Pierre; Jérôme, Christine; Evrard, Brigitte; Dehoux, Jean-Paul; Foidart, Jean-Michel; Donnez, Jacques

2011-10-10

The intraperitoneal biocompatibility of PDMS, polyHEMA and pEVA was investigated in rats, rabbits and rhesus monkeys. No inflammation was evidenced by hematological analyses and measurement of inflammatory markers throughout the experiment and by post-mortem examination of the pelvic cavity. After 3 or 6 months, histological analysis revealed fibrous tissue encapsulating PDMS and PEVA implants in all species and polyHEMA implants in rabbits and monkeys. Calcium deposits were observed inside polyHEMA implants. The intraperitoneal biocompatibility of all 3 polymers makes them suitable for the design of drug delivery systems, which may be of great interest for pathologies confined to the pelvic cavity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual Antiplatelet Therapy for 6 Versus 18 Months After Biodegradable Polymer Drug-Eluting Stent Implantation.

PubMed

Nakamura, Masato; Iijima, Raisuke; Ako, Junya; Shinke, Toshiro; Okada, Hisayuki; Ito, Yoshiaki; Ando, Kenji; Anzai, Hitoshi; Tanaka, Hiroyuki; Ueda, Yasunori; Takiuchi, Shin; Nishida, Yasunori; Ohira, Hiroshi; Kawaguchi, Katsuhiro; Kadotani, Makoto; Niinuma, Hiroyuki; Omiya, Kazuto; Morita, Takashi; Zen, Kan; Yasaka, Yoshinori; Inoue, Kenji; Ishiwata, Sugao; Ochiai, Masahiko; Hamasaki, Toshimitsu; Yokoi, Hiroyoshi

2017-06-26

The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of -2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227). Copyright © 2017. Published by Elsevier Inc.

A new scoring system (DAIGA) for predicting bleeding complications in atrial fibrillation patients after drug-eluting stent implantation with triple antithrombotic therapy.

PubMed

Kobayashi, Norihiro; Yamawaki, Masahiro; Nakano, Masatsugu; Hirano, Keisuke; Araki, Motoharu; Takimura, Hideyuki; Sakamoto, Yasunari; Mori, Shinsuke; Tsutsumi, Masakazu; Ito, Yoshiaki

2016-11-15

No scoring system for evaluating the bleeding risk of atrial fibrillation (AF) patients after drug-eluting stent (DES) implantation with triple antithrombotic therapy (TAT) is available. We aimed to develop a new scoring system for predicting bleeding complications in AF patients after DES implantation with TAT. Between April 2007 and April 2014, 227 AF patients undergoing DES implantation with TAT were enrolled. Bleeding incidence defined as Bleeding Academic Research Consortium criteria≥2 was investigated and predictors of bleeding complications were evaluated using multivariate analysis. Bleeding complications occurred in 58 patients (25.6%) during follow-up. Multivariate analysis revealed dual antiplatelet therapy (DAPT) continuation (OR 3.33, P=0.01), age>75 (OR 2.14, P=0.037), international normalized ratio>2.2 (OR 5.82, P<0.001), gastrointestinal ulcer history (OR 3.06, P=0.037), and anemia (OR 2.15, P=0.042) as predictors of major bleeding complications. A score was created using the weighted points proportional to the beta regression coefficient of each variable. The DAIGA score showed better predictive ability for bleeding complications than the HAS-BLED score (AUC: 0.79 vs. 0.62, P=0.0003). Bleeding incidence was well stratified: 17.8% in low-risk (scores 0-1), 55.5% in moderate-risk (2-3), and 83.0% in high-risk (4-7) patients (P<0.001). This scoring system is useful for predicting bleeding complications and risk stratification of AF patients after DES implantation with TAT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Localization and Tracking of Implantable Biomedical Sensors

PubMed Central

Umay, Ilknur; Fidan, Barış; Barshan, Billur

2017-01-01

Implantable sensor systems are effective tools for biomedical diagnosis, visualization and treatment of various health conditions, attracting the interest of researchers, as well as healthcare practitioners. These systems efficiently and conveniently provide essential data of the body part being diagnosed, such as gastrointestinal (temperature, pH, pressure) parameter values, blood glucose and pressure levels and electrocardiogram data. Such data are first transmitted from the implantable sensor units to an external receiver node or network and then to a central monitoring and control (computer) unit for analysis, diagnosis and/or treatment. Implantable sensor units are typically in the form of mobile microrobotic capsules or implanted stationary (body-fixed) units. In particular, capsule-based systems have attracted significant research interest recently, with a variety of applications, including endoscopy, microsurgery, drug delivery and biopsy. In such implantable sensor systems, one of the most challenging problems is the accurate localization and tracking of the microrobotic sensor unit (e.g., robotic capsule) inside the human body. This article presents a literature review of the existing localization and tracking techniques for robotic implantable sensor systems with their merits and limitations and possible solutions of the proposed localization methods. The article also provides a brief discussion on the connection and cooperation of such techniques with wearable biomedical sensor systems. PMID:28335384

Fungal Biofilms, Drug Resistance, and Recurrent Infection

PubMed Central

Desai, Jigar V.; Mitchell, Aaron P.; Andes, David R.

2014-01-01

A biofilm is a surface-associated microbial community. Diverse fungi are capable of biofilm growth. The significance of this growth form for infection biology is that biofilm formation on implanted devices is a major cause of recurrent infection. Biofilms also have limited drug susceptibility, making device-associated infection extremely difficult to treat. Biofilm-like growth can occur during many kinds of infection, even when an implanted device is not present. Here we summarize the current understanding of fungal biofilm formation, its genetic control, and the basis for biofilm drug resistance. PMID:25274758

First-in-human testing of a wirelessly controlled drug delivery microchip.

PubMed

Farra, Robert; Sheppard, Norman F; McCabe, Laura; Neer, Robert M; Anderson, James M; Santini, John T; Cima, Michael J; Langer, Robert

2012-02-22

The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1-34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1-34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1-34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1-34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.

A Fully Implanted Drug Delivery System for Peripheral Nerve Blocks in Behaving Animals

PubMed Central

Pohlmeyer, Eric A.; Jordon, Luke R.; Kim, Peter; Miller, Lee E.

2009-01-01

Inhibiting peripheral nerve function can be useful for many studies of the nervous system or motor control. Accomplishing this in a temporary fashion in animal models by using peripheral nerve blocks permits studies of the immediate effects of the loss, and/or any resulting short-term changes and adaptations in behavior or motor control, while avoiding the complications commonly associated with permanent lesions, such as sores or self-mutilation. We have developed a method of quickly and repeatedly inducing temporary, controlled motor deficits in rhesus macaque monkeys via a chronically implanted drug delivery system. This assembly consists of a nerve cuff and a subdermal injection dome, and has proved effective for delivering local anesthetics directly to peripheral nerves for many months. Using this assembly for median and ulnar nerve blocks routinely resulted in over 80% losses in hand and wrist strength for rhesus monkeys. The assembly was also effective for inducing ambulatory motor deficits in rabbits through blocks of the sciatic nerve. Interestingly, while standard anesthetics were sufficient for the rabbit nerve blocks, the inclusion of epinephrine was essential for achieving significant motor blockade in the monkeys. PMID:19524613

Comparison of Sequential Drug Release in Vitro and in Vivo

PubMed Central

Sundararaj, Sharath C.; Al-Sabbagh, Mohanad; Rabek, Cheryl L.; Dziubla, Thomas D.; Thomas, Mark V.; Puleo, David A.

2015-01-01

Development of drug delivery devices typically involves characterizing in vitro release performance with the inherent assumption that this will closely approximate in vivo performance. Yet, as delivery devices become more complex, for instance with a sequential drug release pattern, it is important to confirm that in vivo properties correlate with the expected “programming” achieved in vitro. In this work, a systematic comparison between in vitro and in vivo biomaterial erosion and sequential release was performed for a multilayered association polymer system comprising cellulose acetate phthalate and Pluronic F-127. After assessing the materials during incubation in phosphate-buffered saline, devices were implanted supracalvarially in rats. Devices with two different doses and with different erosion rates were harvested at increasing times post-implantation, and the in vivo thickness loss, mass loss, and the drug release profiles were compared with their in vitro counterparts. The sequential release of four different drugs observed in vitro was successfully translated to in vivo conditions. Results suggest, however, that the total erosion time of the devices was longer and release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Whereas many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, the present research demonstrated that sequential release of four drugs can be maintained following implantation. PMID:26111338

Electromagnetic irradiation may be a new approach to therapy for peri-implantitis.

PubMed

Cao, Zhensheng; Chen, Yijia; Chen, Yuxue; Zhao, Qing; Xu, Xiaomei; Chen, Yangxi

2012-03-01

Peri-implantitis can lead to bone destruction around a dental implant through inflammation and immune reactions caused by bacteria adhering to the surface of the implant abutment. Electromagnetic irradiation can inhibit bacterial growth, increase bone formation, decrease bone resorption and reduce the inflammatory response. Our hypothesis is that electromagnetic irradiation may be a new treatment approach for peri-implantitis and may simultaneously maintain bone mass around the dental implant. The results would be more significant when combined with other agents, because the effect of some antibiotics and anti-inflammatory drugs is strengthened by electromagnetic irradiation. This non-invasive therapy is expected to be conducted in a convenient manner, and even by patients at home, thereby facilitating the prevention and treatment of peri-implantitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Novel drug delivery systems in pain therapy.

PubMed

Al Malyan, M; Becchi, C; Boncinelli, S; Ashammakhi, N

2007-03-01

Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drug delivery systems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drug delivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drug delivery systems in the field of pain medicine and their clinical applications. Future perspectives are also presented.

[Cochlear implant in children: rational, indications and cost/efficacy].

PubMed

Martini, A; Bovo, R; Trevisi, P; Forli, F; Berrettini, S

2013-06-01

A cochlear implant (CI) is a partially implanted electronic device that can help to provide a sense of sound and support speech to severely to profoundly hearing impaired patients. It is constituted by an external portion, that usually sits behind the ear and an internal portion surgically placed under the skin. The external components include a microphone connected to a speech processor that selects and arranges sounds pucked up by the microphone. This is connected to a transmitter coil, worn on the side of the head, which transmits data to an internal receiver coil placed under the skin. The received data are delivered to an array of electrodes that are surgically implanted within the cochlea. The primary neural targets of the electrodes are the spiral ganglion cells which innervate fibers of the auditory nerve. When the electrodes are activated by the signal, they send a current along the auditory nerve and auditory pathways to the auditory cortex. Children and adults who are profoundly or severely hearing impaired can be fitted with cochlear implants. According to the Food and Drug Administration, approximately 188,000 people worldwide have received implants. In Italy it is extimated that there are about 6-7000 implanted patients, with an average of 700 CI surgeries per year. Cochlear implantation, followed by intensive postimplantation speech therapy, can help young children to acquire speech, language, and social skills. Early implantation provides exposure to sounds that can be helpful during the critical period when children learn speech and language skills. In 2000, the Food and Drug Administration lowered the age of eligibility to 12 months for one type of CI. With regard to the results after cochlear implantation in relation to early implantation, better linguistic results are reported in children implanted before 12 months of life, even if no sufficient data exist regarding the relation between this advantage and the duration of implant use and how long

Current Trend of Antimicrobial Prescription for Oral Implant Surgery Among Dentists in India.

PubMed

Datta, Rahul; Grewal, Yasmin; Batth, J S; Singh, Amandeep

2014-12-01

The aim of our study was to evaluate antimicrobial prescription behaviour amongst dentists performing oral implant surgery in India. Dentists performing oral implant surgery from different parts of India were personally approached during various national events such as conferences and academic meetings and information regarding their prescription habits for antimicrobial agents in routine oral implant surgery was collected using a structured questionnaire. Out of a total sample of 332 dentists, 85.5 % prescribed 17 different groups or combinations of antibiotics routinely for oral implant surgery in the normal healthy patient. Majority preferred the peri-operative protocol of drug therapy (72.2 %) with variable and prolonged duration of therapy after surgery, ranging from 3 to 10 days. An antimicrobial mouthwash was routinely prescribed by all the doctors (14.5 %) not in favour of prescribing antimicrobials in a normal healthy patient. Our findings suggest that there is a trend of antimicrobial agent misuse by dentists performing oral implant surgery in India, both in terms of drugs used and the protocols prescribed. The majority of these dentists prescribed a variety of antimicrobial agents for prolonged durations routinely even in the normal, healthy patients.

75 FR 69591 - Medicaid Program; Withdrawal of Determination of Average Manufacturer Price, Multiple Source Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

... issue a proposed regulation addressing the Affordable Care Act provisions. Inhalation, Infusion..., infusion, instilled, implanted and injectable drugs that are not generally dispensed through retail... publish a list of drugs that meet the statutory definition of inhalation, infusion, instilled, implanted...

Highly porous drug-eluting structures

PubMed Central

Elsner, Jonathan J.; Kraitzer, Amir; Grinberg, Orly; Zilberman, Meital

2012-01-01

For many biomedical applications, there is need for porous implant materials. The current article focuses on a method for preparation of drug-eluting porous structures for various biomedical applications, based on freeze drying of inverted emulsions. This fabrication process enables the incorporation of any drug, to obtain an “active implant” that releases drugs to the surrounding tissue in a controlled desired manner. Examples for porous implants based on this technique are antibiotic-eluting mesh/matrix structures used for wound healing applications, antiproliferative drug-eluting composite fibers for stent applications and local cancer treatment, and protein-eluting films for tissue regeneration applications. In the current review we focus on these systems. We show that the release profiles of both types of drugs, water-soluble and water-insoluble, are affected by the emulsion's formulation parameters. The former's release profile is affected mainly through the emulsion stability and the resulting porous microstructure, whereas the latter's release mechanism occurs via water uptake and degradation of the host polymer. Hence, appropriate selection of the formulation parameters enables to obtain desired controllable release profile of any bioactive agent, water-soluble or water-insoluble, and also fit its physical properties to the application. PMID:23507890

[Safety profile of etonogestrel contraceptive implant (Nexplanon® and Implanon®) reported in France].

PubMed

Simon, C; Agier, M S; Béné, J; Muller, C; Vrignaud, L; Marret, H; Jonville-Bera, A P

2016-11-01

The aim of the study was to assess the incidence of adverse effects (AE) reported with etonogestrel contraceptive implant in France (Implanon ® and Nexplanon ® ). All cases of AE or unintended pregnancies reported to health authorities or to the firm were analyzed. During 10 years, 5433 AE and 789 unintended pregnancies were reported. Only 388 (7 %) were serious. There were 1137 reports of difficulties to remove, failure to locate or migration, 430 of insertion difficulties and 203 of deformation or expulsion of the implant. Among other AE, the most common were 1694 gynecological AE, 524 skin reactions and 437 metabolic AE. Since the marketing of Nexplanon ® which causes less deep insertions, the incidence of migrations, removal or insertion difficulties has decreased overall (0.92 vs. 1.31/1000 patients), particularly the incidence of removal difficulties, location failures or migrations (0.12 vs 1.01/1000). The infrequent but serious AE were infectious complications at the implant site and pregnancies. When the circumstances of the pregnancy were known, the contraceptive failure was due to the apparent inefficiency of the implant (n=224), to a technique failure (n=203) or to a drug-drug interaction (n=59). This study confirms that AE of this implant are frequent but not serious, except for the pregnancies. The incidence of complications related to insertion decreased with Nexplanon ® . Among other preventable AE, unintended pregnancies due to a drug-drug interaction would require to be better known by the practitioner. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Biocompatible polymer coating of titania nanotube arrays for improved drug elution and osteoblast adhesion.

PubMed

Gulati, Karan; Ramakrishnan, Saminathan; Aw, Moom Sinn; Atkins, Gerald J; Findlay, David M; Losic, Dusan

2012-01-01

Bacterial infection, extensive inflammation and poor osseointegration have been identified as the major reasons for [early] orthopaedic implant failures based on titanium. Creating implants with drug-eluting properties to locally deliver drugs is an appealing way to address some of these problems. To improve properties of titanium for orthopaedic applications, this study explored the modification of titanium surfaces with titaniananotube (TNT) arrays, and approach that combines drug delivery into bone and potentially improved bone integration. A titania layer with an array of nanotube structures (∼120 nm in diameter and 50 μm in length) was synthesized on titanium surfaces by electrochemical anodization and loaded with the water-insoluble anti-inflammatory drug indomethacin. A simple dip-coating process of polymer modification formed thin biocompatible polymer films over the drug-loaded TNTs to create TNTs with predictable drug release characteristics. Two biodegradable and antibacterial polymers, chitosan and poly(lactic-co-glycolic acid), were tested for their ability to extend the drug release time of TNTs and produce favourable bone cell adhesion properties. Dependent on polymer thickness, a significant improvement in the drug release characteristics was demonstrated, with reduced burst release (from 77% to >20%) and extended overall release from 4 days to more than 30 days. Excellent osteoblast adhesion and cell proliferation on polymer-coated TNTs compared with uncoated TNTs were also observed. These results suggest that polymer-modified implants with a TNT layer are capable of delivering a drug to a bone site over an extended period and with predictable kinetics. In addition, favourable bone cell adhesion suggests that such an implant would have good biocompatibility. The described approach is broadly applicable to a wide range of drugs and implants currently used in orthopaedic practice. Crown Copyright © 2011. Published by Elsevier Ltd. All rights

First In-Human Experience With Complete Integration of Neuromodulation Device Within a Customized Cranial Implant.

PubMed

Gordon, Chad R; Santiago, Gabriel F; Huang, Judy; Bergey, Gregory K; Liu, Shuya; Armand, Mehran; Brem, Henry; Anderson, William S

2017-10-06

Neuromodulation devices have the potential to transform modern day treatments for patients with medicine-resistant neurological disease. For instance, the NeuroPace System (NeuroPace Inc, Mountain View, California) is a Food and Drug Administration (FDA)-approved device developed for closed-loop direct brain neurostimulation in the setting of drug-resistant focal epilepsy. However, current methods require placement either above or below the skull in nonanatomic locations. This type of positioning has several drawbacks including visible deformities and scalp pressure from underneath leading to eventual wound healing difficulties, micromotion of hardware with infection, and extrusion leading to premature explantation. To introduce complete integration of a neuromodulation device within a customized cranial implant for biocompatibility optimization and prevention of visible deformity. We report a patient with drug-resistant focal epilepsy despite previous seizure surgery and maximized medical therapy. Preoperative imaging demonstrated severe resorption of previous bone flap causing deformity and risk for injury. She underwent successful responsive neurostimulation device implantation via complete integration within a clear customized cranial implant. The patient has recovered well without complication and has been followed closely for 180 d. Device interrogation with electrocorticographic data transmission has been successfully performed through the clear implant material for the first time with no evidence of any wireless transmission interference. Cranial contour irregularities, implant site infection, and bone flap resorption/osteomyelitis are adverse events associated with implantable neurotechnology. This method represents a novel strategy to incorporate all future neuromodulation devices within the confines of a low-profile, computer-designed cranial implant and the newfound potential to eliminate contour irregularities, improve outcomes, and optimize patient

In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano-decorated subconjunctival implants.

PubMed

Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Kaffashi, Abbas; Çalamak, Semih; Ulubayram, Kezban; Palaska, Erhan; Çakmak, Hasan Basri; Ünlü, Nurşen

2016-11-01

Biodegradable implants are promising drug delivery systems for sustained release ocular drug delivery with the benefits such as minimum systemic side effects, constant drug concentration at the target site and getting cleared without surgical removal. Dry eye syndrome (DES) is a common disease characterized with the changes in ocular epithelia surface and results in inflammatory reaction that might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is frequently employed for the treatment of DES and it needs to be applied several times a day in tear drops form. The aim of this study was to evaluate in vivo behavior and efficacy of the developed nano-decorated subconjunctival implant systems for sustained release CsA delivery. Biodegradable Poly-ɛ-caprolactone (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co-glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve sustained release. Two of the formulations PCL-PLGA-NP-F and PCL-PCL-NP-I were selected for in vivo evaluation based on their in vitro characteristics determined in our previous study. In this study, formulations were implanted to Swiss Albino mice with induced dry eye syndrome to investigate the ocular distribution of CsA following subconjunctival implantation and to evaluate the efficacy. Tissue distribution study indicated that CsA was present in ocular tissues such as cornea, sclera and lens even 90 days after the application and blood CsA levels were found lower than ocular tissues. Efficacy studies also showed that application of CsA-loaded fiber implant formulation resulted in faster recovery based on their staining scores.

Transdermal Photopolymerization for Minimally Invasive Implantation

NASA Astrophysics Data System (ADS)

Elisseeff, J.; Anseth, K.; Sims, D.; McIntosh, W.; Randolph, M.; Langer, R.

1999-03-01

Photopolymerizations are widely used in medicine to create polymer networks for use in applications such as bone restorations and coatings for artificial implants. These photopolymerizations occur by directly exposing materials to light in "open" environments such as the oral cavity or during invasive procedures such as surgery. We hypothesized that light, which penetrates tissue including skin, could cause a photopolymerization indirectly. Liquid materials then could be injected s.c. and solidified by exposing the exterior surface of the skin to light. To test this hypothesis, the penetration of UVA and visible light through skin was studied. Modeling predicted the feasibility of transdermal polymerization with only 2 min of light exposure required to photopolymerize an implant underneath human skin. To establish the validity of these modeling studies, transdermal photopolymerization first was applied to tissue engineering by using "injectable" cartilage as a model system. Polymer/chondrocyte constructs were injected s.c. and transdermally photopolymerized. Implants harvested at 2, 4, and 7 weeks demonstrated collagen and proteoglycan production and histology with tissue structure comparable to native neocartilage. To further examine this phenomenon and test the applicability of transdermal photopolymerization for drug release devices, albumin, a model protein, was released for 1 week from photopolymerized hydrogels. With further study, transdermal photpolymerization potentially could be used to create a variety of new, minimally invasive surgical procedures in applications ranging from plastic and orthopedic surgery to tissue engineering and drug delivery.

Biofilm on dental implants: a review of the literature.

PubMed

Subramani, Karthikeyan; Jung, Ronald E; Molenberg, Aart; Hammerle, Christoph H F

2009-01-01

The aim of this article was to review the current literature with regard to biofilm formation on dental implants and the influence of surface characteristics (chemistry, surface free energy, and roughness) of dental implant and abutment materials and their design features on biofilm formation and its sequelae. An electronic MEDLINE literature search was conducted of studies published between 1966 and June 2007. The following search terms were used: biofilm and dental implants, biofilm formation/plaque bacterial adhesion and implants, plaque/biofilm and surface characteristics/roughness/surface free energy of titanium dental implants, implant-abutment interface and plaque/biofilm, biofilm and supragingival/subgingival plaque microbiology, biofilm/plaque and implant infection, antibacterial/bacteriostatic titanium, titanium nanocoating/nanopatterning, antimicrobial drug/titanium implant. Both in vitro and in vivo studies were included in this review. Fifty-three articles were identified in this review process. The articles were categorized with respect to their context on biofilm formation on teeth and dental implant surfaces and with regard to the influence of surface characteristics of implant biomaterials (especially titanium) and design features of implant and abutment components on biofilm formation. The current state of literature is more descriptive, rather than providing strong data that could be analyzed through meta-analysis. Basic research articles on surface modification of titanium were also included in the review to analyze the applications of such studies on the fabrication of implant surfaces that could possibly decrease early bacterial colonization and biofilm formation. Increase in surface roughness and surface free energy facilitates biofilm formation on dental implant and abutment surfaces, although this conclusion is derived from largely descriptive literature. Surface chemistry and the design features of the implant-abutment configuration also

Short Implants: New Horizon in Implant Dentistry.

PubMed

Jain, Neha; Gulati, Manisha; Garg, Meenu; Pathak, Chetan

2016-09-01

The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration.

Designing multifunctional polymers for cardiovascular implants.

PubMed

Wischke, Christian; Lendlein, Andreas

2011-01-01

Polymer-based biomaterials are extensively used in all disciplines of clinical medicine and innovations in biomaterial science are building a product pipeline, e.g., of future cardiovascular implants. Still, cardiovascular applications demand a number of extensive requirements of properties and functions to be fulfilled by the polymer matrix. This report provides an overview on some of these issues and how they can be addressed by a tailored design of novel polymer-based biomaterials. Multifunctional shape-memory polymers are highlighted as a class of materials that combine biocompatibility and the capability for stimuli-induced active movements for anchoring of implants with a controlled degradation and drug release profile to enable a functional regeneration of the tissue at the application site.

Recent advances in ophthalmic drug delivery

PubMed Central

Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

2011-01-01

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

Impact of Dental Implant Surface Modifications on Osseointegration

PubMed Central

Smeets, Ralf; Stadlinger, Bernd; Schwarz, Frank; Beck-Broichsitter, Benedicta; Jung, Ole; Precht, Clarissa; Kloss, Frank; Gröbe, Alexander; Heiland, Max

2016-01-01

Objective. The aim of this paper is to review different surface modifications of dental implants and their effect on osseointegration. Common marketed as well as experimental surface modifications are discussed. Discussion. The major challenge for contemporary dental implantologists is to provide oral rehabilitation to patients with healthy bone conditions asking for rapid loading protocols or to patients with quantitatively or qualitatively compromised bone. These charging conditions require advances in implant surface design. The elucidation of bone healing physiology has driven investigators to engineer implant surfaces that closely mimic natural bone characteristics. This paper provides a comprehensive overview of surface modifications that beneficially alter the topography, hydrophilicity, and outer coating of dental implants in order to enhance osseointegration in healthy as well as in compromised bone. In the first part, this paper discusses dental implants that have been successfully used for a number of years focusing on sandblasting, acid-etching, and hydrophilic surface textures. Hereafter, new techniques like Discrete Crystalline Deposition, laser ablation, and surface coatings with proteins, drugs, or growth factors are presented. Conclusion. Major advancements have been made in developing novel surfaces of dental implants. These innovations set the stage for rehabilitating patients with high success and predictable survival rates even in challenging conditions. PMID:27478833

Hollow fiber: a biophotonic implant for live cells

NASA Astrophysics Data System (ADS)

Silvestre, Oscar F.; Holton, Mark D.; Summers, Huw D.; Smith, Paul J.; Errington, Rachel J.

2009-02-01

The technical objective of this study has been to design, build and validate biocompatible hollow fiber implants based on fluorescence with integrated biophotonics components to enable in fiber kinetic cell based assays. A human osteosarcoma in vitro cell model fiber system has been established with validation studies to determine in fiber cell growth, cell cycle analysis and organization in normal and drug treated conditions. The rationale for implant development have focused on developing benchmark concepts in standard monolayer tissue culture followed by the development of in vitro hollow fiber designs; encompassing imaging with and without integrated biophotonics. Furthermore the effect of introducing targetable biosensors into the encapsulated tumor implant such as quantum dots for informing new detection readouts and possible implant designs have been evaluated. A preliminary micro/macro imaging approach has been undertaken, that could provide a mean to track distinct morphological changes in cells growing in a 3D matrix within the fiber which affect the light scattering properties of the implant. Parallel engineering studies have showed the influence of the optical properties of the fiber polymer wall in all imaging modes. Taken all together, we show the basic foundation and the opportunities for multi-modal imaging within an in vitro implant format.

Influence of Palatal Coverage and Implant Distribution on Implant Strain in Maxillary Implant Overdentures.

PubMed

Takahashi, Toshihito; Gonda, Tomoya; Mizuno, Yoko; Fujinami, Yozo; Maeda, Yoshinobu

2016-01-01

Maxillary implant overdentures are often used in clinical practice. However, there is no agreement or established guidelines regarding prosthetic design or optimal implant placement configuration. The purpose of this study was to examine the influence of palatal coverage and implant number and distribution in relation to impact strain under maxillary implant overdentures. A maxillary edentulous model with implants and experimental overdentures with and without palatal coverage was fabricated. Four strain gauges were attached to each implant, and they were positioned in the anterior, premolar, and molar areas. A vertical occlusal load of 98 N was applied through a mandibular complete denture, and the implant strains were compared using one-way analysis of variance (P = .05). The palatolabial strain was much higher on anterior implants than on other implants in both denture types. Although there was no significant difference between the strain under dentures with and without palatal coverage, palateless dentures tended to result in higher implant strain than dentures with palatal coverage. Dentures supported by only two implants registered higher strain than those supported by four or six implants. Implants under palateless dentures registered higher strain than those under dentures with palatal coverage. Anterior implants exhibited higher palatolabial strain than other implants regardless of palatal coverage and implant configuration; it is therefore recommended that maxillary implant overdentures should be supported by six implants with support extending to the distal end of the arch.

MAPLE deposition of PLGA:PEG films for controlled drug delivery: Influence of PEG molecular weight

NASA Astrophysics Data System (ADS)

Paun, Irina Alexandra; Moldovan, Antoniu; Luculescu, Catalin Romeo; Staicu, Angela; Dinescu, Maria

2012-09-01

Implantable devices consisting of indomethacin (INC) cores coated with poly(lactide-co-glycolide):polyethylene glycol films (i.e. PLGA:PEG films) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) were produced. To predict their behavior after implantation inside the body, the implants were studied in vitro, in media similar with those encountered inside the body (phosphate buffered saline (PBS) pH 7.4 and blood). The influence of the molecular weight of PEG (i.e. low (1450 Da) versus high (10 kDa) molecular weights) on the characteristics of the implants was investigated, in terms of morphology, blood compatibility and kinetics of the drug release. The use of PEG of high molecular weight resulted in larger pores on the implants surfaces, enhanced blood compatibility of the implants and higher drug delivery rates. For both molecular weights PEGs, sustained release of INC was maintained over a three weeks interval. Theoretical fitting of the drug release data with Higuchi's model indicated that the INC was released mainly by diffusion, most probably through the pores formed in PLGA:PEG films during PBS immersion.

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

Antibiotic prophylaxis patterns of Finnish dentists performing dental implant surgery.

PubMed

Pyysalo, Mikko; Helminen, Mika; Antalainen, Anna-Kaisa; Sándor, George K; Wolff, Jan

2014-11-01

The peri-operative use of prophylactic antibiotics in clinically healthy patients undergoing dental implant surgery is very common in Finland. While antibiotics are prescribed with the hope of preventing both local and systemic complications, their application and utilization is not uniform. The aim of this study was to assess the variation in prescribing patterns among Finnish dentists performing dental implant placement operations. This study also aimed to examine the possible relationship between early implant removal and the use of the prophylactic antibiotics in Finland. The National Institute for Health and Welfare in Finland granted permission to access the Finnish Dental Implant Register. The peri-operative antibiotic prophylaxis prescribing patterns were assessed in a total of 110 543 dental implant placement procedures and 1038 dental implant removal operations performed in Finland between April 1994 and April 2012. A total of 61 different antibiotics or combinations were prescribed peri-operatively during implant placements in Finland between 1994-2012. Phenoxymethylpenicillin was the most commonly prescribed drug (72.2%). No statistically significant difference in early implant removal rates could be found between patients who had or had not received peri-operative prophylaxis. However, patients who had received peri-operative prophylaxis had statistically significant longer implant survival rates. There is a variation in antibiotic prescribing patterns among Finnish dentists placing dental implants. The results suggest that the use of prophylactic antibiotics has little effect on the prevention of primary implant surgery-related complications and, hence, success rates.

Short Implants: New Horizon in Implant Dentistry

PubMed Central

Gulati, Manisha; Garg, Meenu; Pathak, Chetan

2016-01-01

The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration. PMID:27790598

Pattern of Antibiotic Prescription for Oral Implant Treatment Among Dentists in Saudi Arabia.

PubMed

El-Kholey, Khalid E; Wali, Othman; Elkomy, Aamna; Almozayen, Ahmed

2018-06-01

To investigate antibiotic prophylaxis prescription behavior among dentists practicing dental implant surgery in Saudi Arabia. An observational questionnaire study was conducted in the period between October 2016 and December 2016. A link to an online previously validated questionnaire was sent to a convenience sample of dentists practicing dental implant placement in the different areas of Saudi Arabia. Absolute frequencies were used to describe the data. One hundred nine completed questionnaires were received. A total of 59.63% (n = 65) of the respondents routinely prescribed prophylactic antibiotics when performing implant surgery. There was a wide variation in the preoperative and postoperative prescription regimens with the majority (67%) starting the antibiotic immediately postoperatively for 3 to 5 days, with no preoperative antibiotic use. Amoxicillin and clavulanic acid combination was the drug of choice for 50.3% of the respondents, whereas 26.6% prescribed amoxicillin as the drug of choice. Although a small study with a low response rate, a wide variation in antibiotic prescribing patterns with respect to the drugs chosen, timing, and duration was found in implant surgery in Saudi Arabia. Dentists should be aware of the risk of antibiotic overuse and start to share in the efforts that aim to reserve the antibiotics to combat life-threatening infections and to reduce development of bacterial resistance to the available antibiotics.

A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye.

PubMed

Irani, Yazad D; Tian, Yuan; Wang, Mengjia; Klebe, Sonja; McInnes, Steven J; Voelcker, Nicolas H; Coffer, Jeffery L; Williams, Keryn A

2015-10-01

Dysfunction of corneal epithelial stem cells can result in painful and blinding disease of the ocular surface. In such cases, treatment may involve transfer of growth factor and normal adult stem cells to the ocular surface. Our purpose was to develop an implantable scaffold for the delivery of drugs and cells to the ocular surface. We examined the potential of novel composite biomaterials fabricated from electrospun polycaprolactone (PCL) fibres into which nanostructured porous silicon (pSi) microparticles of varying sizes (150-250 μm or <40 μm) had been pressed. The PCL fabric provided a flexible support for mammalian cells, whereas the embedded pSi provided a substantial surface area for efficient delivery of adsorbed drugs and growth factors. Measurements of tensile strength of these composites revealed that the pSi did not strongly influence the mechanical properties of the polymer microfiber component for the Si loadings evaluated. Human lens epithelial cells (SRA01/04) attached to the composite materials, and exhibited enhanced attachment and growth when the materials were coated with foetal bovine serum. To examine the ability of the materials to deliver a small-drug payload, pSi microparticles were loaded with fluorescein diacetate prior to cell attachment. After 6 hours (h), cells exhibited intracellular fluorescence, indicative of transfer of the fluorescein diacetate into viable cells and its subsequent enzymatic conversion to fluorescein. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower

Rapid implantation of dissolving microneedles on an electrospun pillar array.

PubMed

Yang, Huisuk; Kim, Soyoung; Huh, Inyoung; Kim, Suyong; Lahiji, Shayan F; Kim, Miroo; Jung, Hyungil

2015-09-01

Dissolving microneedles (DMNs), designed to release drugs and dissolve after skin insertion, have been spotlighted as a novel transdermal delivery system due to their advantages such as minimal pain and tissue damage, ability to self-administer, and no associated hazardous residues. The drug delivery efficacy of DMNs, however, is limited by incomplete insertion and the extended period required for DMN dissolution. Here, we introduce a novel DMN delivery system, DMN on an electrospun pillar array (DEPA), which can rapidly implant DMNs into skin. DMNs were fabricated on a pillar array covered by a fibrous sheet produced by electrospinning PLGA solution (14%, w/v). DMNs were implanted into the skin by manual application (press and vibration for 10 s) by tearing of the fibers hung on the 300-μm pillars. Separation of DMNs from the fibrous sheet was dependent on both pillar height and the properties of the fibrous sheet. After evaluation of the implantation and dissolution of DMNs with diffusion of red dye by taking cross-sectional images of porcine skin, the hypoglycemic effect of insulin loaded DEPA was examined using a healthy mouse model. This DMN array overcomes critical issues associated with the low penetration efficiency of flat patch-based DMNs, and will allow realization of patient convenience with the desired drug efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Implant healing in experimental animal models of diabetes.

PubMed

Le, Nga N; Rose, Michael B; Levinson, Howard; Klitzman, Bruce

2011-05-01

Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally, there is an increasing number of patients receiving implantable devices such as glucose sensors and orthopedic implants. Thus, it is likely that the number of diabetic patients receiving these devices will also increase. Even though implantable medical devices are considered biocompatible by the Food and Drug Administration, the adverse tissue healing that occurs adjacent to these foreign objects is a leading cause of their failure. This foreign body response leads to fibrosis, encapsulation of the device, and a reduction or cessation of device performance. A second adverse event is microbial infection of implanted devices, which can lead to persistent local and systemic infections and also exacerbates the fibrotic response. Nearly half of all nosocomial infections are associated with the presence of an indwelling medical device. Events associated with both the foreign body response and implant infection can necessitate device removal and may lead to amputation, which is associated with significant morbidity and cost. Diabetes mellitus is generally indicated as a risk factor for the infection of a variety of implants such as prosthetic joints, pacemakers, implantable cardioverter defibrillators, penile implants, and urinary catheters. Implant infection rates in diabetic patients vary depending upon the implant and the microorganism, however, for example, diabetes was found to be a significant variable associated with a nearly 7.2% infection rate for implantable cardioverter defibrillators by the microorganism Candida albicans. While research has elucidated many of the altered mechanisms of diabetic cutaneous wound healing, the internal healing adjacent to indwelling medical devices in a diabetic model has rarely been studied. Understanding this healing process is crucial to facilitating improved device design. The purpose of this article is to summarize the physiologic factors that

Implant Healing in Experimental Animal Models of Diabetes

PubMed Central

Le, Nga N; Rose, Michael B; Levinson, Howard; Klitzman, Bruce

2011-01-01

Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally, there is an increasing number of patients receiving implantable devices such as glucose sensors and orthopedic implants. Thus, it is likely that the number of diabetic patients receiving these devices will also increase. Even though implantable medical devices are considered biocompatible by the Food and Drug Administration, the adverse tissue healing that occurs adjacent to these foreign objects is a leading cause of their failure. This foreign body response leads to fibrosis, encapsulation of the device, and a reduction or cessation of device performance. A second adverse event is microbial infection of implanted devices, which can lead to persistent local and systemic infections and also exacerbates the fibrotic response. Nearly half of all nosocomial infections are associated with the presence of an indwelling medical device. Events associated with both the foreign body response and implant infection can necessitate device removal and may lead to amputation, which is associated with significant morbidity and cost. Diabetes mellitus is generally indicated as a risk factor for the infection of a variety of implants such as prosthetic joints, pacemakers, implantable cardioverter defibrillators, penile implants, and urinary catheters. Implant infection rates in diabetic patients vary depending upon the implant and the microorganism, however, for example, diabetes was found to be a significant variable associated with a nearly 7.2% infection rate for implantable cardioverter defibrillators by the microorganism Candida albicans. While research has elucidated many of the altered mechanisms of diabetic cutaneous wound healing, the internal healing adjacent to indwelling medical devices in a diabetic model has rarely been studied. Understanding this healing process is crucial to facilitating improved device design. The purpose of this article is to summarize the physiologic factors that

[Fabrication of a new composite scaffold material for delivering rifampicin and its sustained drug release in rats].

PubMed

Ma, Xue-Ming; Lin, Zhen; Zhang, Jia-Wei; Sang, Chao-Hui; Qu, Dong-Bin; Jiang, Jian-Ming

2016-03-01

To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

MRI information for commonly used otologic implants: review and update.

PubMed

Azadarmaki, Roya; Tubbs, Rhonda; Chen, Douglas A; Shellock, Frank G

2014-04-01

To review information on magnetic resonance imaging (MRI) issues for commonly used otologic implants. Manufacturing companies, National Library of Medicine's online database, and an additional online database (www.MRIsafety.com). A literature review of the National Library of Medicine's online database with focus on MRI issues for otologic implants was performed. The MRI information on implants provided by manufacturers was reviewed. Baha and Ponto Pro osseointegrated implants' abutment and fixture and the implanted magnet of the Sophono Alpha 1 and 2 abutment-free systems are approved for 3-Tesla magnetic resonance (MR) systems. The external processors of these devices are MR Unsafe. Of the implants tested, middle ear ossicular prostheses, including stapes prostheses, except for the 1987 McGee prosthesis, are MR Conditional for 1.5-Tesla (and many are approved for 3-Tesla) MR systems. Cochlear implants with removable magnets are approved for patients undergoing MRI at 1.5 Tesla after magnet removal. The MED-EL PULSAR, SONATA, CONCERT, and CONCERT PIN cochlear implants can be used in patients undergoing MRI at 1.5 Tesla with application of a protective bandage. The MED-EL COMBI 40+ can be used in 0.2-Tesla MR systems. Implants made from nonmagnetic and nonconducting materials are MR Safe. Knowledge of MRI guidelines for commonly used otologic implants is important. Guidelines on MRI issues approved by the US Food and Drug Administration are not always the same compared with other parts of the world. This monograph provides a current reference for physicians on MRI issues for commonly used otologic implants.

Peri-implantitis.

PubMed

Schwarz, Frank; Derks, Jan; Monje, Alberto; Wang, Hom-Lay

2018-06-01

This narrative review provides an evidence-based overview on peri-implantitis for the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. A literature review was conducted addressing the following topics: 1) definition of peri-implantitis; 2) conversion from peri-implant mucositis to peri-implantitis, 3) onset and pattern of disease progression, 4) characteristics of peri-implantitis, 5) risk factors/indicators for peri-implantitis, and 6) progressive crestal bone loss in the absence of soft tissue inflammation. 1)Peri-implantitis is a pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant connective tissue and progressive loss of supporting bone. 2)The histopathologic and clinical conditions leading to the conversion from peri-implant mucositis to peri-implantitis are not completely understood. 3)The onset of peri-implantitis may occur early during follow-up and the disease progresses in a non-linear and accelerating pattern. 4a)Peri-implantitis sites exhibit clinical signs of inflammation and increased probing depths compared to baseline measurements. 4b)At the histologic level, compared to periodontitis sites, peri-implantitis sites often have larger inflammatory lesions. 4c)Surgical entry at peri-implantitis sites often reveals a circumferential pattern of bone loss. 5a)There is strong evidence that there is an increased risk of developing peri-implantitis in patients who have a history of chronic periodontitis, poor plaque control skills, and no regular maintenance care after implant therapy. Data identifying "smoking" and "diabetes" as potential risk factors/indicators for peri-implantitis are inconclusive. 5b)There is some limited evidence linking peri-implantitis to other factors such as: post-restorative presence of submucosal cement, lack of peri-implant keratinized mucosa and positioning of implants that make it difficult to perform oral hygiene

Action against contraceptive implant threatened.

PubMed

Dyer, C

1995-08-19

Norplant provides contraception over a five-year period through the gradual subcutaneous release of the progestogen levonorgestrel. It has been on the US market since 1991 and available in Great Britain since 1993. Already the subject of group legal actions in several US states, Norplant may soon be the target of lawyers in Britain for litigation. The lawyers allege that insertion of the implant under the skin of the upper arm by untrained doctors has led to painful and difficult removals and left women with scarred arms. Moreover, insufficient warning has been given about possible side effects such as mood swings and continuous vaginal bleeding. Hoechst Roussel, marketer of the implant in Britain, however, argues that only doctors trained in Norplant insertion and removal should attempt either procedure. Removal will be problematic only if preceded by a problem insertion. Hoechst Roussel recently advised gynecologists, in writing, not to attempt to extract the implant unless they are trained in the removal technique. By British law, the application of a drug product once approved for general release to general practitioners and family planning doctors cannot be restricted by a pharmaceutical company.

Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses.

PubMed

Morris, Aaron H; Mahal, Rajwant S; Udell, Jillian; Wu, Michelle; Kyriakides, Themis R

2017-10-01

Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor-κB (NF-κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor-β (TGF-β)-induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose-dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemotherapy drug extravasation in totally implantable venous access port systems: how effective is early surgical lavage?

PubMed

Azaïs, Henri; Bresson, Lucie; Bassil, Alfred; Katdare, Ninad; Merlot, Benjamin; Houpeau, Jean-Louis; El Bedoui, Sophie; Meurant, Jean-Pierre; Tresch, Emmanuelle; Narducci, Fabrice

2015-01-01

Totally implantable venous access port systems (TIVAPS) are a widely used and an essential tool in the efficient delivery of chemotherapy. Chemotherapy drug extravasation (CDE) can have dire consequences and will delay treatment. The purpose of this study is to both clarify the management of CDE and show the effectiveness of early surgical lavage (ESL). Patients who had presented to the Cancer Center of Lille (France) with TIVAPS inserted between January 2004 and April 2013 and CDE had their medical records reviewed retrospectively. Thirty patients and 33 events were analyzed. Implicated agents were vesicants (51.5%), irritants (45.5%) and non-vesicants (3%). Huber needle malpositionning was involved in 27 cases. Surgery was performed in 97% of cases, 87.5% of which were for ESL with 53.1% of the latter requiring TIVAPS extraction. Six patients required a second intervention due to adverse outcomes (severe cases). Vesicants were found to be implicated in four out of six severe cases and oxaliplatin in two others. Extravasated volume was above 50 ml in 80% of cases. Only one patient required a skin graft. CDEs should be managed in specialized centers. ESL allows for limited tissue contact of the chemotherapy drug whilst using a simple, widely accessible technique. The two main factors that correlate with adverse outcome seem to be the nature of the implicated agent (vesicants) and the extravasated volume (above 50 ml) leading to worse outcomes. Oxaliplatin should be considered as a vesicant.

[Biodegradable synthetic implant materials : clinical applications and immunological aspects].

PubMed

Witte, F; Calliess, T; Windhagen, H

2008-02-01

In the last decade biodegradable synthetic implant materials have been established for various clinical applications. Ceramic materials such as calcium phosphate, bioglass and polymers are now routinely used as degradable implants in the clinical practice. Additionally these materials are now also used as coating materials or as microspheres for controlled drug release and belong to a series of examples for applications as scaffolds for tissue engineering. Because immense local concentrations of degradation products are produced during biodegradation, this review deals with the question whether allergic immune reactions, which have been reported for classical metallic and organic implant materials, also play a role in the clinical routine for synthetic biodegradable materials. Furthermore, possible explanatory theories will be developed to clarify the lack of clinical reports on allergy or sensitization to biodegradable synthetic materials.

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications.

PubMed

Angrisani, Nina; Foth, Franziska; Kietzmann, Manfred; Schumacher, Stephan; Angrisani, Gian Luigi; Christel, Anne; Behrens, Peter; Reifenrath, Janin

2013-10-10

In orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity. The magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets. A martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency

Five-year follow-up data from the U.S. clinical trial for Sientra's U.S. Food and Drug Administration-approved Silimed® brand round and shaped implants with high-strength silicone gel.

PubMed

Stevens, W Grant; Harrington, Jennifer; Alizadeh, Kaveh; Berger, Lewis; Broadway, David; Hester, T Roderick; Kress, Donald; dʼIncelli, Rosalyn; Kuhne, JoAnn; Beckstrand, Maggi

2012-11-01

In March of 2012, the U.S. Food and Drug Administration approved Sientra's application for premarket approval for its Silimed brand silicone gel implants, based on data from the largest silicone gel breast implant study to date. This was the first approval for shaped silicone gel breast implants. This article presents the results of Sientra's study through 5 years. Sientra's study is an ongoing, 10-year, open-label, prospective, multicenter clinical study designed to assess the safety and effectiveness of Sientra's implants in patients undergoing augmentation and reconstruction. A total of 1788 subjects were implanted with 3506 implants, including 1116 primary augmentation, 363 revision-augmentation, 225 primary reconstruction, and 84 revision-reconstruction subjects. Physical evaluations and complications were recorded at each visit. Effectiveness was measured by postimplantation bra cup size and assessment of subject satisfaction and quality of life. Of the 1788 subjects, 571 underwent magnetic resonance imaging to assess silent rupture. Safety endpoints were analyzed using the Kaplan-Meier method. Across all cohorts, the risk of rupture was 1.8 percent (95 percent CI, 1.2 to 2.6 percent), the risk of capsular contracture (Baker grade III/IV) was 9.0 percent (95 percent CI, 7.6 to 10.6 percent), and the risk of reoperation was 23.8 percent (95 percent CI, 21.8 to 26.0 percent). Over 99 percent of surgeons reported satisfaction with the postoperative results, and subject satisfaction remained high 5 years after implantation. The 5-year results of Sientra's study continue to provide a comprehensive safety and effectiveness profile of Sientra's portfolio of Silimed brand shaped and round implants. Therapeutic, IV.

Previous coronary stent implantation and cardiac events in patients undergoing noncardiac surgery.

PubMed

Cruden, Nicholas L M; Harding, Scott A; Flapan, Andrew D; Graham, Cat; Wild, Sarah H; Slack, Rachel; Pell, Jill P; Newby, David E

2010-06-01

Noncardiac surgery performed after coronary stent implantation is associated with an increased risk of stent thrombosis, myocardial infarction, and death. The influence of stent type and period of risk still have to be defined. We linked the Scottish Coronary Revascularisation Register with hospital admission data to undertake a Scotland-wide retrospective cohort study examining cardiac outcomes in all patients who received drug-eluting or bare-metal stents between April 2003 and March 2007 and subsequently underwent noncardiac surgery. Of 1953 patients, 570 (29%) were treated with at least 1 drug-eluting stent and 1383 (71%) with bare-metal stents only. There were no differences between drug-eluting and bare-metal stents in the primary end point of in-hospital mortality or ischemic cardiac events (14.6% versus 13.3%; P=0.3) or the secondary end points of in-hospital mortality (0.7% versus 0.6%; P=0.8) and acute myocardial infarction (1.2% versus 0.7%; P=0.3). Perioperative death and ischemic cardiac events occurred more frequently when surgery was performed within 42 days of stent implantation (42.4% versus 12.8% beyond 42 days; P<0.001), especially in patients revascularized after an acute coronary syndrome (65% versus 32%; P=0.037). There were no temporal differences in outcomes between the drug-eluting and bare-metal stent groups. Patients undergoing noncardiac surgery after recent coronary stent implantation are at increased risk of perioperative myocardial ischemia, myocardial infarction, and death, particularly after an acute coronary syndrome. For at least 2 years after percutaneous coronary intervention, cardiac outcomes after noncardiac surgery are similar for both drug-eluting and bare-metal stents.

Biomechanical behavior of 2-implant-and single-implant-retained mandibular overdentures with conventional or mini implants.

PubMed

Pisani, Marina Xavier; Presotto, Anna Gabriella Camacho; Mesquita, Marcelo Ferraz; Barão, Valentim Adelino Ricardo; Kemmoku, Daniel Takanori; Del Bel Cury, Altair Antoninha

2018-04-24

The use of single or mini dental implants to retain mandibular overdentures is still questionable. The purpose of this finite element analysis (FEA) study was to investigate the biomechanical behavior of 2- and single-implant-retained mandibular overdentures with conventional or mini implants. Four 3-dimensional (3D) finite element models were constructed with the following designs of mandibular overdentures: 2 (group 2-C) and single (group 1-C) conventional external hexagon implants with ball or O-ring attachment and 2 (group 2-M) and single (group 1-M) 1-piece mini implants. A 150-N axial load was applied bilaterally and simultaneously on the first molar. Overdenture displacement, von Mises equivalent stress (implants and/or prosthetic components), and maximum principal stresses (peri-implant bone) were recorded numerically and then color-coded and compared among the groups. The overdenture displacement (in mm) was higher for the 1-M (0.16) and 2-M (0.17) groups when compared with 1-C (0.09) and 2-C (0.08). Irrespective of the type of implant, the single-implant groups presented higher values of stress (in MPa) on the implants than did the 2-implant groups (1-C=52.53; 1-M=2.95; 2-C=34.66; 2-M=2.37), ball attachment (1-C=201.33; 2-C=159.06), housing or O-ring (1-C=125.01; 1-M=1.96; 2-C=88.84; 2-M=1.27), and peri-implant cortical bone (1-C=19.37; 1-M=1.47; 2-C=15.70; 2-M=1.06). The mini implant overdentures presented lower stress values on the implants, housing or O-ring, and peri-implant bone than did the conventional implant overdentures, regardless of the number of implants. The 2-implant-retained overdentures exhibited lower stresses than the single- implant-retained overdentures, irrespective of the type of implant. The mini implants demonstrated higher overdenture displacement and lower stresses than did conventional implant overdentures for single- and 2-implant-retained overdentures. Copyright © 2018 Editorial Council for the Journal of Prosthetic

Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases.

PubMed

Bisht, Rohit; Mandal, Abhirup; Jaiswal, Jagdish K; Rupenthal, Ilva D

2018-03-01

Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals

Sustained Zero-Order Release of Intact Ultra-Stable Drug-Loaded Liposomes from an Implantable Nanochannel Delivery System

PubMed Central

Celia, Christian; Ferrati, Silvia; Bansal, Shyam; van de Ven, Anne L.; Ruozi, Barbara; Zabre, Erika; Hosali, Sharath; Paolino, Donatella; Sarpietro, Maria Grazia; Fine, Daniel; Fresta, Massimo; Ferrari, Mauro

2014-01-01

Metronomic chemotherapy supports the idea that long-term, sustained, constant administration of chemotherapeutics, currently not achievable, could be effective against numerous cancers. Particularly appealing are liposomal formulations, used to solubilize hydrophobic therapeutics and minimize side effects, while extending drug circulation time and enabling passive targeting. As liposome alone cannot survive in circulation beyond 48 hrs, sustaining their constant plasma level for many days is a challenge. To address this, we developed, as a proof of concept, an implantable nanochannel delivery system and ultra-stable PEGylated lapatinib loaded-liposomes, and we demonstrate the release of intact vesicles for over 18 days. Further, we investigate intravasation kinetics of subcutaneously delivered liposomes and verify their biological activity post nanochannel release on BT474 breast cancer cells. The key innovation of this work is the combination of two nanotechnologies to exploit the synergistic effect of liposomes, demonstrated as passive-targeting vectors and nanofluidics to maintain therapeutic constant plasma levels. In principle, this approach could maximize efficacy of metronomic treatments. PMID:23881575

Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices.

PubMed

Genina, Natalja; Holländer, Jenny; Jukarainen, Harri; Mäkilä, Ermei; Salonen, Jarno; Sandler, Niklas

2016-07-30

The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcutaneous rods (SR). The goal was to select an EVA grade with optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug in this study. Out of the twelve tested grades of the EVA five were printable. One of them showed superior print quality and was further investigated by printing drug-loaded filaments, containing 5% and 15% indomethacin. The feedstock filaments were fabricated by hot-melt extrusion (HME) below the melting point of the drug substance and the IUS and SR were successfully printed at the temperature above the melting point of the drug. As a result, the drug substance in the printed prototypes showed to be at least partly amorphous, while the drug in the corresponding HME filaments was crystalline. This difference affected the drug release profiles from the filaments and printed prototype products: faster release from the prototypes over 30days in the in vitro tests. To conclude, this study indicates that certain grades of EVA were applicable feedstock material for 3D printing to produce drug-loaded implantable prototypes. Copyright © 2015 Elsevier B.V. All rights reserved.

Painting blood vessels and atherosclerotic plaques with an adhesive drug depot

PubMed Central

Kastrup, Christian J.; Nahrendorf, Matthias; Figueiredo, Jose Luiz; Lee, Haeshin; Kambhampati, Swetha; Lee, Timothy; Cho, Seung-Woo; Gorbatov, Rostic; Iwamoto, Yoshiko; Dang, Tram T.; Dutta, Partha; Yeon, Ju Hun; Cheng, Hao; Pritchard, Christopher D.; Vegas, Arturo J.; Siegel, Cory D.; MacDougall, Samantha; Okonkwo, Michael; Thai, Anh; Stone, James R.; Coury, Arthur J.; Weissleder, Ralph; Langer, Robert; Anderson, Daniel G.

2012-01-01

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques. PMID:23236189

Multicomponent Implant Releasing Dexamethasone

NASA Astrophysics Data System (ADS)

Nikkola, L.; Vapalahti, K.; Ashammakhi, N.

2008-02-01

Several inflammatory conditions are usually treated with corticosteroids. There are various problems like side effects with traditional applications of steroids, e.g. topical, or systemic routes. Local drug delivery systems have been studied and developed to gain more efficient administration with fewer side effects. Earlier, we reported on developing Dexamethasone (DX) releasing biodegradable fibers. However, their drug release properties were not satisfactory in terms of onset of drug release. Thus, we assessed the development of multicomponent (MC) implant to enhance earlier drug release from such biodegradable fibers. Poly (lactide-co-glycolide) (PLGA) and 2 wt-% and 8 wt-% DX were compounded and extruded with twin-screw extruder to form of fibers. Some of the fibers were sterilized to obtain a change in drug release properties. Four different fiber classes were studied: 2 wt-%, 8 wt-%, sterilized 2 wt-%, and sterilized 8 wt-%. 3×4 different DX-releasing fibers were then heat-pressed to form one multicomponent rod. Half of the rods where sterilized. Drug release was measured from initial fibers and multicomponent rods using a UV/VIS spectrometer. Shear strength and changes in viscosity were also measured. Drug release studies showed that drug release commenced earlier from multicomponent rods than from component fibers. Drug release from multicomponent rods lasted from day 30 to day 70. The release period of sterilized rods extended from day 23 to day 57. When compared to the original component fibers, the drug release from MC rods commenced earlier. The initial shear strength of MC rods was 135 MPa and decreased to 105 MPa during four weeks of immersion in phosphate buffer solution. Accordingly, heat pressing has a positive effect on drug release. After four weeks in hydrolysis, no disintegration was observed.

Towards soft robotic devices for site-specific drug delivery.

PubMed

Alici, Gursel

2015-01-01

Considerable research efforts have recently been dedicated to the establishment of various drug delivery systems (DDS) that are mechanical/physical, chemical and biological/molecular DDS. In this paper, we report on the recent advances in site-specific drug delivery (site-specific, controlled, targeted or smart drug delivery are terms used interchangeably in the literature, to mean to transport a drug or a therapeutic agent to a desired location within the body and release it as desired with negligibly small toxicity and side effect compared to classical drug administration means such as peroral, parenteral, transmucosal, topical and inhalation) based on mechanical/physical systems consisting of implantable and robotic drug delivery systems. While we specifically focus on the robotic or autonomous DDS, which can be reprogrammable and provide multiple doses of a drug at a required time and rate, we briefly cover the implanted DDS, which are well-developed relative to the robotic DDS, to highlight the design and performance requirements, and investigate issues associated with the robotic DDS. Critical research issues associated with both DDSs are presented to describe the research challenges ahead of us in order to establish soft robotic devices for clinical and biomedical applications.

Potential applications of biphosphonates in dental surgical implants.

PubMed

Berardi, D; Carlesi, T; Rossi, F; Calderini, M; Volpi, R; Perfetti, G

2007-01-01

Biphosphonates are largely used for their unquestionable properties of inhibiting bone resorption by osteoclasts in the treatment of various osteometabolic illnesses such as osteoporosis, multiple myeloma, tumors which metastasize to the bone and malignant hypercalcemia. In this literature review the physico-chemical properties, biologic activities and the mechanisms of action of biphosphonates are described. The use of these drugs is discussed, analyzing the quantity of results which have emerged through in vitro and in vivo experiments on animal models. In this study the efficiency of these drugs is demonstrated in contrasting the osteolitic processes of the alveolar bone, in promoting the neoformation and in bettering the quality of bone implants. However, it is important to draw attention to a worrying correlation which has emerged during the last 3-4 years, between osteonecrosis of the jaw (ONJ) and the systemic administration of aminobiphosphonates. This collateral effect did not emerge following the use of non-aminobiphosphonates. The aim of this review is to identify the guidelines for the use of biphosphonates in oral implant surgery.

Magnetic Beads Enhance Adhesion of NIH 3T3 Fibroblasts: A Proof-of-Principle In Vitro Study for Implant-Mediated Long-Term Drug Delivery to the Inner Ear

PubMed Central

Aliuos, Pooyan; Schulze, Jennifer; Schomaker, Markus; Reuter, Günter; Stolle, Stefan R. O.; Werner, Darja; Ripken, Tammo; Lenarz, Thomas; Warnecke, Athanasia

2016-01-01

Introduction Long-term drug delivery to the inner ear may be achieved by functionalizing cochlear implant (CI) electrodes with cells providing neuroprotective factors. However, effective strategies in order to coat implant surfaces with cells need to be developed. Our vision is to make benefit of electromagnetic field attracting forces generated by CI electrodes to bind BDNF-secreting cells that are labelled with magnetic beads (MB) onto the electrode surfaces. Thus, the effect of MB-labelling on cell viability and BDNF production were investigated. Materials and Methods Murine NIH 3T3 fibroblasts—genetically modified to produce BDNF—were labelled with MB. Results Atomic force and bright field microscopy illustrated the internalization of MB by fibroblasts after 24 h of cultivation. Labelling cells with MB did not expose cytotoxic effects on fibroblasts and allowed adhesion on magnetic surfaces with sufficient BDNF release. Discussion Our data demonstrate a novel approach for mediating enhanced long-term adhesion of BDNF-secreting fibroblasts on model electrode surfaces for cell-based drug delivery applications in vitro and in vivo. This therapeutic strategy, once transferred to cells suitable for clinical application, may allow the biological modifications of CI surfaces with cells releasing neurotrophic or other factors of interest. PMID:26918945

Short dental implants: an emerging concept in implant treatment.

PubMed

Al-Hashedi, Ashwaq Ali; Taiyeb Ali, Tara Bai; Yunus, Norsiah

2014-06-01

Short implants have been advocated as a treatment option in many clinical situations where the use of conventional implants is limited. This review outlines the effectiveness and clinical outcomes of using short implants as a valid treatment option in the rehabilitation of edentulous atrophic alveolar ridges. Initially, an electronic search was performed on the following databases: Medline, PubMed, Embase, Cochrane Database of Systematic Reviews, and DARE using key words from January 1990 until May 2012. An additional hand search was included for the relevant articles in the following journals: International Journal of Oral and Maxillofacial Implants, Clinical Oral Implants Research, Journal of Clinical Periodontology, International Journal of Periodontics, Journal of Periodontology, and Clinical Implant Dentistry and Related Research. Any relevant papers from the journals' references were hand searched. Articles were included if they provided detailed data on implant length, reported survival rates, mentioned measures for implant failure, were in the English language, involved human subjects, and researched implants inserted in healed atrophic ridges with a follow-up period of at least 1 year after implant-prosthesis loading. Short implants demonstrated a high rate of success in the replacement of missing teeth in especially atrophic alveolar ridges. The advanced technology and improvement of the implant surfaces have encouraged the success of short implants to a comparable level to that of standard implants. However, further randomized controlled clinical trials and prospective studies with longer follow-up periods are needed.

A preliminary randomized clinical trial comparing diode laser and scalpel periosteal incision during implant surgery: impact on postoperative morbidity and implant survival.

PubMed

Shahnaz, Aysan; Jamali, Raika; Mohammadi, Farnush; Khorsand, Afshin; Moslemi, Neda; Fekrazad, Reza

2018-01-01

The aim of this preliminary randomized clinical trial was to compare: (1) post-operative morbidity after application of laser or scalpel incision for flap advancement during implant surgery and bone grafting and (2) implant survival rate following flap advancement with laser or scalpel incision after 6 months of loading. Eighteen patients who were scheduled for dental implant placement and simultaneous bone grafting were randomly assigned to test or control groups. Diode laser (810 nm, 2 W, pulse interval 200 μs; pulse length 100 μs, 400-μm initiated fiber tip), or scalpel (control) was used to sever the periosteum to create a tension-free flap. Visual analogue scale (VAS) pain score, rate of nonsteroid anti-inflammatory drug (NSAID) consumption, intensity of swelling, and ecchymosis were measured for the six postsurgical days. Six months after loading, implant survival was assessed. VAS pain score (during the first four postoperative days), rate of NSAID consumption (during the first three postoperative days), and intensity of swelling (during the first five postoperative days) were significantly lower in the test group compared to the control group (All P values < 0.05). One patient in the control group experienced ecchymosis. All implants were successful in function. Application of laser for performing periosteal releasing incision reduced the incidence and severity of postoperative morbidity of the patients undergone implant surgery in conjunction with bone augmentation procedure. We did not find any detrimental effect of laser incision on the implant survival within 6 months of loading.

Biohybrid cochlear implants in human neurosensory restoration.

PubMed

Roemer, Ariane; Köhl, Ulrike; Majdani, Omid; Klöß, Stephan; Falk, Christine; Haumann, Sabine; Lenarz, Thomas; Kral, Andrej; Warnecke, Athanasia

2016-10-07

The success of cochlear implantation may be further improved by minimizing implantation trauma. The physical trauma of implantation and subsequent immunological sequelae can affect residual hearing and the viability of the spiral ganglion. An ideal electrode should therefore decrease post-implantation trauma and provide support to the residual spiral ganglion population. Combining a flexible electrode with cells producing and releasing protective factors could present a potential means to achieve this. Mononuclear cells obtained from bone marrow (BM-MNC) consist of mesenchymal and hematopoietic progenitor cells. They possess the innate capacity to induce repair of traumatized tissue and to modulate immunological reactions. Human bone marrow was obtained from the patients that received treatment with biohybrid electrodes. Autologous mononuclear cells were isolated from bone marrow (BM-MNC) by centrifugation using the Regenlab™ THT-centrifugation tubes. Isolated BM-MNC were characterised using flow cytometry. In addition, the release of cytokines was analysed and their biological effect tested on spiral ganglion neurons isolated from neonatal rats. Fibrin adhesive (Tisseal™) was used for the coating of silicone-based cochlear implant electrode arrays for human use in order to generate biohybrid electrodes. Toxicity of the fibrin adhesive and influence on insertion, as well on the cell coating, was investigated. Furthermore, biohybrid electrodes were implanted in three patients. Human BM-MNC release cytokines, chemokines, and growth factors that exert anti-inflammatory and neuroprotective effects. Using fibrin adhesive as a carrier for BM-MNC, a simple and effective cell coating procedure for cochlear implant electrodes was developed that can be utilised on-site in the operating room for the generation of biohybrid electrodes for intracochlear cell-based drug delivery. A safety study demonstrated the feasibility of autologous progenitor cell transplantation in

Number of implants for mandibular implant overdentures: a systematic review

PubMed Central

Lee, Jeong-Yol; Kim, Ha-Young; Bryant, S. Ross

2012-01-01

PURPOSE The aim of this systematic review is to address treatment outcomes of Mandibular implant overdentures relative to implant survival rate, maintenance and complications, and patient satisfaction. MATERIALS AND METHODS A systematic literature search was conducted by a PubMed search strategy and hand-searching of relevant journals from included studies. Randomized Clinical Trials (RCT) and comparative clinical trial studies on mandibular implant overdentures until August, 2010 were selected. Eleven studies from 1098 studies were finally selected and data were analyzed relative to number of implants. RESULTS Six studies presented the data of the implant survival rate which ranged from 95% to 100% for 2 and 4 implant group and from 81.8% to 96.1% for 1 and 2 implant group. One study, which statistically compared implant survival rate showed no significant differences relative to the number of implants. The most common type of prosthetic maintenance and complications were replacement or reattaching of loose clips for 2 and 4 implant group, and denture repair due to the fracture around an implant for 1 and 2 implant groups. Most studies showed no significant differences in the rate of prosthetic maintenance and complication, and patient satisfaction regardless the number of implants. CONCLUSION The implant survival rate of mandibular overdentures is high regardless of the number of implants. Denture maintenance is likely not inflenced substantially by the number of implants and patient satisfaction is typically high again regardless os the number of implants. PMID:23236572

Naltrexone implants compared to methadone: outcomes six months after prison release.

PubMed

Lobmaier, Philipp P; Kunøe, Nikolaj; Gossop, Michael; Katevoll, Tormod; Waal, Helge

2010-01-01

After prison release, offenders with heroin use problems are at high risk of relapse and overdose death. There is a particular need for treatments that can be initiated in prison and continued after release into the community. Methadone maintenance treatment has been shown to reduce heroin use, criminality and mortality. Naltrexone implant treatment has not previously been evaluated in prison settings. This study compares the effects of naltrexone implants and methadone treatment on heroin and other illicit drug use, and criminality among heroin-dependent inmates after release from prison. Forty-six volunteers were randomly allocated to naltrexone implants or methadone before release. Intention-to-treat analyses showed reductions in both groups in frequency of use of heroin and benzodiazepines, as well as criminality, 6 months after prison release. Naltrexone implants may be a valuable treatment option in prison settings. 2010 S. Karger AG, Basel.

Cochlear Implants.

ERIC Educational Resources Information Center

Clark, Catherine; Scott, Larry

This brochure explains what a cochlear implant is, lists the types of individuals with deafness who may be helped by a cochlear implant, describes the process of evaluating people for cochlear implants, discusses the surgical process for implanting the aid, traces the path of sound through the cochlear implant to the brain, notes the costs of…

Rupture of poly implant prothèse silicone breast implants: an implant retrieval study.

PubMed

Swarts, Eric; Kop, Alan M; Nilasaroya, Anastasia; Keogh, Catherine V; Cooper, Timothy

2013-04-01

Poly Implant Prothèse implants were recalled in Australia in April of 2010 following concerns of higher than expected rupture rates and the use of unauthorized industrial grade silicone as a filler material. Although subsequent investigations found that the gel filler material does not pose a threat to human health, the important question of what caused a relatively modern breast implant to have such a poor outcome compared with contemporary silicone breast implants is yet to be addressed. From a cohort of 27 patients, 19 ruptured Poly Implant Prothèse breast implants were subjected to a range of mechanical tests and microscopic/macroscopic investigations to evaluate possible changes in properties as a result of implantation. New Poly Implant Prothèse implants were used as controls. All samples, explanted and controls, complied with the requirements for shell integrity as specified in the International Organization for Standardization 14607. Compression testing revealed rupture rates similar to those reported in the literature. Shell thickness was highly variable, with most shells having regions below the minimum thickness of 0.57 mm that was specified by the manufacturer. Potential regions of stress concentration were observed on the smooth inner surfaces and outer textured surfaces. The high incidence of Poly Implant Prothèse shell rupture is most likely a result of inadequate quality control, with contributory factors being shell thickness variation and manufacturing defects on both inner and outer surfaces of the shell. No evidence of shell degradation with implantation time was determined.

Electromagnetic compatibility of implantable neurostimulators to RFID emitters.

PubMed

Pantchenko, Oxana S; Seidman, Seth J; Guag, Joshua W; Witters, Donald M; Sponberg, Curt L

2011-06-09

The objective of this study is to investigate electromagnetic compatibility (EMC) of implantable neurostimulators with the emissions from radio frequency identification (RFID) emitters. Six active implantable neurostimulators with lead systems were tested for susceptibility to electromagnetic fields generated by 22 RFID emitters. These medical devices have been approved for marketing in the U.S. for a number of intended uses that include: epilepsy, depression, incontinence, Parkinsonian tremor and pain relief. Each RFID emitter had one of the following carrier frequencies: 125 kHz, 134 kHz, 13.56 MHz, 433 MHz, 915 MHz and 2.45 GHz. The test results showed the output of one of the implantable neurostimulators was inhibited by 134 kHz RFID emitter at separation distances of 10 cm or less. The output of the same implantable neurostimulator was also inhibited by another 134 kHz RFID emitter at separation distances of 10 cm or less and also showed inconsistent pulsing rate at a separation distance of 15 cm. Both effects occurred during and lasted through out the duration of the exposure. The clinical significance of the effects was assessed by a clinician at the U.S. Food and Drug Administration. The effects were determined to be clinically significant only if they occurred for extended period of time. There were no observed effects from the other 5 implantable neurostimulators or during exposures from other RFID emitters.

Long-term efficacy of biomodeled polymethyl methacrylate implants for orbitofacial defects.

PubMed

Groth, Michael J; Bhatnagar, Aparna; Clearihue, William J; Goldberg, Robert A; Douglas, Raymond S

2006-01-01

To report the long-term efficacy of custom polymethyl methacrylate implants using high-resolution computed tomographic modeling in the reconstruction of complex orbitofacial defects secondary to trauma. Nine patients with complex orbitofacial bone defects after trauma were evaluated for this retrospective, nonrandomized, noncomparative study. All the patients underwent reconstruction using custom, heat-cured polymethyl methacrylate implants. Patients were followed up postoperatively and evaluated for complications. Nine consecutive patients (5 men and 4 women) aged 28 to 63 years who underwent surgical reconstruction using prefabricated, heat-cured polymethyl methacrylate implants were included in the study. The interval between injury and presentation ranged from 1 month to 40 years. There were no significant complications, including infection, extrusion, or displacement of the implant. In all of the patients, wound healing was uneventful, with antibiotic drugs administered perioperatively. Mean follow-up was 4.3 years from the first visit (range, 6 months to 10 years). Computed tomographic biomodeled, prefabricated, heat-cured polymethyl methacrylate implants are well tolerated in the long term. Their advantages include customized design, long-term biocompatibility, and excellent aesthetic results.

Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: 5 years follow-up from the randomized DEDICATION trial (Drug Elution and Distal Protection in Acute Myocardial Infarction).

PubMed

Holmvang, Lene; Kelbæk, Henning; Kaltoft, Anne; Thuesen, Leif; Lassen, Jens Flensted; Clemmensen, Peter; Kløvgaard, Lene; Engstrøm, Thomas; Bøtker, Hans E; Saunamäki, Kari; Krusell, Lars R; Jørgensen, Erik; Tilsted, Hans-Henrik; Christiansen, Evald H; Ravkilde, Jan; Køber, Lars; Kofoed, Klaus Fuglsang; Terkelsen, Christian J; Helqvist, Steffen

2013-06-01

This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) trial evaluated the outcome after DES compared with BMS implantation in patients with STEMI undergoing primary percutaneous coronary intervention. Patients with a high-grade stenosis/occlusion of a native coronary artery presenting with symptoms <12 h and ST-segment elevation were enrolled after giving informed consent. Patients were randomly assigned to receive a DES or a BMS in the infarct-related lesion. Patients were followed for at least 5 years, and clinical endpoints were evaluated from population registries and hospital charts. The main endpoint was the occurrence of the first major adverse cardiac event (MACE), defined as cardiac death, nonfatal recurrent myocardial infarction, and target lesion revascularization. Complete clinical status was available in 623 patients (99.5%) at 5 years follow-up. The combined MACE rate was insignificantly lower in the DES group (16.9% vs. 23%), mainly driven by a lower need of repeat revascularization (p = 0.07). Whereas the number of deaths from all causes tended to be higher in the DES group (16.3% vs. 12.1%, p = 0.17), cardiac mortality was significantly higher (7.7% vs. 3.2%, p = 0.02). The 5-year stent thrombosis rates were generally low and similar between the DES and the BMS groups. No cardiac deaths occurring within 1 month could be clearly ascribed to stent thrombosis, whereas stent thrombosis was involved in 78% of later-occurring deaths. The 5-year MACE rate was insignificantly different, but the cardiac mortality was higher after DES versus BMS implantation in patients with STEMI. Stent thrombosis was the main cause of late cardiac deaths. Copyright © 2013 American

Primary prevention of peri-implantitis: managing peri-implant mucositis.

PubMed

Jepsen, Søren; Berglundh, Tord; Genco, Robert; Aass, Anne Merete; Demirel, Korkud; Derks, Jan; Figuero, Elena; Giovannoli, Jean Louis; Goldstein, Moshe; Lambert, France; Ortiz-Vigon, Alberto; Polyzois, Ioannis; Salvi, Giovanni E; Schwarz, Frank; Serino, Giovanni; Tomasi, Cristiano; Zitzmann, Nicola U

2015-04-01

Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant

PubMed Central

Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine®, which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed. PMID:28546740

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant.

PubMed

Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine ® , which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed.

A classification of growth friendly spine implants.

PubMed

Skaggs, David L; Akbarnia, Behrooz A; Flynn, John M; Myung, Karen S; Sponseller, Paul D; Vitale, Michael G

2014-01-01

Various types of spinal implants have been used with the objective of minimizing spinal deformities while maximizing the spine and thoracic growth in a growing child with a spinal deformity. The aim of this study was to describe a classification system of growth friendly spinal implants to allow researchers and clinicians to have a common language and facilitate comparative studies. Growth friendly spinal implant systems fall into 3 categories based upon the forces of correction the implants exert on the spine, which are as follows: Distraction-based systems correct spinal deformities by mechanically applying a distractive force across a deformed segment with anchors at the top and bottom of the implants, which commonly attach to the spine, rib, and/or the pelvis. The present examples of distraction-based implants are spine-based or rib-based growing rods, vertical expandable titanium rib prosthesis, and remotely expandable devices. Compression-based systems correct spinal deformities with a compressive force applied to the convexity of the curve causing convex growth inhibition. This compressive force may be generated both mechanically at the time of implantation, as well as over time resulting from longitudinal growth of vertebral endplates hindered by the spinal implants. Examples of compression-based systems are vertebral staples and tethers. Guided growth systems correct spinal deformity by anchoring multiple vertebrae (usually including the apical vertebrae) to rods with mechanical forces including translation at the time of the initial implant. The majority of the anchors are not rigidly attached to the rods, thus permitting longitudinal growth over time as the anchors slide over the rods. Examples of guided growth systems include the Luque trolley and Shilla. Each system has its benefits and shortcomings. Knowledge of the fundamental principles upon which these systems are based may aid the clinician to choose an appropriate treatment for patients. Having a

Safety of six-month dual antiplatelet therapy after second-generation drug-eluting stent implantation: OPTIMA-C Randomised Clinical Trial and OCT Substudy.

PubMed

Lee, Byoung-Kwon; Kim, Jung-Sun; Lee, Oh-Huyn; Min, Pil-Ki; Yoon, Young-Won; Hong, Bum-Kee; Shin, Dong-Ho; Kang, Tae-Soo; Kim, Byung Ok; Cho, Duk-Kyu; Jeon, Dong Woon; Woo, Sung-Ill; Choi, Seonghoon; Kim, Yong Hoon; Kang, Woong-Chol; Kim, Seunghwan; Kim, Byeong-Keuk; Hong, Myeong-Ki; Jang, Yangsoo; Kwon, Hyuck Moon

2018-03-20

There are few randomised studies concerning the optimal duration of dual antiplatelet therapy (DAPT) for patients who receive a second-generation drug-eluting stent (DES). This trial aimed to investigate the safety of six-month compared with 12-month DAPT maintenance after second-generation DES implantation. A prospective, randomised, multicentre trial was performed at 10 medical centres. The 1,368 patients included in the study received a biolimus-eluting stent (BES) or a zotarolimus-eluting stent (ZES). The primary outcome measured was the composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), or ischaemia-driven target lesion revascularisation at the 12-month follow-up. The secondary outcome was the percentage of uncovered struts at six months in 60 patients (30 ZES, 30 BES) using optical coherence tomography (OCT) assessment. Each patient was randomly assigned to six-month (n=684) or 12-month DAPT (n=684). Major adverse cardiac events at 12 months occurred in eight patients (1.2%) in the six-month DAPT group and in four patients (0.6%) in the 12-month DAPT group (risk difference 0.6%; 95% confidence interval [CI]: -0.4-1.6%; p=0.24). The upper 95% CI limit was lower than the pre-specified limit of 4% non-inferiority (p for non-inferiority <0.05). The percentage of uncovered struts was 3.16±4.30% at six months in 60 stents of 60 patients. After second-generation DES implantation, six-month DAPT was not inferior to 12-month DAPT in terms of MACE occurrence over the 12-month follow-up period. OCT examination revealed favourable stent strut coverage at six months after stent implantation.

Drug Delivery to the Inner Ear

PubMed Central

Wise, Andrew K; Gillespie, Lisa N

2012-01-01

Bionic devices electrically activate neural populations to partially restore lost function. Of fundamental importance is the functional integrity of the targeted neurons. However, in many conditions the ongoing pathology can lead to continued neural degeneration and death that may compromise the effectiveness of the device and limit future strategies to improve performance. The use of drugs that can prevent nerve cell degeneration and promote their regeneration may improve clinical outcomes. In this paper we focus on strategies of delivering neuroprotective drugs to the auditory system in a way that is safe and clinically relevant for use in combination with a cochlear implant. The aim of this approach is to prevent neural degeneration and promote nerve regrowth in order to improve outcomes for cochlear implant recipients using techniques that can be translated to the clinic. PMID:23186937

Short Implants Versus Standard Implants: Midterm Outcomes of a Clinical Study.

PubMed

Benlidayi, M Emre; Ucar, Yurdanur; Tatli, Ufuk; Ekren, Orhun; Evlice, Burcu; Kisa, Halil Ibrahim; Baksi, Uygar

2018-02-01

The aim of this study was to evaluate the midterm survival rate, marginal bone resorption (MBR), and stability of short implants and to compare the results with standard length implants. A total of 38 patients were included. In total, 147 implants (Nucleoss Implants, Izmir, Turkey) were placed (86 short implants and 61 standard implants). Cement-retained metal-ceramic prostheses were fabricated. MBR was evaluated on periapical radiographs taken at implant placement, at the time of crown insertion and annually thereafter. The stability of the implants was evaluated by resonance frequency analysis. The 3- and 5-year cumulative survival rates for standard implants was 98.4% and for short implants was 96.5% (P = 0.644). The MBR of the short implants was significantly lower than that of the standard implants after 1, 2, and 3 years of loading (P < 0.05). No significant differences were found between 2 groups after 6 and 12 months of loading in terms of implant stability (implant stability quotient values) (P > 0.05). Within the limits of this study, it is concluded that short implants achieved similar results as standard implants after 3 to 5 years of loading.

Implantation of Vascular Grafts Lined with Genetically Modified Endothelial Cells

NASA Astrophysics Data System (ADS)

Wilson, James M.; Birinyi, Louis K.; Salomon, Robert N.; Libby, Peter; Callow, Allan D.; Mulligan, Richard C.

1989-06-01

The possibility of using the vascular endothelial cell as a target for gene replacement therapy was explored. Recombinant retroviruses were used to transduce the lacZ gene into endothelial cells harvested from mongrel dogs. Prosthetic vascular grafts seeded with the genetically modified cells were implanted as carotid interposition grafts into the dogs from which the original cells were harvested. Analysis of the graft 5 weeks after implantation revealed genetically modified endothelial cells lining the luminal surface of the graft. This technology could be used in the treatment of atherosclerosis disease and the design of new drug delivery systems.

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

PubMed Central

2013-01-01

Background In orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity. Results The magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets. Conclusion A martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant

Advancements in ocular drug delivery.

PubMed

Weiner, Alan L; Gilger, Brian C

2010-11-01

This review covers both noninvasive and invasive ophthalmic drug delivery systems that can have application to therapy of veterinary ophthalmic diseases. Noninvasive approaches include gel technologies, permeation enhancement via pro-drug development, solubilization agents and nanoparticle technologies, iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and microdroplets. More invasive systems include both eroding implants and noneroding technologies that encompass diffusion based systems, active pumps, intraocular lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to addressing the physiologic challenges of achieving the necessary duration of delivery, tissue targeting and patient compliance, the commercial development factors of biocompatibility, sterilization, manufacturability and long-term stability will be discussed. © 2010 American College of Veterinary Ophthalmologists.

Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats.

PubMed

Halliday, Amy J; Campbell, Toni E; Nelson, Timothy S; McLean, Karen J; Wallace, Gordon G; Cook, Mark J

2013-01-01

Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site. Copyright © 2012 Elsevier Ltd. All rights reserved.

Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction.

PubMed

Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

2016-04-01

Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI.From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses.The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina.Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy and drug

Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction

PubMed Central

Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

2016-01-01

Abstract Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI. From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses. The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina. Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy

Gastroenterology-urology devices; reclassification of implanted blood access devices. Final rule.

PubMed

2014-07-25

The Food and Drug Administration (FDA) is issuing a final order to reclassify implanted blood access devices, a preamendments class III device, into class II (special controls) based on new information and subject to premarket notification and to further clarify the identification.

A review of acoustic power transfer for bio-medical implants

NASA Astrophysics Data System (ADS)

Basaeri, Hamid; Christensen, David B.; Roundy, Shad

2016-12-01

Bio-implantable devices have been used to perform therapeutic functions such as drug delivery or diagnostic monitoring of physiological parameters. Proper operation of these devices depends on the continuous reliable supply of power. A battery, which is the conventional method to supply energy, is problematic in many of these devices as it limits the lifetime of the implant or dominates the size. In order to power implantable devices, power transfer techniques have been implemented as an attractive alternative to batteries and have received significant research interest in recent years. Acoustic waves are increasingly being investigated as a method for delivering power through human skin and the human body. Acoustic power transfer (APT) has some advantages over other powering techniques such as inductive power transfer and mid range RF power transmission. These advantages include lower absorption in tissue, shorter wavelength enabling smaller transducers, and higher power intensity threshold for safe operation. This paper will cover the basic physics and modeling of APT and will review the current state of acoustic (or ultrasonic) power transfer for biomedical implants. As the sensing and computational elements for biomedical implants are becoming very small, we devote particular attention to the scaling of acoustic and alternative power transfer techniques. Finally, we present current issues and challenges related to the implementation of this technique for powering implantable devices.

Why are mini-implants lost: the value of the implantation technique!

PubMed

Romano, Fabio Lourenço; Consolaro, Alberto

2015-01-01

The use of mini-implants have made a major contribution to orthodontic treatment. Demand has aroused scientific curiosity about implant placement procedures and techniques. However, the reasons for instability have not yet been made totally clear. The aim of this article is to establish a relationship between implant placement technique and mini-implant success rates by means of examining the following hypotheses: 1) Sites of poor alveolar bone and little space between roots lead to inadequate implant placement; 2) Different sites require mini-implants of different sizes! Implant size should respect alveolar bone diameter; 3) Properly determining mini-implant placement site provides ease for implant placement and contributes to stability; 4) The more precise the lancing procedures, the better the implant placement technique; 5) Self-drilling does not mean higher pressures; 6) Knowing where implant placement should end decreases the risk of complications and mini-implant loss.

Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings

PubMed Central

Shen, Jie; Burgess, Diane J.

2011-01-01

Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under “real-time” and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to “real-time” conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict “real-time” release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under “real-time” and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. PMID:22016033

Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings.

PubMed

Shen, Jie; Burgess, Diane J

2012-01-17

Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under "real-time" and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to "real-time" conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict "real-time" release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under "real-time" and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Antibacterial effect of royal jelly for preservation of implant-related spinal infection in rat.

PubMed

Gunaldi, Omur; Daglioglu, Yusuf Kenan; Tugcu, Bekir; Kizilyildirim, Suna; Postalci, Lutfi; Ofluoglu, Ender; Koksal, Fatih

2014-01-01

Implant-related infections are still a significant problem in spinal surgical procedures. Many drugs and methods have been tried to prevent implant-related infections. Our objective in this study was to evaluate whether royal jelly, which was found to hinder the growth of MRSA, has any preventive role in the prognosis of an infection in rats in an implant-related infection model. Rats were divided into 3 groups of eight rats. Group-1 consisted of rats that underwent only a spinal implant, group-2 included those rats that were inoculated bacteria together with a spinal implant and group-3 was administered royal jelly in addition to a spinal implant and infection. The amount of bacteria that grew in vertebral columns and implants was more in Group-2 than in Group-3, which meant that the number of bacteria colonies that grew was more quantitatively. This difference was found to be statistically significant in vertebral columns, but not in implants. Royal jelly could not fully prevent the MRSA infection in this model, but decreased the severity of infection noticeably. More objective and promising results may be obtained if royal jelly can be used at regular intervals in a different model to be designed with respect to implant-related infections.

In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments.

PubMed

Kasinathan, Narayanan; Amirthalingam, Muthukumar; Reddy, Neetinkumar D; Jagani, Hitesh V; Volety, Subrahmanyam M; Rao, Josyula Venkata

2016-01-01

Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes. To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN). In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer. The effect of independent variables was studied in two stages. First, the effect of drug-polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500 nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release. This implant could be further evaluated for pharmacological activities.

Hydroxyapatite ocular implant and non-integrated implants in eviscerated patients

PubMed Central

Gradinaru, S; Popescu, V; Leasu, C; Pricopie, S; Yasin, S; Ciuluvica, R; Ungureanu, E

2015-01-01

Introduction: This study compares the outcomes and complications of hydroxyapatite ocular implant and non-integrated ocular implants following evisceration. Materials and Methods: This is a retrospective study of 90 patients who underwent evisceration for different ocular affections, in the Ophthalmology Department of the University Emergency Hospital Bucharest, between January 2009 and December 2013. The outcomes measured were conjunctival dehiscence, socket infection, implant exposure and extrusion rate. Results: Forty-three patients had the hydroxyapatite implant (coralline–Integrated Ocular Implants, USA or synthetic–FCI, France) and forty-seven received non-integrated ocular implants (24 acrylic and 23 silicone). Five cases of socket infection, thirteen cases of extrusion and two cases of conjunctival dehiscence were encountered. Conclusions: There was a higher rate of conjunctival dehiscence with hydroxyapatite ocular implant, but implant extrusion and socket infection were found in non-integrated ocular implants. PMID:25914747

Immediate direct-to-implant breast reconstruction using anatomical implants.

PubMed

Kim, Sung-Eun; Jung, Dong-Woo; Chung, Kyu-Jin; Lee, Jun Ho; Kim, Tae Gon; Kim, Yong-Ha; Lee, Soo Jung; Kang, Su Hwan; Choi, Jung Eun

2014-09-01

In 2012, a new anatomic breast implant of form-stable silicone gel was introduced onto the Korean market. The intended use of this implant is in the area of aesthetic breast surgery, and many reports are promising. Thus far, however, there have been no reports on the use of this implant for breast reconstruction in Korea. We used this breast implant in breast reconstruction surgery and report our early experience. From November 2012 to April 2013, the Natrelle Style 410 form-stable anatomically shaped cohesive silicone gel-filled breast implant was used in 31 breasts of 30 patients for implant breast reconstruction with an acellular dermal matrix. Patients were treated with skin-sparing mastectomies followed by immediate breast reconstruction. The mean breast resection volume was 240 mL (range, 83-540 mL). The mean size of the breast implants was 217 mL (range, 125-395 mL). Breast shape outcomes were considered acceptable. Infection and skin thinning occurred in one patient each, and hematoma and seroma did not occur. Three cases of wound dehiscence occurred, one requiring surgical intervention, while the others healed with conservative treatment in one month. Rippling did not occur. So far, complications such as capsular contracture and malrotation of breast implant have not yet arisen. By using anatomic breast implants in breast reconstruction, we achieved satisfactory results with aesthetics better than those obtained with round breast implants. Therefore, we concluded that the anatomical implant is suitable for breast reconstruction.

Electrodeposited silk coatings for functionalized implant applications

NASA Astrophysics Data System (ADS)

Elia, Roberto

The mechanical and morphological properties of titanium as well as its biocompatibility and osteoinductive characteristics have made it the material of choice for dental implant systems. Although the success rate of titanium implants exceeds 90% in healthy individuals, a large subset of the population has one or more risk factors that inhibit implant integration. Treatments and coatings have been developed to improve clinical outcomes via introduction of appropriate surface topography, texture and roughness or incorporation of bioactive molecules. It is essential that the coatings and associated deposition techniques are controllable and reproducible. Currently, methods of depositing functional coatings are dictated by numerous parameters (temperature, particle size distribution, pH and voltage), which result in variable coating thickness, strength, porosity and weight, and hinder or preclude biomolecule incorporation. Silk is a highly versatile protein with a unique combination of mechanical and physical properties, including tunable degradation, biocompatibility, drug stabilizing capabilities and mechanical properties. Most recently an electrogelation technique was developed which allows for the deposition of gels which dry seamlessly over the contoured topography of the conductive substrate. In this work we examine the potential use of silk electrogels as mechanically robust implant coatings capable of sequestering and releasing therapeutic agents. Electrodeposition of silk electrogels formed in uniform electric fields was characterized with respect to field intensity and deposition time. Gel formation kinetics were used to derive functions which allowed for the prediction of coating deposition over a range of process and solution parameters. Silk electrogel growth orientation was shown to be influenced by the applied electric field. Coatings were reproducible and tunable via intrinsic silk solution properties and extrinsic process parameters. Adhesion was

Electromagnetic compatibility of implantable neurostimulators to RFID emitters

PubMed Central

2011-01-01

Background The objective of this study is to investigate electromagnetic compatibility (EMC) of implantable neurostimulators with the emissions from radio frequency identification (RFID) emitters. Methods Six active implantable neurostimulators with lead systems were tested for susceptibility to electromagnetic fields generated by 22 RFID emitters. These medical devices have been approved for marketing in the U.S. for a number of intended uses that include: epilepsy, depression, incontinence, Parkinsonian tremor and pain relief. Each RFID emitter had one of the following carrier frequencies: 125 kHz, 134 kHz, 13.56 MHz, 433 MHz, 915 MHz and 2.45 GHz Results The test results showed the output of one of the implantable neurostimulators was inhibited by 134 kHz RFID emitter at separation distances of 10 cm or less. The output of the same implantable neurostimulator was also inhibited by another 134 kHz RFID emitter at separation distances of 10 cm or less and also showed inconsistent pulsing rate at a separation distance of 15 cm. Both effects occurred during and lasted through out the duration of the exposure. Conclusions The clinical significance of the effects was assessed by a clinician at the U.S. Food and Drug Administration. The effects were determined to be clinically significant only if they occurred for extended period of time. There were no observed effects from the other 5 implantable neurostimulators or during exposures from other RFID emitters. PMID:21658266

Comparison of the long-term safety and efficacy of drug-eluting and bare-metal stent implantation in saphenous vein grafts.

PubMed

Latib, Azeem; Ferri, Luca; Ielasi, Alfonso; Cosgrave, John; Godino, Cosmo; Bonizzoni, Erminio; Romagnoli, Enrico; Chieffo, Alaide; Valgimigli, Marco; Penzo, Carlo; Carlino, Mauro; Michev, Iassen; Sangiorgi, Giuseppe M; Montorfano, Matteo; Airoldi, Flavio; Colombo, Antonio

2010-06-01

Concerns about the long-term safety of drug-eluting stents (DES) in saphenous vein grafts has become an area of controversy and uncertainty. In this retrospective registry, we compared the outcomes in 127 patients (143 lesions) treated with DES from April 2002 to June 2006 (DES group) with 131 patients (160 lesions) treated with bare-metal stents in the preceding 36 months (bare-metal stent group). End points analyzed were cumulative death, myocardial infarction, and target vessel revascularization at 2 years after stent implantation. The DES group was significantly (P<0.05) more complex with a greater frequency of diabetes (33.1%versus 15.3%), older grafts (11.6+/-5.3 years versus 9.6+/-5.2 years), restenotic lesions (23.8% versus 4.4%), total occlusions (7.7% versus 1.2%), and smaller grafts (3.16+/-0.66 mm versus 3.44+/-0.76 mm) treated with longer stents (34.1+/-25.1 mm versus 22.7+/-11.6 mm). At 2 years, there was no statistical difference in death (8.7% versus 7.8%), myocardial infarction (6.3% versus 9.4%), or target vessel revascularization (19.7% versus 24.2%) between DES and bare-metal stents, respectively. A propensity analysis to adjust for baseline differences suggested that there was no observed association between DES and increased mortality (hazard ratio, 0.72; 95% CI, 0.21 to 2.44; P=0.60) but possibly an association with a reduction in target vessel revascularization (hazard ratio, 0.31; 95% CI, 0.14 to 0.66; P=0.002). Despite being implanted in patients and lesions more complex than the bare-metal stent group, there was no observed association between DES implantation in saphenous vein grafts and an increase in late mortality. DES may maintain their efficacy in reducing revascularization rates in diseased saphenous vein grafts over a 2-year follow-up period.

Survival of dental implants placed in sites of previously failed implants.

PubMed

Chrcanovic, Bruno R; Kisch, Jenö; Albrektsson, Tomas; Wennerberg, Ann

2017-11-01

To assess the survival of dental implants placed in sites of previously failed implants and to explore the possible factors that might affect the outcome of this reimplantation procedure. Patients that had failed dental implants, which were replaced with the same implant type at the same site, were included. Descriptive statistics were used to describe the patients and implants; survival analysis was also performed. The effect of systemic, environmental, and local factors on the survival of the reoperated implants was evaluated. 175 of 10,096 implants in 98 patients were replaced by another implant at the same location (159, 14, and 2 implants at second, third, and fourth surgeries, respectively). Newly replaced implants were generally of similar diameter but of shorter length compared to the previously placed fixtures. A statistically significant greater percentage of lost implants were placed in sites with low bone quantity. There was a statistically significant difference (P = 0.032) in the survival rates between implants that were inserted for the first time (94%) and implants that replaced the ones lost (73%). There was a statistically higher failure rate of the reoperated implants for patients taking antidepressants and antithrombotic agents. Dental implants replacing failed implants had lower survival rates than the rates reported for the previous attempts of implant placement. It is suggested that a site-specific negative effect may possibly be associated with this phenomenon, as well as the intake of antidepressants and antithrombotic agents. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sub-meninges implantation reduces immune response to neural implants.

PubMed

Markwardt, Neil T; Stokol, Jodi; Rennaker, Robert L

2013-04-15

Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. Published by Elsevier B.V.

Sub-meninges Implantation Reduces Immune Response to Neural Implants

PubMed Central

Markwardt, Neil T.; Stokol, Jodi; Rennaker, Robert L.

2013-01-01

Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. PMID:23370311

The evaluation of doxycycline controlled release gel versus doxycycline controlled release implant in the management of periodontitis

PubMed Central

Chadha, Vandana Srikrishna; Bhat, Khandige Mahalinga

2012-01-01

Background: Investigators have sought different methods to deliver antimicrobials to periodontal pockets. This study was designed to assess the efficacy of locally made doxycycline gel versus locally made doxycycline implant as biodegradable controlled local delivery systems, by evaluating the pharmacological drug release and improvement in gingival status, gain in attachment, and reduction in pocket depth. Materials and Methods: Thirty patients with localized periodontal pockets ≥5 mm were randomly divided into three groups. The first group received the doxycycline gel, the second the doxycycline implant, and the third received only scaling and root planing (the control group). The patients in the first two groups were selected for the drug release. Clinical parameters such as gingival index, plaque index, probing depth, and attachment levels were recorded at baseline and the 90th day. Gingival crevicular fluid (GCF) and saliva samples were collected 1 hour following gel and implant placement and then on the 10th, 30th, and 60th days. Results: There was a statistically significant difference in the release of doxycycline from the gel when compared with the implant in the GCF and saliva on the 10th and 30th days. All the three groups showed improvement in clinical parameters. The improvements in both gel and implant groups were greater when compared with the control group with no statistically significant difference between the implant and gel systems. Conclusion: The use of local delivery of doxycycline through gel and Implant media further enhances the positive changes obtained following scaling and root planing. The release of doxycycline from the implant and the gel was comparable. PMID:23055585

Imaging of common breast implants and implant-related complications: A pictorial essay.

PubMed

Shah, Amisha T; Jankharia, Bijal B

2016-01-01

The number of women undergoing breast implant procedures is increasing exponentially. It is, therefore, imperative for a radiologist to be familiar with the normal and abnormal imaging appearances of common breast implants. Diagnostic imaging studies such as mammography, ultrasonography, and magnetic resonance imaging are used to evaluate implant integrity, detect abnormalities of the implant and its surrounding capsule, and detect breast conditions unrelated to implants. Magnetic resonance imaging of silicone breast implants, with its high sensitivity and specificity for detecting implant rupture, is the most reliable modality to asses implant integrity. Whichever imaging modality is used, the overall aim of imaging breast implants is to provide the pertinent information about implant integrity, detect implant failures, and to detect breast conditions unrelated to the implants, such as cancer.

Management of antithrombotic therapy during cardiac implantable device surgery.

PubMed

AlTurki, Ahmed; Proietti, Riccardo; Birnie, David H; Essebag, Vidal

2016-06-01

Anticoagulants are commonly used drugs that are frequently encountered during device placement. Deciding when to halt or continue the use of anticoagulants is a balance between the risks of thromboembolism versus bleeding. Patients taking warfarin with a high risk of thromboembolism should continue to take their warfarin without interruption during device placement while ensuring their international normalized ratio remains below 3. For patients who are taking warfarin and have low risk of thromboembolism, either interrupted or continued warfarin may be used, with no evidence to clearly support either strategy. There is little evidence to support continuing direct acting oral anticoagulants (DOACs) for device implantation. The timing of halting these medications depends largely on renal function. If bleeding occurs, warfarin׳s anticoagulation effect is reversible with vitamin K and activated prothrombin complex concentrate. There are no DOAC reversal agents currently available, but some are under development. Regarding antiplatelet agents, aspirin alone can be safely continued while clopidogrel alone may also be continued, but with a slightly higher bleeding risk. Dual antiplatelet therapy for bare-metal stent/drug-eluting stent implanted within 4 weeks/6 months, respectively, should be continued due to high risk of stent thrombosis; however, if they are implanted after this period, then clopidogrel can be halted 5 days before the procedure and resumed soon after, while aspirin is continued. If the patient is taking both aspirin and warfarin, aspirin should be halted 5 days prior to the procedure, while warfarin is continued.

Localized Cell and Drug Delivery for Auditory Prostheses

PubMed Central

Hendricks, Jeffrey L.; Chikar, Jennifer A.; Crumling, Mark A.; Raphael, Yehoash; Martin, David C.

2011-01-01

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness. PMID:18573323

Management of Patients With Cardiovascular Implantable Electronic Devices in Dental, Oral, and Maxillofacial Surgery.

PubMed

Tom, James

2016-01-01

The prevalence of cardiovascular implantable electronic devices as life-prolonging and life-saving devices has evolved from a treatment of last resort to a first-line therapy for an increasing number of patients. As these devices become more and more popular in the general population, dental providers utilizing instruments and medications should be aware of dental equipment and medications that may affect these devices and understand the management of patients with these devices. This review article will discuss the various types and indications for pacemakers and implantable cardioverter-defibrillators, common drugs and instruments affecting these devices, and management of patients with these devices implanted for cardiac dysrhythmias.

Management of Patients With Cardiovascular Implantable Electronic Devices in Dental, Oral, and Maxillofacial Surgery

PubMed Central

Tom, James

2016-01-01

The prevalence of cardiovascular implantable electronic devices as life-prolonging and life-saving devices has evolved from a treatment of last resort to a first-line therapy for an increasing number of patients. As these devices become more and more popular in the general population, dental providers utilizing instruments and medications should be aware of dental equipment and medications that may affect these devices and understand the management of patients with these devices. This review article will discuss the various types and indications for pacemakers and implantable cardioverter-defibrillators, common drugs and instruments affecting these devices, and management of patients with these devices implanted for cardiac dysrhythmias. PMID:27269668

Imaging of common breast implants and implant-related complications: A pictorial essay

PubMed Central

Shah, Amisha T; Jankharia, Bijal B

2016-01-01

The number of women undergoing breast implant procedures is increasing exponentially. It is, therefore, imperative for a radiologist to be familiar with the normal and abnormal imaging appearances of common breast implants. Diagnostic imaging studies such as mammography, ultrasonography, and magnetic resonance imaging are used to evaluate implant integrity, detect abnormalities of the implant and its surrounding capsule, and detect breast conditions unrelated to implants. Magnetic resonance imaging of silicone breast implants, with its high sensitivity and specificity for detecting implant rupture, is the most reliable modality to asses implant integrity. Whichever imaging modality is used, the overall aim of imaging breast implants is to provide the pertinent information about implant integrity, detect implant failures, and to detect breast conditions unrelated to the implants, such as cancer. PMID:27413269

Modulated release from implantable ocular silicone oil tamponade drug reservoirs.

PubMed

Cauldbeck, Helen; Le Hellaye, Maude; McDonald, Tom O; Long, Mark; Williams, Rachel L; Rannard, Steve P; Kearns, Victoria R

2018-04-15

Complicated cases of retinal detachment can be treated with silicone oil tamponades. There is the potential for silicone oil tamponades to have adjunctive drug releasing behaviour within the eye, however the lipophilic nature of silicone oil limits the number of drugs that are suitable, and drug release from the hydrophobic reservoir is uncontrolled. Here, a radiometric technique was developed to accurately measure drug solubility in silicone oil and measure release into culture media. All-trans retinoic acid (atRA), a lipophilic drug known to act as an anti-proliferative within the eye, was used throughout this work. Chain-end modification of polydimethylsiloxane with atRA produced a polydimethylsiloxane retinoate (PDMS-atRA), which was used as an additive to silicone oil to modify the solvent environment within the silicone oil and the distribution coefficient. Blends of PDMS-atRA and silicone oil containing different concentrations of free atRA were produced. The presence of PDMS-atRA in silicone oil had a positive effect on atRA solubility and the longevity of release in vitro . The drug release period was independent of atRA starting concentration and dependent on the PDMS-atRA concentration in the blend. A clinically relevant release period of atRA over 7 weeks from a silicone oil blend with PDMS-atRA was observed. © 2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56 , 938-946.

Development of a Microfluidics-Based Intracochlear Drug Delivery Device

PubMed Central

Sewell, William F.; Borenstein, Jeffrey T.; Chen, Zhiqiang; Fiering, Jason; Handzel, Ophir; Holmboe, Maria; Kim, Ernest S.; Kujawa, Sharon G.; McKenna, Michael J.; Mescher, Mark M.; Murphy, Brian; Leary Swan, Erin E.; Peppi, Marcello; Tao, Sarah

2009-01-01

Background Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases. PMID:19923811

Orthopedic implant devices: prevalence and sociodemographic findings from the 1988 National Health Interview Survey.

PubMed

Moore, R M; Hamburger, S; Jeng, L L; Hamilton, P M

1991-01-01

National population-based estimates on the magnitude and distribution of orthopedic implant devices in the United States have not been available to date. The Food and Drug Administration's Center for Devices and Radiological Health (FDA/CDRH) collaborated with the Centers for Disease Control's National Center for Health Statistics (CDC/NCHS) in the design and conduct of a nationwide medical device implant survey to generate the first national population-based prevalence estimates of orthopedic implant devices. A Medical Device Implant Supplement to the 1988 National Health Interview Survey was administered in personal household interviews to a national sample of 47,485 households, which included 122,310 individuals. An estimated 6.5 million orthopedic implants were in use in the general US population in 1988, including 1.6 million artificial joints and 4.9 million fixation devices. As a group, orthopedic implants comprised nearly half of all medical device implants in use, 43.4%. The majority of artificial joint recipients were 65 years of age or older, white, and male. The majority of fixation device recipients were less than 45 years of age, white, and male. The limitations and strengths of these population-based estimates are discussed.

Bioactivity of Ti-6Al-4V alloy implants treated with ibandronate after the formation of the nanotube TiO2 layer.

PubMed

Moon, So-Hee; Lee, Seung-Jae; Park, Il-Song; Lee, Min-Ho; Soh, Yun-Jo; Bae, Tae-Sung; Kim, Hyung-Seop

2012-11-01

Nanostructure surface of titanium implants treated with anodic oxidation, heat, and bisphosphonates, has been introduced to improve osseointegration of the implants. However, no information could be found about the efficiency of these approaches on Ti-6Al-4V alloy surfaces. This study examined the drug loading capacity of anodized nanotubular Ti-6Al-4V alloy surfaces in vitro as well as the bone response to surface immobilized bisphosphonates (BPs) on anodized nanotubular Ti-6Al-4V alloy surface in tibiae of rats. Ti-6Al-4V alloy titanium was divided into two groups: (1) control group (nontreated); (2) test group (anodized, heat-, and bisphosphonate-treated group). In vitro, amount of the drug released from the both groups' specimens was examined; all samples were 1 × 2 cm in size. In vivo, the 10 implants were placed inside of tibias of five rats. After 4 weeks, the bone response of the implants was evaluated using a removal torque test, and measuring bone contact and bone area. In addition, the surfaces of the extracted implants were observed by FE-SEM and EDS. In vitro, the drug loading capacity of the Ti-6Al-4V alloy surfaces was enhanced by anodizing surface modification. The values of the removal torque, bone contact, and bone area were significantly higher in the test group (p < 0.05). Furthermore, according to the EDS analysis, the amounts of Ca and P on the surface of the extracted implants were higher in the test group. Within the limits of this experiment, results of this research demonstrated that bisphosphonate-treated Ti-6Al-4V alloy implants with nanotubular surfaces have positive effects in bone-to-implant contact. Copyright © 2012 Wiley Periodicals, Inc.

Implantable batteryless device for on-demand and pulsatile insulin administration

NASA Astrophysics Data System (ADS)

Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

2017-04-01

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Cochlear implants in children implanted in Jordan: A parental overview.

PubMed

Alkhamra, Rana A

2015-07-01

Exploring the perspective of parents on the cochlear implant process in Jordan. Sixty parents of deaf children were surveyed on the information gathering process prior to cochlear implant surgery, and their implant outcome expectations post-surgery. Whether child or parent characteristics may impact parents' post-surgical expectations was explored. Although parents used a variety of information sources when considering a cochlear implant, the ear, nose and throat doctor comprised their major source of information (60%). Parents received a range of information prior to cochlear implant but agreed (93.3%) on the need for a multidisciplinary team approach. Post-surgically, parents' expected major developments in the areas of spoken language (97%), and auditory skills (100%). Receiving education in mainstream schools (92%) was expected too. Parents perceived the cochlear implant decision as the best decision they can make for their child (98.3%). A significant correlation was found between parents contentment with the cochlear implant decision and expecting developments in the area of reading and writing (r=0.7). Child's age at implantation and age at hearing loss diagnosis significantly affected parents' post-implant outcome expectations (p<0.05). Despite the general satisfaction from the information quantity and quality prior to cochlear implant, parents agree on the need for a comprehensive multidisciplinary team approach during the different stages of the cochlear implant process. Parents' education about cochlear implants prior to the surgery can affect their post-surgical outcome expectations. The parental perspective presented in this study can help professionals develop better understanding of parents' needs and expectations and henceforth improve their services and support during the different stages of the cochlear implant process. Copyright © 2015. Published by Elsevier Ireland Ltd.

Recent developments in drug eluting devices with tailored interfacial properties.

PubMed

Sanchez-Rexach, Eva; Meaurio, Emilio; Sarasua, Jose-Ramon

2017-11-01

Drug eluting devices have greatly evolved during past years to become fundamental products of great marketing importance in the biomedical field. There is currently a large diversity of highly specialized devices for specific applications, making the development of these devices an exciting field of research. The replacement of the former bare metal devices by devices loaded with drugs allowed the sustained and controlled release of drugs, to achieve the desired local therapeutic concentration of drug. The newer devices have been "engineered" with surfaces containing micro- and nanoscale features in a well-controlled manner, that have shown to significantly affect cellular and subcellular function of various biological systems. For example, the topography can be structured to form an antifouling surface mimicking the defense mechanisms found in nature, like the skin of the shark. In the case of bone implants, well-controlled nanostructured interfaces can promote osteoblast differentiation and matrix production, and enhance short-term and long-term osteointegration. In any case, the goal of current research is to design implants that induce controlled, guided, and rapid healing. This article reviews recent trends in the development of drug eluting devices, as well as recent developments on the micro/nanotechnology scales, and their future challenges. For this purpose medical devices have been divided according to the different systems of the body they are focused to: orthopedic devices, breathing stents, gastrointestinal and urinary systems, devices for cardiovascular diseases, neuronal implants, and wound dressings. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrodeposited silk coatings for bone implants

PubMed Central

Elia, Roberto; Michelson, Courtney D.; Perera, Austin L.; Brunner, Teresa F.; Harsono, Masly; Leisk, Gray G.; Kugel, Gerard; Kaplan, David L.

2014-01-01

The aim of this study was to characterize the mechanical properties and drug elution features of silk protein-based electrodeposited dental implant coatings. Silk processing conditions were modified to obtain coatings with a range of mechanical properties on titanium studs. These coatings were assessed for adhesive strength and dissolution, with properties tuned using water vapor annealing or glycerol incorporation to modulate crystalline content. Coating reproducibility was demonstrated over a range of silk concentrations from 1 to 10%. Surface roughness of titanium substrates was altered using industry relevant acid etching and grit blasting, and the effect of surface topography on silk coating adhesion was assessed. Florescent compounds were incorporated into the silk coatings, which were modulated for crystalline content, to achieve four days of sustained release of the compounds. This silk electrogelation technique offers a safe and relatively simple approach to generate mechanically robust, biocompatible and degradable implant coatings that can also be functionalized with bioactive compounds to modulate the local regenerative tissue environment. PMID:25545462

MRI in ocular drug delivery

PubMed Central

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

Breast reconstruction - implants

MedlinePlus

Breast implants surgery; Mastectomy - breast reconstruction with implants; Breast cancer - breast reconstruction with implants ... it harder to find a tumor if your breast cancer comes back. Getting breast implants does not take ...

Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats.

PubMed

Alghamdi, Hamdan S; Bosco, Ruggero; Both, Sanne K; Iafisco, Michele; Leeuwenburgh, Sander C G; Jansen, John A; van den Beucken, Jeroen J J P

2014-07-01

The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by μCT) and bone area (%BA; by histomorphometry) were significantly increased within a distance of 500 μm from implant surfaces functionalized with BP compared to control implants in osteoporotic and healthy conditions. Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The results of real-time PCR revealed similar osteogenic gene expression levels to all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP surface coatings represents an effective strategy for synergistically improvement of bone-implant integration, especially in osteoporotic conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fluocinolone acetonide ophthalmic--Bausch & Lomb: fluocinolone acetonide Envision TD implant.

PubMed

2005-01-01

Bausch & Lomb and Control Delivery Systems have developed an intravitreal implant that can deliver the corticosteroid fluocinolone acetonide [fluocinolone acetonide implant, Retisert] to posterior eye tissue for up to 3 years. The implant uses Bausch & Lomb's Envision TD technology. This fluocinolone acetonide implant has been designed for the treatment of non-infectious uveitis affecting the posterior segment of the eye and other eye disorders, which benefit from local anti-inflammatory therapy. In July 2003, Bausch & Lomb assumed all responsibility for day-to-day clinical development and regulatory activities relating to fluocinolone acetonide implant development from Control Delivery Systems. In May 2002, Control Delivery systems and Bausch & Lomb formally amended their budget for their license and development agreement. Bausch & Lomb will increase its funding to support the development of agents for the treatment of diabetic macular oedema, posterior uveitis and wet age-related macular degeneration to USD $206 million through to 2008. In January 2004, Bausch & Lomb decided to focus development of the fluocinolone acetonide implant in only one indication, non-infectious uveitis affecting the posterior segment of the eye. It had been in development for other indications, including macular oedema and age-related macular degeneration. However, these will be targeted with later-generation implant technologies, different drugs, or combinations of both. The implant delivering fluocinolone acetonide 0.59 mg or 2.1mg has completed enrollment in two pivotal 3-year phase IIb/III trials in the US, Canada, Australia and Asia for the treatment of posterior uveitis. Enrollment in these multicenter randomised, double-masked studies was closed in May 2003. Bausch & Lomb was expected to file an NDA with the US FDA for the use of the agent in the treatment of uveitis in mid-2003. However, in February 2003, the company reported that, after a review of various filing strategies

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type.

PubMed

Camenzind, Edoardo; Boersma, Eric; Wijns, William; Mauri, Laura; Rademaker-Havinga, Tessa; Ordoubadi, Farzin Fath; Suttorp, Maarten J; Al Kurdi, Mohammad; Steg, Ph Gabriel

2014-08-01

To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥ 3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957). Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

International classification of reliability for implanted cochlear implant receiver stimulators.

PubMed

Battmer, Rolf-Dieter; Backous, Douglas D; Balkany, Thomas J; Briggs, Robert J S; Gantz, Bruce J; van Hasselt, Andrew; Kim, Chong Sun; Kubo, Takeshi; Lenarz, Thomas; Pillsbury, Harold C; O'Donoghue, Gerard M

2010-10-01

To design an international standard to be used when reporting reliability of the implanted components of cochlear implant systems to appropriate governmental authorities, cochlear implant (CI) centers, and for journal editors in evaluating manuscripts involving cochlear implant reliability. The International Consensus Group for Cochlear Implant Reliability Reporting was assembled to unify ongoing efforts in the United States, Europe, Asia, and Australia to create a consistent and comprehensive classification system for the implanted components of CI systems across manufacturers. All members of the consensus group are from tertiary referral cochlear implant centers. None. A clinically relevant classification scheme adapted from principles of ISO standard 5841-2:2000 originally designed for reporting reliability of cardiac pacemakers, pulse generators, or leads. Standard definitions for device failure, survival time, clinical benefit, reduced clinical benefit, and specification were generated. Time intervals for reporting back to implant centers for devices tested to be "out of specification," categorization of explanted devices, the method of cumulative survival reporting, and content of reliability reports to be issued by manufacturers was agreed upon by all members. The methodology for calculating Cumulative survival was adapted from ISO standard 5841-2:2000. The International Consensus Group on Cochlear Implant Device Reliability Reporting recommends compliance to this new standard in reporting reliability of implanted CI components by all manufacturers of CIs and the adoption of this standard as a minimal reporting guideline for editors of journals publishing cochlear implant research results.

Surface Modification of Dental Titanium Implant by Layer-by-Layer Electrostatic Self-Assembly

PubMed Central

Shi, Quan; Qian, Zhiyong; Liu, Donghua; Liu, Hongchen

2017-01-01

In vivo implants that are composed of titanium and titanium alloys as raw materials are widely used in the fields of biology and medicine. In the field of dental medicine, titanium is considered to be an ideal dental implant material. Good osseointegration and soft tissue closure are the foundation for the success of dental implants. Therefore, the enhancement of the osseointegration and antibacterial abilities of titanium and its alloys has been the focus of much research. With its many advantages, layer-by-layer (LbL) assembly is a self-assembly technique that is used to develop multilayer films based on complementary interactions between differently charged polyelectrolytes. The LbL approach provides new methods and applications for the surface modification of dental titanium implant. In this review, the application of the LbL technique to surface modification of titanium including promoting osteogenesis and osseointegration, promoting the formation and healing of soft tissues, improving the antibacterial properties of titanium implant, achieving local drug delivery and sustained release is summarized. PMID:28824462

Preparation and biocompatibility study of in situ forming polymer implants in rat brains.

PubMed

Nasongkla, Norased; Boongird, Atthaporn; Hongeng, Suradej; Manaspon, Chawan; Larbcharoensub, Noppadol

2012-02-01

We describe the development of polymer implants that were designed to solidify once injected into rat brains. These implants comprised of glycofurol and copolymers of D: ,L: -lactide (LA), ε-caprolactone and poly(ethylene glycol) (PLECs). Scanning electron microscopy (SEM) and gel permeation chromatography (GPC) showed that the extent of implant degradation was increased with LA: content in copolymers. SEM analysis revealed the formation of porosity on implant surface as the degradation proceeds. PLEC with 19.3% mole of LA: was chosen to inject in rat brains at the volume of 10, 25 and 40 μl. Body weights, hematological and histopathological data of rats treated with implants were evaluated on day 3, 6, 14, 30 and 45 after the injection. Polymer solution at the injection volume of 10 μl were tolerated relatively well compared to those of 25 and 40 μl as confirmed by higher body weight and healing action (fibrosis tissue) 30 days after treatment. The results from this study suggest a possible application as drug delivery systems that can bypass the blood brain barrier.

Current State of Bioabsorbable Polymer-Coated Drug-Eluting Stents

PubMed Central

Akinapelli, Abhilash; Chen, Jack P.; Roy, Kristine; Donnelly, Joseph; Dawkins, Keith; Huibregtse, Barbara; Hou, Dongming

2017-01-01

Drug-eluting stents (DES) have been shown to significantly reduce clinical and angiograph-ic restenosis compared to bare metal stents (BMS). The polymer coatings on DES elute antiproliferative drugs to inhibit intimal proliferation and prevent restenosis after stent implantation. Permanent poly-mers which do not degrade in vivo may increase the likelihood of stent-related delayed arterial healing or polymer hypersensitivity. In turn, these limitations may contribute to an increased risk of late clinical events. Intuitively, a polymer which degrades after completion of drug release, leaving an inert metal scaffold in place, may improve arterial healing by removing a chronic source of inflammation, neoath-erosclerosis, and/or late thrombosis. In this way, a biodegradable polymer may reduce late ischemic events. Additionally, improved healing after stent implantation could reduce the requirement for long-term dual antiplatelet therapy and the associated risk of bleeding and cost. This review will focus on bioabsorbable polymer-coated DES currently being evaluated in clinical trials.

Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.

PubMed

Wang, Lexi; Wang, Aiping; Zhao, Xiaolei; Liu, Ximing; Wang, Dan; Sun, Fengying; Li, Youxin

2012-05-10

Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application. Copyright © 2012 Elsevier B.V. All rights reserved.

Precision of fit between implant impression coping and implant replica pairs for three implant systems.

PubMed

Nicoll, Roxanna J; Sun, Albert; Haney, Stephan; Turkyilmaz, Ilser

2013-01-01

The fabrication of an accurately fitting implant-supported fixed prosthesis requires multiple steps, the first of which is assembling the impression coping on the implant. An imprecise fit of the impression coping on the implant will cause errors that will be magnified in subsequent steps of prosthesis fabrication. The purpose of this study was to characterize the 3-dimensional (3D) precision of fit between impression coping and implant replica pairs for 3 implant systems. The selected implant systems represent the 3 main joint types used in implant dentistry: external hexagonal, internal trilobe, and internal conical. Ten impression copings and 10 implant replicas from each of the 3 systems, B (Brånemark System), R (NobelReplace Select), and A (NobelActive) were paired. A standardized aluminum test body was luted to each impression coping, and the corresponding implant replica was embedded in a stone base. A coordinate measuring machine was used to quantify the maximum range of displacement in a vertical direction as a function of the tightening force applied to the guide pin. Maximum angular displacement in a horizontal plane was measured as a function of manual clockwise or counterclockwise rotation. Vertical and rotational positioning was analyzed by using 1-way analysis of variance (ANOVA). The Fisher protected least significant difference (PLSD) multiple comparisons test of the means was applied when the F-test in the ANOVA was significant (α=.05). The mean and standard deviation for change in the vertical positioning of impression copings was 4.3 ±2.1 μm for implant system B, 2.8 ±4.2 μm for implant system R, and 20.6 ±8.8 μm for implant system A. The mean and standard deviation for rotational positioning was 3.21 ±0.98 degrees for system B, 2.58 ±1.03 degrees for system R, and 5.30 ±0.79 degrees for system A. The P-value for vertical positioning between groups A and B and between groups A and R was <.001. No significant differences were found for

Advantages and disadvantages of biodegradable platforms in drug eluting stents.

PubMed

Rodriguez-Granillo, Agustina; Rubilar, Bibiana; Rodriguez-Granillo, Gaston; Rodriguez, Alfredo E

2011-03-26

Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.

Intracranial EEG fluctuates over months after implanting electrodes in human brain

NASA Astrophysics Data System (ADS)

Ung, Hoameng; Baldassano, Steven N.; Bink, Hank; Krieger, Abba M.; Williams, Shawniqua; Vitale, Flavia; Wu, Chengyuan; Freestone, Dean; Nurse, Ewan; Leyde, Kent; Davis, Kathryn A.; Cook, Mark; Litt, Brian

2017-10-01

Objective. Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings. Approach. Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for the duration of each patient’s recording. Metrics to capture post-implantation feature changes and inflexion points were computed on group and individual levels. A linear mixed model was used to characterize transient group-level changes in feature values post-implantation and independent linear models were used to describe individual variability. Main results. A significant decline in features important to seizure detection and prediction algorithms (mean line length, energy, and half-wave), as well as mean power in the Berger and high gamma bands, was observed in many patients over 100 d following implantation. In addition, spatial variability across electrodes declines post-implantation following a similar timeframe. All selected features decreased by 14-50% in the initial 75 d of recording on the group level, and at least one feature demonstrated this pattern in 13 of the 15 patients. Our findings indicate that iEEG signal features demonstrate increased variability following implantation, most notably in the weeks immediately post-implant. Significance. These findings suggest that conclusions drawn from iEEG, both clinically and for research, should account for spatiotemporal signal variability and that properly assessing the iEEG in

Effect of embedded dexamethasone in cochlear implant array on insertion forces in an artificial model of scala tympani.

PubMed

Nguyen, Yann; Bernardeschi, Daniele; Kazmitcheff, Guillaume; Miroir, Mathieu; Vauchel, Thomas; Ferrary, Evelyne; Sterkers, Olivier

2015-02-01

Loading otoprotective drug into cochlear implant might change its mechanical properties, thus compromising atraumatic insertion. This study evaluated the effect of incorporation of dexamethasone (DXM) in the silicone of cochlear implant arrays on insertion forces. Local administration of DXM with embedded array can potentially reduce inflammation and fibrosis after cochlear implantation procedure to improve hearing preservation and reduce long-term impedances. Four models of arrays have been tested: 0.5-mm distal diameter array (n = 5) used as a control, drug-free 0.4-mm distal diameter array (n = 5), 0.4-mm distal diameter array with 1% eluded DXM silicone (n = 5), and 0.4-mm distal diameter array with 10% eluded DXM silicone (n = 5). Via a motorized insertion bench, each array has been inserted into an artificial scala tympani model. The forces were recorded by a 6-axis force sensor. Each array was tested seven times for a total number of 140 insertions. During the first 10-mm insertion, no difference between the four models was observed. From 10- to 24-mm insertion, the 0.5-mm distal diameter array presented higher insertion forces than the drug-free 0.4-mm distal diameter arrays, with or without DXM. Friction forces for drug-free 0.4-mm distal diameter array and 0.4-mm distal diameter DXM eluded arrays were similar on all insertion lengths. Incorporation of DXM in silicone for cochlear implant design does not change electrode array insertion forces. It does not raise the risk of trauma during array insertion, making it suitable for long-term in situ administration to the cochlea.

An electro-conductive fluid as a responsive implant for the controlled stimuli-release of diclofenac sodium.

PubMed

Bijukumar, Divya; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-11-01

The purpose of this study was to develop an electro-responsive co-polymeric (ERP) implantable gel from polyethylene glycol (PEG), sodium polystyrene sulphonate (NaPss), polyvinyl alcohol (PVA), and diethyl acetomidomalonate (DAA) for electro-liberation of the model drug diclofenac sodium. Various physicochemical and physicomechanical characterization tests were undertaken on the synthesized drug-free gel (ERP G1) and drug-loaded gel (ERP G2). The ability of the gel to release diclofenac sodium following electrical stimulation was evaluated using a galvanostat while Molecular Mechanics (MM) simulations were performed to elucidate the experimental mechanisms. A stable electro-active gel exhibiting superior cycling stability was produced with desirable rheological properties, rigidity (BHN = 35.4 N ± 0.33 N/mm 2 ; resilience = 10.91 ± 0.11%), thermal properties (T g  ≈ 70 °C; T c  ≈ 200 °C) and homogeneous morphology. "ON-OFF" pursatile gradual drug release (37-94% from t 30 min -t 180   min ) kinetics was observed upon applying electric stimulation intermittently, indicating that drug release from the gel was electrically controlled. Overall, the galvanometric and MM evaluation ascertained the suitability of the PEG/NaPss/PVA ERP-Gel for application as a subcutaneously injectable drug delivery implant.

An Overview of Clinical and Commercial Impact of Drug Delivery Systems

PubMed Central

Anselmo, Aaron C.; Mitragotri, Samir

2014-01-01

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. PMID:24747160

An overview of clinical and commercial impact of drug delivery systems.

PubMed

Anselmo, Aaron C; Mitragotri, Samir

2014-09-28

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

[Application of plasma sprayed zirconia coating in dental implant: study in implant].

PubMed

Huang, Z F; Wang, Z F; Li, C H; Hao, D; Lan, J

2018-04-09

Objective: To investigate the osseointegration of a novel coating-plasma-sprayed zirconia in dental implant. Methods: Zirconia coating on non-thread titanium implant was prepared using plasma spraying, the implant surface morphology, surface roughness and wettability were measured. In vivo , zirconia coated implants were inserted in rabbit tibia and animals were respectively sacrificed at 2, 4, 8 and 12 weeks after implantation. The bond strength between implant and bone was measured by push-out test. The osseointegration was observed by scanning electron microscopy (SEM), micro CT and histological analyses. Quantified parameters including removal torque, and bone-implant contact (BIC) percentage were calculated. Results: The surface roughness (1.6 µm) and wettability (54.6°) of zirconia coated implant was more suitable than those of titanium implant (0.6 µm and 74.4°) for osseointegration. At 12 weeks, the push-out value of zirconia coated implant and titanium implant were (64.9±3.0) and (50.4±2.9) N, and BIC value of these two groups were (54.7±3.6)% and (41.5±3.6)%. All these differences had statistical significance. Conclusions: The surface characters of zirconia coated implant were more suitable for osseointegration and present better osseointegration than smooth titanium implant in vivo , especially at early stage.

Cochlear implant – state of the art

PubMed Central

Lenarz, Thomas

2018-01-01

Cochlear implants are the treatment of choice for auditory rehabilitation of patients with sensory deafness. They restore the missing function of inner hair cells by transforming the acoustic signal into electrical stimuli for activation of auditory nerve fibers. Due to the very fast technology development, cochlear implants provide open-set speech understanding in the majority of patients including the use of the telephone. Children can achieve a near to normal speech and language development provided their deafness is detected early after onset and implantation is performed quickly thereafter. The diagnostic procedure as well as the surgical technique have been standardized and can be adapted to the individual anatomical and physiological needs both in children and adults. Special cases such as cochlear obliteration might require special measures and re-implantation, which can be done in most cases in a straight forward way. Technology upgrades count for better performance. Future developments will focus on better electrode-nerve interfaces by improving electrode technology. An increased number of electrical contacts as well as the biological treatment with regeneration of the dendrites growing onto the electrode will increase the number of electrical channels. This will give room for improved speech coding strategies in order to create the bionic ear, i.e. to restore the process of natural hearing by means of technology. The robot-assisted surgery will allow for high precision surgery and reliable hearing preservation. Biological therapies will support the bionic ear. Methods are bio-hybrid electrodes, which are coded by stem cells transplanted into the inner ear to enhance auto-production of neurotrophins. Local drug delivery will focus on suppression of trauma reaction and local regeneration. Gene therapy by nanoparticles will hopefully lead to the preservation of residual hearing in patients being affected by genetic hearing loss. Overall the cochlear implant

Buprenorphine implants for treatment of opioid dependence: a randomized controlled trial.

PubMed

Ling, Walter; Casadonte, Paul; Bigelow, George; Kampman, Kyle M; Patkar, Ashwin; Bailey, Genie L; Rosenthal, Richard N; Beebe, Katherine L

2010-10-13

Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms. To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence. A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants. After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients. The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24. The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface

NASA Astrophysics Data System (ADS)

Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

2016-05-01

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification.

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface.

PubMed

Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

2016-05-27

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification.

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface

PubMed Central

Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

2016-01-01

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification. PMID:27229174

Cochlear implantation in late-implanted adults with prelingual deafness.

PubMed

Most, Tova; Shrem, Hadas; Duvdevani, Ilana

2010-01-01

The purpose of this study was to examine the effect of cochlear implantation (CI) on prelingually deafened participants who were implanted as adults. The effect of the CI was examined with regard to the following variables: communication, family, social skills, education, and work satisfaction with one's life, loneliness, and self-esteem. Thirty-eight adults participated. Four self-report questionnaires were used at 2 points in time: before and after CI. The research findings show significant differences in the reports of most variables before and after implantation. The participants felt better with regard to communication, social skills, education, and work and satisfaction with one's life after implantation in comparison to their feelings before implantation. Furthermore, they felt less lonely after implantation. However, there were no significant differences before and after implantation regarding their feelings within the family and regarding their self-esteem. The results demonstrated the need to evaluate the benefits resulting from the CI not only with traditional clinical measures but with additional measures as well. Furthermore, they demonstrated the benefit of the CI on the positive psychosociological implications of prelingually deafened adults. Copyright © 2010 Elsevier Inc. All rights reserved.

Prevalence of peri-implantitis in patients with implant-supported fixed prostheses.

PubMed

Schuldt Filho, Guenther; Dalago, Haline Renata; Oliveira de Souza, João Gustavo; Stanley, Kyle; Jovanovic, Sascha; Bianchini, Marco Aurélio

2014-01-01

The purpose of this study was to evaluate periimplantitis prevalence in patients using implant-supported fixed prostheses that did not have any routine maintenance care. A total of 161 implants (27 patients) were evaluated in patients using implant-supported fixed prostheses. Collected data included information related to patient general health and local factors such as characteristics of implants, time in function, type of loading, positioning, Modified Bleeding Index, bacterial plaque, bleeding on probing (BOP), marginal recession, probing depth (PD), keratinized mucosa, and radiographic bone loss (BL). Factors related to the prostheses were also evaluated. The exclusion criteria were patients that have had any follow-up visit for plaque control of the prosthesis and/or the implants. From a total of 161 implants, 116 (72%) presented without peri-implantitis (PD > 4 mm + BOP + BL > 2 mm) while 45 (28%) had some sign of the disease. Implants placed in the maxilla were 2.98 times more likely to develop the disease (P < .05). Moreover, patients aged ≤ 60 years old were 3.24 times more likely to develop peri-implantitis (P < .05). Another analysis with statistical relevance (P < .05) was that implants with less than 3 mm interimplant distance were three times more likely to have peri-implantitis. There was no statistical relevance considering other analyses. It can be concluded that patients aged ≤ 60 years have a greater chance of presenting periimplantitis, as well as for implants positioned in the maxilla and those placed with an interimplant distance < 3 mm.

Correlation-based pattern recognition for implantable defibrillators.

PubMed Central

Wilkins, J.

1996-01-01

An estimated 300,000 Americans die each year from cardiac arrhythmias. Historically, drug therapy or surgery were the only treatment options available for patients suffering from arrhythmias. Recently, implantable arrhythmia management devices have been developed. These devices allow abnormal cardiac rhythms to be sensed and corrected in vivo. Proper arrhythmia classification is critical to selecting the appropriate therapeutic intervention. The classification problem is made more challenging by the power/computation constraints imposed by the short battery life of implantable devices. Current devices utilize heart rate-based classification algorithms. Although easy to implement, rate-based approaches have unacceptably high error rates in distinguishing supraventricular tachycardia (SVT) from ventricular tachycardia (VT). Conventional morphology assessment techniques used in ECG analysis often require too much computation to be practical for implantable devices. In this paper, a computationally-efficient, arrhythmia classification architecture using correlation-based morphology assessment is presented. The architecture classifies individuals heart beats by assessing similarity between an incoming cardiac signal vector and a series of prestored class templates. A series of these beat classifications are used to make an overall rhythm assessment. The system makes use of several new results in the field of pattern recognition. The resulting system achieved excellent accuracy in discriminating SVT and VT. PMID:8947674

Prevalences of peri-implantitis and peri-implant mucositis: systematic review and meta-analysis.

PubMed

Lee, Chun-Teh; Huang, Yen-Wen; Zhu, Liang; Weltman, Robin

2017-07-01

Due to the inconsistent definitions, reporting methods and study characteristics, prevalences of peri-implant diseases significantly varied in studies. This study aimed to systematically analyze implant-based and subject-based prevalences of peri-implant diseases and assess clinical variables potentially affecting the prevalence. Electronic search of studies was conducted using MEDLINE (PubMed), EMBASE and Web of Science. Publication screening, data extraction, and quality assessment were performed. Clinical studies having an at least average three-year follow-up period were selected. The numbers of subjects and implants in the studies had to be equal to or more than thirty. Forty seven studies were selected and prevalences of peri-implant diseases were analyzed. Since heterogeneity existed in each outcome (I 2 =94.7, 95.7, 95.3, and 99.3 for implant-based and subject-based peri-implantitis and peri-implant mucositis, respectively), the random-effects model based on the DerSimonian and Laird method, which incorporate an estimate of heterogeneity in the weighting, was applied to obtain the pooled prevalence. Weighted mean implant-based and subject-based peri-implantitis prevalences were 9.25% (95% Confidence Interval (CI): [7.57, 10.93]) and 19.83% (CI [15.38, 24.27) respectively. Weighted mean implant-based and subject-based peri-implant mucositis prevalences were 29.48% (CI: [22.65, 36.32]) and 46.83% (CI: [38.30, 55.36]) respectively. Functional time and implant to subject ratio were associated with subject-based peri-implantitis prevalence, but not peri-implant mucositis prevalences. Peri-implant diseases were prevalent and prevalence of peri-implantitis increased over time. Prevalences of peri-implantitis and peri-implant mucositis might not be highly associated since the prevalences were influenced by distinct variables. The results should be carefully interpreted because of data heterogeneity. Peri-implant diseases affect a significant number of dental

Epicardial cardioverter-defibrillator implantation in a 4-month-old infant bridged to heart transplantation.

PubMed

Carro, Cristina; Cereda, Alberto Francesco; Annoni, Giuseppe; Marianeschi, Stefano Maria

2017-11-01

Implantable cardioverter-defibrillator (ICD) is the gold standard therapy for the prevention of sudden cardiac death. Nevertheless, ICD placement in the paediatric population is still limited because of several technical difficulties. Several implantation techniques have been proposed but experience in infants with very low weight and less than 6 months is very limited. We herein describe a case of a minimally invasive ICD epicardial implantation in a 4-month-old infant weighing 5 kg. A diagnosis of arrhythmic cardiomyopathy with left ventricular non-compaction disease with ventricular tachycardia storms, QT prolongation and Wolff-Parkinson-White pattern was made. Antiarrhythmic drugs, radiofrequency ablation and sympathetic denervation were not effective. ICD implantation was successful allowing the infant to survive and bridging to heart transplantation. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Decontamination of dental implant surface in peri-implantitis treatment: A literature review

PubMed Central

Buitrago-Vera, Pedro; Solá-Ruiz, María F.; Ferrer-García, Juan C.

2013-01-01

Etiological treatment of peri-implantitis aims to reduce the bacterial load within the peri-implant pocket and decontaminate the implant surface in order to promote osseointegration. The aim of this literature review was to evaluate the efficacy of different methods of implant surface decontamination. A search was conducted using the PubMed (Medline) database, which identified 36 articles including in vivo and in vitro studies, and reviews of different decontamination systems (chemical, mechanical, laser and photodynamic therapies). There is sufficient consensus that, for the treatment of peri-implant infections, the mechanical removal of biofilm from the implant surface should be supplemented by chemical decontamination with surgical access. However, more long-term research is needed to confirm this and to establish treatment protocols responding to different implant characterics. Key words:Peri-implantitis, treatment, decontamination, implant surface, laser. PMID:23986023

Two-stage implant systems.

PubMed

Fritz, M E

1999-06-01

Since the advent of osseointegration approximately 20 years ago, there has been a great deal of scientific data developed on two-stage integrated implant systems. Although these implants were originally designed primarily for fixed prostheses in the mandibular arch, they have been used in partially dentate patients, in patients needing overdentures, and in single-tooth restorations. In addition, this implant system has been placed in extraction sites, in bone-grafted areas, and in maxillary sinus elevations. Often, the documentation of these procedures has lagged. In addition, most of the reports use survival criteria to describe results, often providing overly optimistic data. It can be said that the literature describes a true adhesion of the epithelium to the implant similar to adhesion to teeth, that two-stage implants appear to have direct contact somewhere between 50% and 70% of the implant surface, that the microbial flora of the two-stage implant system closely resembles that of the natural tooth, and that the microbiology of periodontitis appears to be closely related to peri-implantitis. In evaluations of the data from implant placement in all of the above-noted situations by means of meta-analysis, it appears that there is a strong case that two-stage dental implants are successful, usually showing a confidence interval of over 90%. It also appears that the mandibular implants are more successful than maxillary implants. Studies also show that overdenture therapy is valid, and that single-tooth implants and implants placed in partially dentate mouths have a success rate that is quite good, although not quite as high as in the fully edentulous dentition. It would also appear that the potential causes of failure in the two-stage dental implant systems are peri-implantitis, placement of implants in poor-quality bone, and improper loading of implants. There are now data addressing modifications of the implant surface to alter the percentage of

Similarities and differences in coatings for magnesium-based stents and orthopaedic implants

PubMed Central

Ma, Jun; Thompson, Marc; Zhao, Nan; Zhu, Donghui

2016-01-01

Magnesium (Mg)-based biodegradable materials are promising candidates for the new generation of implantable medical devices, particularly cardiovascular stents and orthopaedic implants. Mg-based cardiovascular stents represent the most innovative stent technology to date. However, these products still do not fully meet clinical requirements with regards to fast degradation rates, late restenosis, and thrombosis. Thus various surface coatings have been introduced to protect Mg-based stents from rapid corrosion and to improve biocompatibility. Similarly, different coatings have been used for orthopaedic implants, e.g., plates and pins for bone fracture fixation or as an interference screw for tendon-bone or ligament-bone insertion, to improve biocompatibility and corrosion resistance. Metal coatings, nanoporous inorganic coatings and permanent polymers have been proved to enhance corrosion resistance; however, inflammation and foreign body reactions have also been reported. By contrast, biodegradable polymers are more biocompatible in general and are favoured over permanent materials. Drugs are also loaded with biodegradable polymers to improve their performance. The key similarities and differences in coatings for Mg-based stents and orthopaedic implants are summarized. PMID:27695671

Implant decontamination with phosphoric acid during surgical peri-implantitis treatment: a RCT.

PubMed

Hentenaar, Diederik F M; De Waal, Yvonne C M; Strooker, Hans; Meijer, Henny J A; Van Winkelhoff, Arie-Jan; Raghoebar, Gerry M

2017-12-01

Peri-implantitis is known as an infectious disease that affects the peri-implant soft and hard tissue. Today, scientific literature provides very little evidence for an effective intervention protocol for treatment of peri-implantitis. The aim of the present randomized controlled trial is to evaluate the microbiological and clinical effectiveness of phosphoric acid as a decontaminating agent of the implant surface during surgical peri-implantitis treatment. Peri-implantitis lesions were treated with resective surgical treatment aimed at peri-implant granulation tissue removal, bone recontouring, and pocket elimination. Fifty-three implant surfaces in 28 patients were mechanically cleaned and treated with either 35% phosphoric etching gel (test group) or sterile saline (control group). Microbiological samples were obtained during surgery; clinical parameters were recorded at baseline and at 3 months after treatment. Data were analyzed using multi-variable linear regression analysis and multilevel statistics. Significant immediate reductions in total anaerobic bacterial counts on the implant surface were found in both groups. Immediate reduction was greater when phosphoric acid was used. The difference in log-transformed mean anaerobic counts between both procedures was not statistical significant (p = 0.108), but there were significantly less culture-positive implants after the decontamination procedure in the phosphoric acid group (p = 0.042). At 3 months post-surgery, 75% of the implants in the control group and 63.3% of the implants in the test group showed disease resolution. However, no significant differences in clinical and microbiological outcomes between both groups were found. The application of 35% phosphoric acid after mechanical debridement is superior to mechanical debridement combined with sterile saline rinsing for decontamination of the implant surface during surgical peri-implantitis treatment. However, phosphoric acid as implant surface

Chemical, corrosion and topographical analysis of stainless steel implants after different implantation periods.

PubMed

Chrzanowski, Wojciech; Armitage, David Andrew; Knowles, Jonathan Campbell; Szade, Jacek; Korlacki, Wojciech; Marciniak, Jan

2008-07-01

The aim of this work is to examine the corrosion properties, chemical composition, and material-implant interaction after different periods of implantation of plates used to correct funnel chest. The implants are made of 316L stainless steel. Examinations are carried out on three implants: new (nonimplanted) and two implanted for 29 and 35 months. The corrosion study reveals that in the potential range that could occur in the physiological condition the new bar has the lowest current density and the highest corrosion potential. This indicates that the new plate has the highest corrosion resistance and the corrosion resistance could be reduced during implantation by the instruments used during the operation. XPS analysis reveals changes in the surface chemistry. The longer the implantation time the more carbon and oxygen are observed and only trace of elements such as Cr, Mo are detected indicating that surface is covered by an organic layer. On some parts of the implants whitish tissue is observed: the thickness of which increased with the time of implantation. This tissue was identified as an organic layer; mainly attached to the surface on the areas close to where the implant was bent to attain anatomical fit and thus where the implant has higher surface roughness. The study indicates that the chest plates are impaired by the implantation procedure and contact with biological environment. The organic layer on the surface shows that the implant did not stay passive but some reactions at the tissue-implant interface occurred. These reactions should be seen as positive, as it indicates that the implants were accepted by the tissues. Nevertheless, if the implants react, they may continue to release chromium, nickel, and other harmful ions long term as indicated by lower corrosion resistance of the implants following implantation.

Impact of implant design on primary stability of orthodontic mini-implants.

PubMed

Wilmes, Benedict; Ottenstreuer, Stephanie; Su, Yu-Yu; Drescher, Dieter

2008-01-01

Skeletal anchorage with mini-implants has greatly broadened the treatment possibilities in orthodontics over the last few years. To reduce implant failure rates, it is advisable to obtain adequate primary stability. The aim of this study was to quantitatively analyze the impact of implant design and dimension on primary stability. Forty-two porcine iliac bone segments were prepared and embedded in resin. To evaluate the primary stability, we documented insertion torques of the following mini-implants: Aarhus Screw, AbsoAnchor, LOMAS, Micro-Anchorage-System, ORLUS and Spider Screw. In each bone, five Dual Top Screws were inserted for reference purposes to achieve comparability among the specimens. We observed wide variation in insertion torques and hence primary stability, depending on mini-implant design and dimension; the great impact that mini-implant diameter has on insertion torques was particularly conspicuous. Conical mini-implants achieved higher primary stabilities than cylindrical designs. The diameter and design of the mini-implant thread have a distinctive impact on primary stability. Depending on the region of insertion and local bone quality, the choice of the mini-implant design and size is crucial to establish sufficient primary stability.

Gallium and silicon synergistically promote osseointegration of dental implant in patients with osteoporosis.

PubMed

Liu, Jinsong; Wu, Zuosu; He, Hongli; Cai, Kaiyong; Zhang, Hualin; Xu, Lihua

2017-06-01

Over the last few decades, a wide variety of dental implants have been successfully placed in jaw bones to restore tooth function. But major challenges still remain in patients with osteoporosis involving compromised osseointegration, and the therapeutic methods is far from optimism. Gallium can directly inhibit bone osteolysis, prevent bone calcium release and augment bone mass, which makes Ga unique among the potential antiresorptive drugs. Silicon, as an indispensable modulator in bone formation, presents its bone anabolic effects, while reduces, at least doesn't increase, bone resorption. We hypothesize that the combination of bone anabolic effects of Si and antiresorptive effects of Ga will result in synergistic effects on the improvement of osteointegration under osteoporotic condition. In our strategy, in order to maximize the efficacy while minimize the side effects of ions, a novel titania mesoporous layer fabricated by electrochemical anodization on the surface of titanium implant will be employed as a promising local drug delivery system. The synergistic effects of Ga and Si on improving osseointegration will be verified by animal experiments, and be furthered by clinical trials. Our hypothesis could help to create an option to improve success rate of dental implants in osteoporotic patients. Copyright © 2017. Published by Elsevier Ltd.

Effect of implant position, angulation, and attachment height on peri-implant bone stress associated with mandibular two-implant overdentures: a finite element analysis.

PubMed

Hong, Hae Ryong; Pae, Ahran; Kim, Yooseok; Paek, Janghyun; Kim, Hyeong-Seob; Kwon, Kung-Rock

2012-01-01

The aim of this study was to analyze and compare the level and distribution of peri-implant bone stresses associated with mandibular two-implant overdentures with different implant positions. Mathematical models of mandibles and overdentures were designed using finite element analysis software. Two intraosseous implants and ball attachment systems were placed in the interforaminal region. The overdenture, which was supported by the two implants, was designed to withstand bilateral and unilateral vertical masticatory loads (total 100 N). In all, eight types of models, which differed according to assigned implant positions, height of attachments, and angulation, were tested: MI (model with implants positioned in the lateral incisor sites), MC (implants in canine sites), MP (implants in premolar sites), MI-Hi (greater height of attachments), MC-M (canine implants placed with mesial inclination), MC-D (canine implants placed with distal inclination), MC-B (canine implants placed with buccal inclination), and MC-L (canine implants placed with lingual inclination). Peri-implant bone stress levels associated with overdentures retained by lateral incisor implants resulted in the lowest stress levels and the highest efficiency in distributing peri-implant stress. MI-Hi showed increased stress levels and decreased efficiency in stress distribution. As the implants were inclined, stress levels increased and the efficiency of stress distribution decreased. Among the inclined models, MC-B showed the lowest stress level and best efficiency in stress distribution. The lowest stress and the best stability of implants in mandibular two-implant overdentures were obtained when implants were inserted in lateral incisor areas with shorter attachments and were placed parallel to the long axes of the teeth.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats.

PubMed

Guarnieri, M; Brayton, C; Sarabia-Estrada, R; Tyler, B; McKnight, P; DeTolla, L

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

PubMed Central

Brayton, C.; Sarabia-Estrada, R.; McKnight, P.; DeTolla, L.

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy. PMID:28492060

The use of magnetite nanoparticles for implant-assisted magnetic drug targeting in thrombolytic therapy.

PubMed

Kempe, Maria; Kempe, Henrik; Snowball, Ian; Wallén, Rita; Arza, Carlos Rodriguez; Götberg, Matthias; Olsson, Tommy

2010-12-01

Implant-assisted targeting of magnetic particles under the influence of an external magnetic field has previously been verified through mathematical modeling, in vitro studies, and in vivo studies on rat carotid arteries as a feasible method for localized drug delivery. The present study focuses on the development of nanoparticles for the treatment of in-stent thrombosis. Magnetic nanoparticles in the size-range 10-30 nm were synthesized in a one-pot procedure by precipitation of ferrous hydroxide followed by oxidation to magnetite. The nanoparticles were silanized with tetraethyl orthosilicate in the presence of triethylene glycol and/or polyethylene glycol. The surface coated magnetite nanoparticles were activated with either N-hydroxysulfosuccinimide or tresyl chloride for covalent immobilization of tissue plasminogen activator (tPA). Hysteresis loops showed saturation magnetizations of 55.8, 44.1, and 43.0 emu/g for the naked nanoparticles, the surface coated nanoparticles, and the tPA-nanoparticle conjugates, respectively. The hemolytic activity of the nanoparticles in blood was negligible. An initial in vivo biocompatibility test in pig, carried out by intravascular injection of the nanoparticles in a stented brachial artery, showed no short-term adverse effects. In vitro evaluation in a flow-through model proved that the nanoparticles were captured efficiently to the surface of a ferromagnetic coiled wire at the fluid velocities typical for human arteries. A preliminary test of the tPA-nanoparticle conjugates in a pig model suggested that the conjugates may be used for treatment of in-stent thrombosis in coronary arteries. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cochlear implants: a remarkable past and a brilliant future

PubMed Central

Wilson, Blake S.; Dorman, Michael F.

2013-01-01

The aims of this paper are to (i) provide a brief history of cochlear implants; (ii) present a status report on the current state of implant engineering and the levels of speech understanding enabled by that engineering; (iii) describe limitations of current signal processing strategies and (iv) suggest new directions for research. With current technology the “average” implant patient, when listening to predictable conversations in quiet, is able to communicate with relative ease. However, in an environment typical of a workplace the average patient has a great deal of difficulty. Patients who are “above average” in terms of speech understanding, can achieve 100% correct scores on the most difficult tests of speech understanding in quiet but also have significant difficulty when signals are presented in noise. The major factors in these outcomes appear to be (i) a loss of low-frequency, fine structure information possibly due to the envelope extraction algorithms common to cochlear implant signal processing; (ii) a limitation in the number of effective channels of stimulation due to overlap in electric fields from electrodes, and (iii) central processing deficits, especially for patients with poor speech understanding. Two recent developments, bilateral implants and combined electric and acoustic stimulation, have promise to remediate some of the difficulties experienced by patients in noise and to reinstate low-frequency fine structure information. If other possibilities are realized, e.g., electrodes that emit drugs to inhibit cell death following trauma and to induce the growth of neurites toward electrodes, then the future is very bright indeed. PMID:18616994

Non-invasive in vivo evaluation of in situ forming PLGA implants by benchtop magnetic resonance imaging (BT-MRI) and EPR spectroscopy.

PubMed

Kempe, Sabine; Metz, Hendrik; Pereira, Priscila G C; Mäder, Karsten

2010-01-01

In the present study, we used benchtop magnetic resonance imaging (BT-MRI) for non-invasive and continuous in vivo studies of in situ forming poly(lactide-co-glycolide) (PLGA) implants without the use of contrast agents. Polyethylene glycol (PEG) 400 was used as an alternative solvent to the clinically used NMP. In addition to BT-MRI, we applied electron paramagnetic resonance (EPR) spectroscopy to characterize implant formation and drug delivery processes in vitro and in vivo. We were able to follow key processes of implant formation by EPR and MRI. Because EPR spectra are sensitive to polarity and mobility, we were able to follow the kinetics of the solvent/non-solvent exchange and the PLGA precipitation. Due to the high water affinity of PEG 400, we observed a transient accumulation of water in the implant neighbourhood. Furthermore, we detected the encapsulation by BT-MRI of the implant as a response of the biological system to the polymer, followed by degradation over a period of two months. We could show that MRI in general has the potential to get new insights in the in vivo fate of in situ forming implants. The study also clearly shows that BT-MRI is a new viable and much less expensive alternative for superconducting MRI machines to monitor drug delivery processes in vivo in small mammals. Copyright 2009 Elsevier B.V. All rights reserved.

Electrodeposited silk coatings for bone implants.

PubMed

Elia, Roberto; Michelson, Courtney D; Perera, Austin L; Brunner, Teresa F; Harsono, Masly; Leisk, Gray G; Kugel, Gerard; Kaplan, David L

2015-11-01

The aim of this study was to characterize the mechanical properties and drug elution features of silk protein-based electrodeposited dental implant coatings. Silk processing conditions were modified to obtain coatings with a range of mechanical properties on titanium studs. These coatings were assessed for adhesive strength and dissolution, with properties tuned using water vapor annealing or glycerol incorporation to modulate crystalline content. Coating reproducibility was demonstrated over a range of silk concentrations from 1% to 10%. Surface roughness of titanium substrates was altered using industry relevant acid etching and grit blasting, and the effect of surface topography on silk coating adhesion was assessed. Florescent compounds were incorporated into the silk coatings, which were modulated for crystalline content, to achieve four days of sustained release of the compounds. This silk electrogelation technique offers a safe and relatively simple approach to generate mechanically robust, biocompatible, and degradable implant coatings that can also be functionalized with bioactive compounds to modulate the local regenerative tissue environment. © 2014 Wiley Periodicals, Inc.

Burnishing Techniques Strengthen Hip Implants

NASA Technical Reports Server (NTRS)

2010-01-01

In the late 1990s, Lambda Research Inc., of Cincinnati, Ohio, received Small Business Innovation Research (SBIR) awards from Glenn Research Center to demonstrate low plasticity burnishing (LPB) on metal engine components. By producing a thermally stable deep layer of compressive residual stress, LPB significantly strengthened turbine alloys. After Lambda patented the process, the Federal Aviation Administration accepted LPB for repair and alteration of commercial aircraft components, the U.S. Department of Energy found LPB suitable for treating nuclear waste containers at Yucca Mountain. Data from the U.S. Food and Drug Administration confirmed LPB to completely eliminate the occurrence of fretting fatigue failures in modular hip implants.

Surface characterization and biodegradation behavior of magnesium implanted poly(L-lactide/caprolactone) films

NASA Astrophysics Data System (ADS)

Sokullu, Emel; Ersoy, Fulya; Yalçın, Eyyup; Öztarhan, Ahmet

2017-11-01

Biopolymers are great source for medical applications such as drug delivery, wound patch, artificial tissue studies etc., food packaging, cosmetic applications etc. due to their biocompatibility and biodegradability. Particularly, the biodegradation ability of a biomaterial makes it even advantageous for the applications. The more tunable the biodegradation rate the more desired the biopolymers. There are many ways to tune degradation rate including surface modification. In this study ion implantation method applied to biopolymer surface to determine its effect on biodegradation rate. In this study, surface modification of poly(L-lactide/caprolactone) copolymer film is practiced via Mg-ion-implantation using a MEVVA ion source. Mg ions were implanted at a fluence of 1 × 1015 ions/cm2 and ion energy of 30 keV. Surface characterization of Mg-ion-implanted samples is examined using Atomic Force Microscopy, Raman spectroscopy, contact angle measurement and FT-IR Spectroscopy. These analyses showed that the surface become more hydrophilic and rougher after the ion implantation process which is advantageous for cell attachment on medical studies. The in vitro enzymatic degradation of Mg-implanted samples was investigated in Lipase PS containing enzyme solution. Enzymatic degradation rate was examined by mass loss calculation and it is shown that Mg-implanted samples lost more than 30% of their weight while control samples lost around 20% of their weight at the end of the 16 weeks. The evaluation of the results confirmed that Mg-ion-implantation on poly(L-lactide/caprolactone) films make the surface rougher and more hydrophilic and changes the organic structure on the surface. On the other hand, ion implantation has increased the biodegradation rate.

75 FR 38699 - Implantation or Injectable Dosage Form New Animal Drugs; Propofol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

...The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a new animal drug application (NADA) filed by Fort Dodge Animal Health, Division of Wyeth. The NADA provides for veterinary prescription use of propofol as an anesthetic in dogs and cats.

Characterization and antibacterial performance of electrodeposited chitosan-vancomycin composite coatings for prevention of implant-associated infections.

PubMed

Ordikhani, F; Tamjid, E; Simchi, A

2014-08-01

Orthopaedic implant-associated infections are one of the most serious complications in orthopaedic surgery and a major cause of implant failure. In the present work, drug-eluting coatings based on chitosan containing various amounts of vancomycin were prepared by a cathodic electrophoretic deposition process on titanium foils. A three-step release mechanism of the antibiotic from the films in a phosphate-buffered saline solution was noticed. At the early stage, physical encapsulation of the drug in the hydrogel network controlled the release rate. At the late stage, however, in vitro degradation/deattachment of chitosan was responsible for the controlled release. Cytotoxicity evaluation of the drug-eluting coatings via culturing in human osteosarcoma cells (MG-63 osteoblast-like cell line) showed no adverse effect on the biocompatibility. Antibacterial tests against Gram-positive Staphylococcus aureus also demonstrated that the infection risk of titanium foils was significantly reduced due to the antibiotic release. Additionally, in vitro electrochemical corrosion studies by polarization technique revealed that the corrosion current density was significantly lower for the titanium foils with drug-eluting coatings compared to that of uncoated titanium. Copyright © 2014 Elsevier B.V. All rights reserved.

Implant Insertion Torque: Its Role in Achieving Primary Stability of Restorable Dental Implants.

PubMed

Greenstein, Gary; Cavallaro, John

2017-02-01

A literature review was conducted to determine the role of insertion torque in attaining primary stability of dental implants. The review is comprised of articles that discussed the amount of torque needed to achieve primary implant stability in healed ridges and fresh extraction sockets prior to immediate implant loading. Studies were appraised that addressed the effects of minimum and maximum forces that can be used to successfully place implants. The minimum torque that can be employed to attain primary stability is undefined. Forces ≥30 Ncm are routinely used to place implants into healed ridges and fresh extraction sockets prior to immediate loading of implants. Increased insertion torque (≥50 Ncm) reduces micromotion and does not appear to damage bone. In general, the healing process after implant insertion provides a degree of biologic stability that is similar whether implants are placed with high or low initial insertion torque. Primary stability is desirable when placing implants, but the absence of micromotion is what facilitates predictable implant osseointegration. Increased insertion torque helps achieve primary stability by reducing implant micromotion. Furthermore, tactile information provided by the first surgical twist drill can aid in selecting the initial insertion torque to achieve predictable stability of inserted dental implants.

Osseointegration of zirconia implants: an SEM observation of the bone-implant interface.

PubMed

Depprich, Rita; Zipprich, Holger; Ommerborn, Michelle; Mahn, Eduardo; Lammers, Lydia; Handschel, Jörg; Naujoks, Christian; Wiesmann, Hans-Peter; Kübler, Norbert R; Meyer, Ulrich

2008-11-06

The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level. A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Göttinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface. Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography. The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.

An approach to ablate and pace:AV junction ablation and pacemaker implantation performed concurrently from the same venous access site.

PubMed

Issa, Ziad F

2007-09-01

Atrioventricular junction (AVJ) ablation combined with permanent pacemaker implantation (the "ablate and pace" approach) remains an acceptable alternative treatment strategy for symptomatic, drug-refractory atrial fibrillation (AF) with rapid ventricular response. This case series describes the feasibility and safety of catheter ablation of the AVJ via a superior vena caval approach performed during concurrent dual-chamber pacemaker implantation. A total of 17 consecutive patients with symptomatic, drug-refractory, paroxysmal AF underwent combined AVJ ablation and dual-chamber pacemaker implantation procedure using a left axillary venous approach. Two separate introducer sheaths were placed into the axillary vein. The first sheath was used for implantation of the pacemaker ventricular lead, which was then connected to the pulse generator. Subsequently, a standard ablation catheter was introduced through the second axillary venous sheath and used for radiofrequency (RF) ablation of the AVJ. After successful ablation, the catheter was withdrawn and the pacemaker atrial lead was advanced through that same sheath and implanted in the right atrium. Catheter ablation of the AVJ was successfully achieved in all patients. The median number of RF applications required to achieve complete AV block was three (range 1-10). In one patient, AV conduction recovered within the first hour after completion of the procedure, and AVJ ablation was then performed using the conventional femoral venous approach. There were no procedural complications. Catheter ablation of the AVJ can be performed successfully and safely via a superior vena caval approach in patients undergoing concurrent dual-chamber pacemaker implantation.

Development and Characterization of a Scalable Microperforated Device Capable of Long-Term Zero Order Drug Release

DTIC Science & Technology

2010-06-29

posterior segment of the eye and include posterior uveitis , age-related macular degeneration, and macular edema (Hsu 2007). Long term drug therapy may be...device for local and controlled delivery of drugs; as a protective carrier to transport labile drugs; and as an implant for treatment of various chronic

Additive manufacturing: From implants to organs.

PubMed

Douglas, Tania S

2014-05-12

Additive manufacturing (AM) constructs 3D objects layer by layer under computer control from 3D models. 3D printing is one example of this kind of technology. AM offers geometric flexibility in its products and therefore allows customisation to suit individual needs. Clinical success has been shown with models for surgical planning, implants, assistive devices and scaffold-based tissue engineering. The use of AM to print tissues and organs that mimic nature in structure and function remains an elusive goal, but has the potential to transform personalised medicine, drug development and scientific understanding of the mechanisms of disease. 

Testing a Method for Quantifying the Output of Implantable Middle Ear Hearing Devices

PubMed Central

Rosowski, J.J.; Chien, W.; Ravicz, M.E.; Merchant, S.N.

2008-01-01

This report describes tests of a standard practice for quantifying the performance of implantable middle ear hearing devices (also known as implantable hearing aids). The standard and these tests were initiated by the Food and Drug Administration of the United States Government. The tests involved measurements on two hearing devices, one commercially available and the other home built, that were implanted into ears removed from human cadavers. The tests were conducted to investigate the utility of the practice and its outcome measures: the equivalent ear canal sound pressure transfer function that relates electrically driven middle ear velocities to the equivalent sound pressure needed to produce those velocities, and the maximum effective ear canal sound pressure. The practice calls for measurements in cadaveric ears in order to account for the varied anatomy and function of different human middle ears. PMID:17406105

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes.

PubMed

Zaher, A; Li, S; Wolf, K T; Pirmoradi, F N; Yassine, O; Lin, L; Khashab, N M; Kosel, J

2015-09-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5-2 μg/h for higher release rate designs, and 12-40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

PubMed Central

Zaher, A.; Li, S.; Wolf, K. T.; Pirmoradi, F. N.; Yassine, O.; Lin, L.; Khashab, N. M.; Kosel, J.

2015-01-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source. PMID:26487899

Molecular & phenotypic characterization of Staphylococcus epidermidis in implant related infections

PubMed Central

Prasad, Sujata; Nayak, N.; Satpathy, G.; Nag, H.L.; Venkatesh, P.; Ramakrishnan, S.; Ghose, Supriyo; Nag, T.C.

2012-01-01

Background & objectives: The discrimination between the Staphylococcus epidermidis colonizing the deep seated indwelling devices and those which are mere commensals has always been a challenge for the clinical microbiologist. This study was aimed to characterize the S. epidermidis isolates obtained from device related infection for their phenotypic and molecular markers of virulence and to see whether these markers can be used to differentiate the pathogenic S. epidermidis from the commensals. Methods: Fifty five S. epidermidis isolates from various device related infections such as endophthalmitis following intra-ocular lens (IOL) implantation, intravascular (IV) catheter related sepsis and orthopaedic implant infections, were studied for slime production, biotyping, antibiotic sensitivity; and mec A and ica positivity by the recommended procedures. Results: Twenty three (41.8%) isolates were multi-drug resistant, 26 (65.2%) were slime producers, 30 (54.5%) were adherent, 23 (41.8%) possessed the intercellular adhesin (ica) gene, and 28 (50.9%) harboured the mec A gene. Biotypes I and III were the commonest, most members of which were multi- drug resistant. Twenty two (73.3%) of the 30 adherent bacteria were slime producers as opposed to only 4 (16%) of the 25 non-adherent bacteria (P<0.001). A vast majority i.e. 21 (91.3%) of the 23 ica positive organisms were adherent to artificial surfaces in contrast to only 9 (28.1%) of the 32 non-ica positive organisms (P<0.001). Twenty (86.9%) of the 23 ica positive bacteria were slime producers, as opposed to only 6 (18.7%) of the 32 ica negative bacteria (P<0.001). Of the 23 multi-drug resistant isolates, 19 (82.6%) carried the mec A gene. Interpretation & conclusions: The present findings showed that ica AB and mec A were the two important virulence markers of S. epidermidis in implant infections and slime was responsible for the sessile mode of attachment on the devices. PMID:23041744

Influence of controlled immediate loading and implant design on peri-implant bone formation.

PubMed

Vandamme, Katleen; Naert, Ignace; Geris, Liesbet; Vander Sloten, Jozef; Puers, Robert; Duyck, Joke

2007-02-01

Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.

Recent progress on fabrication and drug delivery applications of nanostructured hydroxyapatite.

PubMed

Mondal, Sudip; Dorozhkin, Sergy V; Pal, Umapada

2018-07-01

Through this brief review, we provide a comprehensive historical background of the development of nanostructured hydroxyapatite (nHAp), and its application potentials for controlled drug delivery, drug conjugation, and other biomedical treatments. Aspects associated with efficient utilization of hydroxyapatite (HAp) nanostructures such as their synthesis, interaction with drug molecules, and other concerns, which need to be resolved before they could be used as a potential drug carrier in body system, are discussed. This review focuses on the evolution of perceptions, practices, and accomplishments in providing improved delivery systems for drugs until date. The pioneering developments that have presaged today's fascinating state of the art drug delivery systems based on HAp and HAp-based composite nanostructures are also discussed. Special emphasis has been given to describe the application and effectiveness of modified HAp as drug carrier agent for different diseases such as bone-related disorders, carriers for antibiotics, anti-inflammatory, carcinogenic drugs, medical imaging, and protein delivery agents. As only a very few published works made comprehensive evaluation of HAp nanostructures for drug delivery applications, we try to cover the three major areas: concepts, practices and achievements, and applications, which have been consolidated and patented for their practical usage. The review covers a broad spectrum of nHAp and HAp modified inorganic drug carriers, emphasizing some of their specific aspects those needed to be considered for future drug delivery applications. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Nanotechnology Approaches to Biology > Cells at the Nanoscale. © 2017 Wiley Periodicals, Inc.

Ahmed Glaucoma Valve Implantation in Vitrectomized Eyes.

PubMed

Erçalık, Nimet Yeşim; İmamoğlu, Serhat

2018-01-01

To evaluate the outcomes of Ahmed glaucoma valve (AGV) implantation in vitrectomized eyes. The medical records of 13 eyes that developed glaucoma due to emulsified silicon oil or neovascularization following pars plana vitrectomy and underwent AGV implantation were retrospectively reviewed. The main outcome measures were intraocular pressure (IOP), best-corrected visual acuity (BCVA), number of antiglaucoma medications, and postoperative complications. Surgical success was defined as last IOP ≤21 mmHg or ≥6 mmHg and without loss of light perception. The mean follow-up duration was 11.7 ± 5.5 (range, 6-23) months. The mean IOP before the AGV implantation was 37.9 ± 6.7 mmHg with an average of 3.5 ± 1.2 drugs. At the final visit, the mean IOP was 15.9 ± 4.6 mmHg ( p =0.001) and the mean number of glaucoma medications decreased to 2.3 ± 1.3 ( p =0.021). At the last visit, 11 eyes (84.4%) had stable or improved VA and one eye (7.7%) had a final VA of no light perception. Surgical success was achieved in 11 of the 13 eyes (84.4%). Postoperative complications were bleb encapsulation (69.2%), early hypotony (38.5%), hyphema (23.1%), decompression retinopathy (23.1%), choroidal detachment (15.4%), intraocular hemorrhage (7.7%), and late endophthalmitis (7.7%). One eye (7.7%) was enucleated because of late endophthalmitis. Despite complications necessitating medical and surgical interventions, vitrectomized eyes were effectively managed with AGV implantation.

Ahmed Glaucoma Valve Implantation in Vitrectomized Eyes

PubMed Central

İmamoğlu, Serhat

2018-01-01

Purpose To evaluate the outcomes of Ahmed glaucoma valve (AGV) implantation in vitrectomized eyes. Materials and Methods The medical records of 13 eyes that developed glaucoma due to emulsified silicon oil or neovascularization following pars plana vitrectomy and underwent AGV implantation were retrospectively reviewed. The main outcome measures were intraocular pressure (IOP), best-corrected visual acuity (BCVA), number of antiglaucoma medications, and postoperative complications. Surgical success was defined as last IOP ≤21 mmHg or ≥6 mmHg and without loss of light perception. Results The mean follow-up duration was 11.7 ± 5.5 (range, 6–23) months. The mean IOP before the AGV implantation was 37.9 ± 6.7 mmHg with an average of 3.5 ± 1.2 drugs. At the final visit, the mean IOP was 15.9 ± 4.6 mmHg (p=0.001) and the mean number of glaucoma medications decreased to 2.3 ± 1.3 (p=0.021). At the last visit, 11 eyes (84.4%) had stable or improved VA and one eye (7.7%) had a final VA of no light perception. Surgical success was achieved in 11 of the 13 eyes (84.4%). Postoperative complications were bleb encapsulation (69.2%), early hypotony (38.5%), hyphema (23.1%), decompression retinopathy (23.1%), choroidal detachment (15.4%), intraocular hemorrhage (7.7%), and late endophthalmitis (7.7%). One eye (7.7%) was enucleated because of late endophthalmitis. Conclusions Despite complications necessitating medical and surgical interventions, vitrectomized eyes were effectively managed with AGV implantation. PMID:29862068

Influence of Implant Positions and Occlusal Forces on Peri-Implant Bone Stress in Mandibular Two-Implant Overdentures: A 3-Dimensional Finite Element Analysis.

PubMed

Alvarez-Arenal, Angel; Gonzalez-Gonzalez, Ignacio; deLlanos-Lanchares, Hector; Brizuela-Velasco, Aritza; Dds, Elena Martin-Fernandez; Ellacuria-Echebarria, Joseba

2017-12-01

The aim of this study was to evaluate and compare the bone stress around implants in mandibular 2-implant overdentures depending on the implant location and different loading conditions. Four 3-dimensional finite element models simulating a mandibular 2-implant overdenture and a Locator attachment system were designed. The implants were located at the lateral incisor, canine, second premolar, and crossed-implant levels. A 150 N unilateral and bilateral vertical load of different location was applied, as was 40 N when combined with midline load. Data for von Mises stress were produced numerically, color coded, and compared between the models for peri-implant bone and loading conditions. With unilateral loading, in all 4 models much higher peri-implant bone stress values were recorded on the load side compared with the no-load side, while with bilateral occlusal loading, the stress distribution was similar on both sides. In all models, the posterior unilateral load showed the highest stress, which decreased as the load was applied more mesially. In general, the best biomechanical environment in the peri-implant bone was found in the model with implants at premolar level. In the crossed-implant model, the load side greatly altered the biomechanical environment. Overall, the overdenture with implants at second premolar level should be the chosen design, regardless of where the load is applied. The occlusal loading application site influences the bone stress around the implant. Bilateral occlusal loading distributes the peri-implant bone stress symmetrically, while unilateral loading increases it greatly on the load side, no matter where the implants are located.

Development of drug-loaded polymer microcapsules for treatment of epilepsy.

PubMed

Chen, Yu; Gu, Qi; Yue, Zhilian; Crook, Jeremy M; Moulton, Simon E; Cook, Mark J; Wallace, Gordon G

2017-09-26

Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles. Here we report the development of fibre- and sphere-based microcapsules that exhibit controllable uniform morphologies and drug release profiles as predicted by mathematical modelling. Importantly, both forms of fabricated microcapsules are compatible with human brain derived neural stem cells and differentiated neurons and neuroglia, indicating clinical compliance for neural implantation and therapeutic drug delivery.

Peri-implant bone formation and implant integration strength of peptide-modified p(AAM-co-EG/AAC) interpenetrating polymer network-coated titanium implants.

PubMed

Barber, Thomas A; Ho, James E; De Ranieri, Aladino; Virdi, Amarjit S; Sumner, Dale R; Healy, Kevin E

2007-02-01

Interpenetrating polymer networks (IPNs) of poly (acrylamide-co-ethylene glycol/acrylic acid) functionalized with an -Arg-Gly-Asp- (RGD) containing 15 amino acid peptides, derived from rat bone sialoprotein (bsp-RGD(15), were grafted to titanium implants in an effort to modulate bone formation in the peri-implant region in the rat femoral ablation model. Bone-implant contact (BIC) and bone formation within the medullary canal were determined using microcomputed tomography at 2 and 4 weeks postimplantation. BIC for bsp-RGD(15)-IPN implants was enhanced relative to hydroxyapatite tricalcium phosphate (HA-TCP) coated implants, but was similar to all other groups. Aggregate bone formation neither indicated a dose-dependent effect of bsp-RGD(15) nor a meaningful trend. Mechanical testing of implant fixation revealed that only the HA-TCP coated implants supported significant (>1 MPa) interfacial shear strength, despite exhibiting lower overall BIC, an indication that bone ingrowth into the rougher coating was the primary mode of implant fixation. While no evidence was found to support the hypothesis that bsp-RGD(15)-modified IPN coated implants significantly impacted bone-implant bonding, these results point to the lack of correlation between in vitro studies employing primary osteoblasts and in vivo wound healing in the peri-implant region. Copyright 2006 Wiley Periodicals, Inc.

Study design of the influence of SErotonin inhibition on patients with RENAl impairment or diabetes undergoing drug-eluting stent implantation (SERENADE) study: A multicenter, open-label, prospective, randomized study.

PubMed

Lee, Seung-Ah; Suh, Jung-Won; Park, Jin Joo; Yoon, Chang-Hwan; Cho, Young-Suk; Youn, Tae-Jin; Chae, In-Ho; Kim, Hyo-Soo; Kim, Sang-Hyun; Choi, Dong-Ju

2015-07-01

The rates of stent failure after percutaneous coronary intervention have decreased since the introduction of the drug-eluting stent (DES). However, chronic kidney disease (CKD) and diabetes mellitus (DM) remain strong clinical predictors of poor prognosis despite DES implantation. Sarpogrelate, a selective serotonin (5-hydroxytryptamine (HT)2a [5-HT2A]) receptor antagonist, has antiproliferative effects, reducing neointimal hyperplasia and smooth muscle cell proliferation, as well as potent antiplatelet action, inhibiting 5-HT-induced platelet aggregation. However, efficacy and safety data for sarpogrelate in patients with CKD or DM are limited. We aim to determine whether sarpogrelate has beneficial effects in patients with CDK or DM treated with DES implantation. The SERENADE trial is a multicenter, open-label, prospective, randomized study that will test the superiority of triple anti-platelet therapy (TAT; aspirin, clopidogrel, and sarpogrelate) to conventional dual antiplatelet therapy (DAT; aspirin and clopidogrel) in preventing late lumen loss 9 months after the index procedure in patients with CKD or DM. A total of 220 patients diagnosed with coronary artery disease with DM or CKD will be randomized to the TAT or DAT groups (1:1 ratio) after DES implantation. The primary endpoint is late lumen loss at 9 months assessed by quantitative coronary angiography. Secondary efficacy endpoints are composites of major adverse cardiovascular events including cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Secondary safety endpoints are major bleeding events and hepatic or renal impairment. The SERENADE trial will provide insight on the efficacy of adjunctive therapy with sarpogrelate after DES implantation for patients with high-risk profiles such as CKD or DM. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov NCT02294643). Copyright © 2015. Published by Elsevier Inc.