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Iskandar M.E.,University of California at Riverside | Iskandar M.E.,N2 Biomedical LLC | Aslani A.,University of California at Riverside | Aslani A.,N2 Biomedical LLC | And 4 more authors.
Journal of Materials Science: Materials in Medicine | Year: 2015

This article reports the deposition and characterization of nanostructured calcium phosphate (nCaP) on magnesium–yttrium alloy substrates and their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs). The nCaP coatings were deposited on magnesium and magnesium–yttrium alloy substrates using proprietary transonic particle acceleration process for the dual purposes of modulating substrate degradation and BMSC adhesion. Surface morphology and feature size were analyzed using scanning electron microscopy and quantitative image analysis tools. Surface elemental compositions and phases were analyzed using energy dispersive X-ray spectroscopy and X-ray diffraction, respectively. The deposited nCaP coatings showed a homogeneous particulate surface with the dominant feature size of 200–500 nm in the long axis and 100–300 nm in the short axis, and a Ca/P atomic ratio of 1.5–1.6. Hydroxyapatite was the major phase identified in the nCaP coatings. The modulatory effects of nCaP coatings on the sample degradation and BMSC behaviors were dependent on the substrate composition and surface conditions. The direct culture of BMSCs in vitro indicated that multiple factors, including surface composition and topography, and the degradation-induced changes in media composition, influenced cell adhesion directly on the sample surface, and indirect adhesion surrounding the sample in the same culture. The alkaline pH, the indicator of Mg degradation, played a role in BMSC adhesion and morphology, but not the sole factor. Additional studies are necessary to elucidate BMSC responses to each contributing factor. © 2015, Springer Science+Business Media New York.


News Article | November 17, 2015
Site: www.materialstoday.com

3D printing has been around for at least 25 years, but it is only recently that it has started to go mainstream and given innovative researchers a tool with which to get creative. Now, Randall Erb and colleagues at Northeastern University are using magnetic fields to print detailed geometries from fiber-reinforced composite materials with the highest resolution to date. One possible future application of this technology could be the fabrication of medical devices, such as catheters for use in neonatal care. As such, the team is working as a subcontractor under funding awarded to N2 Biomedical LLC of Bedford, Massachusetts by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number 1R41HD086043. Almost half a million babies are born prematurely in the USA alone and their wellbeing relies on a range of tubes and catheters to deliver air to their lungs, as well as nutrients, fluids, and medications to their bodies and to remove urine. Standard catheters come only in set shapes and sizes and are not necessarily suitable for a particular baby. "With neonatal care, each baby is a different size, each baby has a different set of problems," explains Erb. "If you can print a catheter whose geometry is specific to the individual patient, you can insert it to a certain critical spot, you can avoid puncturing veins, and you can expedite delivery of the contents." A first step in the development of this technology is to demonstrate the necessary control in 3D printing. Erb and his colleagues have now used magnetic fields to shape composite materials - polymer-ceramic blends - to assist the 3D printing process and control the flow of ceramic fibers, lightly dusted with magnetic iron oxide. This allowed them to make 3d composite objects that show remarkable strength, stiffness. These products also show new mechanical properties such as programmable fracture toughness, Erb told us. "We [now] have the ability to manipulate crack paths through failing materials," he explains. [Nature Commun, 2015, 6, online DOI: 10.1038/ncomms9641] An ultralow magnetic field is sufficient to align the ceramic fibers within individual sections of the composite material immersed in liquid polymer to be 3D printed to a very specific device design. "Stereolithography then builds the product, layer by layer, using a computer-controlled projector to cure the polymer. That control will be critical if one is crafting devices with complex architectures, such as customized miniature biomedical devices. Within a single patient-specific device, the corners, the curves, and the holes must all be reinforced by ceramic fibers arranged in just the right configuration to make the device durable. "We are following nature's lead," explains team member Joshua Martin, "By taking really simple building blocks but organizing them in a fashion that results in really impressive mechanical properties." Until now there has been a gap between design and practical production. 3D printing with composite materials and magnetic control is filling that gap, the team suggests. David Bradley blogs at Sciencebase Science Blog and tweets @sciencebase, he is author of the bestselling science book "Deceived Wisdom".


Linden K.J.,N2 Biomedical LLC
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2016

This paper describes the use of a 420 nm blue laser diode for possible surgery and hemostasis. The optical absorption of blood-containing tissue is strongly determined by the absorption characteristics of blood. Blood is primarily comprised of plasma (yellowish extracellular fluid that is approximately 95% water by volume) and formed elements: red blood cells (RBCs), white blood cells (WBCs) and platelets. The RBCs (hemoglobin) are the most numerous, and due to the spectral absorption characteristics of hemoglobin, the optical absorption of blood has a strong relative maximum value in the 420 nm blue region of the optical spectrum. Small, low-cost laser diodes emitting at 420 nm with tens of watts of continuous wave (CW) optical power are becoming commercially available. Experiments on the use of such laser diodes for tissue cutting with simultaneous hemostasis were carried out and are here described. It was found that 1 mm deep x 1 mm wide cuts can be achieved in red meat at a focused laser power level of 3 W moving at a velocity of ∼ 1 mm/s. The peripheral necrosis and thermal damage zone extended over a width of approximately 0.5 mm adjacent to the cuts. Preliminary hemostasis experiments were carried out with fresh equine blood in Tygon tubing, where it was demonstrated that cauterization can occur in regions of intentional partial tubing puncture. © 2016 SPIE.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2015

DESCRIPTION provided by applicant Peri implantitis is a disease characterized by progressive loss of bone surrounding dental implants which may occur many years after successful implantation In this program a dual mode surface treatment will be developed that will encourage a strong interface between the implant and living bone and gingival tissue while also providing a long lasting anti bacterial effect to discourage the bacterial precursors to peri implantitis To achieve this goal two complementary surface modifications will be applied A nano textured surface will be developed based on predictive modeling in which anti bacterial pro osteoblast and pro gingival fibroblast properties will be selected The textured coating material will be an amorphous silver doped titania deposited by ion beam assisted deposition This coating will bond aggressively to the Ti implant surface and itself provide significant and very long lasting antimicrobial efficacy Efficacy will be demonstrated through combination perio pathogenic bacteria osteoblast and gingival fibroblast cell assays This combination of morphologic and material approaches will promote osseointegration and a healthy mucosal seal while also providing very long lasting antimicrobial protection that will significantly reduc the occurrence of peri implantitis associated with dental implants PUBLIC HEALTH RELEVANCE Peri implantitis is a disease characterized by progressive loss of the bone surrounding dental implants which may occur many years after successful implantation In this program a dual mode surface treatment will be developed that will encourage a strong interface between the implant and living bone while also providing an extremely long lasting antimicrobial action to discourage the bacterial precursors of peri implantitis


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 224.99K | Year: 2015

DESCRIPTION provided by applicant Clinical treatment of infants in the neonatal intensive care unit NICU is particularly challenging due to their small anatomies medical instability and immature physiological processes Treatment is often complicated by the lack of therapeutic devices and instrumentation designed specifically to accommodate this unique patient population For instance current vascular access catheters are not specifically designed and customized for the very small vasculature of neonatal patients which exacerbates common complications including vessel perforation thrombotic occlusions catheter breakage and infection Creating sophisticated patient specific neonatal catheters would dramatically reduce these complications and work to better serve this population D printing offers the ability to generate complex and patient specific D architectures Our collaborators at Northeastern University are pioneering D Magnetic Printing a new technique in which reinforcing ceramic fibers are aligned with magnetic fields during the printing process to create composites with highly tunable reinforcement architectures We will use D Magnetic Printing to produce strong flexible patient specific neonatal vascular access catheters Specifically we will generate customizable composite catheter tubing with enhanced wall stiffness and strength while maintaining flexibility burst strength and kink resistance Such a novel design approach will allow production of next generation neonatal vascular access catheters with thinner walls permitting reduction of catheter diameters and or higher fluid transport rates D Magnetic Printing of neonatal catheters offers the advantages of improved resistance to catheter sidewall collapse and kinking that often leads to catheter occlusion and higher fluid transport rates which will minimize the probability of thrombus and fibrin sheath formation Furthermore the D printing technique is compatible with conventional catheter materials such as polyurethane and silicone and allows utilization of biocompatible fibers like hydroxyapatite facilitating regulatory approval pathways The printing method is robust low cost and scalable In Phase I we will print a variety of catheter tubing with customized fiber architectures including longitudinal lateral and radial reinforcement using both polyurethane and silicone Sample characterization will be used to fine tune a finite element analysis model of the material This model will be used to design improved tubing for comparison to conventionally extruded tubing Our primary objective is to demonstrate the production of tubing with reduced wall thickness optimized mechanical properties and enhanced flow characteristics In Phase II this model will be used to design functional catheters having complex reinforcement architecture PUBLIC HEALTH RELEVANCE In this program a novel Magnetic D Printing technique will be developed for printing pediatric catheters This technique will enable highly customized immediate printing of devices for a population that often has unique and underserved requirements The technique introduces a novel means of controlling the alignment of reinforcing fibers which will give the designer a powerful tool to improve critical catheter characteristics such as wall thickness flow rate and kink resistance which are especially important in the small sizes required by pediatric patients These improvements will ultimately improve performance and reduce catheter related complications


Grant
Agency: National Aeronautics and Space Administration | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 123.42K | Year: 2016

The proposed program will develop a ceramic coating with surface features, ranging from nanometer to micrometer size-scale, that will be optimized to prevent the attachment of biofilm-forming bacteria found in wastewater plumbing in life support systems in space. The coating technology offers several advantages compared to presently available processes, including low temperature deposition, a range of surface feature sizes, strong adhesion, and no toxic waste products. Phase I will deposit the anti-microbial coating on metallic and polymer samples of materials typical of those in the International Space Station (ISS), measure the mechanical and physical characteristics of the coatings, and compare bacterial and biofilm formation rate with uncoated controls. The coating with the greatest anti-microbial activity will also be demonstrated on the interior surface of tubing sections of the same ISS materials. If Phase I is successful, Phase II would expand testing to other biofilm-forming bacterial types and to other organic materials found in wastewater piping, and demonstrate coating deposition on realistic-size plumbing configurations. Phase II would also initiate intellectual property protection and develop partnerships for NASA and commercial applications. Phase III of the proposed program would see strong commercialization efforts, both in-house and through external licensing agreements.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 529.75K | Year: 2016

Project Summary Magnesium Mg and its alloys have attracted increasing interest for use as biodegradable implants such as fixation devices for orthopedic and cranio maxillofacial surgeries due to their promising mechanical and biological properties as well as their ability to degrade and resorb in the body The overall aim of the Phase II program is to extend encouraging Phase I results in which biodegradable magnesium beads coated with hydroxyapatite HA with an incorporated antibiotic showed significant reduction of bacterial growth rate and retained their mechanical properties during extended immersion in simulated body fluid Uncoated controls lost much of their mechanical strength during the immersion tests Phase II will extend the promising results by optimizing the hydroxyapatite coating which is applied by N Biomedicalandapos s proprietary process to produce a thin durable layer at low temperature thereby retaining the properties of the HA source material and viability of temperature sensitive material such as an antibiotic We will continue to develop a coating in which the HA will not only help initiate bone growth but also regulate the dissolution rate of the magnesium substrate and the release of the antibiotic thus preventing infection In vivo studies will use optimized HA coated Mg implants in a rat model to study initiation of bone growth implant dissolution and antibacterial efficacy of the antibiotic that is incorporated in the coating Success of this program could lead to reduction or elimination of the present need for a subsequent operation to remove an implant or beads from the patient Overall success through Phase III commercialization could start a revolution in the implant industry and a significant shift of the clinical paradigm in craniofacial and orthopedic surgery by reducing cost and pain associated with revision surgeries for implant removal Project Narrative Millions of screws pins plates beads and suture anchors are used for fixation in orthopedic and cranio maxilla facial surgeries annually Despite their widespread use the choice of materials for these surgical fixation devices has been limited to non degradable metals like stainless steel and titanium Ti alloys or bioabsorbable polymers like poly L lactic acid PLLA poly glycolic acid PGA and their copolymers or polyester ceramic composites If successful HA coated Mg beads plates and screws could be used for craniofacial maxillofacial orthopedic and many other applications especially in pediatric surgery Considering the pain caused in young patients surgical complication and healthcare cost there is a critical need in pediatric surgeries to have degradable beads plates and screws to eliminate the necessity of a second surgery

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