Nanoroughness, Surface Chemistry and Drug Delivery Control by Atmospheric Plasma Jet on Implantable Devices

Implantable devices need specific tailored surface morphologies and chemistries to interact with the living systems or to actively induce a biological response also by the release of drugs or proteins. These customised requirements foster technologies that can be implemented in additive manufacturing systems. Here we present a novel approach based on spraying processes that allows to control separately topographic features in the submicron range ( 3d 60 nm - 2 \ub5m), ammine or carboxylic chemistry and fluorophore release even on temperature sensitive biodegradable polymers such as polycaprolactone (PCL). We developed a two-steps process with a first deposition of 220 nm silica and poly(lactic-co-glycolide) (PLGA) fluorescent nanoparticles by aerosol followed by the deposition of a fixing layer by atmospheric pressure plasma jet (APPJ). The nanoparticles can be used to create the nano-roughness and to include active molecule release, while the capping layer ensures stability and the chemical functionalities. The process is enabled by a novel APPJ which allows deposition rates of 10 - 20 nm\ub7s-1 at temperatures lower than 50 \ub0C using argon as process gas. This approach was assessed on titanium alloys for dental implants and on PCL films. The surfaces were characterized by FT-IR, AFM and SEM. Titanium alloys were tested with pre-osteoblasts murine cells line, while PCL film with fibroblasts. Cell behaviour was evaluated by viability and adhesion assays, protein adsorption, cell proliferation, focal adhesion formation and SEM. The release of a fluorophore molecule was assessed in the cell growing media, simulating a drug release. Osteoblast adhesion on the plasma treated materials increased by 20% with respect to commercial titanium alloys implants. Fibroblast adhesion increased by a 100% compared to smooth PCL substrate. The release of the fluorophore by the dissolution of the PLGA nanoparticles was verified and the integrity of the encapsulated drug model confirmed

Influence of the substrate temperature on the layer properties made by an atmospheric plasma jet using different precursors

In this work the surface temperature of porous polymer scaffolds treated with an atmospheric plasma jet was determined by theoretical estimations and infrared was measurements. Based on these results the scaffolds were coated with functional plasma polymer layers using this plasma jet and different precursors. The influence of the substrate temperature on the plasma polymer layer properties like thickness and chemical reactivity was investigated

A novel plasma jet with RF and HF coupled electrodes

In order to achieve low processing temperature and efficient coatings deposition for manufacturing applications, a novel torch has been developed that couples in a double DBD design high frequency (HF ~17 kHz) and radio frequency (RF ~27 MHz) excitations. The design allows to obtain a stable RF plasma also in reactive processes and with the possibility to control on the treated substrates ions flux and surface charging, avoiding the micro-discharges. The plasma has been electrically and optically characterized by emission spectroscopy

Cyclophilin A modulates bone marrow-derived CD117+ cells and enhances ischemia-induced angiogenesis via the SDF-1/CXCR4 axis

Abstract Background Critical limb ischemia (CLI) is a major health problem with no adequate treatment. Since CLI is characterized by insufficient tissue vascularization, efforts have focused on the discovery of novel angiogenic factors. Cyclophilin A (CyPA) is an immunophilin that has been shown to promote angiogenesis in vitro and to enhance bone marrow (BM) cell mobilization in vivo . However, its potential as an angiogenic factor in CLI is still unknown. Thus, this study aimed to evaluate whether CyPA might induce neo-angiogenesis in ischemic tissues. Methods and results Wild-type C57Bl/6j mice underwent acute hind-limb ischemia (HLI) and received a single intramuscular administration of recombinant CyPA or saline. Limb perfusion, capillary density and arteriole number in adductor muscles were significantly increased after CyPA treatment. Interestingly, BM-derived CD117 + cell recruitment was significantly higher in ischemic adductor tissue of mice treated with CyPA versus saline. Therefore, the effect of CyPA on isolated BM-derived CD117 + cells in vitro was evaluated. Low concentrations of CyPA stimulated CD117 + cell proliferation while high concentrations promoted cell death. Moreover, CyPA enhanced CD117 + cell adhesion and migration in a dose-dependent manner. Mechanistic studies revealed that CyPA up-regulated CXCR4 in CD117 + cells and in adductor muscles after ischemia. Additionally, SDF-1/CXCR4 axis inhibition by the CXCR4 antagonist AMD3100 decreased CyPA-mediated CD117 + cell recruitment in the ischemic limb. Conclusion CyPA induces neo-angiogenesis by recruiting BM-derived CD117 + cell into ischemic tissues, at least in part, through SDF-1/CXCR4 axis

3D additive manufactured composite scaffolds with antibiotic-loaded lamellar fillers for bone infection prevention and tissue regeneration

Bone infections following open bone fracture or implant surgery remain a challenge in the orthopedics field. In order to avoid high doses of systemic drug administration, optimized local antibiotic release from scaffolds is required. 3D additive manufactured (AM) scaffolds made with biodegradable polymers are ideal to support bone healing in non-union scenarios and can be given antimicrobial properties by the incorporation of antibiotics. In this study, ciprofloxacin and gentamicin intercalated in the interlamellar spaces of magnesium aluminum layered double hydroxides (MgAl) and α-zirconium phosphates (ZrP), respectively, are dispersed within a thermoplastic polymer by melt compounding and subsequently processed via high temperature melt extrusion AM (~190 °C) into 3D scaffolds. The inorganic fillers enable a sustained antibiotics release through the polymer matrix, controlled by antibiotics counterions exchange or pH conditions. Importantly, both antibiotics retain their functionality after the manufacturing process at high temperatures, as verified by their activity against both Gram + and Gram - bacterial strains. Moreover, scaffolds loaded with filler-antibiotic do not impair human mesenchymal stromal cells osteogenic differentiation, allowing matrix mineralization and the expression of relevant osteogenic markers. Overall, these results suggest the possibility of fabricating dual functionality 3D scaffolds via high temperature melt extrusion for bone regeneration and infection prevention.We are grateful to the FAST project funded under the H2020-NMP- PILOTS-2015 scheme (GA n. 685825) for financial support. Some of the materials used in this work were provided by the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White through a grant from NCRR of the NIH (Grant #P40RR017447)

Method for generating an atmospheric plasma jet and atmospheric plasma minitorch device

A method and a device for generating a plasma in atmospheric-pressure, low-temperature conditions are described herein. The device described for the generation of the plasma comprises a first pair of electrodes, each of which separated by a dielectric layer and externally positioned with respect to a tubular duct where the gas flows, and a second pair of electrodes, also in this case each of which separated by a dielectric layer and externally positioned with respect to said tubular duct where the same gas flows downstream with respect to the first pair with respect to the direction of the flow. A high-frequency excitation is applied to the first pair of electrodes while a Radio-Frequency excitation is applied to the second pair of electrodes. The plasma generated in this manner emerges from the gas flow at the outlet of the transport duct. The high-frequency excitation can be applied in pulse trains and the Radio-Frequency generator is substantially activated in said pulse trains for the purpose of limiting the thermal load on the treated substrate. Chemical precursors and reagents can be added to the plasma as vapors or aerosols by means of a central transport duct coaxial with the tubular duct for the gas

Innovative Composites Based on Organic Modified Zirconium Phosphate and PEOT/PBT Copolymer

Polymers are key building blocks in the development of smart materials for biomedical applications, and many polymers offer unique properties for specific applications. A wide range of materials is available through the use of polymer compounds. These compounds can incorporate performance-enhancing fillers, which provide properties not reachable with ordinary neat polymers (e.g., bending stiffness, tensile strength, elongation, torque, biological activity such as antimicrobial properties, cell differentiation). In this work, the preparation of functional biocomposites containing organic modified zirconium phosphate (ZrP) as drug carrier is presented. The composites were prepared by melt compounding, which offers significant promise since it allows an easy customization of the plastic compounds that well suit biomedical applications (devices, long-term implantable polymers, bioresorbable polymers). The obtained polymer composites based on ZrP intercalated with gentamicin (GMT) and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) were characterized