Shape fidelity and sterility assessment of 3D printed polycaprolactone and hydroxyapatite scaffolds

AbstractPolycaprolactone (PCL) and hydroxyapatite (HA) composite are widely used in tissue engineering (TE). They are fit to being processed with three-dimensional (3D) printing technique to create scaffolds with verifiable porosity. The current challenge is to guarantee the reliability and reproducibility of 3D printed scaffolds and to create sterile scaffolds which can be used for in vitro cell cultures. In this context it is important for successful cell culture, to have a protocol in order to evaluate the sterility of the printed scaffolds. We proposed a systematic approach to sterilise 90%PCL-10%HA pellets using a 3D bioprinter before starting the printing process. We evaluated the printability of PCL-HA composite and the shape fidelity of scaffolds printed with and without sterilised pellets varying infill pattern, and the sterility of 3D printed scaffolds following the method established by the United States Pharmacopoeia. Finally, the thermal analyses supported by the Fourier Transform Infrared Spectroscopy were useful to verify the stability of the sterilisation process in the PCL solid state with and without HA. The results show that the use of the 3D printer, according to the proposed protocol, allows to obtain sterile 3D PCL-HA scaffolds suitable for TE applications such as bone or cartilage repair

Study of the compounding process parameters for morphology control of LDPE/layered silicate nanocomposites

AbstractA careful insight into melt compounding procedure is proposed in order to achieve a better understanding and control of the dispersion and orientation mechanisms of organo-clay platelets into LDPE nanocomposites. The method involved is the preparation of a maleic anhydride grafted polyethylene masterbatch containing 10 wt% organo-clay via twin-screw extrusion. A substantial nanodispersion and orientation of clay platelets was obtained as observed by X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses. Moreover, the nanocomposites prepared by diluting the master-batch through the blend mixing with additional LDPE preserved or improved the exfoliation and lamellae orientation. Finally, the thermo-gravimetric analysis (TGA) showed a significant improvement of the thermal stability while both differential scanning calorimetry (DSC) and XRD evidenced a slight increase of the LDPE crystallinity degree with respect to neat polymer matrices thus suggesting the occurrence of orientation also for the polymer

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)

Fire Retardant Action of Layered Double Hydroxides and Zirconium Phosphate Nanocomposites Fillers in Polyisocyanurate Foams

Modern day energy codes are driving the design and multi-layered configuration of exterior wall systems with a significant emphasis on achieving high performance insulation towards improving energy performance of building envelopes. Use of highly insulating polyisocyanurate (PIR) based materials enhanced with eco-friendly lamellar inorganic fillers reinforces energy performance requirements, environmental challenges and cost reduction without compromising the overall building fire safety. The current work assessed the fire behaviour of PIR modified with three layered fillers, namely MgAlCO3 (PIR-LDH1), MgAl Stearate (PIR-LDH2) and Zirconium Phosphate octadecylamine (PIR-ZrP3). For each of the fillers, three loadings (2, 4 and 6% by weight) were used. Optical analysis by X-ray diffraction patterns (XRD), cone calorimeter (CC), thermogravimetric (TGA) analysis, post-burning morphological evaluation using field emission scanning electron microscope (FESEM) and diffuse reflectance infrared spectroscopy (DRIFT) analysis, were performed. The results indicated that fire reaction properties and thermal stability of foam samples were enhanced with all three different lamellar inorganic smart fillers. The initial degradation temperature of PIR-layered filler samples was increased, demonstrating that incorporation of flame retardants decelerated the degradation of the PIR foam and contributed to significant char formation, from 19.5% in pure PIR samples to 33% in PIR-6%LDH1 samples. Increasing the filler content also resulted in improved char properties and decreased peak Heat Release Rates (HRR) in the cone calorimeter. Due to the development of a stable char layer, samples containing 6% of ZrP3 did not ignite at 20 kW/m2 and a reduction of up to 40% in the peak HRR was achieved in PIR-2%ZrP3 samples

Additive Manufactured Scaffolds for Bone Tissue Engineering: Physical Characterization of Thermoplastic Composites with Functional Fillers

Thermoplastic polymer–filler composites are excellent materials for bone tissue engineering (TE) scaffolds, combining the functionality of fillers with suitable load-bearing ability, biodegradability, and additive manufacturing (AM) compatibility of the polymer. Two key determinants of their utility are their rheological behavior in the molten state, determining AM processability and their mechanical load-bearing properties. We report here the characterization of both these physical properties for four bone TE relevant composite formulations with poly(ethylene oxide terephthalate)/poly(butylene terephthalate (PEOT/PBT) as a base polymer, which is often used to fabricate TE scaffolds. The fillers used were reduced graphene oxide (rGO), hydroxyapatite (HA), gentamicin intercalated in zirconium phosphate (ZrP-GTM) and ciprofloxacin intercalated in MgAl layered double hydroxide (MgAl-CFX). The rheological assessment showed that generally the viscous behavior dominated the elastic behavior (G″ > G′) for the studied composites, at empirically determined extrusion temperatures. Coupled rheological–thermal characterization of ZrP-GTM and HA composites showed that the fillers increased the solidification temperatures of the polymer melts during cooling. Both these findings have implications for the required extrusion temperatures and bonding between layers. Mechanical tests showed that the fillers generally not only made the polymer stiffer but more brittle in proportion to the filler fractions. Furthermore, the elastic moduli of scaffolds did not directly correlate with the corresponding bulk material properties, implying composite-specific AM processing effects on the mechanical properties. Finally, we show computational models to predict multimaterial scaffold elastic moduli using measured single material scaffold and bulk moduli. The reported characterizations are essential for assessing the AM processability and ultimately the suitability of the manufactured scaffolds for the envisioned bone regeneration application.The work was supported by a Horizon 2020 Research and Innovation Programme grant from the European Union, called the FAST project (grant no. 685825, project website: http:// project-fast.eu). The authors acknowledge the support of the FAST project consortium for the various aspects of this wor

Air Embolism after Central Venous Catheter Removal: Fibrin Sheath as the Portal of Persistent Air Entry

Central venous catheterization is of common practice in intensive care units; despite representing an essential device in various clinical circumstances, it represents a source of complications, sometimes even fatal, related to its management. We report the removal of a central venous catheter (CVC) that had been wrongly positioned through left internal jugular vein. The vein presented complete thrombosis at vascular ultrasonography. An echocardiogram performed 24 hours after CVC removal showed the presence, apparently unjustified, of microbubbles in right chambers of the heart. A neck-thorax CT scan showed the presence of air bubbles within the left internal jugular vein, left innominate vein, and left subclavian vein. A vascular ultrasonography, focused on venous catheter insertion site, disclosed the presence of a vein-to-dermis fistula, as portal of air entry. Only after air occlusive dressing, we documented echographic disappearance of air bubbles within the right cardiac cavity. This report emphasizes possible air entry even many hours after CVC removal, making it mandatory to perform 24–72-hour air occlusive dressing or, when inadequate, to perform a purse string

The Rheology of PEOT/PBT Block Copolymers in the Melt State and in the Thermally-Induced Sol/Gel Transition. Implications on the 3D-Printing Bio-Scaffold Process

Poly(ethyleneoxideterephthalate)/poly(butyleneterephthalate) (PEOT/PBT) segmented block copolymers are widely used for the manufacturing of 3D-printed bio-scaffolds, due to a combination of several properties, such as cell viability, bio-compatibility, and bio-degradability. Furthermore, they are characterized by a relatively low viscosity at high temperatures, which is desired during the injection stages of the printing process. At the same time, the microphase separated morphology generated by the demixing of hard and soft segments at intermediate temperatures allows for a quick transition from a liquid-like to a solid-like behavior, thus favoring the shaping and the dimensional stability of the scaffold. In this work, for the first time, the rheology of a commercial PEOT/PBT material is studied over a wide range of temperatures encompassing both the melt state and the phase transition regime. Non-isothermal viscoelastic measurements under oscillatory shear flow allow for a quantitative determination of the material processability in the melt state. Additionally, isothermal experiments below the order–disorder temperature are used to determine the temperature dependence of the phase transition kinetics. The importance of the rheological characterization when designing the 3D-printing scaffold process is also discussed