Nuclear Medicine Clinical Practice in the United States During the COVID-19 Era and Beyond.

Traditionally, practice in nuclear medicine has involved strong emphasis on radiation safety principles. Nuclear medicine technologists (NMTs) focus on practices that keep patients, the public, and the technologist safe from potentially harmful effects of unnecessary radiation exposure using concepts of time, distance, and shielding as well as ALARA (As low as reasonably achievable) principles. The current COVID-19 pandemic has brought to light the need to apply focus on infection prevention in practice and update knowledge and procedures on such measures. In this article, the authors outline the need for NMTs to develop practices and values focused on infection prevention measures.

Teaching Professional Behavior.

The goal of this article is to discuss the teaching of professional behavior to nuclear medicine technologists. The focus is on the present-day student situation and practices in the programs at Bellevue College and at Oregon Institute of Technology. Professional behavior is defined, and ways to communicate and assess it are described. Additionally, approaches to remedy unprofessional behavior are presented. The needs and expectations of clinical sites and of future employers of nuclear medicine graduates, as well as current avenues for promoting professionalism, are also discussed.

High refractive index polysiloxane as injectable, in situ curable accommodating intraocular lens.

Functionalised siloxane macromonomers, with properties designed for application as an injectable, in situ curable accommodating intraocular lens (A-IOL), were prepared via re-equilibration of a phenyl group-containing polysiloxane of very high molecular weight with octamethylcyclotetrasiloxane (D4) and 2,4,6,8-tetra(n-propyl-3-methacrylate)-2,4,6,8-tetramethyl-cyclotetrasiloxane (D4(AM)) in toluene using trifluoromethanesulfonic acid as a catalyst. Hexaethyldisiloxane was used as an end group to control the molecular weight of the polymer. The generated polymers had a consistency suitable for injection into the empty lens capsule. The polymers contained a low ratio of polymerisable groups so that, in the presence of a photo-initiator, they could be cured on demand in situ within 5 min under irradiation of blue light to form an intraocular lens within the lens capsule. All resulting polysiloxane soft gels had a low elastic modulus and thus should be able to restore accommodation. The pre-cure viscosity and post-cure modulus of the generated polysiloxanes were controlled by the end group and D4(AM) concentrations respectively in the re-equilibration reactions. The refractive index could be precisely controlled by adjusting the aromatic ratio in the polymer to suit such application as an artificial lens. Lens stretching experiments with both human and non-human primate cadaver lenses of different ages refilled with polysiloxane polymers provided a significant increase in amplitude of accommodation (up to 4 D more than that of the respective natural lens). Both in vitro cytotoxicity study using L929 cell lines and in vivo biocompatibility study in rabbit models demonstrated the non-cytotoxicity and ocular biocompatibility of the polymer.

One step multifunctional micropatterning of surfaces using asymmetric glow discharge plasma polymerization.

Micropatterning of surfaces with varying chemical, physical and topographical properties usually requires a number of fabrication steps. Herein, we describe a micropatterning technique based on plasma enhanced chemical vapour deposition (PECVD) that deposits both protein resistant and protein repellent surface chemistries in a single step. The resulting multifunctional, selective surface chemistries are capable of spatially controlled protein adhesion, geometric confinement of cells and the site specific confinement of enzyme mediated peptide self-assembly.

The influence of surface topography of a porous perfluoropolyether polymer on corneal epithelial tissue growth and adhesion.

Design principles for corneal implants are challenging and include permeability which inherently involves pore openings on the polymer surface. These topographical cues can be significant to a successful clinical outcome where a stratified epithelium is needed over the device surface, such as with a corneal onlay or corneal repair material. The impact of polymer surface topography on the growth and adhesion of corneal epithelial tissue was assessed using porous perfluoropolyether membranes with a range of surface topography. Surfaces were characterised by AFM and XPS, and the permeability and water content of membranes was measured. Biological testing of membranes involved a 21-day in vitro tissue assay to evaluate migration, stratification and adhesion of corneal epithelium. Similar parameters were monitored in vivo by surgically implanting membranes into feline corneas for up to 5 months. Data showed optimal growth and adhesion of epithelial tissue in vitro when polymer surface features were below a 150 nm RMS value. Normal processes of tissue growth and adhesion were disrupted when RMS values approached 300 nm. Data from the in vivo study confirmed these findings. Together, outcomes demonstrated the importance of surface topography in the design of implantable devices that depend on functional epithelial cover.

A perfluoropolyether corneal inlay for the correction of refractive error.

This study assessed the long-term biological response of a perfluoropolyether-based polymer developed as a corneal inlay to correct refractive error. The polymer formulation met chemical and physical specifications and was non-cytotoxic when tested using standard in vitro techniques. It was cast into small microporous membranes that were implanted as inlays into corneas of rabbits (n = 5) and unsighted humans (n = 5 + 1 surgical control) which were monitored for up to 23 and 48 months respectively. Overall, the inlays were well tolerated during study period with the corneas remaining clear and holding a normal tear film and with no increased vascularisation or redness recorded. Inlays in three human corneas continued past 48 months without sequelae. Inlays in two human corneas were removed early due to small, focal erosions developing 5 and 24 months post-implantation. Polymer inlays maintained their integrity and corneal position for the study duration although the optical clarity of the inlays reduced slowly with time. Inlays induced corneal curvature changes in human subjects that showed stability with time and the refractive effect was reversed when the inlay was removed. Outcomes showed the potential of a perfluoropolyether inlay as a biologically acceptable corneal implant with which to provide stable correction of refractive error.

A highly elastic tissue sealant based on photopolymerised gelatin.

Gelatin is widely used as a medical biomaterial because it is readily available, cheap, biodegradable and demonstrates favourable biocompatibility. Many applications require stabilisation of the biomaterial by chemical crosslinking, and this often involves derivatisation of the protein or treatment with cytotoxic crosslinking agents. We have previously shown that a facile photochemical method, using blue light, a ruthenium catalyst and a persulphate oxidant, produces covalent di-tyrosine crosslinks in resilin and fibrinogen to form stable hydrogel biomaterials. Here we show that various gelatins can also be rapidly crosslinked to form highly elastic (extension to break >650%) and adhesive (stress at break >100 kPa) biomaterials. Although the method does not require derivatisation of the protein, we show that when the phenolic (tyrosine-like) content of gelatin is increased, the crosslinked material becomes resistant to swelling, yet retains considerable elasticity and high adhesive strength. The reagents are not cytotoxic at the concentration used in the photopolymerisation reaction. When tested in vivo in sheep lung, the photopolymerised gelatin effectively sealed a wound in lung tissue from blood and air leakage, was not cytotoxic and did not produce an inflammatory response. The elastic properties, thermal stability, speed of curing and high tissue adhesive strength of this photopolymerised gelatin, offer considerable improvement over current surgical tissue sealants.

Biocompatibility and modification of the protein-based adhesive secreted by the Australian frog Notaden bennetti.

When provoked, Notaden bennetti frogs secrete a proteinaceous exudate, which rapidly forms a tacky and elastic glue. This material has potential in biomedical applications. Cultured cells attached and proliferated well on glue-coated tissue culture polystyrene, but migrated somewhat slower than on uncoated surfaces. In organ culture, dissolved glue successfully adhered collagen-coated perfluoropolyether lenses to debrided bovine corneas and supported epithelial regrowth. Small pellets of glue implanted subcutaneously into mice were resorbed by surrounding tissues, and all of the animals made a full recovery. An initial but transient skin necrosis at the implant site was probably caused by some of the potentially toxic metabolites present in the frog secretion; these include sterols and carotenoids, as well as fatty alcohols, aldehydes, ketones, acids, and aromatic compounds. Removal of the carotenoid pigments did not significantly alter the glue's material properties. In contrast, peroxidase treatment of dissolved glue introduced unnatural crosslinks between molecules of the major protein (Nb-1R) and resulted in the formation of a soft hydrogel, which was very different to the original material.

Multifunctional polymer coatings for cell microarray applications.

Biocompatible coatings with suitable chemistries for the immobilization of biomolecules are increasingly in demand, as they can be applied in a wide range of biomedical applications. In particular, multifunctional polymer coatings displaying reactive functional groups for the immobilization of specific biological factors that can influence the cellular response while at the same time exhibiting low nonspecific protein adsorption and cell attachment properties have the potential to significantly advance the fields of biomaterials and regenerative medicine. In this study, multifunctional polymer surface chemistries were developed for a cell microarray application with the aim of screening cellular interactions with surface immobilized factors. Coatings were prepared by the deposition of an allylamine plasma polymer pinning layer followed by the deposition of random copolymers of glycidyl methacrylate (GMA) and poly(ethylene glycol) methacrylate (PEGMA). Coatings were characterized by X-ray photoelectron spectroscopy (XPS), infrared spectroscopy, ellipsometry, and contact angle measurements. A variety of proteins as well as synthetic polymers were printed onto copolymer-coated slides using a high-precision contact microarrayer. Printing conditions were optimized for a fluorescently labeled model protein in regard to the temperature, humidity, pin geometry, concentration, and pH of the printing solution. Finally, the suitability of the surface chemistry for the evaluation of cellular responses to surface immobilized factors in a microarray format was demonstrated using HeLa cells.

Approaches to improving the biocompatibility of porous perfluoropolyethers for ophthalmic applications.

Porous perfluoropolyether (PFPE) membranes for ophthalmic applications were prepared with a zwitterion monomer, 3-[[2-(methacryloxy) ethyl](N,N-dimethyl)ammonio]-propane-1-sulphonate, copolymerized in weight ratios of 0-10%. The polymer samples were assessed for a range of physical properties, including equilibrium water content, bovine serum albumin permeability, transparency, refractive index and the ability to support corneal epithelial cell and tissue attachment, growth and migration. In vitro assessment of the polymers using bovine corneal epithelial cells and tissue showed that a zwitterion incorporation level of between 0% and 6% in the PFPE membranes supported the migration of an intact sheet of epithelial tissue without compromising epithelial cell attachment and growth, with 4-6% being the optimal level for these properties. Binding patterns of the cell adhesion glycoprotein fibronectin were also found to reflect the cell and tissue response. Effective nutrient permeability, refractive index and optical transparency were also maintained by the porous PFPE polymers containing this concentration of zwitterionic monomer. The presence of amounts of zwitterion greater than 6% was inhibitory to both tissue migration and cell growth and was associated with increased optical haze. These results demonstrated that it is possible to achieve the potential for increased biocompatibility in zwitterion-containing PFPE polymers without compromising existing beneficial characteristics.

The use of corneal organ culture in biocompatibility studies.

This study investigated the potential of a corneal organ culture system in the evaluation of polymers for ophthalmic devices that require epithelialisation. Two different polymers were tested in lenticule form to explore the sensitivity of this in vitro assay. Polycarbonate and perfluoropolyether-based lenticules were surgically implanted into bovine corneas and compared with a parallel series of sham-wounded corneas. Following surgery, all corneas were maintained in an air/liquid organ culture system for up to 8 days during which time they were evaluated clinically to monitor the rate of epithelial growth across the lenticule surface (implanted) or wound bed (sham). Data showed differences in the kinetics of epithelial migration according to the underlying surface with full epithelialisation of the sham series occurring on day 5+/-0.5, the perfluoropolyether lenticules on day 6+0.5 and polycarbonate lenticules on day 8+/-0.5. Histology revealed differences in the structure and morphology of the migrating and stable epithelium in each series of corneas. The differential response of the corneal epithelium was related to the physiochemical characteristics of the natural (sham) or synthetic (perfluoropolyether or polycarbonate) substrata which the epithelium could detect when maintained in organ culture. This assay system has utility for screening candidate polymers for certain ophthalmic applications.