This work investigates the influence of Ag (1 wt%) on the mechanical properties, in vitro and in vivo corrosion, and biocompatibility of Fe-35Mn. The microstructure of Fe-35Mn-1Ag possesses a uniform ...dispersion of discrete silver particles. Slight improvements in compressive properties are attributed to enhanced density and low porosity volume. Fe-35Mn-1Ag exhibits good in vitro and in vivo corrosion rate of Fe-35Mn due to an increase in microgalvanic corrosion. Gas pockets, which originate from an inflammatory response to the implants, are observed in the rats after 4 weeks implantation but are undetectable after 12 weeks. No chronic toxicity is observed with the Fe-35Mn-1Ag, suggesting acceptable in vivo biocompatibility. The high corrosion rate of the alloy triggers an increased level of nonadverse tissue inflammatory responses 4 weeks after implantation, which subsequently subsides at 12 weeks. The Fe-35Mn-1Ag displays properties that are suitable for orthopedic applications.
We investigated effects of the neuroactive steroid anesthetic alfaxalone on intrinsic excitability, and on inhibitory and excitatory synaptic transmission to hypoglossal motor neurons (HMNs). Whole ...cell recordings were made from HMNs in brainstem slices from 7 to 14-day-old Wistar rats. Spontaneous, miniature, and evoked inhibitory post-synaptic currents (IPSCs), and spontaneous and evoked excitatory PSCs (EPSCs) were recorded at -60 mV. Alfaxalone did not alter spontaneous glycinergic IPSC peak amplitude, rise-time or half-width up to 10 μM, but reduced IPSC frequency from 3 μM. Evoked IPSC amplitude was reduced from 30 nM. Evoked IPSC rise-time was prolonged and evoked IPSC decay time was increased only by 10 μM alfaxalone. Alfaxalone also decreased evoked IPSC paired pulse ratio (PPR). Spontaneous glutamatergic EPSC amplitude and frequency were not altered by alfaxalone, and evoked EPSC amplitude and PPR was also unchanged. Alfaxalone did not alter HMN repetitive firing or action potential amplitude. Baseline holding current at -60 mV with a CsCl-based pipette solution was increased in an inward direction; this effect was not seen when tetrodotoxin (TTX) was present. These results suggest that alfaxalone modulates glycine receptors (GlyRs), causing a delayed and prolonged channel opening, as well as causing presynaptic reduction of glycine release, and activates a membrane current, which remains to be identified. Alfaxalone selectively reduces glycinergic inhibitory transmission to rat HMNs via a combination of pre- and post-synaptic mechanisms. The net effect of these responses to alfaxalone is to increase HMN excitability and may therefore underlie neuro-motor excitation during neurosteroid anesthesia.
A magnesium alloy containing essential, non-toxic, biodegradable elements such as Ca and Zn has been fabricated using a novel twin-roll casting process (TRC). Microstructure, mechanical properties, ...in vivo corrosion and biocompatibility have been assessed and compared to the properties of the rare earth (RE) element containing WE43 alloy. TRC Mg-0.5 wt% Zn- 0.5 wt% Ca exhibited fine grains with an average grain size ranging from 70 to 150 μm. Mechanical properties of a TRC Mg-0.5Zn-0.5Ca alloy showed an ultimate tensile strength of 220 MPa and ductility of 9.3%. The TRC Mg-0.5Zn-0.5Ca alloy showed a degradation rate of 0.51 ± 0.07 mm/y similar to that of the WE43 alloy (0.47 ± 0.09 mm/y) in the rat model after 1 week of implantation. By week 4 the biodegradation rates of both alloys studied were lowered and stabilized with fewer gas pockets around the implant. The histological analysis shows that both WE43 and TRC Mg-0.5Zn-0.5Ca alloy triggered comparable tissue healing responses at respective times of implantation. The presence of more organized scarring tissue around the TRC Mg-0.5Zn-0.5Ca alloys suggests that the biodegradation of the RE-free alloy may be more conducive to the tissue proliferation and remodelling process.
Display omitted
•Mg-0.5Zn-0.5Ca alloy plates were fabricated by a twin-roll casting (TRC) process.•TRC alloy showed an ultimate strength and elongation of 221 ± 2 MPa and 9 ± 2%.•Gas development during in vivo degradation was analysed using μ-CT techniques.•Histological analysis revealed a good biocompatibility and promoted healing.
While limbal epithelial cells are used for treating ocular surface wounds, the therapeutic potential of mesenchymal cells cultivated from the limbal stroma (LMSC) is less clear. We have therefore ...examined the effects of LMSC when applied to acute ocular surface wounds. LMSC derived from male rabbits (RLMSC) were applied to the ocular surface of female rabbits immediately following removal of the corneal and limbal epithelium. Human amniotic membrane (HAM) was used as the vehicle for implanting the RLMSC. The effects of RLMSC were examined when applied alone (n = 3) and in conjunction with a stratified culture of human limbal epithelial cells (HLE) grown on the opposing surface of the HAM (n = 3). Outcomes were monitored over 3 months in comparison with animals receiving no treatment (n = 3) or treatment with HLE alone on HAM (n = 3). Animals treated with RLMSC (n = 6) displayed faster re-epithelialization (∼90% versus 70% healing after 12 weeks), with best results being observed when RLMSC were pre-cultivated and implanted in the presence of HLE (p < 0.01; 90% healing by 7 weeks). While all animals displayed conjunctival cells on the corneal surface (by presence of goblet cells and/or keratin 13 expression) and corneal neovascularization, evidence of corneal epithelial regeneration was observed in animals that received RLMSC in the presence of HLE (by staining for keratin 3 and the absence of goblet cells). Conversely, corneal neovascularization was significantly greater when RLMSC were applied in the absence of HLE (<0.05; 90% of cornea compared with 20–30% in other cohorts). Nevertheless, neither human nuclear antigen nor rabbit Y chromosome were detected within the regenerated epithelium. Our results demonstrate that while cultured LMSC encourage corneal re-epithelialization, healing is improved by the pre-cultivation and implantation of these mesenchymal cells in the presence of limbal epithelial cells.
Objectives
Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continue at pace. Here, we describe rational antigen design through to ...manufacturability and vaccine efficacy of a prefusion‐stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 ‘MF59C.1’ (Seqirus, Parkville, Australia).
Methods
A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo‐electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat.
Results
In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S‐specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level.
Conclusion
The SARS‐CoV‐2 Sclamp vaccine candidate is compatible with large‐scale commercial manufacture, stable at 2–8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T‐cell responses and provides protection in animal challenge models.
We describe preclinical development of a prefusion stabilized spike protein subunit vaccine for SARS‐CoV‐2. Results include structural resolution by cryo‐electron microscopy, mouse immunogenicity and a hamster protection study.
Wireless capsule endoscopy (WCE) is a modern, non-invasive method of gastrointestinal examination that can significantly reduce mortality and morbidity. One of the current challenges in WCE is the ...precise localization of the capsule. An accurate path loss propagation model can be used to find the exact distance from the surface to the capsule inside the abdominal cavity. Unfortunately, there are no standardized In-to-On-Body channel models describing the signal propagation at ultra-high frequencies that are used in the most commercially available WCE systems. This study addresses the gap by conducting an experimental validation of a new propagation model for WCE applications at 2.45 GHz. The results were confirmed by conducting two separate in-vivo trials on porcine animals under general anesthesia. The performance of the model as well as the corresponding ranging errors were evaluated when it was used as an inverse solution for distance estimation to an ingested transmitter. The main advantage of the model is its theoretical basis, which can help further generalize the findings for similar communication scenarios. The obtained ranging error was smaller than one centimeter, suggesting that it can be used for accurate range-based positioning of implanted transmitters.
Biomedical researchers use of inhalational anesthetics has increased in recent years. Use of isoflurane as an inhalational anesthetic may result in human exposure to waste anesthetic gas. Potential ...health effects from exposure include genotoxic and hepatotoxic effects with some evidence of teratogenic and reproductive effects. Research suggests that exposure to waste anesthetic gas within human hospital settings has improved substantially but exposures to biomedical researchers and veterinarians still requires improvement. A number of biomedical research facilities are located at The University of Queensland, Australia, where researchers and animal handlers are potentially exposed to waste isoflurane gas. There is limited published data on the exposures received by biomedical researchers performing routine procedures. This project aimed to assess isoflurane exposure received during routine rodent anesthetic protocols performed at the university. Atmospheric concentrations of isoflurane were assessed via two methods-personal active gas sampling using sorbent tubes and direct readings using infrared spectroscopy. Total procedure and isoflurane exposure times ranged from 135-268 min. Personal sorbent tube sampling detected isoflurane levels from below detectable limits (<0.01 ppm) to a Time Weighted Average for the task (TWA-Task) of 6.20 ppm (0.73 ± 9.13). Participants were not exposed to isoflurane outside of the sampling period during the remainder of the workday. TWA-8 hr adjusted levels ranged from below the limit of detection to 1.76 ppm isoflurane (0.69 ppm ± 0.61 ppm). The infrared spectroscopy readings taken in the breathing zone of participants ranged from 0.1-68 ppm. Results indicate that if adequately controlled through good room ventilation, effective active gas scavenging and well constructed anesthetic equipment, waste anesthetic exposures are minimal. However, where industry standards are not met exposures may occur, including some high peak exposures.
A zinc-nutrient element alloy (Zn-1.0Cu-0.5Ca) was developed into subcuticular absorbable staples (SAS) as a robust alternative to the commercially available poly(l-lactide-co-glycolide) (PLGA) SAS ...for the first time. The fixation properties of the Zn SAS were measured via pull-out tests and in-situ lap-shear pull-out test comparatively against the PLGA SAS. The Zn SAS exhibited fixation force of 18.9±0.2 N, which was over three times higher than that of PLGA SAS (5.5±0.1 N). The Zn SAS was used to close incision wounds in a SD rat model for biodegradability and biocompatibility characterisation at 1, 4 and 12 weeks. The Zn SAS showed uniform degradation behaviour after in vivo implantation at the average rate of 198±54, 112±28, and 70±24 μm/y after 1, 4, and 12 weeks, which reduced the fixation force to 16.8±1.1 N, 15.4±0.9 N, 12.7±0.7 N, respectively. These findings showed the potential of the Zn SAS for the closure of heavy loading and slowing healing tissues. The Zn SAS enabled successful closure and healing of the incision wound, similar to the PLGA staples. However, the slow long-term degradation rate of the Zn SAS may lead to unnecessary implant retention. In addition, the alloy SAS resulted in higher local foreign body responses due to their stiffness. Reducing the implant cross-section profile and applying low stiffness and a corrosion-accelerating coating are suggested as possible approaches to reduce post-service implant retention and improve the biocompatibility of the Zn SAS.
This work reports the fabrication of the first metallic subcuticular absorbable staples (SAS) made from ZnCuCa alloy for skin wound closure applications. The Zn-based SAS were characterised in vitro and in vivo (SD rat model) for biodegradability, fixation properties, biocompatibility and inflammatory responses, which were compared against the commercially available PLGA-based SAS. The Zn-based SAS provided a secure attachment of the full-thickness wounds on SD rats and allowed successful healing during the 12-week service period. In addition, the in vitro results showed that the Zn-based SAS provided more than three times higher fixation strength than the commercial PLGA, indicating the potential of the Zn-based SAS for load-bearing wound closure application.
Display omitted
A prototype magnesium (Mg) surgical tack is tested comparatively against commercially available tacks made of titanium (ProTacktm, Medtronic) and PLGA (AbsorbaTacktm, Medtronic). The pull-out force ...is measured in situ in a lap-shear pull-out test, using porcine abdominal muscle tissue as a model. The Mg tack had a pull-out force comparable to those of the commercially available tacks. The majority of the Mg tacks also had a more ductile failure mode (i.e. the tacks deformed prior to failure), compared to the commercial tacks which pulled directly from the tissue with no deformation. The Mg tacks deformed as they were removed from the tissue, causing less damage to the tissue in the process. This is the first reported use of a Mg alloy in this application, and the proof of concept indicates that this is an area that deserves further interest and study.
Display omitted
•A Prototype magnesium (Mg) surgical tack is developed.•This is the first reported use of this material in this application.•Fixation strength tested in an in situ pull-out test using porcine tissue.•Mg tack compared to commercially available titanium and PLA tacks.•Prototype Mg tack performed comparably to commercial alternatives.
PDF
