Nanoindentation Creep Behavior of Additively Manufactured H13 Steel by Utilizing Selective Laser Melting Technology.

Nowadays, H13 hot work steel is a commonly used hot work die material in the industry; however, its creep behavior for additively manufactured H13 steel parts has not been widely investigated. This research paper examines the impact of volumetric energy density (VED), a critical parameter in additive manufacturing (AM), and the effect of post heat-treatment nitrification on the creep behavior of H13 hot work tool steel, which is constructed through selective laser melting (SLM), which is a powder bed fusion process according to ISO/ASTM 52900:2021. The study utilizes nanoindentation tests to investigate the creep response and the associated parameters such as the steady-state creep strain rate. Measurements and observations taken during the holding phase offer a valuable understanding of the behavior of the studied material. The findings of this study highlight a substantial influence of both VED and nitrification on several factors including hardness, modulus of elasticity, indentation depth, and creep displacement. Interestingly, the creep strain rate appears to be largely unaltered by these parameters. The study concludes with the observation that the creep stress exponent (n) shows a decreasing trend with an increase in VED and the application of nitrification treatment.

Evaluation of 3D-Printed Solid Microneedles Coated with Electrosprayed Polymeric Nanoparticles for Simultaneous Delivery of Rivastigmine and N-Acetyl Cysteine.

In the current study, coated microneedle arrays were fabricated by means of digital light processing (DLP) printing. Three different shapes were designed, printed, and coated with PLGA particles containing two different actives. Rivastigmine (RIV) and N-acetyl-cysteine (NAC) were coformulated via electrohydrodynamic atomization (EHDA), and they were incorporated into the PLGA particles. The two actives are administered as a combined therapy for Alzheimer's disease. The printed arrays were evaluated regarding their ability to penetrate skin and their mechanical properties. Optical microscopy and scanning electron microscopy (SEM) were employed to further characterize the microneedle structure. Confocal laser microscopy studies were conducted to construct 3D imaging of the coating and to simulate the diffusion of the particles through artificial skin samples. Permeation studies were performed to investigate the transport of the drugs across human skin ex vivo. Subsequently, a series of tape strippings were performed in an attempt to examine the deposition of the APIs on and within the skin. Light microscopy and histological studies revealed no drastic effects on the membrane integrity of the stratum corneum. Finally, the cytocompatibility of the microneedles and their precursors was evaluated by measuring cell viability (MTT assay and live/dead staining) and membrane damages followed by LDH release.

Fabrication of 3D Printed Hollow Microneedles by Digital Light Processing for the Buccal Delivery of Actives.

In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device. Light microscopy was used to quality control the printability of the designs, confirming that the actual dimensions are in agreement with the digital design. Non-destructive volume imaging by means of microfocus computed tomography was employed for dimensional and defect characterization of the DLP-printed devices, demonstrating the actual volumes of the reservoirs and the malformations that occurred during printing. The penetration test and finite element analysis showed that the maximum stress experienced by the needles during the insertion process (10 N) was below their ultimate compressive strength (240-310 N). Permeation studies showed the increased permeability of three model drugs when delivered with the MN devices. Size-exclusion chromatography validated the stability of all the actives throughout the permeability tests. The safety of these printed devices for buccal administration was confirmed by histological evaluation and cell viability studies using the TR146 cell line, which indicated no toxic effects.

Delayed union, non-union and mal-union in 442 dogs.

OBJECTIVES: (1) To estimate the prevalence of delayed union, non-union and mal-union in canine fractures; (2) to describe fracture, demographic, and treatment characteristics for these outcomes; (3) to identify risk factors for delayed or non-union. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Four hundred and forty two dogs (461 fractures). METHODS: A review was conducted of clinical records and radiographs from 2 teaching hospitals. "Union," "delayed union," "non-union" and "mal-union" were defined, and fracture, demographic, treatment, and outcome variables described. Differences in proportions or medians between "union," "delayed union" and "non-union" were tested using χ2 and Mann-Whitney U-tests for categorical and continuous variables respectively. Potential explanatory variables for "delayed or non-union" were tested using logistic regression to identify risk factors. RESULTS: Median radiographic follow up was 53 days (14-282). Delayed union occurred in 13.9% of fractures (64/461), non-union in 4.6% (21/461), and mal-union in 0.7% (3/461). Risk factors for delayed or non-union were age (OR 1.21, 95% CI 1.12-1.31); comminuted fracture (OR 4.24, 95% CI 2.4-7.5); treatment with bone graft (all types) (OR 3.32, 95% CI 1.3-8.5); surgical site infection (OR 3.24, 95% CI 1.17-8.97), and major implant failure (OR 12.94, 95% CI 5.06-33.1). CONCLUSION: Older dogs, dogs with comminuted fractures, surgical site infection, or major implant failure were at increased odds of delayed or non-union. Radius and ulna fractures in toy breed dogs were not at increased odds of delayed or non-union. CLINICAL SIGNIFICANCE: The identified risk factors should inform fracture planning and prognosticating. The prognosis for radial fractures in toy breeds appears better than historically believed.

Automated digital design for 3D-printed individualized therapies.

Customization of pharmaceutical products is a central requirement for personalized medicines. However, the existing processing and supply chain solutions do not support such manufacturing-on-demand approaches. In order to solve this challenge, three-dimensional (3D) printing has been applied for customization of not only the dose and release characteristics, but also appearance of the product (e.g., size and shape). A solution for customization can be realized via non-expert-guided processing of digital designs and drug dose. This study presents a proof-of-concept computational algorithm which calculates the optimal dimensions of grid-like orodispersible films (ODFs), considering the recommended dose. Further, the algorithm exports a digital design file which contains the required ODF configuration. Cannabidiol (CBD) was incorporated in the ODFs, considering the simple correspondence between the recommended dose and the patient's weight. The ODFs were 3D-printed and characterized for their physicochemical, mechanical, disintegration and drug release properties. The algorithm was evaluated for its accuracy on dose estimation, highlighting the reproducibility of individualized ODFs. The in vitro performance was principally affected by the thickness and volume of the grid-like structures. The concept provides an alternative approach that promotes automation in the manufacturing of personalized medications in distributed points of care, such as hospitals and local pharmacies.

Fabrication of hollow microneedles using liquid crystal display (LCD) vat polymerization 3D printing technology for transdermal macromolecular delivery.

The present study aimed to fabricate a hollow microneedle device consisting of an array and a reservoir by means of 3D printing technology for transdermal peptide delivery. Hollow microneedles (HMNs) were fabricated using a biocompatible resin material, while PLA filament was used for the reservoirs. The fabricated microdevice was characterized by means of optical microscopy, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), contact angle measurements and leakage inspection studies to ensure the passageway of liquid formulations. Mechanical failure and penetration tests were carried out and supported by Finite Element Analysis (FEA). The cytocompatibility of the microneedle arrays was assessed to human keratinocytes (HaCaT). Finally, the transport of the model peptide octreotide acetate across artificial membranes was assessed in Franz cells using the aforementioned HMN design.

Body Temperature Fluctuation After Ovariohysterectomy in Dogs in Luteal Phase, Inactive Phase and Pyometra: A Clinical Study of 77 Cases.

Progesterone (P4) has a thermogenic effect in the bitch and a decrease in P4 has been associated with a mild transient decrease in body temperature. The aim of this study was to investigate the presence, the extent and the pattern of possible hypothermia after ovariohysterectomy (OHE) in healthy dogs in luteal phase and in bitches with pyometra that underwent therapeutic OHE. Sixty-two healthy dogs and 15 dogs with pyometra that underwent standardized OHE were included. Rectal temperature was measured 1 hour preoperatively (pre-op) and 6, 9, 12, 18, 24, 30, 36, 42, and 48 hours postoperatively (post-op). Serum P4 was measured 30 minutes pre-op and 6 and 24 hours post-op. Healthy dogs were classified in 3 groups based on their initial P4 concentration and in 3 separate groups based on their oestrus cycle stage. The temperature differentiation between the groups of the study was assessed using the repeated measures mixed-design ANOVA analysis. Temperature measured 18-42 hours post-op was significantly decreased compared to pre-op when initial P4 >8 ng/mL but not significantly decreased when P4 <8 ng/mL. Post-op temperature fluctuation in pregnant dogs showed no significant difference compared to dogs in diestrus. Dogs with pyometra had significantly lower temperature 6-48 hours post-op compared to all other groups. Conclusively, mild hypothermia (37.5-37.9°C) may be anticipated 18-42 hours after OHE performed in early diestrus or pregnancy in healthy dogs. More significant hypothermia (37.1-37.5°C) may be anticipated in normally recovering pyometra cases.

Electrospun Orodispersible Films of Isoniazid for Pediatric Tuberculosis Treatment.

Child-appropriate dosage forms are critical in promoting adherence and effective pharmacotherapy in pediatric patients, especially those undergoing long-term treatment in low-resource settings. The present study aimed to develop orodispersible films (ODFs) for isoniazid administration to children exposed to tuberculosis. The ODFs were produced from the aqueous solutions of natural and semi-synthetic polymer blends using electrospinning. The spinning solutions and the resulting fibers were physicochemically characterized, and the disintegration time and isoniazid release from the ODFs were assessed in simulated salivary fluid. The ODFs comprised of nanofibers with adequate thermal stability and possible drug amorphization. Film disintegration occurred instantly upon contact with simulated salivary fluid within less than 15 s, and isoniazid release from the ODFs in the same medium followed after the disintegration profiles, achieving rapid and total drug release within less than 60 s. The ease of administration and favorable drug loading and release properties of the ODFs may provide a dosage form able to facilitate proper adherence to treatment within the pediatric patient population.

Fabrication of an osmotic 3D printed solid dosage form for controlled release of active pharmaceutical ingredients.

In pharmaceutical formulations, pharmacokinetic behavior of the Active Pharmaceutical Ingredients (API's) is significantly affected by their dissolution profiles. In this project, we attempted to create personalized dosage forms with osmotic properties that exhibit different API release patterns via Fused Deposition Modelling (FDM) 3D printing. Specifically, cellulose acetate was employed to create an external shell of an osmotically active core containing Diltiazem (DIL) as model drug. By removing parts of the shell (upper surface, linear lateral segments) were created dosage forms that modify their shape at specific time frames under the effect of the gradually induced osmotic pressure. Hot-Melt Extrusion (HME) was employed to fabricate two different 3DP feeding filaments, for the creation of either the shell or the osmotic core (dual-extrusion printing). Printed formulations and filaments were characterized by means of (TGA, XRD, DSC) and inspected using microscopy (optical and electron). The mechanical properties of the filaments were assessed by means of micro- and macro mechanical testing, whereas micro-Computed Tomography (µCT) was employed to investigate the volumetric changes occurring during the hydration process. XRD indicated the amorphization of DIL inside HME filaments and printed dosage forms, whereas the incorporated NaCl (osmogen) retained its crystallinity. Mechanical properties' testing confirmed the printability of produced filaments. Dissolution tests revealed that all formulations exhibited sustained release differing at the initiation time of the API dissolution (0, 120 and 360 min for the three different formulations). Finally, µCT uncovered the key structural changes associated with distinct phases of the release profile. The above results demonstrate the successful utilization of an FDM 3D printer in order to create osmotic 3D printed formulations exhibiting sustained and/or delayed release, that can be easily personalized containing API doses corresponding to each patient's specific needs.

Investigation of leakage holes created by four needle types used for closure of canine enterotomies.

The creation of leakage holes in the intestinal wall by four types of swaged-on needles used to close enterotomy incisions in canine cadavers was studied. Twenty-four enterotomies were performed in 10 cm jejunal sections obtained from five dogs following euthanasia. After placement of Doyen intestinal forceps to the ends of each section, a 3 cm antimesenteric incision was performed and closed using 4-0 polydioxanone suture armed in a swaged-on needle in a simple interrupted pattern. One group served as control, with no enterotomies performed. The four groups that we used consisted of six sections each: group CC was closed with a polydioxanone suture armed in a conventional cutting needle, group RC was closed with a reversed cutting needle, group TPP was closed with a taper point plus needle, and group TC was closed with a taper cutting needle. Leak testing was performed by infusion of 13.5 mL methylene blue solution into the intestinal lumen. Significant differences between leakage and non-leakage sections of group CC were detected (P=.027). No statistical differences were detected among other groups. Conventional cutting needles seem to create leaking holes in cadaveric healthy jejunum during needle passage for closing an enterotomy incision.

Successful management of jejunojejunal anastomosis dehiscence by extra-abdominal exteriorization and bandaging in a cat with septic peritonitis.

Duodenal and jejunal resections were performed in a cat with septic peritonitis due to small intestinal perforations by a linear foreign body. Three days later jejunal resection and anastomosis were repeated due to dehiscence of the anastomosis site. This segment of intestine was exteriorized through the body wall and managed with bandages for 5 days before it was surgically replaced into the abdomen. The cat made a full recovery.

Gestion réussie d'une déhiscence d'une anastomose jéjunojéjunale par l'extériorisation extraabdominale et des pansements chez un chat atteint de péritonite septique. Des résections duodénale et jéjunale ont été réalisées chez un chat atteint de péritonite septique en raison de petites perforations intestinales par un corps étranger linéaire. Trois jours plus tard, la résection jéjunale et l'anastomose ont été répétées en raison d'une déhiscence du site de l'anastomose. Ce segment de l'intestin était extériorisé au travers de la paroi du corps et il a été géré à l'aide de pansements pendant 5 jours jusqu'à ce qu'il soit replacé dans l'abdomen par une chirurgie. Le chat s'est complètement rétabli.(Traduit par Isabelle Vallières).