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Frontiers in Bioengineering and... 2024Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to...
Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant's biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.
PubMed: 38766649
DOI: 10.3389/fbioe.2024.1352023 -
Cureus Apr 2024The management of choroidal neovascularization (CNVM) in pregnant young females has been a lacuna due to the rarity of the condition as well as the non-availability of...
The management of choroidal neovascularization (CNVM) in pregnant young females has been a lacuna due to the rarity of the condition as well as the non-availability of comprehensive data to showcase the efficacy of currently available treatment regimes in order to achieve a positive outcome for both the growing fetus as well the patient herself. In a review of available literature, the condition has been treated with anti-vascular endothelial growth factors (anti-VEGF), laser photocoagulation, and intravitreal dexamethasone implants (IDI), with varied results ranging from the successful outcome in terms of pregnancy to abortions. When faced with such circumstances, healthcare professionals usually proceed cautiously, balancing the possible advantages against the hazards to the mother and the fetus. Here we present a case report of a young 30-year-old pregnant lady who developed idiopathic CNVM during her third month of gestation. Being a rare entity, CNVM in young pregnant women raises severe concerns due to potential consequences on the mother's and fetus's health. In certain previously documented cases, pregnant ladies with CNVM have been successfully treated with IDI. Hence, after much deliberation, we chose to go with IDI rather than anti-VEGF, which resulted in the successful management of her CNVM as well as achieving full-term normal delivery without any fetal anomalies. In this particular case, the pregnancy and the visual rehabilitation have both had favorable outcomes. There was no associated increased intraocular pressure (IOP) or changes to the lenticular structure. The literature review also suggests that IDI may still be as effective in managing CNVM during pregnancy, but at a lower risk than anti-VEGF drug. Even with the favorable outcomes revealed in case reports, larger-scale studies to properly examine IDI's safety profile would be required for regulatory clearance of its safety in pregnancy.
PubMed: 38765334
DOI: 10.7759/cureus.58458 -
Heliyon May 2024The study of fluid flow over curved surfaces is crucial in various engineering applications, such as designing aircraft wings, turbines, and submarines. Curved surfaces...
The study of fluid flow over curved surfaces is crucial in various engineering applications, such as designing aircraft wings, turbines, and submarines. Curved surfaces are being explored in various biomedical applications, such as designing stents for blood vessels and implants for bones and joints. Concerning the present applications of curved stretching sheets on fluid dynamics along with trihybrid nanofluids, this study is unique and fills the research gaps and offers solutions to several issues. This work looks at the flow through the boundary layer of an electrically conductive trihybrid nanofluid and the convection heat exchange of a Casson fluid across a curved stretched surface encircled within a circle of radius . The study considers the effects of thermal radiation using the non-linearized Rosseland approximation, as well as a magnetic field, and hydromagnetic slip. The flow as well as the transfer of heat problem is mathematically described by curvilinear coordinates. Using the combination of the shooting technique and the Runge-Kutta method, similar solutions to the modeled partial differential equations are produced, and the set of non-linear ordinary differential equations with a boundary value solver is implemented through the MATLAB program. The study finds the influence of several limits on critical characteristics such as fluid velocity, coefficient of skin friction, pressure, temperature, and rate of heat exchange over a surface. The findings are shown in tables and graphs. Additionally, a comparative analysis between the current findings and those found in the literature is provided. Blood-containing nanoparticles () on curved surfaces could improve drug delivery effectiveness, growth of synthetic tissues or organs with complex structures and effective cancer therapy treatment.
PubMed: 38765143
DOI: 10.1016/j.heliyon.2024.e30638 -
BMC Veterinary Research May 2024Beneficial weight-loss properties of glucagon-like peptide-1 receptor agonists (GLP-1RA) in obese people, with corresponding improvements in cardiometabolic risk...
Beneficial weight-loss properties of glucagon-like peptide-1 receptor agonists (GLP-1RA) in obese people, with corresponding improvements in cardiometabolic risk factors, are well established. OKV-119 is an investigational drug delivery system that is being developed for the long-term delivery of the GLP-1RA exenatide to feline patients. The purpose of this study was to evaluate the drug release characteristics of subcutaneous OKV-119 implants configured to release exenatide for 84 days. Following a 7-day acclimation period, five purpose-bred cats were implanted with OKV-119 protypes and observed for a 112-day study period. Food intake, weekly plasma exenatide concentrations and body weight were measured. Exenatide plasma concentrations were detected at the first measured timepoint (Day 7) and maintained above baseline for over 84 Days. Over the first 28 days, reduced caloric intake and a reduction in body weight were observed in four of five cats. In these cats, a body weight reduction of at least 5% was maintained throughout the 112-day study period. This study demonstrates that a single OKV-119 implant can deliver the GLP-1RA exenatide for a months long duration. Results suggest that exposure to exenatide plasma concentrations ranging from 1.5 ng/ml to 4 ng/ml are sufficient for inducing weight loss in cats.
Topics: Animals; Exenatide; Cats; Male; Female; Drug Delivery Systems; Hypoglycemic Agents; Body Weight; Drug Liberation; Drug Implants; Eating; Venoms; Glucagon-Like Peptide-1 Receptor
PubMed: 38762728
DOI: 10.1186/s12917-024-04051-6 -
Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
Ophthalmology and Therapy Jul 2024The travoprost intracameral implant was recently approved by the US Food and Drug Administration for sustained release medical treatment of open-angle glaucoma in the...
The travoprost intracameral implant was recently approved by the US Food and Drug Administration for sustained release medical treatment of open-angle glaucoma in the USA. The approval represents a substantial and progressive step forward in the area of sustained-release glaucoma therapy. Topical intraocular pressure-lowering medications for the treatment of glaucoma are faced with a host of challenges for long-term and usually lifelong care. A changing paradigm in glaucoma management involves first-line interventions with laser modalities, micro-invasive surgeries, and sustained-release treatment platforms. Future needs in the area of sustained-release therapy include a non-prostaglandin drug delivery platform and longer-term treatments that do not require surgical reintervention.
PubMed: 38761359
DOI: 10.1007/s40123-024-00965-4 -
Bioactive Materials Jul 2024Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still...
Imidazole functionalized photo-crosslinked aliphatic polycarbonate drug-eluting coatings on zinc alloys for osteogenesis, angiogenesis, and bacteriostasis in bone regeneration.
Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn-Li) alloys to inhibit Zn release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn release inhibition properties. Benefiting from the regulated release of Zn and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both and . The rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.
PubMed: 38756420
DOI: 10.1016/j.bioactmat.2024.03.037 -
The Journal of Clinical Pediatric... May 2024To explore a new method to implant deciduous tooth pulp into the canal of young permanent teeth with necrotic pulps and apical periodontitis for the regenerative...
To explore a new method to implant deciduous tooth pulp into the canal of young permanent teeth with necrotic pulps and apical periodontitis for the regenerative endodontic treatment of tooth no: 41 in a 7-year-old male. Briefly, 1.5% Sodium Hypochlorite (NaOCl) irrigation and calcium hydroxide-iodoform paste were used as root canal disinfectant at the first visit. After 2 weeks, the intracanal medication was removed, and the root canal was slowly rinsed with 17% Ethylene Diamine Tetraacetic Acid (EDTA), followed by flushing with 20 mL saline and then drying with paper points. Tooth no: 72 was extracted, and its pulp was extracted and subsequently implanted into the disinfected root canal along with induced apical bleeding. Calcium hydroxide iodoform paste was gently placed over the bleeding clot, and after forming a mineral trioxide aggregate (MTA) coronal barrier, the accessed cavities were restored using Z350 resin composite. The root developments were evaluated radiographic imaging at 6 months, 1 year and 5 years after treatment. Imaging and clinical analysis showed closure of the apical foramen, thickening of the root canal wall, and satisfactory root length growth. Autologous transplantation might be useful to regenerate dental pulp in necrotic young permanent teeth.
Topics: Humans; Male; Child; Dental Pulp; Tooth, Deciduous; Incisor; Calcium Compounds; Aluminum Compounds; Oxides; Drug Combinations; Dental Pulp Necrosis; Silicates; Follow-Up Studies; Regenerative Endodontics; Mandible; Calcium Hydroxide; Neovascularization, Physiologic; Root Canal Therapy; Root Canal Irrigants; Root Canal Filling Materials; Periapical Periodontitis; Sodium Hypochlorite; Dental Pulp Cavity; Hydrocarbons, Iodinated
PubMed: 38755996
DOI: 10.22514/jocpd.2024.071 -
Journal of Orthopaedic Surgery and... May 2024This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone...
BACKGROUND
This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone regeneration.
METHODS
Specialized titanium hollow implants (5 mm in diameter and 6 mm in height for rabbit; 6 mm in diameter and 5 mm in height for pig) were designed and manufactured using 3D printing technology. The implants were divided into three groups and filled with different bone graft combinations, namely (1) SBG alone; (2) PRF to SBG in 1:1 ratio; (3) PRF to SBG in 2:1 ratio. These three groups were replicated tightly into each bone defect in distal femurs of rabbits (nine implants, n = 3) and femoral shafts of pigs (fifteen implants, n = 5). Animal tissue sections were obtained after euthanasia at the 8th postoperative week. The rabbit specimens were stained with analine blue, while the pig specimens were stained with Masson-Goldner's trichrome stain to perform histologically examination. All titanium hollow implants were well anchored, except in fracture specimens (three in the rabbit and one fracture in the pig).
RESULT
Rabbit specimens under analine blue staining showed that collagen tissue increased by about 20% and 40% in the 1:1 ratio group and the 2:1 ratio group, respectively. Masson-Goldner's trichrome stain results showed that new bone growth increased by 32% in the 1:1 ratio PRF to SBG, while - 8% in the 2:1 ratio group.
CONCLUSION
This study demonstrated that placing a 1:1 ratio combination of PRF and SBG in a stabilized titanium 3D printed implant resulted in an optimal increase in bone growth.
Topics: Animals; Printing, Three-Dimensional; Rabbits; Platelet-Rich Fibrin; Bone Regeneration; Swine; Titanium; Femur; Bone Substitutes; Bone Transplantation; Prostheses and Implants
PubMed: 38755635
DOI: 10.1186/s13018-024-04784-y -
Frontiers in Immunology 2024The release of mature interleukin (IL-) 1β from osteoblasts in response to danger signals is tightly regulated by the nucleotide-binding oligomerization domain...
INTRODUCTION
The release of mature interleukin (IL-) 1β from osteoblasts in response to danger signals is tightly regulated by the nucleotide-binding oligomerization domain leucine-rich repeat and pyrin-containing protein 3 (NLRP3) inflammasome. These danger signals include wear products resulting from aseptic loosening of joint arthroplasty. However, inflammasome activation requires two different signals: a nuclear factor-kappa B (NF-κB)-activating priming signal and an actual inflammasome-activating signal. Since human osteoblasts react to wear particles via Toll-like receptors (TLR), particles may represent an inflammasome activator that can induce both signals.
METHODS
Temporal gene expression profiles of TLRs and associated intracellular signaling pathways were determined to investigate the period when human osteoblasts take up metallic wear particles after initial contact and initiate a molecular response. For this purpose, human osteoblasts were treated with metallic particles derived from cobalt-chromium alloy (CoCr), lipopolysaccharides (LPS), and tumor necrosis factor-alpha (TNF) alone or in combination for incubation times ranging from one hour to three days. Shortly after adding the particles, their uptake was observed by the change in cell morphology and spectral data.
RESULTS
Exposure of osteoblasts to particles alone increased NLRP3 inflammasome-associated genes. The response was not significantly enhanced when cells were treated with CoCr + LPS or CoCr + TNF, whereas inflammation markers were induced. Despite an increase in genes related to the NLRP3 inflammasome, the release of IL-1β was unaffected after contact with CoCr particles.
DISCUSSION
Although CoCr particles affect the expression of NLRP3 inflammasome-associated genes, a single stimulus was not sufficient to prime and activate the inflammasome. TNF was able to prime the NLRP3 inflammasome of human osteoblasts.
Topics: Humans; NLR Family, Pyrin Domain-Containing 3 Protein; Osteoblasts; Inflammasomes; Tumor Necrosis Factor-alpha; Gene Expression Regulation; Cells, Cultured; Signal Transduction
PubMed: 38751427
DOI: 10.3389/fimmu.2024.1397432