Rabbit Model Research Articles

Effect of cyclic loading on the ultimate tensile strength of small metallic suture anchors used for attaching artificial tendons in rabbits.

Suture anchor failures can lead to revision surgeries which are costly and burdensome for patients. The durability of musculoskeletal reconstructions is therefore partly affected by the design of the suture anchors. The purpose of the study was to quantify the strength of different suture anchors whose sizes are suitable for attaching artificial Achilles and tibialis cranialis tendons in a rabbit model, as well as determine the effect of cyclic loading on the anchoring strength. Four anchors (two with embedded eyelet and two with raised eyelet, n=5 per group) were tested with cyclical loading (1000 cycles and 4.5 mm/sec) and without cycling, to inform the failure loads and mode of failure of the suture anchors. An eyebolt screw with smooth eyelet was used as a control for the test groups. All samples in all groups completed 1000 cycles and failed via suture breakage in both test conditions. All anchors had failure loads exceeding the peak Achilles tendon force in rabbits during hopping gait. The data analysis showed an effect of anchor type on the maximum tensile force at failure (F max ) in all suture categories but not an effect of loading condition. Also, the Anika anchor had a significantly less adverse effect on suture strength compared to Arthrex anchor (p=0.015), IMEX anchor (p=0.004) and Jorvet anchor (p<0.001). We observed a greater percentage of failure at the mid-section for the anchors with the raised eyelets compared to the anchors with embedded eyelets, which all failed at the knot. Anchors with embedded eyelets had clinically preferred mode of failure with less adverse effects on suture and, may be more reliable than anchors with raised eyelets for attaching artificial Achilles and tibialis cranialis tendons in rabbits.

Physiologically Based Pharmacokinetic Modeling and Clinical Extrapolation for Topical Application of Pilocarpine on Eyelids: A Comprehensive Study

Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases. To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.

Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe3O4 magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Establishment of orthotopic osteosarcoma animal models in immunocompetent rats through muti-rounds of in-vivo selection

Immunodeficient murine models are usually used as the preclinical models of osteosarcoma. Such models do not effectively simulate the process of tumorigenesis and metastasis. Establishing a suitable animal model for understanding the mechanism of osteosarcoma and the clinical translation is indispensable. The UMR-106 cell suspension was injected into the marrow cavity of Balb/C nude mice. Tumor masses were harvested from nude mice and sectioned. The tumor fragments were transplanted into the marrow cavities of SD rats immunosuppressed with cyclosporine A. Through muti-rounds selection in SD rats, we constructed orthotopic osteosarcoma animal models using rats with intact immune systems. The primary tumor cells were cultured in-vitro to obtain the immune-tolerant cell line. VX2 tumor fragments were transplanted into the distal femur and parosteal radius of New Zealand white rabbit to construct orthotopic osteosarcoma animal models in rabbits. The rate of tumor formation in SD rats (P1 generation) was 30%. After four rounds of selection and six rounds of acclimatization in SD rats with intact immune systems, we obtained immune-tolerant cell lines and established the orthotopic osteosarcoma model of the distal femur in SD rats. Micro-CT images confirmed tumor-driven osteolysis and the bone destruction process. Moreover, the orthotopic model was also established in New Zealand white rabbits by implanting VX2 tumor fragments into rabbit radii and femurs. We constructed orthotopic osteosarcoma animal models in rats with intact immune systems through muti-rounds in-vivo selection and the rabbit osteosarcoma model.

Impact of Zinc Oxide on the Development of Aspergillus-Induced Maxillary Sinusitis Rabbit Model.

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1β and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

Regeneration of dental pulp via collagen hydrogel composited with resveratrol-loaded chitosan nanoparticle in a rabbit model of dental pulp injury

Regeneration of dental pulp via collagen hydrogel composited with resveratrol-loaded chitosan nanoparticle in a rabbit model of dental pulp injury

Ruthenium Antivenom Inhibits the Defibrinogenating Activity of Crotalus adamanteus Venom in Rabbits.

Eastern Diamondback Rattlesnake (Crotalus adamanteus) envenomation is a medical emergency encountered in the Southeastern United States. The venom contains a snake venom thrombin-like enzyme (SVTLE) that is defibrinogenating, causing coagulopathy without effects on platelets in humans. This investigation utilized thrombelastographic methods to document this coagulopathy kinetically on the molecular level in a rabbit model of envenomation via the analyses of whole blood samples without and with platelet inhibition. Subsequently, the administration of a novel ruthenium compound containing site-directed antivenom abrogated the coagulopathic effects of envenomation in whole blood without platelet inhibition and significantly diminished loss of coagulation in platelet-inhibited samples. This investigation provides coagulation kinetic insights into the molecular interactions and results of SVTLE on fibrinogen-dependent coagulation and confirmation of the efficacy of a ruthenium antivenom. These results serve as a rationale to investigate the coagulopathic effects of other venoms with this model and assess the efficacy of this site-directed antivenom.

Celastrol alleviates subconjunctival fibrosis induced by silicone implants mimicking glaucoma surgery

Subconjunctival fibrosis is critical to the outcomes of several ophthalmic conditions or procedures, such as glaucoma filtering surgery. This study aimed to investigate the anti-fibrotic effect of celastrol on subconjunctival fibrosis and to further reveal the underlying mechanisms. We used celastrol-loaded nanomicelles hydrogel hybrid as a sustained-release drug. A rabbit model of subconjunctival fibrosis following silicone implantation was used for in vivo study, and TGF-β1-induced human pterygium fibroblast (HPF) activation as an in vitro model. The effects of celastrol on inhibiting TGF-β1-induced migration and proliferation of HPFs were evaluated by scratch wound assay and CCK-8, respectively. Immunofluorescence and western blotting were used to examine the effect of celastrol on the expression of α-SMA, collagen I, fibronectin, and the targets of the Hippo signaling pathway. We found that in vivo celastrol treatment reduced the expression of YAP and TAZ in subconjunctival tissue. Moreover, celastrol alleviated collagen deposition and subconjunctival fibrosis at 8 weeks. No obvious tissue toxicity was observed in the rabbit models. Mechanistically, celastrol significantly inhibited TGF-β1-induced proliferation and migration of HPFs. Pretreatment of HPFs with celastrol also suppressed the TGF-β1-induced protein expression of α-SMA, collagen I, fibronectin, TGF-βRII, phosphorylated Smad2/3, YAP, TAZ, and TEAD1. In conclusion, celastrol effectively prevented subconjunctival fibrosis through inhibiting TGF-β1/Smad2/3-YAP/TAZ pathway. Celastrol could serve as a promising therapy for subconjunctival fibrosis.

Sympathetic structural and electrophysiological remodeling in a rabbit model of reperfused myocardial infarction.

Here we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypo-innervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between species, with hypo-innervation likely associated with enhanced β-adrenergic sensitivity.

No Evidence of Neutrophil Response Modulation in Goats after Immunization against Paratuberculosis with a Heat-Inactivated Vaccine.

Neutrophils are believed to play a role in the initial stages of paratuberculosis, and it has recently been demonstrated that vaccination can modulate their function via priming or through epigenetic and metabolic reprogramming (training). Modulation of the neutrophil response against Mycobacterium avium subspecies paratuberculosis (Map) through vaccination has been demonstrated in a rabbit model but not in ruminants. Therefore, in the present work, the effect of vaccination on the response of caprine neutrophils against Map was studied. Neutrophils were isolated from non-vaccinated (n = 7) and Gudair®-vaccinated goat kids (n = 7), before vaccination and 30 days post-vaccination. Then, several neutrophil functions were quantified ex vivo: cell-free and anchored neutrophil extracellular trap (NET) release, phagocytosis, and the differential expression of several cytokines and TLR2. The induction of cell-free NETosis and TLR2 expression by Map is reported for the first time. However, vaccination showed no significant effect on any of the functions studied. This suggests that the protection conferred by Gudair® vaccination is based on mechanisms that are independent of the neutrophil function modulation. Further research into the impact of alternative vaccination strategies or the paratuberculosis infection stage on ruminant neutrophil function could provide valuable insights into its role in paratuberculosis.

Application of modified no-touch technique in rabbit arteriovenous fistula model and its effect on venous neointimal hyperplasia.

To investigate the technical advantages of a modified no-touch technique (MNTT) in constructing arteriovenous fistulas (AVF) compared to the conventional technique (CT) and assess its potential to reduce neointimal hyperplasia in the outflow vein. Forty-seven New Zealand rabbits were randomly divided into three groups: control, CT, and MNTT. Rabbits in control group were observed using ultrasound and then euthanized to obtain external jugular vein (EJV) for Hematoxylin-eosin (H-E). We established common carotid artery (CCA)-EJV AVF using MNTT in the MNTT group and the CT in the CT group. AVF patency and complications were compared between the CT and MNTT groups. Rabbits with patent AVF in both groups were observed using ultrasound 2 weeks after surgery to evaluate changes in the vessel diameter and blood flow spectrum of the AVFs. H-E staining measured the intima thickness of EJV adjacent to the anastomosis and histologic characteristics of the AVF at 2 and 4 weeks after surgery. Five rabbits died after surgery with common symptoms of sneezing, coughing, runny nose, anorexia, and diarrhea; two in the MNTT group and three in the CT group. There were significant differences in the diameter (p = 0.010) and peak systolic velocities (PSV) (p = 0.001) of EJV between the CT and MNTT groups 2 weeks after surgery. Spiral laminar flow (SLF) was observed in CCA and EJV adjacent to anastomosis in the MNTT group. Additionally, histological observations showed less venous neointimal hyperplasia in the MNTT group than in the CT group 4 weeks after surgery. The rabbit model of CCA-EJV AVF established using MNTT demonstrated fewer complications, larger vein diameters, and reduced venous neointimal hyperplasia, indicating that this maybe an ideal animal model to further investigate the application of MNTT in AVF surgery.

Probiotic bacteria can modulate immune responses to paratuberculosis vaccination.

Mycobacterium avium subsp. paratuberculosis (Map) is the etiological agent of paratuberculosis (PTB), a chronic intestinal inflammatory disease that causes high economical losses in dairy livestock worldwide. Due to the absence of widely available preventive or therapeutical treatments, new alternative therapies are needed. In this study, the effect of a probiotic alone or in combination with a commercial vaccine has been evaluated in a rabbit model. Vaccination enhanced the humoral response, exerted a training effect of peripheral polymorphonuclear neutrophils (PMNs) against homologous and heterologous stimuli, stimulated the release of pro-inflammatory cytokines by gut-associated lymphoid tissue (GALT) macrophages, and reduced the bacterial burden in GALT as well. However, the administration of the probiotic after vaccination did not affect the PMN activity, increased metabolic demand, and supressed pro-inflammatory cytokines, although humoral response and bacterial burden decrease in GALT was maintained similar to vaccination alone. The administration of the probiotic alone did not enhance the humoral response or PMN activity, and the bacterial burden in GALT was further increased compared to the only challenged group. In conclusion, the probiotic was able to modulate the immune response hampering the clearance of the infection and was also able to affect the response of innate immune cells after vaccination. This study shows that the administration of a probiotic can modulate the immune response pathways triggered by vaccination and/or infection and even exacerbate the outcome of the disease, bringing forward the importance of verifying treatment combinations in the context of each particular infectious agent.

Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model

IntroductionIntra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model.MethodsThirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume.ResultsIn terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect.ConclusionRegeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.

Neurokinin-1 Receptor Antagonism Reduces Nonallergic Ocular Redness in a Rabbit Model.

Purpose: To evaluate the therapeutic efficacy of topical application of a neurokinin-1 receptor (NK1R) antagonist in a rabbit model of nonallergic ocular redness. Methods: Nonallergic ocular redness was induced in rabbits by a single, topical application of dapiparzole hydrochloride eye drops (0.5%, 1%, 2%, or 5%). The NK1R antagonist L-703,606 was topically applied to the eye at the same time of induction or 20 min after induction, and phosphate buffered saline (PBS) treatment served as the control. Superior bulbar conjunctival images were taken every 30 s for the first 2 min, followed by every 4 min for 8 min, and then every 10 min until 1 h. The severity of ocular redness was evaluated on the images using ImageJ-based ocular redness index (ORI) calculations. Results: The ORI scores were significantly increased after the application of 0.5%, 1%, 2%, or 5% dapiparzole at each time point evaluated, with the most severe redness induced by the 5% dapiprazole that led to a maximal mean increase in ORI score of 14 at 20 min post-induction and thus used for subsequent evaluation of therapeutic efficacy of NK1R antagonism. Topical L-703,606, when applied at the same time as dapiprazole induction, significantly suppressed the increase of ORI scores at all time points (∼40% decrease). Furthermore, when applied at 20 min after dapiprazole induction, L-703,606 rapidly and effectively suppressed the increase of ORI scores at 30, 40, 50, and 60 min (∼30% decrease). Conclusions: Topical blockade of NK1R effectively prevents and alleviates nonallergic ocular redness in a novel animal model.

Bismuth Chelate-Mediated Digital Subtraction Angiography.

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time. Bi-DTPA Dimeglumine possesses a simple synthesis process without the need for purification, large-scale production ability (over 200g in the lab), superior X-ray imaging capability, renal clearance capacity, and good biocompatibility. Bi-DTPA-enhanced DSA can clearly display the arteries of the rabbit's head and lower limbs, with a minimum vascular resolution of 0.5mm. The displayed integrity of terminal vessels by Bi-DTPA-enhanced DSA is superior to that of iopromide-enhanced DSA. In a rabbit model of thrombotic disease, Bi-DTPA Dimeglumine-enhanced DSA enables the detection of embolism and subsequent reevaluation of vascular conditions after recanalization therapy. This proposed iodine-free DSA provides a promising and universal approach for diagnosing vascular diseases.

Stimulated Full-Thickness Cutaneous Wound Healing with Bioactive Dressings of Zinc and Cobalt Ion-Doped Bioactive Glass-Coated Eggshell Membranes in a Diabetic Rabbit Model.

Eggshell membrane-based biomedical applications have recently received great attention for their wound-healing properties. However, there are limited studies on diabetic wound healing. In this regard, we devised four types of composite eggshell membrane mats with nanoscale coatings of bioactive glass/Zn/Co-doped bioactive glass (ESM + BAG, ESM + ZnBAG, ESM + CoBAG, and ESM + ZnCoBAG) as wound-dressing materials for chronic nonhealing diabetic wounds. A detailed study of the physicochemical properties of the mats was conducted. In vitro studies demonstrated cytocompatibility and viability of human dermal fibroblasts on all four types of mats. The cells also attached finely on the mats with the help of cellular extensions, as evident from scanning electron microscopy (SEM) and rhodamine-phalloidin and Hoechst 33342 staining of cellular components. Endowed with bioactive properties, these mats influenced all aspects of full-thickness skin wound healing in diabetic animal model studies. All of the mats, especially the ESM + ZnCoBAG mat, showed the earliest wound closure, effective renewal, and restructuring of the extracellular matrix in terms of an accurate and timely accumulation of collagen, elastin, and reticulin fibers. Hydroxyproline and sulfated glycosaminoglycans were significantly (p < 0.01, p < 0.05) higher in ESM-ZnCoBAG-treated wounds in comparison to ESM-BAG-treated wounds, which suggests that these newly developed mats have potential as an affordable diabetic wound care solution in biomedical research.

Glucocorticoids disrupt longitudinal advance of cortical bone basic multicellular units in the rabbit distal tibia

Glucocorticoids (GCs) are the leading cause of secondary osteoporosis. The emerging perspective, derived primarily from 2D histological study of trabecular bone, is that GC-induced bone loss arises through the uncoupling of bone formation and resorption at the level of the basic multicellular unit (BMU), which carries out bone remodeling. Here we explore the impact of GCs on cortical bone remodeling in the rabbit model. Based upon the rapid reduction of bone formation and initial elevation of resorption caused by GCs, we hypothesized that the rate of advance (longitudinal erosion rate; LER) of cortical BMUs would be increased. To test this hypothesis we divided 20 female New Zealand White rabbits into four experimental groups: ovariohysterectomy (OVH), glucocorticoid (GC), OVH + GC and SHAM controls (n = 5 animals each). Ten weeks post-surgery (OVH or sham), and two weeks after the initiation of dosing (daily subcutaneous injections of 1.5 mg/kg of methylprednisolone sodium succinate in the GC-treated groups and 1 ml of saline for the others), the right tibiae were scanned in vivo using Synchrotron Radiation (SR) in-line phase contrast micro-CT at the Canadian Light Source. After an additional 2 weeks of dosing, the rabbits were euthanized and ex vivo images were collected using desktop micro-CT. The datasets were co-registered in 3D and LER was calculated as the distance traversed by BMU cutting-cones in the 14-day interval between scans. Counter to our hypothesis, LER was greatly reduced in GC-treated rabbits. Mean LER was lower in GC (4.27 μm/d; p < 0.001) and OVH + GC (4.19 μm/d; p < 0.001), while similar in OVH (40.13 μm/d; p = 0.990), compared to SHAM (40.44 μm/d). This approximately 90 % reduction in LER with GCs was also associated with an overall disruption of BMU progression, with radial expansion of the remodeling space occurring in all directions. This unexpected outcome suggests that GCs do not simply uncouple formation and resorption within cortical BMUs and highlights the value of the time-lapsed 4D approach employed.

Alteration of transmural electrophysiological gradient in a rabbit model with a RyR2 mutation

Alteration of transmural electrophysiological gradient in a rabbit model with a RyR2 mutation

Osteoimmunological Principles Adapted to Achieve Mechanically Superior Posterolateral Fusion in a New Zealand White Rabbit Model Using Antigen-Coated, Electrospun Beta-Tricalcium Phosphate.

Introduction Triggering the immune system via antigenic stimulation at the time of spinal fusion surgery may enhance bone morphogenesis and result in successful bony arthrodesis. We sought to demonstrate that bone morphogenesis could be enhanced via antigenic immunologic stimulation of a surgical fusion site. Methods New Zealand white rabbits underwent non-instrumented posterolateral fusion of L5-6 with implantation of either an immunologically activated graft (inert beta-tricalcium phosphate) or harvested autograft. Fusion was evaluated using plain radiographs, micro-computed tomography (CT), mechanical palpation, and biomechanical testing. The final evaluation was carried out at 12 weeks postoperatively. Results Eight rabbits received immunologically activated grafts; 10 received autografts and served as historical controls. Fusion rates were identical between groups (both 50%). Radiographs and micro CT of the fusion mass showed no significant difference between groups, and both showed good incorporation of the transverse processes into the fusion masses with radiographic evidence confirming trabeculation and bone remodeling. However, mechanical testing of the fusion sites showed superior fusion strength in the rabbits that received immunologically activated grafts, approaching a factor of two on flexion/extension, lateral bending, and axial rotation. Little to no graft material was appreciable in the non-fused antigen-treated specimens. Conclusions There is a long-standing need for a graft material that can replace autograft bone, due to the negative clinical consequences and financial costs pertaining to autologous bone harvesting. No allograft bone substitute to date has been able to reliably replicate the success of harvested autograft bone. This study suggests that immunological enhancement of inert beta-tricalcium phosphate can potentially be a substitute for allograft bone that can meet and even exceed the success of harvested autograft bone.

Reduction of oxidative stress response and protection of liver and renal cell functions by reduced glutathione in lower limb arterial ischemia–reperfusion in New Zealand white rabbits with high triglyceride levels

ObjectiveAcute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia–reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated. MethodsNew Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated. ResultsAfter IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted. ConclusionThis study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.