Suture Model Research Articles

The Effect of 0.5% Timolol Maleate on Corneal(Lymph)Angiogenesis in a Murine Suture Model.

To investigate the anti(lymph)angiogenic and anti-inflammatory effects of 0.5% timolol maleate in a murine corneal suture model. Corneal neovascularization and lymphangiogenesis were compared in groups of mice that underwent corneal suture and were subsequently administered a subconjunctival injection of 0.5% timolol maleate, dexamethasone, or phosphate-buffered saline (PBS). Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction (RT-PCR) was performed to quantify the expression of inflammatory cytokines [TNF-alpha and interleukin (IL)-6], vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, and VEGFR-3. When corneas from the timolol-treated group were compared to the PBS-treated group, we observed decreases in angiogenesis, lymphangiogenesis, and inflammatory infiltration in the timolol-treated group (P value <0.05 in all respective comparisons). Corneas from the timolol-treated group showed reduced expression of VEGF-A, VEGF-C, TNF-alpha, IL-6, VEGFR-2, and VEGFR-3 compared to corneas from the PBS group (P value <0.05 in all respective comparisons). Blocking adrenergic signaling in the cornea with 0.5% timolol maleate decreased corneal neovascularization and lymphangiogenesis.

A simulation model of nail bed suture and nail fixation: description and preliminary evaluation

BackgroundWounds of the finger nail bed represent a frequent injury, especially in children. Residents often learn nail bed repair on patients without prior training. We aimed to develop and evaluate a “low-fidelity” simulation model of nail bed repair. MethodsThe model consists of a false nail on a plastic finger and a hydrocolloid dressing, which is pasted on the nail bed site and cut horizontally. This model allows nail bed suture and nail fixation. The cost of each model is about $1. Thirty-three doctors evaluated this model on 10 items, rated out of five, concerning the realism, the difficulty of the procedure, and the educational value. The duration of the procedure was also noted. We evaluated the clinical effectiveness by comparing through Fisher's exact test the ratio of unsuitable events (revision surgeries, surgical site infections, and complaint letters) on two periods—3 y before and 18 mo after the implementation of this model in our institution, respectively. ResultsAverage mark was 4.16/5. The model was considered reliable, reproducible, and realistic. All the testers recognized a big educational value. The overall duration of the procedure averaged 23 min for residents and 11 min for surgeons. We collected 17 unsuitable events out of 84 patients from the period “before” and 2 out of 54 patients from the period “after” (P = 0.005). Revision surgeries were 10/84 from the period before and 2/54 from the period after (P = 0.04). ConclusionsThe results of the internal and clinical evaluations are encouraging. We suggest integration of this model into the training program of residents.

Substance P Modulation of Human and Murine Corneal Neovascularization.

The purpose of this study was to investigate the role of substance P (SP) in patients affected with corneal neovascularization (CNV) and in three different Tac1-knockout (KO) murine models of CNV. SP levels in tears were measured with a multiplex bead assay. The extent of human CNV was quantified as number of affected corneal quadrants. Murine CNV was induced in both strains by means of total disepithelization, alkali burn, and intrastromal sutures. After death, CNV (blood and lymphatic) and leukocyte infiltration were quantified by CD31, LYVE1, and CD45 immunofluorescence, respectively. Trigeminal ganglions were collected for quantitatitive PCR IL1β quantification. Hematoxylin-eosin corneal cross sections and whole-mounted β-3-tubulin nerve staining were used to compare anatomy and nerve density of wild-type (WT) versus Tac1-KO normal mice. SP tear levels correlate positively with CNV extension in patients (r = 0.49, P = 0.03). After disepithelization, Tac1-KO corneas showed reduced blood and lymphatic vascularization (-34% and -51% respectively) compared with the WT counterpart. CD45+ leukocytes infiltrating the cornea were reduced in Tac1-KO mice as opposed to WT in the disepithelization (P = 0.0001), alkali burn (P = 0.0258), and suture (P = 0.0149) models. Tac1-KO mice showed reduced IL1β expression in the trigeminal ganglion. Normal WT and Tac1-KO corneas did not show significant differences in transparency, thickness, and nerve density. Our results suggest (1) the involvement of SP in human CNV; (2) the key role of SP in promoting inflammatory CNV in three different mouse models; and (3) that absence of SP is not associated with obvious ocular surface pathology in a KO model.

Abstract WP250: Evaluating &amp; Optimizing the Model of Thrombotic MCAO in Mice

Background: The embolic model of middle cerebral artery occlusion (MCAO) by thrombus mimics the ischemic stroke in human and is amenable to thrombolytic therapies with recombinant tissue plasminogen activator. However, this model has not been thoroughly investigated and standardized. The present study was performed to optimize this model in mice. Methods: Male C57BL/6 mice (8-10 week old) were subjected to MCAO induced by autologous or allogeneic thrombus measuring 5, 10, or 15 mm in length. Blood was placed in a tube (20μm diameter) with thrombin before injecting with sterile saline into internal carotid artery (ICA). Cerebral blood flow (CBF) was monitored by laser-Doppler or laser speckle before MCAO. Infarct was assessed by TTC staining 24 hours after MCAO. Neurological deficits were evaluated by modified neurological severity score (mNSS), rotarod test and corner test 1-7 days after ischemia. Results: Thrombus injection resulted in an abrupt drop of CBF to less than 30% of baseline in the MCA territory. The areas with more than 50% CBF decrease at 3 h after thrombus injection was significantly correlated to infarct volume at 24 h after MCAO (r=0.792, P=0.019, Pearson′s correlation analysis), suggesting that continuous decrease in CBF within 3 h can predict brain damage after stroke. No significant differences in infarct volume between autologous and allogeneic thrombus were observed (25.31±6.45 mm 3 vs 23.00±6.31 mm 3 , p&gt;0.05). Allogeneic thrombi of 10 mm and 15 mm lengths caused reproducible infarct with detectable neurological deficits in mice. The 10 mm thrombus was chosen as the optimal thrombus length as it caused similar morphological and functional alterations compared with 60 min suture model of MCAO. In contrast, 15 mm thrombus resulted in significantly larger infract volume, worse sensorimotor functions and higher mortality in mice. Conclusion: Embolic MCAO did not yield stable CBF reduction compared to the classical suture MCAO. However, continuous decrease in CBF in the embolic model for at least 3 h resulted in successful infarct induction. The 10 mm autologous thrombus is suitable to induce reproducible infarct with neurological deficits in adult mice.

Abstract TP260: A Novel Neurogenic-Stem Cell Stimulating Curcumin Analog to Treat Acute Ischemic Stroke

While nerve cells rapidly die in stroke, and patients do initiate a neurogenic response to replace these cells, there has been no attempt to develop pleiotropic cytoprotective compounds to further promote neurogenesis in stroke patients, and there are no neurogenic or cytoprotective drugs approved by the FDA. In this study, we focused on the parent compound J-147, a curcumin derivative that is a 5-LOX inhibitor, and has potent neuroprotective and neurogenic activities. J-147 rescues HT22 cells from iodoacetic acid challenge (EC 50 50 nM), and oxytosis (EC 50 115 nM). J-147 is neuroprotective against glutamate excitotoxcity in E18 cortical neuron culture (EC 50 27 nM), and prevents cell death in an embryonic cortical cell trophic factor withdrawal assay (EC 50 25 nM). J-147 can rescue a clone of the hippocampal nerve cell line HT22 expressing TrkB, from serum starvation under conditions where the cells can be protected by BDNF (EC 50 50 nM). In mice, J-147 is neurogenic and can stimulate cell division in germinal regions of the brain (increase BrdU + DCX + labeled cells), enhances endogenous neurotrophic factors and energy metabolism. With this basis, we tested J-147 in 2 translational stroke models. First, using a rodent intraluminal suture model, in combination with a quantal analysis method to determine the effect of increasing ischemia duration (5-90 minutes) on behavioral deficits, IV J-147 treatment (10 mg/kg) administered 5 minutes following the end of occlusion (5-90 minutes), significantly (P=0.045) reduced stroke-induced behavioral deficits and increased the P 50 value to 36.37 ± 1.72 (n=19) minutes from P 50 = 20.1 ± 4.07 minutes (n=19) for the control group. J-147 also reduced infarct volume following IV administration (p&lt;0.05). Second, using the standardized rabbit small clot embolic stroke model, IV J-147 treatment (10mg/kg) administered 1 hour post-embolization increased the P 50 value (behavior) to 1.88 ± 0.10 mg (n=20) compared to P 50 = 1.07 ± 0.07 (n=19) for control(p&lt;0.05). Additional studies showed that J-147 was not mitogenic, or cytotoxic using the CeeTox assay (Raking 90μM) and had a good IV PK profile in rabbits/rats (t 1/2 5.89-8.56 hours). These data support the development of J-147 and neurogenic analogs as a novel class of drug to treat stroke.

Preparation of A Spaceflight: Apoptosis Search in Sutured Wound Healing Models.

To prepare the ESA (European Space Agency) spaceflight project “Wound healing and Sutures in Unloading Conditions”, we studied mechanisms of apoptosis in wound healing models based on ex vivo skin tissue cultures, kept for 10 days alive in serum-free DMEM/F12 medium supplemented with bovine serum albumin, hydrocortisone, insulin, ascorbic acid and antibiotics at 32 °C. The overall goal is to test: (i) the viability of tissue specimens; (ii) the gene expression of activators and inhibitors of apoptosis and extracellular matrix components in wound and suture models; and (iii) to design analytical protocols for future tissue specimens after post-spaceflight download. Hematoxylin-Eosin and Elastica-van-Gieson staining showed a normal skin histology with no signs of necrosis in controls and showed a normal wound suture. TdT-mediated dUTP-biotin nick end labeling for detecting DNA fragmentation revealed no significant apoptosis. No activation of caspase-3 protein was detectable. FASL, FADD, CASP3, CASP8, CASP10, BAX, BCL2, CYC1, APAF1, LAMA3 and SPP1 mRNAs were not altered in epidermis and dermis samples with and without a wound compared to 0 day samples (specimens investigated directly post-surgery). BIRC5, CASP9, and FN1 mRNAs were downregulated in epidermis/dermis samples with and/or without a wound compared to 0 day samples. BIRC2, BIRC3 were upregulated in 10 day wound samples compared to 0 day samples in epidermis/dermis. RELA/FAS mRNAs were elevated in 10 day wound and no wound samples compared to 0 day samples in dermis. In conclusion, we demonstrate that it is possible to maintain live skin tissue cultures for 10 days. The viability analysis showed no significant signs of cell death in wound and suture models. The gene expression analysis demonstrated the interplay of activators and inhibitors of apoptosis and extracellular matrix components, thereby describing important features in ex vivo sutured wound healing models. Collectively, the performed methods defining analytical protocols proved to be applicable for post-flight analyzes of tissue specimens after sample return.

Effect of itraconazole on the cornea in a murine suture model and penetrating keratoplasty model.

To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty (PK) model. Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline (PBS) and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction (RT-PCR) was performed to quantify the expression of inflammatory cytokines (TNF-alpha, IL-6) and vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGFR-2, and VEGFR-3. In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group (all P<0.05). The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group (all P<0.05). In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group (P=0.057, 0.096, 0.012, respectively). The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group (all P<0.05). Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-(lymph)-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.

Changes in the expression and localization of signaling molecules in mouse facial motor neurons during regeneration of facial nerves

After injury, peripheral axons usually re-extend toward their target, and neuronal functions recover. Previous studies have reported that expression of various molecules are transiently altered in motor neurons after nerve injury, but the time course of these changes and their relationship with functional recovery have not been clearly demonstrated. We used the mouse facial nerve transection and suturing model, and examined the changes in expression of five molecules, choline acetyl transferase (ChAT), galanin, calcitonin gene-related protein (CGRP), gephyrin, and potassium chloride co-transporter 2 (KCC2) in the facial motor neurons after surgery until recovery. Number of ChAT-positive neurons was markedly decreased at days 3 and 7, and recovered to the normal level by day 60, when facial motor functions recovered. Localization of two neuropeptides, CGRP and galanin, was increased in the perikarya and axons during regeneration, and returned to the normal levels by days 60 and 28, respectively. Expression of two postsynaptic elements of γ-amino butyric acid synapses, gephyrin and KCC2, was decreased at days 3 and 7, and recovered by day 60. These results suggest that ChAT, CGRP, and KCC2 may be objective indicators of regeneration, and altering their expression may be related to the functional recovery and axonal re-extension.

Isotopic evidence for Neoarchean continuity across the Snowbird Tectonic Zone, western Churchill Province, Canada

The Snowbird Tectonic Zone (STZ), the ca. 2800km-long boundary between Rae and Hearne domains of the western Canadian Shield, remains of uncertain tectonic significance, but is currently interpreted as a ca. 1.9Ga suture. The eastern Rae domain is well studied and underlain by a >20,000km2 region of high pressure granulites, containing ca. 2.60Ga arc rocks, and granulite to amphibolite-grade structures, which formed at ca 2.57Ga (D1/M1) and 1.90Ga (D2/M2). The 1.85Ga Legs Lake shear zone juxtaposed the high-P granulites of the eastern Rae domain structurally above lower amphibolite- to greenschist-grade supracrustal gneisses of the Hearne domain. Zircon U-Pb and Hf isotopic analyses were acquired from igneous and metasedimentary rocks across the STZ and Rae-Hearne boundary to assess the validity of the suture model, with specific focus given to the >5km wide Legs Lake shear zone. Results indicate that both 2.60–2.55Ga magmatism and deformation continue unimpeded across the STZ and Rae-Hearne boundary. Furthermore, Hf isotopic data from igneous zircon from 2.60Ga plutonic rocks across the STZ display little variation in εHf indicating that no major crustal-break corresponds to the Rae-Hearne boundary, or any of the shear zones that parallel the STZ on the ground. Older plutonic rocks show a greater variability in εHf, which may indicate a disparate origin. Grade, intensity, and timing of Paleoproterozoic features vary along the transect and display little continuity across the Rae-Hearne domain boundary. In conjunction with existing field and isotopic data, we interpret that the Rae and Hearne domains were together by 2.60Ga, and that the STZ was host to repeated Paleoproterozoic reactivation driven by the latter stages of Taltson-Thelon orogenesis, final indentation of the Slave craton into the Rae domain, and accretionary processes on the southern periphery of the Hearne domain from 1.93 to 1.84Ga. Furthermore, assessing the viability of major shear zones within high grade terranes as potential sutures is complicated by the lateral and vertical heterogeneity of the crust juxtaposed by them.

Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic studies demonstrated that regulatory T cells completely abolished the tPA-induced elevation of MMP9 and CCL2 after stroke. Using MMP9 and CCL2 knockout mice, we discovered that both molecules partially contributed to the protective actions of regulatory T cells. In an in vitro endothelial cell-based model of the blood-brain barrier, we confirmed that regulatory T cells inhibited tPA-induced endothelial expression of CCL2 and preserved blood-brain barrier integrity after an ischaemic challenge. Lentivirus-mediated CCL2 knockdown in endothelial cells completely abolished the blood-brain barrier protective effect of regulatory T cells in vitro. Altogether, our studies suggest that regulatory T cell adoptive transfer may alleviate thrombolytic treatment-induced haemorrhage in stroke victims. Furthermore, regulatory T cell-afforded protection in the tPA-treated stroke model is mediated by two inhibitory mechanisms involving CCL2 and MMP9. Thus, regulatory T cell adoptive transfer may be useful as a cell-based therapy to improve the efficacy and safety of thrombolytic treatment for ischaemic stroke.

The effects of morphological irregularity on the mechanical behavior of interdigitated biological sutures under tension

Irregular interdigitated morphology is prevalent in biological sutures in nature. Suture complexity index has long been recognized as the most important morphological parameter to govern the mechanical properties of biological sutures. However, the suture complexity index alone does not reflect all aspects of suture morphology. The goal of this investigation was to determine that besides suture complexity index, whether the degree of morphological irregularity of biological sutures has influences on the mechanical properties, and if there is any, how to quantify these influences. To explore these issues, theoretical and finite element (FE) suture models with the same suture complexity index but different levels of morphological irregularity were developed. The quasi-static stiffness, strength for damage initiation and post-failure process of irregular sutures were studied. It was shown that for the same suture complexity index, when the level of morphological irregularity increases, the overall strain to failure will increase while tensile stiffness is retained; also, the total energy to fracture increases with a sacrifice in strength to damage initiation. These results reveal that morphological irregularity is another important independent parameter to govern and balance the mechanical properties of biological sutures. Therefore, from the mechanics point of view, the prevalence of irregular suture morphology in nature is a merit, not a defect.

Benefits of Combinatorial Therapies for Improving Functional Recovery in a Rat Model of Facial Nerve Injury

Injury to the facial nerve due to trauma or surgical intervention for head and neck pathologies is common; however, few effective treatments eliciting full functional recovery following facial nerve injuries exist. Previous studies in our laboratory have found that single‐agent therapies, while effective in improving functional recovery, are insufficient in promoting complete functional recovery after nerve injury. Consequently, our objective is to determine the efficacy of combination therapies for treatment of facial nerve injury. We have found that treating the repaired injured nerve with polyethylene glycol (PEG), a sealant that acts to fuse damaged cell membranes, and methylene blue (MB), an antioxidant, improves functional recovery in a rat model of facial nerve transection and suture. Given the ease in application of these therapies, either singularly or in combination, we anticipate that these and future studies will aid translation of such methods for application in human facial nerve injury patients.Support or Funding InformationSupported by a Roudebush VA IIMR Young Investigator Award (CLW) and IUCRG grant fromm IUSM (KJJ).

Characterization of the Circumlimbal Suture Model of Chronic IOP Elevation in Mice and Assessment of Changes in Gene Expression of Stretch Sensitive Channels.

To consider whether a circumlimbal suture can be used to chronically elevate intraocular pressure (IOP) in mice and to assess its effect on retinal structure, function and gene expression of stretch sensitive channels. Anesthetized adult C57BL6/J mice had a circumlimbal suture (10/0) applied around the equator of one eye. In treated eyes (n = 23) the suture was left in place for 12 weeks whilst in sham control eyes the suture was removed at day two (n = 17). Contralateral eyes served as untreated controls. IOP was measured after surgery and once a week thereafter. After 12 weeks, electroretinography (ERG) was performed to assess photoreceptor, bipolar cell and retinal ganglion cell (RGC) function. Retinal structure was evaluated using optical coherence tomography. Retinae were processed for counts of ganglion cell density or for quantitative RT-PCR to quantify purinergic (P2x7, Adora3, Entpd1) or stretch sensitive channel (Panx1, Trpv4) gene expression. Immediately after suture application, IOP spiked to 33 ± 3 mmHg. After 1 day, IOP had recovered to 27 ± 3 mmHg. Between weeks 2 and 12, IOP remained elevated above baseline (control 14 ± 1 mmHg, ocular hypertensive 19 ± 1 mmHg). Suture removal at day 2 (Sham) restored IOP to baseline levels, where it remained through to week 12. ERG analysis showed that 12 weeks of IOP elevation reduced photoreceptor (−15 ± 4%), bipolar cell (−15 ± 4%) and ganglion cell responses (−19 ± 6%) compared to sham controls and respective contralateral eyes (untreated). The retinal nerve fiber layer was thinned in the presence of normal total retinal thickness. Ganglion cell density was reduced across all quadrants (superior −12 ± 5%; temporal, −7% ± 2%; inferior −9 ± 4%; nasal −8 ± 5%). Quantitative RT-PCR revealed a significant increase in Entpd1 gene expression (+11 ± 4%), whilst other genes were not significantly altered (P2x7, Adora3, Trpv4, Panx1). Our results show that circumlimbal ligation produces mild chronic ocular hypertension and retinal dysfunction in mice. Consistent with a sustained change to purinergic signaling we found an up-regulation of Entpd1.

Commentary on “Tacrolimus Eluting Suture Inhibits Neointimal Hyperplasia: An Experimental In Vivo Study in Rats”

In their paper Ak et al. deal with one of the main issues in vascular surgery, anastomotic neointimal hyperplasia.1Ak K. Ak E. Dericioglu O. Canak T. Akbguba J. Ozkan N. et al.Tacrolimus eluting sutures inhibits neointimal hyperplasia: an experimental in vivo study in rats.Eur J Vasc Endovasc Surg. 2017; 53: 438PubMed Google Scholar The paper offers some interesting points of research that could lead to clinical applications; however, some parts of the paper require discussion. The technology and the drug elution distribution: the authors evaluated in vitro tacrolimus elution but there is no proof that in vivo, after suture completion, the same elution occurs with the same quantity of tacrolimus on the overall length of the running suture. For example, it cannot be excluded that pulling the suture thread through the arterial or synthetic prosthetic wall would not partially wash out the tacrolimus on the surface of the suture or modify further elution of the drug. This point, related to the strength of the link of the coating to the biomaterial, should be assessed. Different strategies have been proposed to control arterial remodelling after trauma, such as the suturing of the anastomosis including luminal2Thierry B. Winnik F.M. Merhi Y. Tabrizian M. Nanocoatings onto arteries via layer-by-layer deposition: toward the in vivo repair of damaged blood vessels.J Am Chem Soc. 2003; 125: 7494-7495Crossref PubMed Scopus (181) Google Scholar and adventitial3Mátyás L. Berry M. Menyhei G. Tamás L. Acsády G. Cuypers P. et al.The safety and efficacy of a paclitaxel-eluting wrap for preventing peripheral bypass graft stenosis: a 2-year controlled randomized prospective clinical study.Eur J Vasc Endovasc Surg. 2008; 35: 715-722Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar approaches. The present approach allows delivery of the drug to the three arterial layers but not homogeneously on the suture line. These differences could mainly be observed on larger anastomoses where the specific surface of the threads and consequently the amount of drug delivered is lower. Further studies with longer than 1 month duration of implantation should be considered to exclude the potential adverse effects of drugs.4Kolodgie F.D. Pacheco E. Yahagi K. Mori H. Ladich E. Virmani R. Comparison of particulate embolization after femoral artery treatment with IN.PACT Admiral versus Lutonix 035 paclitaxel-coated balloons in healthy swine.J Vasc Interv Radiol. 2016; 27: 1676-1685Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 5Kollum M. Farb A. Schreiber R. Terfera K. Arab A. Geist A. et al.Particle debris from a nanoporous stent coating obscures potential antiproliferative effects of tacrolimus-eluting stents in a porcine model of restenosis.Catheter Cardiovasc Interv. 2005; 64: 85-90Crossref PubMed Scopus (75) Google Scholar These adverse effects could be potentiated by tissue anoxia or necrosis related to the stitches. The relevance of the model: the authors chose a model of longitudinal suture on rat abdominal aorta using a 7/0 polypropylene running suture. Even though the authors appropriately discussed their choice, performing such a longitudinal anastomosis is at risk of stenosis and consequently of calibre variability leading to haemodynamic differences that could influence healing, as intra-operative angiographic evaluation of the quality of the surgical procedure was not performed. Further studies including models of bypasses with an end to side anastomosis to an artery or for performing an arterio-venous fistula are suggested, as they are most often responsible for neointimal hyperplasia in clinical practice. As a conclusion, this interesting work suggests opportunities for improving the performance of anastomoses at high risk of neointimal hyperplasia. However, the concept must be more extensively evaluated by experimental studies as recommended, and next on clinical studies evaluating the optimal indications and cost effectiveness of the technology. Tacrolimus-Eluting Suture Inhibits Neointimal Hyperplasia: An Experimental In Vivo Study in RatsEuropean Journal of Vascular and Endovascular SurgeryVol. 53Issue 3PreviewNeointimal hyperplasia (NIH) remains one of the leading causes of graft failure after vascular anastomoses. Cytotoxic drugs, such as rapamycin and tacrolimus, have been shown to inhibit the development of NIH. In this study, the aim was to test the impact of a sustained releasing tacrolimus–chitosan-eluting suture on the development of NIH in a rat model. Full-Text PDF Open Archive

The importance of nonlinear tissue modelling in finite element simulations of infant head impacts

Despite recent efforts on the development of finite element (FE) head models of infants, a model capable of capturing head responses under various impact scenarios has not been reported. This is hypothesized partially attributed to the use of simplified linear elastic models for soft tissues of suture, scalp and dura. Orthotropic elastic constants are yet to be determined to incorporate the direction-specific material properties of infant cranial bone due to grain fibres radiating from the ossification centres. We report here on our efforts in advancing the above-mentioned aspects in material modelling in infant head and further incorporate them into subject-specific FE head models of a newborn, 5- and 9-month-old infant. Each model is subjected to five impact tests (forehead, occiput, vertex, right and left parietal impacts) and two compression tests. The predicted global head impact responses of the acceleration–time impact curves and the force–deflection compression curves for different age groups agree well with the experimental data reported in the literature. In particular, the newly developed Ogden hyperelastic model for suture, together with the nonlinear modelling of scalp and dura mater, enables the models to achieve more realistic impact performance compared with linear elastic models. The proposed approach for obtaining age-dependent skull bone orthotropic material constants counts both an increase in stiffness and decrease in anisotropy in the skull bone—two essential biological growth parameters during early infancy. The profound deformation of infant head causes a large stretch at the interfaces between the skull bones and the suture, suggesting that infant skull fractures are likely to initiate from the interfaces; the impact angle has a profound influence on global head impact responses and the skull injury metrics for certain impact locations, especially true for a parietal impact.

Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization.

To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P<0.05), but with no such effects in non-dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P<0.05). The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreased compared with those in the PBS subgroup in the dry eye group. Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.

Reversal of functional loss in a rat model of chronic intraocular pressure elevation.

This pilot study considered whether intraocular pressure (IOP) lowering could reverse ganglion cell dysfunction in a rat model of chronic ocular hypertension. A circumlimbal suture was applied in one eye to induce ocular hypertension (n = 7) in Long-Evans rats. The contralateral eye served as an untreated control. After 8 weeks of IOP elevation the suture was removed to lower IOP for the remaining 7 weeks. Electroretinogram (ERG) and optical coherence tomography (OCT) were measured at baseline, 2, 4, 8, 12 and 15 weeks. Retinae were collected for histology at week 15. In sutured eyes, IOP was elevated by 7-11 mmHg above control eyes (12 ± 0.2 mmHg [standard error of the mean]). Eight weeks of chronic IOP elevation resulted in a reduction of the ganglion cell mediated positive Scotopic Threshold Response (pSTR, -25 ± 7% of baseline), as well as smaller photoreceptor (-7 ± 4%) and bipolar cell mediated responses (-6 ± 5%). After suture removal, IOP recovered to normal. By 15 weeks the a-wave (0 ± 6%), b-wave (-2 ± 6%) and pSTR had recovered back to baseline (from -25 ± 7% to -4 ± 6%). The retinal nerve fiber layer was thinned by -9 ± 3% at week 8 and showed no further decline at week 15 (-10 ± 2%). Cell numbers in the ganglion cell layer were similar between suture removal and control eyes at week 15 (3543 ± 478 vs 4057 ± 476 cells mm-2 ). The circumlimbal suture model might be a useful platform to study the reversibility of neuronal dysfunction from chronic IOP challenge.

Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice.

Stroke is a leading cause of death worldwide and continues to be one of the major causes of long-term adult disabilities. About 87% of strokes are ischemic in origin and occur in the territory of the middle cerebral artery (MCA). Currently the only Food and Drug Administration (FDA) approved drug for the treatment of this devastating disease is tissue plasminogen activator (tPA). However, tPA has a small therapeutic window for administration (3 - 6 hr), and is only effective in 4% of the patients who actually receive it. Current research focuses on understanding the pathophysiology of stroke in order to find potential therapeutic targets. Thus, reliable models are crucial, and the MCA occlusion (MCAo) model (also termed the intraluminal filament or suture model) is deemed to be the most clinically relevant surgical model of ischemic stroke, and is fairly non-invasive and easily reproducible. Typically the MCAo model is used with rodents, especially with mice due to all the genetic variations available for this species. Here we describe (and present in the video) how to successfully perform the MCAo model (with reperfusion) in mice to generate reliable and reproducible data.

A novel postoperative immobilization model for murine Achilles tendon sutures.

The body's motion and function are all in part effected by a vital tissue, the tendon. Tendon injury often results in limited functioning after postoperative procedures and even for a long time after rehabilitation. Although numerous studies have reported surgical procedures using animal models which have contributed to both basic and clinical research, modeling of tendon sutures or postoperative immobilizations has not been performed on small experimental animals, such as mice. In this study we have developed an easy Achilles tendon suture and postoperative ankle fixation model in a mouse. Right Achilles tendons were incised and 10-0 nylons were passed through the proximal and distal ends using a modified Kessler method. Subsequently, the right ankle was immobilized in a plantarflexed position with novel splints, which were made from readily available extension tubes. Restriction of the tendon using handmade splints reduced swelling, as opposed to fixating with the usual plaster of Paris. Using this method, the usage of the right Achilles tendons began on postoperative days 13.5 ± 4.6, which indicated healing within two weeks. Therefore our simple short-term murine Achilles tendon suture procedure is useful for studying immediate tendon repair mechanisms in various models, including genetically-modified mice.

Assessment of Intracorporeal Suturing in Single-Port Surgery Using an Experimental Suturing Model.

The aim of this study is to assess the difficulty of intracorporeal suturing in single-port surgery, using experimental suturing model in dry box. Subjects were divided for three groups: seven experienced laparoscopic surgeons, seven surgical residents, and seven interns. An experimental suturing model is developed, and working angle was set from 0° to 90°. The completion rate in 0° was significantly lower than that in the other angles. Completion rate of group A was higher than that of the other groups. Precision of task in group A was significantly higher than that of group B and group C in 0° and 60°. Stress score in 0° were significantly higher than that in the other angles. Our study demonstrated that intracorporeal suturing in single-port surgery seems to be more difficult than conventional laparoscopic surgery. Our data should be taken the institution under consideration for introduction of single-port surgery.