Comparative efficacy of growth factor therapy in healing diabetes-related foot ulcers: A network meta-analysis of randomized controlled trials

Introduction: This study examined the relative efficacy of growth factor therapies in healing diabetes-related foot ulcers (DFU). Methods: PubMed and Cochrane databases were searched for randomized controlled trials testing growth factor therapies for treating DFU. The primary outcome was complete wound closure. Results were reported as relative risk (RR) ± 95% credible intervals (CrI). The risk of bias was assessed using Cochrane's RoB-2 tool. Results: A total of 31 RCTs involving 2174 participants were included. Only 13 of the trials (n = 924) reported on the aetiology of the ulcers (85.4% neuropathic and 14.6% ischaemic). Epidermal growth factor (RR 3.83; 95% CrI 1.81, 9.10), plasma-rich protein (PRP) (RR 3.36; 95% CrI 1.66, 8.03) and platelet-derived growth factor (PDGF) (RR 2.47; 95% CrI 1.23, 5.17) significantly improved the likelihood of complete ulcer healing compared to control. Sub-analyses suggested that PRP (3 trials - RR 9.69; 95% CrI 1.37, 103.37) and PDGF (6 trials - RR 2.22; 95% CrI 1.12, 5.19) significantly improved the likelihood of wound closure amongst trial mainly recruiting participants with neuropathic ulcers. Eleven trials had a low risk of bias, 9 had some concerns and 11 had a high risk of bias. Sub-analysis of trials with a low risk of bias suggested that none of the growth factors significantly improved ulcer healing compared with control. Discussion: This network meta-analysis found low-quality evidence that Epidermal growth factor, PRP and PDGF therapy improved DFU healing likelihood compared with control. Larger well-designed trials are needed

Development of titanium dioxide nanowire incorporated poly(vinylidene fluoride–trifluoroethylene) scaffolds for bone tissue engineering applications

Critical size bone defects that do not heal spontaneously are among the major reasons for the disability in majority of people with locomotor disabilities. Tissue engineering has become a promising approach for repairing such large tissue injuries including critical size bone defects. Three-dimension (3D) porous scaffolds based on piezoelectric polymers like poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) have received a lot of attention in bone tissue engineering due to their favorable osteogenic properties. Owing to the favourable redox properties, titanium dioxide (TiO2) nanostructures have gained a great deal of attention in bone tissue engineering. In this paper, tissue engineering scaffolds based on P(VDF-TrFE) loaded with TiO2 nanowires (TNW) were developed and evaluated for bone tissue engineering. Wet-chemical method was used for the synthesis of TNW. Obtained TNW were thoroughly characterized for the physicochemical and morphological properties using techniques such as X-Ray diffraction (XRD) analysis and transmission electron microscopy (TEM). Electrospinning was used to produce TNW incorporated P(VDF-TrFE) scaffolds. Developed scaffolds were characterized by state of art techniques such as Scanning Electron Microscopy (SEM), XRD and Differential scanning calorimetry (DSC) analyses. TEM analysis revealed that the obtained TiO2 nanostructures possess nanofibrous morphology with an average diameter of 26 ± 4 nm. Results of characterization of nanocomposite scaffolds confirmed the effective loading of TNW in P(VDF-TrFE) matrix. Fabricated P(VDF-TrFE)/TNW scaffolds possessed good mechanical strength and cytocompatibility. Osteoblast like cells showed higher adhesion and proliferation on the nanocomposite scaffolds. This investigation revealed that the developed P(VDF-TrFE) scaffolds containing TNW can be used as potential scaffolds for bone tissue engineering applications.This work was supported by the French PIA project « Lorraine university d’excellence » reference ANR-15-IDEX-04-LUE. This article was also made possible by the NPRP9-144-3-021 grant funded by Qatar National Research Fund (a part of Qatar Foundation). The statements made here are the sole responsibility of the authors. Open Access funding was provided by the Qatar National Library

Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model

Background and Aims. The nacht domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is upregulated in human abdominal aortic aneurysm (AAA), but its pathogenic role is unclear. The aims of this study were firstly to examine whether the inflammasome was upregulated in a mouse model of AAA and secondly to test whether the inflammasome inhibitor colchicine limited AAA growth. Methods. AAA was induced in eight-week-old male C57BL6/J mice with topical application of elastase to the infrarenal aorta and oral 3-aminopropionitrile (E-BAPN). For aim one, inflammasome activation, abdominal aortic diameter, and rupture were compared between mice with AAA and sham controls. For aim two, 3 weeks after AAA induction, mice were randomly allocated to receive colchicine (n=28, 0.2 mg/kg/d) or vehicle control (n=29). The primary outcome was the rate of maximum aortic diameter increase measured by ultrasound over 13 weeks. Results. There was upregulation of NLRP3 markers interleukin- (IL-) 1 beta (median, IQR; 15.67, 7.11-22.60 pg/mg protein versus 6.87, 4.54-11.60 pg/mg protein, p=.048) and caspase-1 (109, 83-155 relative luminosity units (RLU) versus 45, 38-65 RLU, p <.001) in AAA samples compared to controls. Aortic diameter increase over 80 days (mean difference, MD, 4.3 mm, 95% CI 3.3, 5.3, p <.001) was significantly greater in mice in which aneurysms were induced compared to sham controls. Colchicine did not significantly limit aortic diameter increase over 80 days (MD -0.1 mm, 95% CI -1.1, 0.86, p=.922). Conclusions. The inflammasome was activated in this mouse model of AAA; however, daily oral administration of colchicine did not limit AAA growth

Yttrium oxide nanoparticle loaded scaffolds with enhanced cell adhesion and vascularization for tissue engineering applications

In situ tissue engineering is emerging as a novel approach in tissue engineering to repair damaged tissues by boosting the natural ability of the body to heal itself. This can be achieved by providing suitable signals and scaffolds that can augment cell migration, cell adhesion on the scaffolds and proliferation of endogenous cells that facilitate the repair. Lack of appropriate cell proliferation and angiogenesis are among the major issues associated with the limited success of in situ tissue engineering during in vivo studies. Exploitation of metal oxide nanoparticles such as yttrium oxide (Y2O3) nanoparticles may open new horizons in in situ tissue engineering by providing cues that facilitate cell proliferation and angiogenesis in the scaffolds. In this context, Y2O3 nanoparticles were synthesized and incorporated in polycaprolactone (PCL) scaffolds to enhance the cell proliferation and angiogenic properties. An optimum amount of Y2O3-containing scaffolds (1% w/w) promoted the proliferation of fibroblasts (L-929) and osteoblast-like cells (UMR-106). Results of chorioallantoic membrane (CAM) assay and the subcutaneous implantation studies in rats demonstrated the angiogenic potential of the scaffolds loaded with Y2O3 nanoparticles. Gene expression study demonstrated that the presence of Y2O3 in the scaffolds can upregulate the expression of cell proliferation and angiogenesis related biomolecules such as VEGF and EGFR. Obtained results demonstrated that Y2O3 nanoparticles can perform a vital role in tissue engineering scaffolds to promote cell proliferation and angiogenesis. - 2019This research was supported by Science and Engineering Research Board (SERB), New Delhi (NPDF, No. PDF/2016/000499 ). In addition, this article was made possible by the NPRP9-144-3-021 grant funded by Qatar National Research Fund (a part of Qatar Foundation). The statements made here are totally responsibility of authors. Appendix AScopu

Development of titanium dioxide nanowire incorporated poly(vinylidene fluoride–trifluoroethylene) scaffolds for bone tissue engineering applications

International audienc

Development of titanium dioxide nanowire incorporated poly(vinylidene fluoride–trifluoroethylene) scaffolds for bone tissue engineering applications

Critical size bone defects that do not heal spontaneously are among the major reasons for the disability in majority of people with locomotor disabilities. Tissue engineering has become a promising approach for repairing such large tissue injuries including critical size bone defects. Three-dimension (3D) porous scaffolds based on piezoelectric polymers like poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) have received a lot of attention in bone tissue engineering due to their favorable osteogenic properties. Owing to the favourable redox properties, titanium dioxide (TiO2) nanostructures have gained a great deal of attention in bone tissue engineering. In this paper, tissue engineering scaffolds based on P(VDF-TrFE) loaded with TiO2 nanowires (TNW) were developed and evaluated for bone tissue engineering. Wet-chemical method was used for the synthesis of TNW. Obtained TNW were thoroughly characterized for the physicochemical and morphological properties using techniques such as X-Ray diffraction (XRD) analysis and transmission electron microscopy (TEM). Electrospinning was used to produce TNW incorporated P(VDF-TrFE) scaffolds. Developed scaffolds were characterized by state of art techniques such as Scanning Electron Microscopy (SEM), XRD and Differential scanning calorimetry (DSC) analyses. TEM analysis revealed that the obtained TiO2 nanostructures possess nanofibrous morphology with an average diameter of 26 ± 4 nm. Results of characterization of nanocomposite scaffolds confirmed the effective loading of TNW in P(VDF-TrFE) matrix. Fabricated P(VDF-TrFE)/TNW scaffolds possessed good mechanical strength and cytocompatibility. Osteoblast like cells showed higher adhesion and proliferation on the nanocomposite scaffolds. This investigation revealed that the developed P(VDF-TrFE) scaffolds containing TNW can be used as potential scaffolds for bone tissue engineering applications.Other Information Published in: Journal of Materials Science: Materials in Medicine License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s10856-019-6300-4</p

Population Explosions of Tiger Moth Lead to Lepidopterism Mimicking Infectious Fever Outbreaks

<div><p>Lepidopterism is a disease caused by the urticating scales and toxic fluids of adult moths, butterflies or its caterpillars. The resulting cutaneous eruptions and systemic problems progress to clinical complications sometimes leading to death. High incidence of fever epidemics were associated with massive outbreaks of tiger moth <i>Asota caricae</i> adult populations during monsoon in Kerala, India. A significant number of monsoon related fever characteristic to lepidopterism was erroneously treated as infectious fevers due to lookalike symptoms. To diagnose tiger moth lepidopterism, we conducted immunoblots for tiger moth specific IgE in fever patients’ sera. We selected a cohort of patients (n = 155) with hallmark symptoms of infectious fevers but were tested negative to infectious fevers. In these cases, the total IgE was elevated and was detected positive (78.6%) for tiger moth specific IgE allergens. Chemical characterization of caterpillar and adult moth fluids was performed by HPLC and GC-MS analysis and structural identification of moth scales was performed by SEM analysis. The body fluids and chitinous scales were found to be highly toxic and inflammatory in nature. To replicate the disease in experimental model, wistar rats were exposed to live tiger moths in a dose dependant manner and observed similar clinico-pathological complications reported during the fever epidemics. Further, to link larval abundance and fever epidemics we conducted cointegration test for the period 2009 to 2012 and physical presence of the tiger moths were found to be cointegrated with fever epidemics. In conclusion, our experiments demonstrate that inhalation of aerosols containing tiger moth fluids, scales and hairs cause systemic reactions that can be fatal to human. All these evidences points to the possible involvement of tiger moth disease as a major cause to the massive and fatal fever epidemics observed in Kerala.</p></div