Decellularised extracellular matrix decorated PCL PolyHIPE scaffolds for enhanced cellular activity, integration and angiogenesis

Wound healing involves a complex series of events where cell–cell and cell-extracellular matrix (ECM) interactions play a key role. Wounding can be simple, such as the loss of the epithelial integrity, or deeper and more complex, reaching to subcutaneous tissues, including blood vessels, muscles and nerves. Rapid neovascularisation of the wounded area is crucial for wound healing as it has a key role in supplying oxygen and nutrients during the highly demanding proliferative phase and transmigration of inflammatory cells to the wound area. One approach to circumvent delayed neovascularisation is the exogenous use of pro-angiogenic factors, which is expensive, highly dose-dependent, and the delivery of them requires a very well-controlled system to avoid leaky, highly permeable and haemorrhagic blood vessel formation. In this study, we decorated polycaprolactone (PCL)-based polymerised high internal phase emulsion (PolyHIPE) scaffolds with fibroblast-derived ECM to assess fibroblast, endothelial cell and keratinocyte activity in vitro and angiogenesis in ex ovo chick chorioallantoic membrane (CAM) assays. Our results showed that the inclusion of ECM in the scaffolds increased the metabolic activity of three types of cells that play a key role in wound healing and stimulated angiogenesis in ex ovo CAM assays over 7 days. Herein, we demonstrated that fibroblast-ECM functionalised PCL PolyHIPE scaffolds appear to have great potential to be used as an active wound dressing to promote angiogenesis and wound healing

Synergistic effect of type and concentration of surfactant and diluting solvent on the morphology of emulsion templated matrices developed as tissue engineering scaffolds

Emulsion templating is an advantageous route for the fabrication of tissue engineering scaffolds. Emulsions are mostly stabilised using surfactants, and the performances of the surfactants depend on various parameters such as emulsification temperature and the presence of the electrolytes. In this study, we suggest that diluting solvent type also has a dramatic impact on the efficiency of the surfactant and morphology of the polymerised emulsions. For this, morphologies of polycaprolactone methacrylate-based polymerised emulsions, which are designed for tissue engineering applications and in vitro biocompatibilities, were shown by our group, prepared using four different surfactants, and three different solvents were investigated. Results showed that the diluting solvent used in the emulsion composition has a strong impact on the performance of the surfactant and consequently on the morphology of polymerised emulsions. Increasing surfactant concentration and diluting solvent volume have an opposite impact on the characteristics of emulsions. Scaffolds with average pore sizes changing from 10 to 78 μm could be fabricated. Establishing these relations enables us to have control over the overall morphology of polymerised emulsions and precisely engineer them for specific tissue engineering applications by tuning solvent and surfactant type and concentration

Assessment of the angiogenic potential of 2-deoxy-D-ribose using a novel in vitro 3D dynamic model in comparison with established in vitro assays

Angiogenesis is a highly ordered physiological process regulated by the interaction of endothelial cells with an extensive variety of growth factors, extracellular matrix components and mechanical stimuli. One of the most important challenges in tissue engineering is the rapid neovascularization of constructs to ensure their survival after transplantation. To achieve this, the use of pro-angiogenic agents is a widely accepted approach. The study of angiogenesis has gained momentum over the last two decades. Although there are various in vitro, ex vivo, and in vivo angiogenesis models that enable testing of newly discovered pro-angiogenic agents, the problem with researching angiogenesis is the choice of the most appropriate assay. In vivo assays are the most representative and reliable models, but they are expensive, time-consuming and can cause ethical concerns whereas in vitro assays are relatively inexpensive, practical, and reproducible, but they are usually lack of enabling the study of more than one aspect of angiogenesis, and they do not fully represent the complexity of physiological angiogenesis. Therefore, there is a need for the development of an angiogenesis model that allows the study of angiogenesis under physiologically more relevant, dynamic conditions without causing ethical concerns. Accordingly, in this study, we developed 3D in vitro dynamic angiogenesis model, and we tested the angiogenic potential of 2-deoxy-D-ribose (2dDR) in comparison with vascular endothelial growth factor (VEGF) using newly developed in vitro 3D dynamic model and well-established in vitro models. Our results obtained using conventional in vitro assays demonstrated that 2dDR promoted proliferation, migration and tube formation of human aortic endothelial cells (HAECs) in a dose-dependent manner. Then, the angiogenic activity of 2dDR was further assessed using the newly developed 3D in vitro model, which enabled the monitoring of cell proliferation and infiltration simultaneously under dynamic conditions. Our results showed that the administration of 2dDR and VEGF significantly enhanced the outgrowth of HAECs and the cellular density under either static or dynamic conditions

Landmarks in vaginal mesh development: polypropylene mesh for treatment of SUI and POP

Vaginal meshes used in the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) have produced highly variable outcomes, causing life-changing complications in some patients while providing others with effective, minimally invasive treatments. The risk:benefit ratio when using vaginal meshes is a complex issue in which a combination of several factors, including the inherent incompatibility of the mesh material with some applications in pelvic reconstructive surgeries and the lack of appropriate regulatory approval processes at the time of the premarket clearance of these products, have contributed to the occurrence of complications caused by vaginal mesh. Surgical mesh used in hernia repair has evolved over many years, from metal implants to knitted polymer meshes that were adopted for use in the pelvic floor for treatment of POP and SUI. The evolution of the material and textile properties of the surgical mesh was guided by clinical feedback from hernia repair procedures, which were also being modified to obtain the best outcomes with use of the mesh. Current evidence shows how surgical mesh fails biomechanically when used in the pelvic floor and materials with improved performance can be developed using modern material processing and tissue engineering techniques

Bioengineering vascular networks to study angiogenesis and vascularisation of physiologically relevant tissue models in vitro

Angiogenesis assays are essential for studying aspects of neovascularisation and angiogenesis and investigating drugs that stimulate or inhibit angiogenesis. To date, there are several in vitro and in vivo angiogenesis assays that are used for studying different aspects of angiogenesis. Although in vivo assays are the most representative of native angiogenesis, they raise ethical questions, require considerable technical skills, and are expensive. In vitro assays are inexpensive and easier to perform, but the majority of them are only two-dimensional cell monolayers which lack the physiological relevance of three-dimensional structures. Thus, it is important to look for alternative platforms to study angiogenesis under more physiologically relevant conditions in vitro. Accordingly, in this study, we developed polymeric vascular networks to be used to study angiogenesis and vascularisation of a 3D human skin model in vitro. Our results showed that this platform allowed the study of more than one aspect of angiogenesis, endothelial migration and tube formation, in vitro when combined with Matrigel®. We successfully reconstructed a human skin model, as a representative of a physiologically relevant and complex structure, and assessed the suitability of the developed in vitro platform for studying endothelialisation of the tissue-engineered skin model

In vivo bone regeneration capacity of multiscale porous polycaprolactone-based high internal phase emulsion (PolyHIPE) scaffolds in a rat calvarial defect model

Globally, one of the most common tissue transplantation procedures is bone grafting. Lately, we have reported the development of polymerized high internal phase emulsions (PolyHIPEs) made of photocurable polycaprolactone (4PCLMA) and shown their potential to be used as bone tissue engineering scaffolds in vitro. However, it is essential to evaluate the in vivo performance of these scaffolds to investigate their potential in a clinically more relevant manner. Therefore, in this study, we aimed to compare in vivo performances of macroporous (fabricated using stereolithography), microporous (fabricated using emulsion templating), and multiscale porous (fabricated using emulsion templating and perforation) scaffolds made of 4PCLMA. Also, 3D-printed macroporous scaffolds (fabricated using fused deposition modeling) made of thermoplastic polycaprolactone were used as a control. Scaffolds were implanted into a critical-sized calvarial defect, animals were sacrificed 4 or 8 weeks after implantation, and the new bone formation was assessed by micro-computed tomography, dental radiography, and histology. Multiscale porous scaffolds that include both micro- and macropores resulted in higher bone regeneration in the defect area compared to only macroporous or only microporous scaffolds. When one-grade porous scaffolds were compared, microporous scaffolds showed better performance than macroporous scaffolds in terms of mineralized bone volume and tissue regeneration. Micro-CT results revealed that while bone volume/tissue volume (Bv/Tv) values were 8 and 17% at weeks 4 and 8 for macroporous scaffolds, they were significantly higher for microporous scaffolds, with values of 26 and 33%, respectively. Taken together, the results reported in this study showed the potential application of multiscale PolyHIPE scaffolds, in particular, as a promising material for bone regeneration

Developing wound dressings using 2-deoxy-D-Ribose to induce angiogenesis as a backdoor route for stimulating the production of vascular endothelial growth factor

2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound dressings based on the delivery of this sugar to induce angiogenesis in chronic wounds. In this review, we will survey the small volume of conflicting literature on this and related sugars, some of which are reported to be anti-angiogenic. We review the evidence of 2dDR having the ability to stimulate a range of pro-angiogenic activities in vitro and in a chick pro-angiogenic bioassay and to stimulate new blood vessel formation and wound healing in normal and diabetic rat models. The biological actions of 2dDR were found to be 80 to 100% as effective as VEGF in addition to upregulating the production of VEGF. We then demonstrated the uptake and delivery of the sugar from a range of experimental and commercial dressings. In conclusion, its pro-angiogenic properties combined with its improved stability on storage compared to VEGF, its low cost, and ease of incorporation into a range of established wound dressings make 2dDR an attractive alternative to VEGF for wound dressing development

Computationally designed peptides for zika virus detection: An incremental construction approach

Herein, and in contrast to current production of anti-Zika virus antibodies, we propose a semi-combinatorial virtual strategy to select short peptides as biomimetic antibodies/binding agents for the detection of intact Zika virus (ZIKV) particles. The virtual approach was based on generating different docking cycles of tetra, penta, hexa, and heptapeptide libraries by maximizing the discrimination between the amino acid motif in the ZIKV and dengue virus (DENV) envelope protein glycosylation site. Eight peptides, two for each length (tetra, penta, hexa, and heptapeptide) were then synthesized and tested vs. intact ZIKV particles by using a direct enzyme linked immunosorbent assay (ELISA). As a reference, we employed a well-established anti-ZIKV antibody, the antibody 4G2. Three peptide-based assays had good detection limits with dynamic range starting from 105 copies/mL of intact ZIKV particles; this was one order magnitude lower than the other peptides or antibodies. These three peptides showed slight cross-reactivity against the three serotypes of DENV (DENV-1,-2, and-3) at a concentration of 106 copies/mL of intact virus particles, but the discrimination between the DENV and ZIKV was lost when the coating concentration was increased to 107 copies/mL of the virus. The sensitivity of the peptides was tested in the presence of two biological matrices, serum and urine diluted 1:10 and 1:1, respectively. The detection limits decreased about one order of magnitude for ZIKV detection in serum or urine, albeit still having for two of the three peptides tested a distinct analytical signal starting from 106 copies/mL, the concentration of ZIKV in acute infection

The association of thinking styles with research agendas among academics in the social sciences

Research agendas are understudied, despite being key to academic knowledge creation. The literature suggests that the ways that academics determine their research agendas are conditioned by individual, organisational and environmental characteristics. This study explores the cognitive aspects of academics' research agendas in the social sciences by using a theory on thinking styles as an analytical framework. The results suggest that the research agendas of academics in the social sciences are significantly associated with their thinking styles. These findings aid understanding of how academics set their research agendas. This study also represents an important landmark in research on thinking styles, focusing on academic research work as a potential venue for further studies. The findings are relevant for policymakers, research funding agencies, university administrators and academics because they have implications for academic research development processes, outcomes, and for research and academic identity socialisation during doctoral studies.info:eu-repo/semantics/acceptedVersio