Curcumin nanofibers for the purpose of wound healing

Poor wound healing is a highly prevalent clinical problem with, as yet, no entirely satisfactory solution. A new technique, termed electrospinning, may provide a solution to improve wound healing. Due to their large surface area to volume ratio and porosity, the nanofibers created by electrospinning are able to deliver sustained drug release and oxygen to the wound. Using different types of polymers with varying properties helps strengthening nanofiber and exudates absorption. The nanofibers appear to have an ideal structure applicable for wound healing and, in combination with curcumin, can blend the anti-inflammatory and antioxidant properties of curcumin into a highly effective wound dressing. The use of suitable curcumin solvents and the slow release of curcumin from the nanofiber help in overcoming the known limitations of curcumin, specifically its low stability and limited bioavailability. Here, we review the studies which have been done on synthesized nanofibers containing curcumin, produced by the electrospinning technique, for the purpose of wound healing.     

Engineering the migration and attachment behaviour of primary dermal fibroblasts

The availability of primary cells present in pathological conditions is often very limited due to stringent ethical regulation and patient consent. One such condition is chronic wounds, where dermal fibroblasts show a deficient migration. In vitro models with cellular tools that mimic the in vivo scenario would be advantageous to test new therapies for these challenging wounds. Since the availability of primary dermal fibroblasts present in chronic wounds is restricted and their “shelf-life” limited due to the increased senescence, our aim was to engineer human dermal fibroblasts with impaired migration using synthetic Arg-Gly-Asp (RGD) peptides. We studied fibroblast behaviour on three different two dimensional (2D) surfaces, representative of the dermal extracellular matrix and the materials used in the development of dermal scaffolds, in addition to commercially available, collagen-based 3D dermal scaffolds, demonstrating that the concentration of synthetic RGD peptides necessary to impair migration of dermal fibroblasts should be tailored to the particular surface/material and cell population used. The described technology could be translated to other cell types including established cell lines. A wide range of synthetic peptides exists, which differ in the amino acid sequence, thus increasing the possibilities of this technology.     

Autophagy–mediated plasma membrane removal promotes the formation of epithelial syncytia

Epithelial wound healing in Drosophila involves the formation of multinucleate cells surrounding the wound. We show that autophagy, a cellular degradation process often deployed in stress responses, is required for the formation of a multinucleated syncytium during wound healing, and that autophagosomes that appear near the wound edge acquire plasma membrane markers. In addition, uncontrolled autophagy in the unwounded epidermis leads to the degradation of endo‐membranes and the lateral plasma membrane, while apical and basal membranes and epithelial barrier function remain intact. Proper functioning of TORC1 is needed to prevent destruction of the larval epidermis by autophagy, in a process that depends on phagophore initiation and expansion but does not require autophagosomes fusion with lysosomes. Autophagy induction can also affect other sub‐cellular membranes, as shown by its suppression of experimentally induced laminopathy‐like nuclear defects. Our findings reveal a function for TORC1‐mediated regulation of autophagy in maintaining membrane integrity and homeostasis in the epidermis and during wound healing.     

Oriented cell division: new roles in guiding skin wound repair and regeneration

Tissue morphogenesis depends on precise regulation and timely co-ordination of cell division and also on the control of the direction of cell division. Establishment of polarity division axis, correct alignment of the mitotic spindle, segregation of fate determinants equally or unequally between daughter cells, are essential for the realization of oriented cell division. Furthermore, oriented cell division is regulated by intrinsic cues, extrinsic cues and other cues, such as cell geometry and polarity. However, dysregulation of cell division orientation could lead to abnormal tissue development and function. In the present study, we review recent studies on the molecular mechanism of cell division orientation and explain their new roles in skin repair and regeneration.     

负压封闭引流对兔颅骨外露创面愈合效果的实验研究

目的:探讨负压封闭引流技术(VSD)对兔颅骨外露缺损创面愈合的治疗效果。方法:选取成年新西兰大白兔76只,平均分为四组并建立兔颅骨外露实验模型。其中,A组(19只):于兔颅骨上方制作直径为2.0cm的圆形创面,保留骨膜,采用-120mmHg负压引流和常规换药治疗;B组(19只):实验动物处理同A组,仅采用常规换药治疗;C组(19只):在兔颅骨上制作直径2.0cm的圆形创面,剔除骨膜,治疗方法同A组;D组(19只):实验动物处理同C组,治疗方法同B组。每组各抽取10只,观察创面愈合率和创面愈合时间;其余9只分别在第7天、10天、20天、30天进行取材检测,分析疗效机制。结果:A组创面愈合时间为19.40±1.65天,B组为24.00±2.31天;C组为25.40±4.43天,D组为30.00±5.50天。运用VSD治疗和常规治疗创面愈合时间比较有统计学意义(P0.05)。结论:VSD治疗兔骨外露缺损创面能有效缩短创面愈合时间,促进血管再生,胶原蛋白合成。     

The lactate conundrum in wound healing: Clinical and experimental findings indicate the requirement for a rapid point-of-care diagnostic

The increasing prevalence of chronic wounds has significant financial implications for nations with advanced healthcare provision. Although the diseases that predispose to hard‐to‐heal wounds are recognized, their etiology is less well understood, partly because practitioners in wound management lack specialized diagnostic support. Prognostic indicators for healing may be inherent to wound biochemistry but remain invisible under routine clinical investigation; lactate is an example of this. In this study, lactate concentration in exudate obtained from 20 patients undergoing wound management in hospital was variable but in some cases approached or exceeded 20 mM. In vitro viability studies indicated that fibroblasts and endothelial cells tolerated low levels of lactate (1–10 mM), but cell viability was severely compromised by high lactate concentrations (=20 mM). Scratched monolayer experiments revealed that cell migration was affected earlier than viability in response to increasing lactate dose, and this was shown by immunocytochemistry to be associated with cytoskeletal disruption. A prototype enzyme‐based colorimetric assay for lactate generating a color change that was rapid in the context of clinical practise, and capable of functioning within a gel vehicle, was developed with point‐of‐care dipstick applications in mind. A randomized single‐blinded trial involving 30 volunteers and using a color chart to calibrate the assay demonstrated that lactate concentration could be reliably estimated with 5 mM precision; this suggesting that “physiological” and “pathological” lactate concentration could be distinguished. The present data suggest that a dipstick‐type colorimetric assay could comprise a viable diagnostic tool for identifying patients at‐risk from high‐wound lactate. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 917–924, 2012     

Plasminogen activator inhibitor-1 and tenascin-C secreted by equine mesenchymal stromal cells stimulate dermal fibroblast migration in vitro and contribute to wound healing in vivo

Background

Impaired cutaneous wound healing is common in humans, and treatments are often ineffective. Based on the significant emotional and economic burden of impaired wound healing, innovative therapies are needed. The potential of mesenchymal stromal cell (MSC)–secreted factors to treat cutaneous wounds is an active area of research that is in need of refinement before effective clinical trials can be initiated. The aims of the present study were to (i) study which MSC-secreted factors stimulate dermal fibroblast (DF) migration in vitro and (ii) evaluate the potential of these factors to promote wound healing in vivo.

How Methylammonium Cations and Chlorine Dopants Heal Defects in Lead Iodide Perovskites

Lead tri‐iodide methylammonium (MAPbI₃) perovskite polycrystalline materials show complex optoelectronic behavior, largely because their 3D semiconducting inorganic framework is strongly perturbed by the organic cations and ubiquitous structural or chemical inhomogeneities. Here, a newly developed time‐dependent density functional theory‐based theoretical formalism is taken advantage of. It treats electron–hole and electron–nuclei interactions on the same footing to assess the many‐body excited states of MAPbI₃ perovskites in their pristine state and in the presence of point chemical defects. It is shown that lead and iodine vacancies yield deep trap states that can be healed by dynamic effects, namely rotation of the methylammonium cations in response to point charges, or through slight changes in chemical composition, namely by introducing a tiny amount of chlorine dopants in the defective MAPbI₃. The theoretical results are supported by photoluminescence experiments on MAPbI_3?mCl_m and pave the way toward the design of defect‐free perovskite materials with optoelectronic performance approaching the theoretical limits.     

Synthesis,characterization, antioxidant power and acute toxicity of some new azo-benzamide and azo-imidazolone derivatives with in vivo and in vitro antimicrobial evaluation

In this research paper, a stepwise chemical reaction was conducted to synthesize and develop of a new potent azo-oxazolone, which was used as prototypical molecule for production of two series of azo-benzimide (5a–j) and azo-imidazolone (6a–j). FT-IR, ¹H NMR, ¹³C NMR and CHN analysis were used for the structural elucidation. The high biological efficiency of newly obtained compounds was confirmed by in vitro antioxidant efficacy and in vitro antimicrobial activity against gram-positive and gram-negative bacteria via disc diffusion and tube dilution techniques. In addition, in vivo anti-microbial activity of some of the synthesized compounds was determined by using burnt rats which infected by Staphylococcus aureus. Tested compounds have shown high anti-microbial activity and wound healing in comparison to ucederm as a control. In vivo acute toxicity was carried out by up and down method for the compounds 4, 5d and 6d. The limited test dose was 2000 mg/kg, while the maximum tolerated dose was 5000 mg/kg which has administered no lethality recorded.