Fibroblast migration and collagen deposition during dermal wound healing: mathematical modelling and clinical implications,

The extent to which collagen alignment occurs during dermal wound healing determines the severity of scar tissue formation. We have modelled this using a multiscale approach, in which extracellular materials, for example collagen and fibrin, are modelled as continua, while fibroblasts are considered as discrete units. Within this model framework, we have explored the effects that different parameters have on the alignment process, and we have used the model to investigate how manipulation of transforming growth factor-β levels can reduce scar tissue formation. We briefly review this body of work, then extend the modelling framework to investigate the role played by leucocyte signalling in wound repair. To this end, fibroblast migration and collagen deposition within both the wound region and healthy peripheral tissue are considered. Trajectories of individual fibroblasts are determined as they migrate towards the wound region under the combined influence of collagen/fibrin alignment and gradients in a paracrine chemoattractant produced by leucocytes. The effects of a number of different physiological and cellular parameters upon the collagen alignment and repair integrity are assessed. These parameters include fibroblast concentration, cellular speed, fibroblast sensitivity to chemoattractant concentration and chemoattractant diffusion coefficient. Our results show that chemoattractant gradients lead to increased collagen alignment at the interface between the wound and the healthy tissue. Results show that there is a trade-off between wound integrity and the degree of scarring. The former is found to be optimized under conditions of a large chemoattractant diffusion coefficient, while the latter can be minimized when repair takes place in the presence of a competitive inhibitor to chemoattractants

Human vascular endothelial cells with extended life spans: In vitro cell response, protein expression, and angiogenesis

An in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists. In order to obtain large quantities of cells and reproducibility, human endothelial cells with extended life spans were developed by retroviral transfection. The resulting cells grown in a serum-free medium containing endothelial cell growth supplement (ECGS) have a telomerase activity, extended life spans of at least 21 passages, and an endothelial cell phenotype (diI-acetylated-LDL upake, factor VIII-related antigen, VEGFR-1 and R-2, and tissue-type plasminogen activator (tPA)) that resembled that of unaltered primary endothelial cells. Exceptions were (i) a higher expression of tPA, and (ii) a non-significant growth response to FGF-2 or VEGF stimulation. Within three-dimensional fibrin gels, specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells. Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS, respectively. Both cell types produced FGF-2 and VEGF cytokines. Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines. These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds

Next Generation of Electrosprayed Fibers for Tissue Regeneration

Electrospinning is a widely established polymer-processing technology that allows generation of fibers (in nanometer to micrometer size) that can be collected to form nonwoven structures. By choosing suitable process parameters and appropriate solvent systems, fiber size can be controlled. Since the technology allows the possibility of tailoring the mechanical properties and biological properties, there has been a significant effort to adapt the technology in tissue regeneration and drug delivery. This review focuses on recent developments in adapting this technology for tissue regeneration applications. In particular, different configurations of nozzles and collector plates are summarized from the view of cell seeding and distribution. Further developments in obtaining thick layers of tissues and thin layered membranes are discussed. Recent advances in porous structure spatial architecture parameters such as pore size, fiber size, fiber stiffness, and matrix turnover are summarized. In addition, possibility of developing simple three-dimensional models using electrosprayed fibers that can be utilized in routine cell culture studies is described

Potential of Natural Biomaterials in Nano-scale Drug Delivery

Background: The usage of natural biomaterials or naturally derived materials intended for interface with biological systems has steadily increased in response to the high demand of amenable materials, which are suitable for purpose, biocompatible and biodegradable. There are many naturally derived polymers which overlap in terms of purpose as biomaterials but are equally diverse in their applications. Methods: This review examines the applications of the following naturally derived polymers; hyaluronic acid, silk fibroin, chitosan, collagen and tamarind polysaccharide (TSP); further focusing on the biomedical applications of each as well as emphasising on individual novel applications. Results: Each of the polymer was found to demonstrate a wide variety of successful biomedical applications fabricated as wound dressings, scaffolds, matrices, films, sponges, implants or hydrogels to suit the therapeutic need. Interestingly, blending and amelioration of polymer structures were but two of a selection of strategies to modify the functionality of the polymers to suit the purpose. Further these polymers have shown promise to deliver small molecule drugs, proteins and genes as nano-scale delivery systems. Conclusion: The review highlights the breadth and depth of applications of the aforementioned polymers as biomaterials. Hyaluronic acid, silk fibroin, chitosan, collagen and TSP have been successfully utilised as biomaterials in the subfields of implant enhancement, wound management, drug delivery, tissue engineering and nanotechnology. Whilst there are a number of associated advantages (i.e. biodegradability, biocompatibility, non-toxic, non-antigenic as well as amenability) the select disadvantages of each individual polymer provide significant scope for their further exploration and overcoming challenges like feasibility of mass production at a relatively low cost