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      Adult Stem Cell Therapies for Wound Healing: Biomaterials and Computational Models

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          The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles), has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells (SCs) have been proposed for the treatment of these wounds, thanks to the ability of SCs to self-renew and specifically differentiate in response to the target bimolecular environment. Here, we discuss how advanced biomedical devices can be developed by combining SCs with properly engineered biomaterials and computational models. Examples include composite skin substitutes and bioactive dressings with controlled porosity and surface topography for controlling the infiltration and differentiation of the cells. In this scenario, mathematical frameworks for the simulation of cell population growth can provide support for the design of bioconstructs, reducing the need of expensive, time-consuming, and ethically controversial animal experimentation.

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          Most cited references 63

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          Wound repair and regeneration.

          The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of fibrotic tissue known as a scar. By contrast, early in gestation, injured fetal tissues can be completely recreated, without fibrosis, in a process resembling regeneration. Some organisms, however, retain the ability to regenerate tissue throughout adult life. Knowledge gained from studying such organisms might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.
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            Wound healing--aiming for perfect skin regeneration.

             Tamara Martin (1997)
            The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis, and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
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              COPASI--a COmplex PAthway SImulator.

              Simulation and modeling is becoming a standard approach to understand complex biochemical processes. Therefore, there is a big need for software tools that allow access to diverse simulation and modeling methods as well as support for the usage of these methods. Here, we present COPASI, a platform-independent and user-friendly biochemical simulator that offers several unique features. We discuss numerical issues with these features; in particular, the criteria to switch between stochastic and deterministic simulation methods, hybrid deterministic-stochastic methods, and the importance of random number generator numerical resolution in stochastic simulation. The complete software is available in binary (executable) for MS Windows, OS X, Linux (Intel) and Sun Solaris (SPARC), as well as the full source code under an open source license from

                Author and article information

                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                11 January 2016
                : 3
                1Department of Mechanical Engineering, Insigneo Institute for in silico Medicine, University of Sheffield , Sheffield, UK
                2Department of Materials, Loughborough University , Loughborough, UK
                Author notes

                Edited by: Alessandro Polini, Radboud University Medical Centre, Netherlands

                Reviewed by: Mikaël M. Martino, Osaka University, Japan; Elizabeth R. Balmayor, Technical University Munich, Germany

                *Correspondence: Daniele Tartarini, d.tartarini@ ; Elisa Mele, e.mele2@

                Specialty section: This article was submitted to Tissue Engineering and Regenerative Medicine, a section of the journal Frontiers in Bioengineering and Biotechnology

                Copyright © 2016 Tartarini and Mele.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 67, Pages: 7, Words: 6041
                Funded by: Engineering and Physical Sciences Research Council 10.13039/501100000266
                Award ID: Project “Accelerating in silico cancer research with graphic processors“
                Bioengineering and Biotechnology
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