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      Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration

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          Abstract

          Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.

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          Wound healing--aiming for perfect skin regeneration.

          P. 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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            Regulation of wound healing by growth factors and cytokines.

            Sabine Werner, Richard P Grose, Alan Morgan (2003)
            Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.
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              Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family.

              Xiuqin Zhang, Omar Ibrahimi, Shaun Olsen … (2006)
              In mammals, fibroblast growth factors (FGFs) are encoded by 22 genes. FGFs bind and activate alternatively spliced forms of four tyrosine kinase FGF receptors (FGFRs 1-4). The spatial and temporal expression patterns of FGFs and FGFRs and the ability of specific ligand-receptor pairs to actively signal are important factors regulating FGF activity in a variety of biological processes. FGF signaling activity is regulated by the binding specificity of ligands and receptors and is modulated by extrinsic cofactors such as heparan sulfate proteoglycans. In previous studies, we have engineered BaF3 cell lines to express the seven principal FGFRs and used these cell lines to determine the receptor binding specificity of FGFs 1-9 by using relative mitogenic activity as the readout. Here we have extended these semiquantitative studies to assess the receptor binding specificity of the remaining FGFs 10-23. This study completes the mitogenesis-based comparison of receptor specificity of the entire FGF family under standard conditions and should help in interpreting and predicting in vivo biological activity.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 27 July 2017
                Publication date Collection: August 2017
                Volume: 22
                Issue: 8
                Electronic Location Identifier: 1259
                Affiliations
                [1 ]Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam 58554, Korea; jwpark@ 123456mokpo.ac.kr
                [2 ]Department of Pharmacy, College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea; srhwang@ 123456chosun.ac.kr
                [3 ]College of Pharmacy, Pusan National University, Geumjeong-gu, Busan 46241, Korea
                Author notes
                [* ]Correspondence: insoo.yoon@ 123456pusan.ac.kr ; Tel.: +82-51-510-2806
                [†]

                These authors contributed equally to this work.

                Article
                Publisher ID: molecules-22-01259
                DOI: 10.3390/molecules22081259
                PMC ID: 6152378
                PubMed ID: 28749427
                SO-VID: 3ef02f13-df4a-4ea0-8a1a-685f01c9e8a8
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 04 July 2017
                Date accepted : 25 July 2017
                Categories
                Subject: Review

                Keywords: chronic wound,drug delivery system,growth factor,wound healing
                Data availability:
                Keywords: chronic wound, drug delivery system, growth factor, wound healing

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