Salmerón-Sánchez Manuel, Dalby Matthew J
Division of Biomedical Engineering, School of Engineering, University of Glasgow, Rankine Building, Oakfield Avenue, Glasgow G12 8LT, UK.
Center for Cell Engineering, Institute of Molecular Cell and Systems Biology, University of Glasgow, Joseph Black Building, Glasgow G12 8QQ, UK.
Chem Commun (Camb). 2016 Nov 8;52(91):13327-13336. doi: 10.1039/c6cc06888j.
Growth factors (GF) are remarkably powerful signalling molecules that orchestrate developmental biology. GFs are currently used in medical applications with limited success but it is clear that if their potential can be harnessed for biomedicine then they could underpin the discipline of regenerative medicine. However, while we understand that biology uses cell-secreted growth factors tethered to the ECM, biologists typically employ GFs in soluble format at high concentrations. When used in vivo, this causes off-target, unwanted effects, which severely limits their use. There is a vast amount of literature dealing with material systems that control the delivery of GFs. However, it was soon observed that GFs could be more effectively presented bound to surfaces from a solid-phase state rather than in soluble form, recapitulating the way the extracellular matrix (ECM) binds GFs. In parallel, evidence was found that within the ECM, GFs can actually work in cooperation with integrins and that this produced enhanced GF signalling due to the crosstalk between both receptors. Recently this knowledge was used to engineer microenvironments that target simultaneous integrin and GF receptor engagement seeking to maximise GF effects in vitro (e.g. in terms of stem cell differentiation) but also tissue repair in vivo (e.g. bone regeneration and wound healing). This feature article introduces the concept of synergistic GF/integrin signalling and then introduces GF delivery systems that were key in the development of more advanced synergistic growth factor microenvironments.
生长因子（GF）是一类极具强大作用的信号分子，它们在发育生物学过程中发挥着协调作用。目前，生长因子在医学应用中的成效有限，但很明显，如果能够将其潜力应用于生物医学领域，那么它们将为再生医学学科奠定基础。然而，尽管我们知道生物学中细胞分泌的生长因子会与细胞外基质（ECM）相连，但生物学家通常使用高浓度的可溶性生长因子。在体内使用时，这会导致脱靶的不良影响，严重限制了它们的应用。有大量文献涉及控制生长因子递送的材料系统。然而，很快人们就观察到，生长因子以固相状态结合在表面上比以可溶形式呈现时能更有效地发挥作用，这重现了细胞外基质结合生长因子的方式。与此同时，有证据表明在细胞外基质中，生长因子实际上可以与整合素协同作用，并且由于两种受体之间的相互作用，这种协同作用会增强生长因子信号传导。最近，这一知识被用于构建微环境，旨在同时靶向整合素和生长因子受体，以在体外（例如在干细胞分化方面）以及体内组织修复（例如骨再生和伤口愈合）中最大化生长因子的作用。这篇专题文章介绍了生长因子/整合素协同信号传导的概念，然后介绍了在更先进的协同生长因子微环境发展中起关键作用的生长因子递送系统。
