A biomimetic macromolecular platform for tissue healing and diagnostics at medical device interfaces: a personalised wound dressing model

仿生生物材料是模仿天然组织特征的材料，主要用于制造能够通过与生物分子和细胞的生物特异性相互作用与宿主组织完全融合的医疗植入物。有人认为，开发具有生物特异性相互作用的生物材料的能力也可用于开发针对疾病标志物的非常特异性和敏感的诊断方法。自1991年以来，Matteo Santin教授通过许多研究项目揭示了生物材料的表面特性及其与蛋白质、炎症细胞和组织细胞的相互作用之间的联系，为这一研究领域做出了贡献。所获得的知识导致了对新的仿生生物材料的研究，与其他试图模仿组织的自然微观和宏观结构的方法不同，这种材料一直专注于在大分子水平上再现自然特征。特别是，通过国际学术和工业合作，研究导致了生物材料表面改性的新方法的发展，主要基于合成或天然大分子的化学接枝或通过其粗糙度的工程；在这两种情况下，目的是使它们的表面特征与细胞和大分子所在的自然环境相似，并促进与组织愈合和诊断相关的生物特异性识别过程；这些研究已经通过在植入物表面的宿主组织再生导致植入物的整合和疾病检测的方法。这个为期6年的项目将开发一个用于组织愈合和疾病监测的仿生大分子新平台，重点是开发一类具有治疗性能的新型伤口敷料；即敷料能够愈合伤口，同时诊断其临床状态。该平台的开发将通过布莱顿大学再生医学和设备中心的多学科团队的努力来实现。与以往的研究不同，生物化学家将使用模拟体液来研究生物分子在单独或接近伤口敷料表面时周围水壳的形成，并确定影响其天然结构的因素。然后，计算机模型科学家将使用分子可溶解性的数据来建立一个“自然相互作用”中的润湿性数据库，该数据库能够保存生物分子的天然结构。化学家将根据这个数据库设计和合成新的大分子，以在修整表面重现相同的润湿性条件，并抑制它们不必要的污垢。这种新型大分子将与肽和已知的糖结合在一起，以驱动特定的生物识别过程。细胞生物学家将分析患者的免疫细胞和组织细胞与新型仿生表面接触时的行为，并将其与临床医生在伤口敷料界面观察到的行为进行比较。获得的生物特异性识别将在患者个体反应的背景下进行分析，并用于制造组织愈合敷料，整合基于视觉检查的疾病生物标志物检测系统。因此，一系列大分子将按照工业标准设计和合成，并具有相对的质量控制，以使工业合作伙伴受益，并基于“共享创新”原则，将基础知识和新技术应用于各种市场和临床用途，促进工业协同效应，避免利益冲突。当地生物医学产业网络将受益于项目成果，同时布莱顿大学为新合格人员提供培训。

Biomimetic biomaterials are materials mimicking the features of natural tissues and mainly advocated for the manufacturing of medical implants capable of achieving a complete integration with the host tissue through biospecific interactions with biomolecules and cells. It is argued that the ability to develop biomaterials capable of biospecific interactions can be exploited also for the development of very specific and sensitive diagnostics targeting disease markers. Prof Matteo Santin has contributed to this field of research since 1991 through many research projects unveiling the links between the surface properties of biomaterials and their interaction with proteins, inflammatory cells and tissue cells. The knowledge acquired has led to the research for new biomimetic biomaterials that, unlike other approaches trying to mimic the natural micro- and macro-structures of tissues, has been focussing on the reproduction of natural features at macromolecular level. In particular, through international academic and industrial collaborations, the research has led to the development of novel methods of biomaterial surface modification mainly based on the chemical grafting of synthetic or natural macromolecules or through the engineering of their roughness; in both cases the aim was to make their surface features similar to those of the natural environment where cells and macromolecule reside and to encourage biospecific recognition processes relevant to tissue healing and diagnosis; these studies have led to the integration of implants through the regeneration of the host tissue at the implant surface and to methods of detection of diseases.This 6-years project will develop a novel platform of biomimetic macromolecules for tissue healing and disease monitoring focussing its application on the development of a novel class of wound dressings with theranostic properties; i.e. dressings able to heal wounds while diagnosing their clinical status. The development of this platform will be pursued through the effort of a multidisciplinary team at the Centre for Regenerative Medicine and Devices, University of Brighton. Unlike previous studies, biochemists will use simulated body fluids to study the formation of the water shell around biomolecules when alone or in proximity of the surface of wound dressing materials and will establish the factors affecting their native structure. The data of molecular solvability will then be used by computer model scientists to produce a database of wettability in 'natural interactions' capable of preserving the biomolecules' native structure. Chemists will design and synthesise new classes of macromolecules according to this database to reproduce the same wettability conditions at the dressing surface and inhibit their unwanted fouling. The novel macromolecules will be coupled to the dressing in conjunction with peptides and sugars known to drive specific bio-recognition processes. Cell biologists will analyse the behaviours of patients' immune and tissue cells when in contact with the novel biomimetic surfaces and compare them with those observed by clinicians at the interface of retrieved wound dressing. The obtained biospecific recognition will be analysed in the context of patient's individual responses and exploited to manufacture tissue healing dressings integrating disease biomarker detection systems based on visual inspection.A range of macromolecules will therefore be designed and synthesised at industrial standard and with relative quality controls to the benefit of industrial partners and on the basis of the principle of 'shared innovation' whereby fundamental knowledge and new technology are applied to various markets and clinical uses promoting industrial synergies and avoiding conflicts of interest. A network of local biomedical industry will benefit from the project outcomes alongside the training provided by the University of Brighton to newly qualified personnel.