Novel Photocrosslinkable Hyperbranched Polymers for Injectable Scaffolds: Design, synthesis, characterisations and in vitro evaluation

用于注射支架的新型光交联超支化聚合物：设计、合成、表征和体外评估

• 批准号: EP/E042619/2
• 负责人: Hongyun Tai
• 金额: --
• 依托单位: Bangor University
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FE042619%2F2
• 关键词: Novel; Photocrosslinkable; Hyperbranched; Polymers; Injectable

Injectable scaffolds can offer the possibility of homogeneously distributing cells and molecular signals throughout the scaffold, and can be injected directly into cavities with irregular shape and size. Most studies have been on the development of injectable scaffolds for bone and cartilage tissue repair, some others for corneal wound healing. The most challenging issue is to find suitable materials which can solidify in situ to form 3-D scaffolds. Crosslinking via photopolymerisation provides many benefits, including rapid polymerisation times under physiological conditions. At present, most synthetic polymers used in tissue engineering are linear structure, however, they suffer from poor solution properties, non-homogenous crosslinking properties and limited control of polymer modification. Dendritic polymers have unique properties, such as good solubility, low viscosity and high functionality, due to their 3-D architecture. Grinstaff synthesised a photocrosslinkable dendrimer for corneal wound healing sealant and cartilage repair. However, dendrimers have to be prepared by solvent-intensive and multi-step synthetic routes, most importantly, it is difficult to tailor the composition and structure of dendrimers for a wide range of special applications. By contrast, hyperbranched polymers, less controlled dendritic polymer architectures, can be synthesised more easily by a single-step reaction via a range of synthetic strategies. Could the use of such hyperbranched polymers overcome the synthetic barrier of dendrimers? The limitation of current synthetic strategies for hyperbranched polymers are either the need of special monomers (ABn or AB* inimer), and/or, only poor controlled structure and low degree of branching polymers can be obtained. Therefore, up till now, such materials are difficult to be considered in medical applications. I have recognised that a breakthrough in synthesis of hyperbranched materials with controlled chain structure and high degree of branching using more accessible monomers could facilitate a completely new approach to their biological and biomedical applications.Recently, the Nottingham team has developed a deactivation enhanced ATRP method, which opens up the field significantly and allows simple use of readily available and inexpensive multifunctional vinyl monomers to synthesise hyperbranched polymers with high degree of branching, controlled molecular weight and chain structure. Such hyperbranched polymer materials could be extremely important for biological and biomedical applications. Furthermore, the products carry a multitude of reactive functionalities (e.g. double bonds and halogen functional groups) that can be post-functionalised and modified for specific applications by end capping with short chains, organic molecules and terminal grafting. By these modifications, the material properties, such as functionality, polarity, solubility and flexibility of the hyperbranched polymers, can be conveniently tailored to meet the application requirements. The polyvinyl functional groups can be used as corsslinking sites by photo stimuli to form 3-D structure. My aim is to design and synthesise a broad spectrum of tailored, novel hyperbranched polymers for biological and biomedical applications using the recently developed facile synthetic strategy, deactivation enhanced ATRP. This proposal targets the development of novel photocrosslinkable hyperbranched polymers as injectable scaffold materials for cartilage tissue repair. The hydrogels from the targeted hyperbranched polymers will achieve better biological response with tailored mechanical properties, integrin-mediated cell adhesion and control of growth factor release. The research will include three tasks with some subtasks as detailed in the Case of Support.

可注射支架可以提供在整个支架中均匀分布细胞和分子信号的可能性，并且可以直接注射到形状和尺寸不规则的空腔中。大多数研究都致力于开发用于骨和软骨组织修复的可注射支架，还有一些研究用于角膜伤口愈合。最具挑战性的问题是找到可以原位固化形成 3D 支架的合适材料。通过光聚合进行交联具有许多优点，包括在生理条件下快速聚合。目前，组织工程中使用的合成聚合物大多为线性结构，但存在溶液性能差、交联性能不均匀、聚合物改性控制有限等问题。树枝状聚合物由于其 3D 结构而具有独特的性能，例如良好的溶解性、低粘度和高功能性。格林斯塔夫合成了一种可光交联的树枝状聚合物，用于角膜伤口愈合密封剂和软骨修复。然而，树枝状聚合物必须通过溶剂密集型和多步合成路线来制备，最重要的是，很难针对广泛的特殊应用定制树枝状聚合物的组成和结构。相比之下，超支化聚合物（控制较少的树枝状聚合物结构）可以通过一系列合成策略通过单步反应更容易地合成。使用这种超支化聚合物能否克服树枝状聚合物的合成障碍？目前超支化聚合物合成策略的局限性在于需要特殊单体（ABn 或 AB* 单体），和/或只能获得结构控制较差和支化度较低的聚合物。因此，到目前为止，此类材料还很难考虑在医学上的应用。我认识到，使用更容易获得的单体合成具有受控链结构和高度支化的超支化材料的突破可以促进其生物和生物医学应用的全新方法。最近，诺丁汉团队开发了一种失活增强的 ATRP 方法，该方法显着开拓了该领域，并允许简单地使用易于获得且廉价的多功能乙烯基单体来合成 具有高支化度、可控分子量和链结构的超支化聚合物。这种超支化聚合物材料对于生物和生物医学应用极其重要。此外，该产品带有多种反应性官能团（例如双键和卤素官能团），可以通过短链、有机分子封端和末端接枝进行后官能化和改性，以适应特定应用。通过这些改性，可以方便地定制超支化聚合物的材料性能，例如功能性、极性、溶解性和柔韧性，以满足应用要求。聚乙烯基官能团可在光刺激下用作交联位点以形成 3-D 结构。我的目标是使用最近开发的简便合成策略（失活增强 ATRP）设计和合成用于生物和生物医学应用的广泛定制的新型超支化聚合物。该提案的目标是开发新型光交联超支化聚合物作为软骨组织修复的可注射支架材料。来自目标超支化聚合物的水凝胶将通过定制的机械性能、整合素介导的细胞粘附和生长因子释放的控制来实现更好的生物反应。该研究将包括三项任务以及一些子任务，如支持案例中详述。

项目成果

Hydrogels from Dextran and Soybean Oil by UV Photo-Polymerization

• DOI: 10.1002/app.41446
• 发表时间: 2015-02-10
• 期刊: JOURNAL OF APPLIED POLYMER SCIENCE
• 影响因子: 3
• 作者: Omer, Rebaz A.;Hughes, Alan;Tai, Hongyun
• 通讯作者: Tai, Hongyun