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

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.