Advanced acrylate based hybrid materials for osteochondral regeneration

点击翻译按钮获取中文摘要

The world's population is increasing and ageing so incidences of degenerative diseases (e.g. osteoporosis and osteoarthritis), bone cancer, and trauma are also increasing. Bone is currently the second most transplanted tissue after blood and without enough natural graft material available for transplantation, focus has shifted towards recruiting the body's natural regenerative properties by using temporary scaffolds to stimulate and support the healing process. Regenerative materials currently used in the clinic include bioceramics and degradable polyesters. However, bioceramics have serious limitations, such as a highly brittle nature, that exclude their use in cyclically loaded bone repair applications. Despite having regulatory approval, conventional polyesters degrade via autocatalysis making their degradation occur suddenly. It is essential that bespoke materials are synthesised that combine the strength and bioactivity of bioceramics with the toughness of polymers whilst also maintaining stringent control over the degradation rates, so that the material degrades concurrently with new tissue growth. In order to achieve this, the field of structural biomaterials must shift from focussing on conventional bioceramics and polyesters and instead embrace the opportunities available from bottom-up design and synthesis.New hybrid materials, with nanoscale interactions and bonding between co-networks of carefully designed tough degradable polymers and silica, will create a step change in biomaterials research and lead the way towards better osteochondral regeneration. Crucial to this step change is the design of new polymers with well-defined molecular size, architectures, chemical composition and degradability. This requires a synergy between materials engineering, polymer chemistry and cell culture. Acrylate based polymers synthesised with techniques that will enable control of molecular weight and composition will be used. These polymers will contain important functional groups. Key aspects are controlling the hydrophilicity of the hybrid and type of bonding between the polymer and the silica. The degree of hydrophilicity dictates the degree of swelling and to obtain optimal cell attachment. While acrylates are not inherently degradable, chains that are small enough to pass through the kidneys can be linked by biodegradable crosslinks, hence the need for control of size of the acrylate chains. The type of bonding (covalent or dynamic or combinations of) will determine the mechanical properties and rate of degradation. The hybrid materials will be fabricated into 3D porous structures, by developing a novel 3-D printing approach, where the hybrid sol will be directly printed. Due to the complexity of the materials and the interdependence of processing variables, it is essential that the structure of materials are understood at multiple length scales. State of the art techniques will be employed to probe and optimise the materials' structures from the nano- to macro-scale with respect to cellular response.An essential component for clinical success is that all stakeholders (clinicians and medical device companies) play an early role in scaffold development and technology transfer. The success of this interdisciplinary and complementary team, spanning polymer and inorganic chemistry; materials processing; hierarchical characterisation; cell biology; orthopaedic surgery; and technology transfer, will encourage internationally renowned researchers to move to and stay in the UK.Within 20-50 years, the UK will experience significant impact, speeding up return to work and maintaining the population's activity into older age. This exciting and innovative project bringing together international and UK collaborators will focus on developing a dynamic and supportive research environment. This project will produce leaders of new fields created by this project and ensures that the UK remains at the forefront of Biomaterials research.