Advanced acrylate based hybrid materials for osteochondral regeneration

世界人口正在增加和老龄化，因此退行性疾病（如骨质疏松症和骨关节炎）、骨癌和创伤的发病率也在增加。骨是目前仅次于血液的第二大移植组织，并且没有足够的天然移植材料可用于移植，焦点已经转向通过使用临时支架来刺激和支持愈合过程来恢复身体的天然再生特性。目前临床上使用的再生材料包括生物陶瓷和可降解聚酯。然而，生物陶瓷具有严重的局限性，例如高度易碎的性质，这排除了它们在循环加载的骨修复应用中的使用。尽管已获得监管部门的批准，但常规聚酯通过自催化降解，使其降解突然发生。合成定制材料至关重要，该材料将生物陶瓷的强度和生物活性与聚合物的韧性相结合，同时还保持对降解速率的严格控制，以便材料在新组织生长的同时降解。为了实现这一目标，结构生物材料领域必须从传统的生物陶瓷和聚酯转变为自下而上的设计和合成。新的杂化材料，具有纳米级的相互作用和精心设计的坚韧可降解聚合物和二氧化硅之间的共网络之间的键合，将在生物材料研究中创造一个台阶式的变化，并引领更好的骨软骨再生。这一步变化的关键是设计具有明确分子大小、结构、化学组成和降解性的新聚合物。这需要材料工程、聚合物化学和细胞培养之间的协同作用。将使用通过能够控制分子量和组成的技术合成的丙烯酸酯基聚合物。这些聚合物将含有重要的官能团。关键方面是控制杂化物的亲水性和聚合物与二氧化硅之间的键合类型。亲水性的程度决定了溶胀的程度并获得最佳的细胞附着。虽然丙烯酸酯本身不是可降解的，但小到足以穿过肾脏的链可以通过可生物降解的交联连接，因此需要控制丙烯酸酯链的尺寸。结合类型（共价或动态或组合）将决定机械性能和降解速率。通过开发一种新的3D打印方法，将混合材料制成3D多孔结构，其中混合溶胶将被直接打印。由于材料的复杂性和加工变量的相互依赖性，必须在多个长度尺度上理解材料的结构。将采用最先进的技术来探测和优化从纳米到宏观尺度的材料结构，以适应细胞反应。临床成功的一个重要组成部分是所有利益相关者（临床医生和医疗器械公司）在支架开发和技术转让中发挥早期作用。这个跨学科和互补的团队的成功，跨越聚合物和无机化学，材料加工，分层表征，细胞生物学，整形外科和技术转让，将鼓励国际知名的研究人员搬到并留在英国。在20-50年内，英国将经历重大影响，加速重返工作岗位，并保持人口的活动进入老年。这个令人兴奋和创新的项目汇集了国际和英国的合作者将专注于开发一个充满活力和支持性的研究环境。该项目将产生由该项目创建的新领域的领导者，并确保英国保持在生物材料研究的最前沿。

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.