pH-Responsive hollow particle gels for cartilage regeneration

骨关节炎（OA）是覆盖关节骨末端的软骨逐渐退化。这是一种使人衰弱的疾病，33%的成年人在45岁左右发病，影响着世界上15%的人口。2007年，英国国民健康服务（NHS）的OA治疗费用为8.5亿英镑（占NHS预算的5%），并且还在增加。目前迫切需要一种可注射的液体，这种液体可以在体内转化为凝胶，为受损的软骨提供即时的负载支持，并导致软骨组织的再生。中空聚合物颗粒具有使软骨组织再生的潜力。在我们的概念验证研究中，我们建立了一种新的可注射液体，其中含有ph响应的可生物降解中空聚合物颗粒，在生理条件下从液体变为凝胶。在本提案中，我们的目标是建立将中空颗粒连接在一起的方法，以制备可注射的凝胶，这些凝胶既具有机械稳定性，又能够使用体内自然存在的分子按需拆卸。这些都是必不可少的步骤，如果成功，将导致制备可注射、高强度、中空颗粒凝胶的设计规则，这可能使新的OA治疗成为可能。这个雄心勃勃的提案极大地扩展了我们早期的研究，将由一名博士后研究员进行为期30个月的研究。

Osteoarthritis (OA) is the gradual degeneration of cartilage covering the bony ends of joints. It is a debilitating disease which develops in 33% of adults in the mid 40s and affects 15% of the worlds population. The cost of OA treatment for the UK National Health Service (NHS) was £850M in 2007 (5% of the NHS budget) and is increasing. There is an urgent need for an injectable fluid that transforms into a gel in the body that provides both immediate load support to damaged cartilage and results in regeneration of cartilage tissue. Hollow polymer particles have potential to enable regeneration of cartilage tissue. In our proof-of-concept study we established a new injectable fluid containing pH-responsive biodegradable hollow polymer particles that change from a fluid to a gel at physiological conditions. In this proposal we aim to establish methods for linking the hollow particles together to prepare injectable gels that are both mechanically stable and are able to be disassembled on demand using molecules that naturally occur in the body. These are essential steps which, if successful, will result in design rules for preparing injectable, high strength, hollow particle gels that could enable a new OA therapy. This ambitious proposal greatly extends our earlier study and will be conducted by a postdoctoral research associate over a period of 30 months.