pH-Responsive hollow particle gels for cartilage regeneration

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.

A successful outcome to our proposed research would deliver injectable biodegradable hydrogel /cell composites that provide immediate load support and subsequent cartilage tissue regeneration. This could lead to a future minimally invasive treatment for osteoarthritis (OA). OA affects hip, knee and finger joints. OA is a major health problem for society and is projected to increase as western society ages and obesity increases. If successful, our approach could lead to new, minimally-invasive, therapy for cartilage repair. This would benefit the large numbers of patients suffering from OA. It could also be of benefit to younger patients requiring cartilage regeneration,.e.g., craniofacial cartilage, cartilage in jaws and growth plates of long bones. Because of this the beneficiaries from a successful outcome of this research will be patients, the NHS and UK biomedical companies.

A future OA treatment that could result from a successful outcome to this project would benefit patients through reduced durations in hospital and faster recovery times. Clinicians would benefit from a reduction in surgical procedures. This would also reduce cost for the NHS and waiting times for surgery. An injectable dispersion that transformed in-vivo into a load bearing cartilage implant and tissue scaffold could of benefit to UK medical device companies interested in hip, knee and finger-joint strategies (e.g., Smith and Nephew and Depuy). There are over 800,000 hip replacement procedures per year worldwide. Because of this there continues to be a strong drive toward developing minimally-invasive technologies that provide immediate structural support and offer the prospect of removing (or delaying) the requirement for surgery.

The beneficiaries listed above could only benefit directly from this research if the results were translated into new medical devices. The key first step for this is patent protection. Once obtained, and supported by high impact peer-reviewed journal articles, the PI and Co-I will actively pursue licencing opportunities with companies that have mutual development interests in this area or spin-out company formation. The PIs have a strong track record of collaborating with UK industry. They both have networks of UK polymer and medical device companies that will be used to explore collaborative development of the new regenerative medicine platform that should emerge from this project.

The dissemination of the results in the wider media will occur through joint university press releases (after peer-reviewed publication in high impact journals). The applicants have found this to be an excellent means of promoting the benefits of EPSRC-funded science to the broader community and also for attracting interest from UK and international companies.