Controlled release therapeutic coatings for orthopaedic devices based upon novel sol-gel formulations

Infection is a major complication of arthroplasty surgery with a reported incidence after primary surgery of approx 1-2%. The costs of treatment to eradicate infection are substantial to both patient and institution, and in terms of clinical expenditure are typically up to 4-5 times that of the primary intervention. Prevention of infection is therefore mandatory and prophylaxis with antibiotics plays a significant role. In cemented arthroplasty surgery, antibiotics elute from the bone cement during the crucial early perioperative period. However, the number of cemented hips in the UK has dropped from 54 to 36% while cementless arthroplasty has increased from 22 to 43%. The concept of cementless biological fixation is particularly attractive, especially for the young and active patient, hence the need for an antibiotic-release coating on cementless implants.

This multidisciplinary project addresses the clinical need to produce a coating system enabling controlled release of antibiotics local to the point of surgery on an optimal timescale to minimise the risk of infection. At the same time the coating may include additional therapeutic agents, such as growth factors to promote osseointegration. This will be achieved by encapsulating single or mixed therapeutic agents within a sol-gel coating. By exploiting the unique property variations (physical and mechanical) of a hybrid sol-gel coating chemistry a new coating will be developed which is specifically designed to counteract the effects of infection arising during implant surgery whilst simultaneously promoting osseointegration between the bone and the implant. The proposed concept is based on a single-layer hybrid sol-gel coating system that contains a depot of active molecules to provide both rapid-activated controlled-release, with zero-release times of less than 15 minutes and sustained release activity of both antibiotic and growth factors up to a period of several weeks. An additional benefit of adopting the sol-gel chemistry route is that, where necessary, it can be tailored to meet the specific clinical need of the individual patient.

Prosthetic joint-associated infections in hospitals impose significant economic consequence on both the nation's healthcare system and the consequential economic loss to business due to the prolonged absence of individuals from the workplace. More specifically in 2010, there were 76,759 hip replacement procedures recorded on the National Joint Register, representing a 6% increase compared with the same reporting period last year [see reference 1 in the "case for Support"]. Of these, 68,907 were primary procedures and 7,852 were revision surgeries, representing a revision 'burden' of 11.4%. It is specifically this revision burden that the development of an anti-infective prosthetic joint coating seeks to address.

The beneficiaries of this research include;

a. Patients. It is clear that a reduced risk of infection is of clear benefit to the patient. Since 2009 the number of cementless fixations has overtaken that of cemented systems [1]. Cementless systems are now considered to offer improved biological fixation which leads to improved rehabilitation, more rapid recovery and joint longevity.

b. Hospitals. Lower infection rates reduce the rate of revision surgery with the consequential benefits both in treatment and avoidance of possible litigation.

c. Surgeons. A successful outcome of this project is that of increased options for surgeons in the use of devices incorporating an anti-infective coating.

d. Academics. Understanding of the synthesis of encapsulation and the mechanisms of release within coating systems opens up the technology base for different applications, both within the medical sector and elsewhere, for example enzyme and bacteria laden coatings for synthetic photosynthesis and photocatalyst applications.

e. Industry. With the exception of one known application, (intramedullary tibial nails for trauma surgery) antimicrobial coated implantable medical devices do not exist. Success in the development of a clinically acceptable coated device would provide manufacturing opportunities for both the coatings industry and medical device manufacturers.