Orthopaedic implants have been the subject of intense research in recent years, with academics, clinicians and industrialists seeking to broaden our understanding of their function and potential consequences within the human body. Current research is focussed on ways to improve the integration of an orthopaedic device within the body, whether it be to encourage better osseointegration, combat possible infection or stem the foreign body response. A key emerging strategy is the controlled delivery of therapeutics from the device, which may take the form of, for example, antibiotics, analgesics, anti-inflammatories or growth factors. However, the optimal device design that gives rise to the desired controlled release has yet to be defined. There are many examples in the literature of experimental approaches which attempt to tackle this issue. However, the necessity of having to conduct multiple experiments to test different scenarios is a major drawback of this approach. So enter stage left: mathematical modelling. Using a mathematical modelling approach can provide much more than experiments in isolation. For instance, a mathematical model can help identify key drug release mechanisms and uncover the rate limiting processes; allow for the estimation of values of the parameters controlling the system; quantify the effect of the interaction with the biological environment; and aid with the design of optimisation strategies for controlled drug release. In this paper we review current experimental approaches and some relevant mathematical models and suggest the future direction of such approaches in this field.
Orthopaedic implants; Controlled release; Mathematical modelling; Drug delivery
Citation: David King, Sean McGinty Assessing The Potential Of Mathematical Modelling In Designing Drug-releasing Orthopaedic Implants doi:10.1016/j.jconrel.2016.08.009
Received: 5 July 2016, Revised: 4 August 2016, Accepted: 7 August 2016, Available online: 10 August 2016
Copyright: © 2016 Elsevier B.V. or its licensors or contributors. ScienceDirect ® is a registered trademark of Elsevier B.V.
In this review we have highlighted some of the key issues from the use of OIs and have provided examples of experimental approaches to aid in the understanding of drug release from OIs via prototype devices, coatings and materials. Based on the encouraging results of recent experimental work, we believe that mathematically analysing drug release from OIs would very likely be a fruitful endeavour. Such an approach has the potential of accelerating the design of the enhanced drug-releasing OIs of the future.
David King would like to gratefully acknowledge the funding provided by EPSRC under grant number EP/M506539/1.