Theranostic doubly crosslinked microgels: From a new materials class to an injectable load supporting medical device

Lead Research Organisation: University of Manchester
Department Name: Materials

Abstract

Degeneration of the intervertebral disc (DIVD) and osteoarthritis (OA) result in chronic pain. They are major UK healthcare problems that are projected to grow as society ages, leading to reduced productivity and increased NHS costs. Double crosslinked microgels (DX MGs) are load supporting gels made from pre-formed microgel (MG) particles that can be linked together in vivo. MG particles are crosslinked polymer colloid particles that swell when the pH approaches the pKa of the polymer. My previous EPSRC-funded DX MG research established the concept of injectable biocompatible DX MGs for restoring the mechanical properties of degenerated IVDs. Recently we have shown that injectable DX MGs are a potential treatment for DIVD. Unfortunately, like all gels, our first generation DX MGs cannot provide optimal stress distributions throughout degenerated IVDs due to the complex, irregular shape of the voids that they fill. Unfortunately, there is no possibility of external tuning of the load distributions once injected. Achieving optimal load support will give the best pain relief and prevent further degeneration. This goal requires new gels with externally controlled compressive strain tuning abilities which can be informed by the strain present in vivo. In this proposal I plan to establish next generation theranostic DXMGs which provide therapeutic (load support) benefit and diagnostic strain information from within IVDs. I plan to construct new DX MGs that use deeply penetrating near-infrared (NIR) light, i.e., NIR DX MGs. These new injectable gels will report their mechanical environment in vivo and enable this to be tuned and optimised remotely. NIR DX MGs will also be photo-degradable which will enable their light-guided replacement by native tissue. My proposed theranostic NIR DX MGs are a new materials class that will act as an injectable load supporting medical device. A successful outcome will enable personalised, low cost, load supporting soft tissue repair.

Planned Impact

A minimally-invasive therapy for degeneration of the intervertebral disc (DIVD) and cartilage which optimised load support and repair would benefit both patients and the NHS by reducing hospitalisation times. The cost of treating osteoarthritis (OA) consumed 5% of the NHS budget in 2007. The direct healthcare cost of chronic back pain to UK plc was £1.6 billion in 1998. These major healthcare problems have substantial economic costs and are sources of chronic pain that will become increasingly prevalent in our ageing population. Success in this project could lead to a wide-spread, low cost, minimally-invasive personalised therapy for degeneration of the IVD and cartilage (due to OA). Furthermore, my proposed near-infrared doubly crosslinked microgels (NIR DX MGs) have potential use as therapies for non-load bearing tissue repair (e.g., craniofacial defect regeneration). Because my proposed gels may lead to fewer spinal fusion (and knee or hip) operations being required in the longer term, clinicians would benefit from a reduction in surgical procedures, allowing limited resources to be targeted elsewhere. In the US alone, 122,000 spinal fusion operations were performed in 2001 for DIVD.

Whilst enabling optimal load support and repair for damaged soft tissue is the primary goal of this proposal a successful outcome would also mean that the injectable gels proposed here enable remote (non-invasive) reporting of stress and strain within the IVDs (or hips and knees) of patients. These injectable gels could enable personalised biomechanical monitoring by clinicians which would have enormous beneficial implications for lifestyle assessment and management. Low cost biomechanical monitoring would be help the NHS assess the need for surgery more effectively.

The beneficiaries of my proposed research are patients, the NHS and also UK-based medical device companies developing load supporting implants. These beneficiaries would only gain directly from this project if the research findings were to be translated into new medical devices, for which the essential first step is patent protection. Once obtained, and supported by high impact peer-reviewed journal articles, I will actively pursue licensing opportunities with companies that have mutual development interests in this area (e.g., Smith & Nephew, Depuy Spine and Biointeractions). I have a strong record of collaborating with UK industry and also recent experience of the formation of a successful biomaterials spin-out company (Gelexir Healthcare Ltd). I have extensive networks with UK polymer and medical device companies that will be used to explore collaborative development of the new injectable medical device platform that is expected to emerge from this project. The scientific findings will be disseminated to the wider media through university press releases (after peer-reviewed publication in high impact journals). I have found this approach to be an effective mechanism to promote the benefits of EPSRC-funded science to the UK public and also for attracting interest from both UK and international companies.

This proposal aims to establish a new materials class and use it to demonstrate proof-of-concept injectable load supporting medical devices for personalised soft tissue repair. A successful outcome will be highly relevant to the EPSRC Healthcare Technologies Therapeutics priority area. (A successful outcome would also contribute to the Healthcare Technologies priority areas of Diagnostics and Regenerative Medicine.) My fellowship proposal also has beneficial implications for the EPSRC Nanoscale Design of Functional Materials Grand Challenge and aligns with the EPSRC Delivery Plan in the context of greater multidisciplinary working.

Publications

10 25 50
 
Description The work has just begun and is progressing well.
Exploitation Route For IVD repair.
Sectors Healthcare

 
Description To increase the understanding of hydrogels for healthcare.
 
Description School Visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I gave an outreach lecture to a local secondary school of biomaterials and their future role in medicine. The feedback was very positive from the school.
Year(s) Of Engagement Activity 2017