Title: Safety and efficacy of a Class III medical device loaded with nanoparticles for non-union fracture repair
Funder: Versus Arthritis

Abstract: The UK’s General Practice Research Database indicates that 1/2 women, and 1/5 men suffer a fracture after the age of 50. It is estimated that 5-10% of fractures are non-union which have an increased risk of injury associated arthritis and osteoarthritis. Non-weight bearing non-unions can cost on average £43,000 per patient. Ceramics such as hydroxyapatite (HA) are routinely used in fracture repair [1]. However, HA is not readily bioavailable and agglomeration significantly reduces efficacy through lack of cell entry. Previous studies have demonstrated that osteogenesis and bone regeneration are significantly increased when our patented RALA peptide (WO2014087023) is used to limit particle size distribution, conferring ideal physiochemical characteristics of HA for intracellular bioavailability and efficacy . Previous studies have also shown that our RALA-HA nanoparticles (NP) can be loaded and delivered via a thermo-responsive hydrogel (TH) that we have engineered to be liquid at room temperature and can gelate (at >32oC) upon delivery to the fracture site via a cannulated needle. Previous grants have been used to demonstrate that the TH degrades over 8 weeks and the medical device is capable of both controlling NP release and supporting new tissue growth. The overarching aim of this proposal is to validate our injectable medical device in vivo to provide evidence for further development and progress from TRL3 to TRL5/6. Therefore, the key objectives are to: Determine the in vivo optimal dose of NP in TH for a non-union repair using a rat model and correlate this to therapeutic response. Evaluate pharmacokinetic and pharmacodynamic profiles along with key immunohistochemistry for safety. Formulise large-scale manufacture of TH-NP technology. Validate osteogenic properties of the scaled-up TH-NP technology in a regulatory acceptable rabbit model. Develop a comprehensive marketing strategy, file IP for technology scale-up and engage with regulatory authorities. Versus Arthritis seeks to address the need for new commercial solutions in the treatment of musculoskeletal conditions to improve the quality-of-life for those affected by arthritis. The proposed medical device-based technology presents a minimally invasive and cost-effective solution for bone repair that offers improvement for those with non-union fractures. This fits well within the translational medical technologies call for TRL3-stage devices that are aiming to translate encouraging Proof-of-Concept technology to a pre-clinical level of validation (TRL5-6), with the aim of commercialisation and obtaining further investment. The proposed medical device is designed to address the 'gap in the market' that meets the imperative clinical need for new technology for bone regeneration. At this time, no one else has developed a nanoHA-loaded technology that addresses the low bioavailability of HA. Our proposed medical device overcomes this issue through modifications of the physiochemical characteristics of the contained HA-NP. Furthermore, the TH component of the medical device is a new formulation developed in-house and can boast injectable and in situ forming capabilities distinct from other current bone regeneration devices. Once combined, the innovation in both the NP and TH components results in an original and easy-to-implant solution for increasing the efficacy of bone regeneration in a clinical setting.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL