Pre-clinical Investigations of Innovative Medical Devices based on Peptide-Enhanced Calcium Phosphates for Enhanced Bone Tissue Regeneration

Synthetic calcium phosphate (CaP) bone graft substitutes are widely used in surgery, including orthopedic and spinal surgeries.

However, tissue healing is frequently unpredictable, especially in ageing or compromised patients (e.g. those with diabetes and/or osteoarthritis). Attempts to overcome these limitations by mixing the CaP bone substitute with growth factors (e.g.

BMPs) have met with limited success, but these combinations have also introduced new hazards including adverse reactions that have curtailed their clinical use.

More recently, attention has instead been focussed on adding small osteogenic peptides, however these are yet to fully impact the market due to their cost, likely due to scale up issues, medical grade manufacture and the complex changing regulatory pathway.

The only commercially available peptide-containing bone graft substitute available is based on processed bovine bone rather than a truly synthetic CaP, which introduces additional risks and ethical issues.

The purpose of this project is overcome the established limitations of mixtures of bone graft substitutes with growth factors or peptides by developing an innovative, peptide-enhanced synthetic CaP material that is regulated as a medical device yet elicits consistent and predictable bone tissue healing, even in ageing or compromised patients.

The osteogenic peptide will be bound to the synthetic CaP surface using a proven technology that has been demonstrated by our previous research.

In reaching technology readiness level (TRL) 4, we have developed a method for anchoring osteogenic peptides to the CaP surface, identified the most promising peptide, established the optimal range of concentrations using in vitro testing, and demonstrated the safety of the device through a small animal (rabbit) in vivo study.

We have also performed a market evaluation, defined the regulatory pathway, and engaged extensively with patient groups in order to align our technology with their priorities and the market.

These previous studies further suggest that the resulting synthetic peptide-enhanced bone graft substitute will present a far lower risk of side effects, as well as being considerably cheaper to manufacture to a medical grade standard.

The work described in this proposal will move this highly promising new technology from TRL 4 to 5 by demonstrating enhanced in vivo bone tissue regeneration, performing ageing and shelf life studies, evaluating the market, and engaging with key stakeholders, including patients, surgeons and regulators.

On completion of the project, the efficacy of this innovative enhanced bone graft substitute will therefore have been demonstrated, and the final stages of the pathway to market will be defined.

This aligns closely with the ambitions of Versus Arthritis, moving an innovative technology towards the clinic where it will have a transformative impact on musculoskeletal surgery and therefore the lives of patients.