A modular strategy for the repair of critical sized bone fractures

Project Information

HEALIKICK

Grant agreement ID: 874889

DOI

10.3030/874889

Project closed

EC signature date 4 May 2020

Start date 1 June 2020

End date 31 May 2026

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 5 243 535,50

EU contribution

€ 5 243 535,50

Coordinated by

UNIVERSITY OF GLASGOW
United Kingdom

Periodic Reporting for period 3 - HEALIKICK (A modular strategy for the repair of critical sized bone fractures)

Reporting period: 2023-06-01 to 2024-11-30

Summary of the context and overall objectives of the project

Disruptive technologies for bone regeneration must be able to tackle complex fracture environments that have developed into non-union bone defects. These types of fractures are common and increasingly prevalent when considering the rise in osteoporosis cases alone. We aim to develop graft technologies that will provide the efficacy of an autograft with the benefits of being an off-the-shelf product. Bioengineered bone graft systems need to be able to guide the regrowth of new bone into substantial voids and therefore implants pre-seeded with mineralising cells are of significant clinical interest. We will implement a surgical co-administration of two robust technologies 1) a granular graft material with a highly osteogenic coating that presents relevant biologics very efficiently and 2) pre-differentiated osteogenic mesenchymal stromal cells (MSCs) that together will underpin efficient bone regeneration. Within the project we aim to take these two technologies into GMP and ISO rated manufacture as required for any clinical therapy. We will then implement these therapies in pre-clinical studies to obtain efficacy and safety data to support a full clinical trial application. Our aim is to develop these technologies into a new medical device and a new cellular therapy with pre-clinical validation for their co-administration.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Since the start of the project, we have made progress in developing new technologies for bone regeneration. We have successfully shifted the production of our specialized cells (aMSCs) and our advanced bone graft materials from research setting to a professional manufacturing process that meets industry standards. This change is important for making our technologies more accessible to larger groups of patients. We have also conducted economic assessments to understand the potential market for these new clinical therapies. Early testing in animals has shown promising results, and we are working with an external organization to conduct safety tests that meet regulatory standards. These efforts will help us prepare important documents needed for clinical trials. Recently, we've been focusing on how our advanced therapy products are released, stored, and validated. We have looked to use PRP as an alternate to fibronectin and BMP-2 with Healiost; this has produced some mixed data compared to use of BMP-2. In vivo data seem to suggest that bone regeneration is more closely associated with BMP-2 presence, indicating that FN may be a more effective delivery method. We have established a reliable manufacturing process and received regulatory approval for clinical use, and we have completed a long-term stability study for our graft materials. Initial studies in animals suggest that our coatings are effective, and we are addressing some challenges related to the use of PRP. Overall, these insights will help us guide future research and improve the real-world applications of our innovations in bone regeneration.

We have hosted three Translation Days for invited clinicians to share progress on the project to date, gain feedback and build relationships for future research development and clinical trials. As a result of these sessions, in principle, we have identified a group of sufficient clinician interest across Europe to run a multi-centre trial of non-union repair in the future. As a consortium, we have highlighted and presented results of the project to date at local, national, and international conferences aimed at relevant scientific, clinical and other industrial stakeholders. We have also participated in public engagement events with demonstrations and activities to exhibit our HEALIKICK technologies to the wider public. Results produced from the project have also been shared in open access, peer reviewed journal publications.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

There is a widespread clinical and economic need for cost-effective bone graft substitutes that can restore functional outcome and improve patient quality of life. Non-union fractures are common, and their treatment is a significant healthcare burden, particularly when considering the growing incidence of osteoporosis fragility fractures alone. This modular application of two highly advanced therapies is itself highly novel in terms of clinical strategy and by the end of the project we aim to have made the required regulatory and technical developments to submit them for clinical trial. By developing innovative bone graft solutions for complex fractures, non-union or mal-union conditions, we hope to improve clinical outcomes of current complex injuries and enable currently unrealisable treatments to repair defective, diseased bone tissues caused by trauma and aging.

Immunofluorescent labelling of Osteopontin (OPN) in hMSCs cultured on monetite coated with PEA+FN+BM