Local delivery of PTH(1-34) from an injectable collagen-hydroxyapatite scaffold for non-invasive treatment of bisphosphonate associated atypical femoral fractures

Informations projet

InjectCHA

N° de convention de subvention: 705994

DOI

10.3030/705994

Projet clôturé

Date de signature de la CE 25 Avril 2016

Date de début 1 Mai 2016

Date de fin 2 Mai 2019

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 175 866,00

Contribution de l’UE

€ 175 866,00

Coordonné par

ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland

Periodic Reporting for period 1 - InjectCHA (Local delivery of PTH(1-34) from an injectable collagen-hydroxyapatite scaffold for non-invasive treatment of bisphosphonate associated atypical femoral fractures)

Période du rapport: 2016-05-01 au 2018-04-30

Résumé du contexte et des objectifs généraux du projet

Osteoporosis is a major disease burden - 22 million women and 5.5 million men aged between 50-84 years of age were estimated to have osteoporosis in the EU (2010 figures). Due to the EU’s aging population, this is expected to increase by 25% by 2025. The majority of these patients are treated with bisphosphonates (BPs), a drug that prevents bone loss. However, many patients remain on these drugs for years, if not for the remainder of their lives. Long-term BP therapy leads to over-suppression of bone remodelling, an impaired ability to repair skeletal micro-fractures, and increased skeletal fragility. As a result, there is an emerging and devastating challenge associated with prolonged BP use known as atypical femoral fracture (AFF). These fractures are excruciatingly painful and associated with high levels of morbidity and mortality. The intrinsic challenge with this medical problem is that these fractures are recalcitrant to treatment and there are currently no effective therapies available. During this MSCA fellowship, the goal was to design and develop a novel injectable therapeutic biomaterial technology that would stimulate repair of AFFs. The devise consisted of a thermoresponsive shear-thinning collagen-hydroxyapatite biomaterial that would serve as a regenerative template. In addition, therapeutics can be incorporated within the biomaterial to promote bone repair. The overall objective was to formulate and fabricate this injectable therapeutic device and to test the idea that continuous local delivery of parathyroid hormone (PTH(1-34)) would restore remodelling and facilitate bone healing.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

This project achieved the development of a novel minimally invasive biomaterial technology for orthopaedic applications. An extensive characterisation of the biomaterial formulation and fabrication was carried out in vitro (i.e. outside the body) and demonstrated the effect of composition variations on the structural and rheological properties of the biomaterial. Furthermore, its ability to support cell growth was demonstrated. In addition, the effect of continuous dosing of PTH(1-34) on bone cell activity was validated. During the course of the project, additional opportunities arose as a result of the thermoresponsive and shear-thinning biomaterial technology developed, including a spin-off project investigating the technology as a thermoresponsive therapeutic biomaterial for skin regeneration.

The work completed as a Marie Skłowdowska Curie fellow has, to date, resulted in 3 conference talks, 2 poster presentations at conferences and 4 invited talks to date; 2 papers in preparation.

(Note: Some results and details are omitted due to confidentiality).

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The work in InjectCHA has resulted in a novel injectable therapeutic biomaterial technology for the local delivery of therapeutics within a regenerative biomaterial capable of self-setting and shape elasticity.
After the end of the project, work in my lab will continue on this device, which we hope will demonstrate the ability to locally deliver bone cell manipulating therapeutics within a minimally invasive regenerative biomaterial. Ultimately, the aim of this medical device is to promote bone repair in metabolically challenged defects in osteoporotic patients. This treatment strategy is less invasive, more effective, and lower in cost with major socioeconomic benefits to patients’ quality of life. In addition, the health care system will also benefit in terms of patient load, cost, and reduced reimbursements by insurers.

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