BoneFix: A Paradigm Shift in Fracture Fixations via On-Site Fabrication of Bone Restoration Patches

Project Information

BoneFix

Grant agreement ID: 952150

DOI

10.3030/952150

Project closed

EC signature date 24 June 2020

Start date 1 October 2020

End date 30 June 2025

Funded under

• EXCELLENT SCIENCE - Future and Emerging Technologies (FET)

Total cost

€ 3 983 468,13

EU contribution

€ 3 983 468,13

Coordinated by

KUNGLIGA TEKNISKA HOEGSKOLAN
Sweden

Periodic Reporting for period 3 - BoneFix (BoneFix: A Paradigm Shift in Fracture Fixations via On-Site Fabrication of Bone Restoration Patches)

Reporting period: 2023-10-01 to 2025-06-30

Summary of the context and overall objectives of the project

BoneFix aims to overcome the short-comings of the current standard-of-care for complex bone fractures and voids by providing an alternative in the form of light-curable hydrogels and composites. While open reduction internal fixation (ORIF) implants provide exceptional stability to bone fractures, their rigid design only allows for minimal contouring, making them ill-suited for thin, fragile and shattered bone while also necessitating the purchasing of large expensive inventories of different sized plates. Post-surgical problems are often encountered, such as stress-shielding and soft-tissue adhesions, which may require the removal of the implants in a second surgery. Bone voids are commonly treated with grafts, which require painful additional surgeries. All of these operations carry a risk of surgical site infections; the treatment of which with antibiotics is becoming more difficult due to the emergence of antimicrobial resistance.

In BoneFix, a series of three technologies were developed: (i) an injectable bone scaffold hydrogel, for treating critical sized bone defects, (ii) a topological fixation patch, for stabilizing the fracture throughout the healing process, and (iii) an anti-bacterial hydrogel coating, for protecting against surgical site infections. All three technologies are based on formulations which can be applied directly to the fracture, shaped to fit the specific geometric requirements, and then cured on-demand with high energy visible light via thiol-ene coupling chemistry. This shapeability allows for the personalization of the bone fracture and defect treatment, while the biocompatibility of the technologies will reduce post-surgical complications. As a result, BoneFix will reduce the healthcare burden of fractures on society, by resulting in better treatment for a wider range of patients.

The BoneFix project demonstrated the bone regenerative potential of the bone scaffold hydrogel in a rodent bone void model. A variation of the fixation patch, which involved a shapeable composite patch held to the bone with screws, was demonstrated to be able to withstand significant bending loads in animal and human bone fracture models. The antibacterial hydrogel demonstrated activity against both Gram-positive and Gram-negative bacteria. The technologies were able to be applied under surgical conditions and showed promise; however, further studies are needed to determine their limitations before progressing to clinical trials.

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

A range of alkene and thiol functionalized polymers and monomers were synthesized and subsequently used to formulate the BoneFix technologies. Variations of the three technologies were evaluated, and the most promising candidates were assessed in bone void and fracture scenarios. In all cases, the formulations were injectable fluids which could be shaped and then cured into solid materials via high energy visible light induced thiol-ene coupling chemistry.

A family of bone scaffold hydrogels were evaluated with regards to their physical and biological properties, such as their modulus, swelling and their ability to support the survival and mineralization of stem cells into bone tissue. The most promising formulation was evaluated for its ability to promote bone growth in rodents and sheep. While the hydrogel promoted bone growth in the rodent model it was not effective in the sheep model. The formulation was optimized for 3D printing together with cells, allowing for the pre-fabrication of implants designed to fit the patient.

The fixation patch was evaluated on dissected animal bones, human cadaver hands and in an in vivo sheep toe fracture model. These evaluations focused on the use of the patch to fixate finger and hand fractures. Tests on animals showed the patch provided similar stability to the metal plates under low-loading scenarios. Cyclic testing in an environment mimicking physiological conditions investigated the fatigue behaviour of the patch. Human cadavers were used to evaluate the stability of the patch while simple rehabilitation exercises were simulated. The patches survived these exercises and the forces they could withstand during cyclic testing surpassed the bending forces involved in finger flexing exercises. Unfortunately, the patch was not strong enough to stabilize the fracture in the sheep model. Pain evaluation studies in mice showed that the patch resulted in favourable outcomes relative to traditional metal plates.

New degradable composites and fibre components were developed and tested, along with a primer for adhering the fixation patch to bone without the need for screws. The goal of this work was to realize a fully resorbable fixation patch, which would degrade slowly enough that its mechanical integrity would not be impaired during bone healing. To accomplish this, several libraries of degradable chemicals were synthesized and added to the fixation patch composite with the aim of increasing degradation without compromising the composite’s rigidity and strength. Formulations were identified which showed enhanced degradation over an 8-week period relative to the non-degradable composite. A prototype porous shape-deployable fibre component was developed through printing of resorbable polylactic acid, which was designed to provide reinforcement to the fixation patch.

BoneFix resulted in 15 scientific publications, with 2 additional manuscripts drafted. Results were also disseminated via 29 posters and presentations at international conferences. Two patent applications were filed and the consortium has engaged with stakeholders and mapped out the regulatory pathway to progress the technologies towards clinical trials and eventual commercialization. Prototypes of the three technologies were designed with instructions for use and demonstration videos. Project news has been communicated through the project website and LinkedIn channels.

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)

As a revolutionary alterative to standard-of-care fixators, the development of the BoneFix technologies is expected to have significant impacts for (i) scientific research, by demonstrating the potential of thiol-ene coupling based biomedical technologies; (ii) the healthcare industry, by providing surgeons with a highly customizable and tissue friendly alternative to ORIF plating; and (iii) society, by enhancing quality of life of patients suffering from fractures by reducing rehabilitation times and the incidence of post-surgical complications.

By the end of the project, significant impacts were made for scientific research, through the dissemination of scientific articles and conference presentations demonstrating the medical uses of BoneFix’s thiol-ene technologies. In terms of impacts for the healthcare industry and society, the BoneFix project represents a successful first step towards realizing these goals. The project results demonstrated the potential of the three technologies; however, limitations were revealed for the bone scaffold hydrogel and the fixation patch in the in vivo sheep model. Further studies will be necessary to determine the use-cases of these technologies before they can progress to clinical trials.

BoneFix successfully brought together chemists, surgeons and engineers into a multidisciplinary consortium, which will continue to collaborate beyond this project. The project also provided experience and results for young researchers in the consortium, aiding them in the development of their scientific careers.

The three domains that make up the BoneFix technology.