Periodic Reporting for period 1 - BoneFix (BoneFix: A Paradigm Shift in Fracture Fixations via On-Site Fabrication of Bone Restoration Patches)
Reporting period: 2020-10-01 to 2022-03-31
As the age of Europe’s population rapidly increases, so too does the socioeconomic cost of bone fractures. The WHO estimates that the total number of osteoporosis-related fractures in EU patients will rise to 4.5 million in 2025, which translates to 8.5 incidents per minute. The standard-of-care for treating complex or unstable bone fractures is currently open reduction internal fixation (ORIF) with metal plates and screws. Unfortunately, their rigid design combined with open surgery and general anaesthesia make them poor fixators for fractures on thin, fragile, inaccessible and shattered bone. Their incompatibility with the surrounding soft tissue can create post-surgical problems such as stress-shielding and soft-tissue adhesions, which may necessitate re-operations and the removal of the implant. Additionally, reconstruction of the fracture site may require autologous bone transplants which require additional surgeries, resulting in higher costs, longer rehabilitation periods and an increased chance of infections.
Our solution is BoneFix, a combination of light-curable, polymer-based technologies which allow for personalized surgical treatment of bone fractures via minimally invasive surgery under local anaesthesia. This will be accomplished by developing a novel library of biocompatible, biodegradable monomers, linear polycarbonates and multi-purpose dendritic materials together with strong biodegradable organic/ceramic composites. Building from the bottom up, the concept involves three domains: a bone substitute void filler, a topological mechanical fixation patch, and a protective anti-bacterial hydrogel layer. The injectable domains will be applied to the fracture site and shaped to fit the unique geometry and mechanical requirements of the fracture before being cured on demand via High Energy Visible Light Off-Stoichiometric Thiol-Ene Coupling chemistry (HEV-OSTEC). Collectively, these domains will form a Bone Restoration Patch (BRP) - a customizable, universal solution for fractures that upon complete healing will be fully resorbed. The BRPs will be thoroughly evaluated by stakeholders in order to assess relevant properties, both in vitro and finally in vivo on relevant animal models. The ultimate goal is to cement a new disruptive technology and a paradigm shift in clinical interventions of bone fractures in which BoneFix heals, fixates and protects complex fractures, making open surgery with metal screws and plates obsolete.
Our solution is BoneFix, a combination of light-curable, polymer-based technologies which allow for personalized surgical treatment of bone fractures via minimally invasive surgery under local anaesthesia. This will be accomplished by developing a novel library of biocompatible, biodegradable monomers, linear polycarbonates and multi-purpose dendritic materials together with strong biodegradable organic/ceramic composites. Building from the bottom up, the concept involves three domains: a bone substitute void filler, a topological mechanical fixation patch, and a protective anti-bacterial hydrogel layer. The injectable domains will be applied to the fracture site and shaped to fit the unique geometry and mechanical requirements of the fracture before being cured on demand via High Energy Visible Light Off-Stoichiometric Thiol-Ene Coupling chemistry (HEV-OSTEC). Collectively, these domains will form a Bone Restoration Patch (BRP) - a customizable, universal solution for fractures that upon complete healing will be fully resorbed. The BRPs will be thoroughly evaluated by stakeholders in order to assess relevant properties, both in vitro and finally in vivo on relevant animal models. The ultimate goal is to cement a new disruptive technology and a paradigm shift in clinical interventions of bone fractures in which BoneFix heals, fixates and protects complex fractures, making open surgery with metal screws and plates obsolete.
The first objective of the project was the identification and then synthesis of a library of diverse chemicals which would be used to formulate the three BoneFix domains. KTH designed a strategy for the synthesis of these chemicals, all of which are functionalized with allyl or thiol groups to allow for light-induced crosslinking via TEC chemistry. KTH has since synthesized enough of the library to allow for the production of the first generation formulations of each domain. An initial bone scaffold formulation has been shared with UiB, who have begun evaluating its cytocompatability and suitability as a bone scaffold. Prototype primer and composite formulations have been sent to ARI, RegionH and MINES, who have been trained by KTH on how to create fixation patches. ARI and RegionH have since started the mechanical evaluation of the fixation composite with PET fibre mesh, while MINES have been studying the integration and mechanics of the composite with different fibre membranes. The first BoneFix antibacterial hydrogel has also been prepared and was found to crosslink in water. It’s cytotoxicity and anti-bacterial activity are being investigated.
UiB have isolated, expanded and characterized bone marrow-derived mesenchymal stem/stromal cells from humans and rats for insertion into the bone scaffold domain. Their work on the initial BoneFix bone scaffold formulation has suggested it is not-toxic to these cells but its rate of degradation is too rapid. KTH are developing a new, more stable formulation.
In the meantime, KTH have been evaluating the adhesive strength of the fixation patch primer and the mechanics of the composite. The primer has been identified as the weak link in the fixation patch system and the consortium have determined that its application is hard to reproduce and its adhesive strength is too unreliable. Therefore, the use of the primer for attachment of the fixation patch to the bone has been replaced with traditional metal screws. This approach has allowed ARI and RegionH to closely collaborate on the initial biomechanical testing of the fixation patch on ovine phalanges. Samples were evaluated with respect to four-point bending and torsion testing and the fixation patch with screws was found to have similar mechanical properties to metal plates under biologically relevant loads. A manuscript is currently being prepared based on this evaluation.
These initial biomechanical tests have laid the groundwork for the large range of biomechanical experiments that will be conducted during the BoneFix project on ex vivo cadaver bones and in vivo animal studies. RegionH have applied for all the necessary ethical approvals for the cadaver experiments and are developing the large animal studies which will be the ultimate evaluation of the BoneFix technology.
The project website (bonefix.org) has been established by BMB, who have also written the dissemination, exploitation and communication plan for BoneFix. The website acts as the main platform for promoting information about BoneFix and is continuously updated by BMB based on feed-back from the consortium members. BMB has been active in clinical and industry stakeholder meetings as well as continuously working on securing funding for the exploitation of BoneFix results after the project ends. BMB has secured funding from Eurostars to establish its first regulatory compliant light-cured implant, which will be very beneficial for the commercialisation of BoneFix. A promotional video was also produced to communicate the BoneFix concept. The video has been released on the webpage and spread on social media. With the progress of the project BMB has together with KTH established first prototypes and training material to enable partners to use the technology currently available.
UiB have isolated, expanded and characterized bone marrow-derived mesenchymal stem/stromal cells from humans and rats for insertion into the bone scaffold domain. Their work on the initial BoneFix bone scaffold formulation has suggested it is not-toxic to these cells but its rate of degradation is too rapid. KTH are developing a new, more stable formulation.
In the meantime, KTH have been evaluating the adhesive strength of the fixation patch primer and the mechanics of the composite. The primer has been identified as the weak link in the fixation patch system and the consortium have determined that its application is hard to reproduce and its adhesive strength is too unreliable. Therefore, the use of the primer for attachment of the fixation patch to the bone has been replaced with traditional metal screws. This approach has allowed ARI and RegionH to closely collaborate on the initial biomechanical testing of the fixation patch on ovine phalanges. Samples were evaluated with respect to four-point bending and torsion testing and the fixation patch with screws was found to have similar mechanical properties to metal plates under biologically relevant loads. A manuscript is currently being prepared based on this evaluation.
These initial biomechanical tests have laid the groundwork for the large range of biomechanical experiments that will be conducted during the BoneFix project on ex vivo cadaver bones and in vivo animal studies. RegionH have applied for all the necessary ethical approvals for the cadaver experiments and are developing the large animal studies which will be the ultimate evaluation of the BoneFix technology.
The project website (bonefix.org) has been established by BMB, who have also written the dissemination, exploitation and communication plan for BoneFix. The website acts as the main platform for promoting information about BoneFix and is continuously updated by BMB based on feed-back from the consortium members. BMB has been active in clinical and industry stakeholder meetings as well as continuously working on securing funding for the exploitation of BoneFix results after the project ends. BMB has secured funding from Eurostars to establish its first regulatory compliant light-cured implant, which will be very beneficial for the commercialisation of BoneFix. A promotional video was also produced to communicate the BoneFix concept. The video has been released on the webpage and spread on social media. With the progress of the project BMB has together with KTH established first prototypes and training material to enable partners to use the technology currently available.
As a revolutionary alternative to the current standard-of-care fixators, the development of BoneFix is expected to have significant impacts for (i) scientific research, by demonstrating the vast potential of thiol-ene coupling based biomedical technologies; (ii) the healthcare industry, by providing surgeons with a highly customizable, biodegradable and minimally invasive solution to ORIF which will allow them to treat a wider variety of patients and fracture types while reducing costs by eliminating the need for reoperations; and (iii) society as a whole, by providing enhanced quality of life to patients suffering from fractures by reducing rehabilitation times and the incidence of post-surgical complications. Furthermore, our multi-disciplinary consortium will lay the foundation for a rich, Euro-centric, innovative ecosystem which will drive the BoneFix technology towards commercialization.
This project aims to create a paradigm shift in clinical interventions of bone fractures, in which adhesive based bone restoration patches heal, fixate and protect complex fractures, making primitive metal screws and plates obsolete.
This project aims to create a paradigm shift in clinical interventions of bone fractures, in which adhesive based bone restoration patches heal, fixate and protect complex fractures, making primitive metal screws and plates obsolete.