Approach
GreenNanoBone comprises of five Modules (Figure 3), each with defined Sub-Objectives (SO). The methodology chosen for each Module will enable delivery of individual SO and KPI (Key Performance Indicators), which will be monitored based on the target Pathways Towards Impact (PTIs).
Module 1 - Material Design
Module 1 essentially comprises of the development of the GreenNanoBone hydrogel. The first step in this process is to extract pectin from byproducts of the starch industry. Rhamnogalacturonan I (RG-I), a major structural component of pectin will work as a chemical precursor for our hydrogel. One important innovation delivered by the project will be refined pectin- extraction processes. The next step is to process RG-I into microgels, which are hydrogels made up of microparticles and characterise its parameters. AI will help identify the best conditions for desired microgel properties. Results from Module 2, preclinical testing will inform the fine tuning process.
Eventually the formulation of a bioink, for bioprinting, will enable the fabrication of the scaffolds for the in vivo studies and the assessment of the cytocompatibility of the printed GreenNanoBone product (Module 2). Throughout the duration of Module 1, production processes will be refined towards Good Manufacturing Practice (GMP) standards.
Module 1 - Manufacture
Module 1 essentially comprises of the development of the GreenNanoBone hydrogel. The first step in this process is to extract pectin from byproducts of the starch industry. Rhamnogalacturonan I (RG-I), a major structural component of pectin will work as a chemical precursor for our hydrogel. One important innovation delivered by the project will be refined pectin- extraction processes. The next step is to process RG-I into microgels, which are hydrogels made up of microparticles and characterise its parameters. AI will help identify the best conditions for desired microgel properties. Results from Module 2, preclinical testing will inform the fine tuning process.
Eventually the formulation of a bioink, for bioprinting, will enable the fabrication of the scaffolds for the in vivo studies and the assessment of the cytocompatibility of the printed GreenNanoBone product (Module 2). Throughout the duration of Module 1, production processes will be refined towards Good Manufacturing Practice (GMP) standards.
Module 2 - Pre-Clinical Testing
Module 2 has two main objectives: understanding the biological mechanisms underlying human MRONJ and validating the efficacy of our injected and printed hydrogel.
MRONJ will be simulated in 2D in vitro models, by establishing the negative effects bisphosphonates have on bones. This results in inhibiting osteoclast function, osteogenesis and bone resorption, as well as the body’s capacity to form new blood vessels, which is further contributing to the occurrence of MRONJ, especially after dental trauma or surgery. Additionally, a 3D MRONJ model will be developed to investigate cellular interactions in the development of MRONJ. Ultimately, the goal is to develop a single-cell atlas of human MRONJ, highlighting all cells involved, which will contribute to better understanding of the underlying biological mechanisms involved in MRONJ.
Additionally, Module 2 comprises of the different phases of preclinical testing. First, the biosafety of the materials has to be tested, this means, whether they might have negative effects on healthy cells. Then the developed 2D models will be used to study the osteogenic and pro-regenerative efficacy of the GreenNanoBone hydrogel. The 3D in vitro model will subsequently be used to validate the effects of the injectable GreenNanoBone by capturing the mechanism of action of the hydrogel in each relevant tissue model (bone and gingival tissue as well as immune cells). Additionally, a microbiological study will test the antibacterial properties of GreenNanoBone. Ultimately, the soft and hard tissue response to 4D injected and printed hydrogels will be evaluated in in vivo animal models. The results from this study will form the basis for future clinical trials.
Module 3 - Social & Health system foundations
Module 3 lays the foundation for the uptake of GreenNanoBone into clinical practice, by ensuring the social acceptability of the novel treatment and by carrying out an early economic evaluation to estimate the potential impact of GreenNanoBon on health systems. To this end the “mental model” approach will be deployed to develop communication materials for healthcare practitioners (lead user) and patients (end user). Additionally, a cost of illness study will be carried out to support the planning of a business case.
Module 4 - Regulations & Ethics
Based on a regulatory workshop and a regulatory draft dossier, Module 4 will develop a regulatory roadmap for the future of the GreenNanoBone product, following relevant EU regulations such as the Medicinal Product Directive or the ATMP or combined ATMP regulation. Additionally, ethical considerations will be mapped and considered.
Module 5 - Business plan, innovation management & IP management
Module 5 comprises the development of a communication, dissemination and exploitation strategy including a go-to-market strategy, a detailed business case and IP management plan.