Work Package 1 – Development of RNA-based Nanoformulations
Work Package 1 aims at establishing the production of siRNA delivery nanoformulations targeting specifically human NGF and IL1ß and designing targeted siRNA nanoformulations with moieties such as peptides for cell-specific delivery. This WP also focuses on the production of HA-based (nano)emulsions containing anti-inflammatory drugs.
- Selection of effective siRNAs
- Synthesis and characterisation of lipid- and polymer-based siRNA nanoformulations
- Synthesis and characterisation of HA-MA-based (nano)emulsions
- Functionalisation of siRNA-nanovehicles with targeting moieties
- Bioburden and in vitro toxicity studies of nanoformulations
Work Package 2 – Immunological Interaction and Safety Studies of the Advanced Nanotherapeutics
WP 2 focuses on the development of IA-HA with improved rheological properties. In addition to the creation of 1st, 2nd, 3rd, and 4th generation nanotherapeutics (nanoformulations + IA-HA), this WP also assesses immunological interactions and the safety of the materials.
- Functionalization of IA-HA with dynamic properties and antagonist peptide
- Assembly and preliminary testing of the advanced nanotherapeutics
- Immunological interactions of nanotherapeutics with relevant human immune cells
- Blood contact properties
- Inflammasome studies for nanoformulations and nanotherapeutics
Work Package 3 – In vitro Mode of Action for Osteoarthritis (OA)
WP3 analyses the main cell populations expressing IL1, and NGF in OA joint tissues to unveil gender-related discriminants, immunomics and innervation profiles in OA joint tissues relationship. This WP also aims to understand the role of pericytes at successive stages of OA development, evaluate immunotoxicity, silencing efficacy and bioactivity of nanoformulations/nanotherapeutics in addition to developing and validating relevant 3D models of early and late OA.
- Deep characterisation of the OA joint by integrating single-cell technologies
- Characterisation of pericytes in OA
- Silencing efficiency and bioactivity of selected nanoformulations/nanotherapeutics
- Development of the 3D OA model
- Testing of RNA-based therapy in 3D OA model
Work Package 4 – Bioreactor-based Model for Potency Assay
WP4 centres on establishing OA chondrocytes-pericytes and OA chondrocytes-neurons 3D coculture models under dynamic loading conditions in a bioreactor. WP4 also strives to assess the efficacy of nanotherapeutics in OA chondrocytes-pericytes and OA chondrocytes-neurons 3D coculture models in a bioreactor.
- Establishment of OA chondrocytes-pericytes 3D coculture models in bioreactor
- Establishment of OA chondrocytes-neurons 3D coculture models in bioreactor
- Efficacy of nanotherapeutics in OA chondrocytes-pericytes 3D coculture models in bioreactor
- Efficacy of RNA therapy in OA chondrocytes-neurons 3D coculture models in bioreactor
Work Package 5 – In vivo Validation
WP5 aims to assess the efficacy of the clinically relevant in vivo OA model and strives to demonstrate in vivo biocompatibility of the advanced nanotherapeutic.
- Development of a relevant in vivo model
- Preclinical validation
- Preclinical toxicity testing
Work Package 6 – Regulation and Quality-by-Design
WP6’s objectives are to analyse the regulatory pathway of the proposed nanotherapeutics and establish the production process of the novel nanotherapeutics.
- Regulatory activities
- Production according to regulatory pathway
Work Package 7 – Cartilage Assessment and Digitalization: Patient-specific Profiling
WP7 seeks to establish the most predictive parameters and image features for knee bone and cartilage assessment based on X-ray, CT, and MR images. WP7 also aims at developing a highly sensitive metric of cartilage and bone conditions which can serve to design a patient-specific tissue-engineered solution.
- Measurement and feature extraction
- Feature selection and profiling
- Validation of the profile
Work Package 8 – Innovation Management: Communication, Dissemination, Exploitation
WP8 focuses on communication activities within the project, creating visibility, encouraging project outreach and disseminating results to targeted stakeholders and the scientific community. WP8 also fosters innovation capacity and exploitation of results, including intellectual property (IP) management.
- Project communication
- Dissemination of project results
- Exploitation of project results including IP management
Work Package 9 – Project Management
WP9 aims to manage communication structures, processes, and monitoring of project activities and results through scientific coordination and impact-oriented project management. WP9 also ensures efficiency, high quality and maximum usability of project outcomes with proper risk analysis and conflict management.
- Implementation of efficient management and support structures
- Scientific coordination, quality assurance and risk management.
- Legal and contractual settings
- Reporting, financial management and controlling
Work Package 10 – Ethics Requirements
WP10 will closely monitor and safeguard that activities envisaged within SINPAIN, such as personal data protection, development of machine learning technologies and clinical trials, meet the highest quality control standards and ethical requirements. The appointment of an external Independent Ethics Advisor will further strengthen these efforts.