Periodic Reporting for period 1 - CellMembrane (Development of delignified nanocellulose based gas transfer scaffold membrane for artificial lungapplications.)
Periodo di rendicontazione: 2023-12-01 al 2024-11-30
Lung Lung disease (emphysema, chronic bronchitis, Idiopathic pulmonary fibrosis) is the third most frequent cause of death worldwide. Despite non-invasive ventilation, patients suffer from extreme shortness of breath because of insufficient pulmonary oxygen transfer into the blood and CO2 elimination from the blood, become immobile, and are mostly no longer able to cope with stress. Lung transplantation remains the only long-term therapy for these terminal lung diseases. Every year, approximately 4,600 lung transplantations are performed worldwide, of which 55% are performed in North America and 36% in Europe. The average waiting time for a lung transplant in the EU is 18 months due to the severely limited availability of the lung donors. There are more than 100,000 patients in the US alone who are on lung donor waiting list. Therefore, there is a great need for an artificial lung as a bridge to transplantation and to support patient lungs in the medium term.
Our goal is to manufacture a nanocellulose artificial lung which will support the patient as a bridge to transplantation for periods of >30 days and support out of clinic patient use. 30 days is considered long term use for artificial lung devices. An artificial lung is a technical device for providing life support; it will be put in use when the natural lungs are failing and are unable to maintain sufficient oxygenation of the body's organ systems. Artificial lung devices are membranes made of synthetic material that are connected to blood vessels through tubes and cannulas. Existing artificial lung devices (membrane oxygenation) contain bundles of hollow fibres made of polypropylene or polymethylpentene to achieve gas exchange. The blood flows around the fibres within these bundles, and oxygen flows through them. The required blood flow through the gas exchange module can be generated by a pump connected to the patient’s venous vascular system or far less commonly, passively by connecting to the patient’s arterial system.
Our goal is to manufacture a nanocellulose artificial lung which will support the patient as a bridge to transplantation for periods of >30 days and support out of clinic patient use. 30 days is considered long term use for artificial lung devices. An artificial lung is a technical device for providing life support; it will be put in use when the natural lungs are failing and are unable to maintain sufficient oxygenation of the body's organ systems. Artificial lung devices are membranes made of synthetic material that are connected to blood vessels through tubes and cannulas. Existing artificial lung devices (membrane oxygenation) contain bundles of hollow fibres made of polypropylene or polymethylpentene to achieve gas exchange. The blood flows around the fibres within these bundles, and oxygen flows through them. The required blood flow through the gas exchange module can be generated by a pump connected to the patient’s venous vascular system or far less commonly, passively by connecting to the patient’s arterial system.
The following lists the main technical objectives for the CellMembrane project. For each objective the work completed within the first reporting period is also listed.
1. NC Specification: To evaluate the suitability of the NC for the artificial lungs scaffold-membrane applications.
Work carried out during 1st reporting period towards the objective achievement:
- A comprehensive database of information has been generated relating to the necessary background required for the development and enhancement of nanocellulose for the use in artificial lungs (D2.1)
- Characterization of the nanocellulose used for the production of the first 3D printed and electrospun membranes has also bee carried out (D2.1)
- A framework has been developed, covering issues related to nanocellulose resources, fundamentals of nanocellulose production including pre-treatments, processing parameters, and resultant physical and mechanical properties.
2. Processing of NC into 3D scaffolds: To define a 3D model for the gas exchange in artificial lung applications.
Work carried out during the 1st reporting period towards the objective achievement:
- Different parameters were taken into account to create the first design of 3D scaffold membrane, including the size and geometry of membranes suitable for testing in other WPs, minimal thickness that ensures reproducible fabrications and mechanical stability, porosity generated by introducing channels via printing sacrificial materials.
- Different NC materials were included into the project scope, having various sources, grade levels, chemical modifications. One source was chosen for the initial 3D printing experiments based on the properties analysis.
- Co-axial printing with sacrificial materials was tested to fabricate 3D scaffold membranes with open channels.
3. Scaffold Evaluation: To undertake toxicity, sterilization, mechanical, fluid perfusion and in-vitro oxygen transfer efficacy pf NC scaffolds.
Work carried out during the 1st reporting period towards the objective achievement:
- One of the NC sources available in the project is already supplied sterilized, which does not require further sterilization steps if the biomaterial is maintained and used in aseptic conditions.
- Completion of in vitro analysis of first round of NC formulations by assessing the cytotoxicity (Live/Dead assay, Alamar Blue) using HUVEC cells (D 4.1).
1. NC Specification: To evaluate the suitability of the NC for the artificial lungs scaffold-membrane applications.
Work carried out during 1st reporting period towards the objective achievement:
- A comprehensive database of information has been generated relating to the necessary background required for the development and enhancement of nanocellulose for the use in artificial lungs (D2.1)
- Characterization of the nanocellulose used for the production of the first 3D printed and electrospun membranes has also bee carried out (D2.1)
- A framework has been developed, covering issues related to nanocellulose resources, fundamentals of nanocellulose production including pre-treatments, processing parameters, and resultant physical and mechanical properties.
2. Processing of NC into 3D scaffolds: To define a 3D model for the gas exchange in artificial lung applications.
Work carried out during the 1st reporting period towards the objective achievement:
- Different parameters were taken into account to create the first design of 3D scaffold membrane, including the size and geometry of membranes suitable for testing in other WPs, minimal thickness that ensures reproducible fabrications and mechanical stability, porosity generated by introducing channels via printing sacrificial materials.
- Different NC materials were included into the project scope, having various sources, grade levels, chemical modifications. One source was chosen for the initial 3D printing experiments based on the properties analysis.
- Co-axial printing with sacrificial materials was tested to fabricate 3D scaffold membranes with open channels.
3. Scaffold Evaluation: To undertake toxicity, sterilization, mechanical, fluid perfusion and in-vitro oxygen transfer efficacy pf NC scaffolds.
Work carried out during the 1st reporting period towards the objective achievement:
- One of the NC sources available in the project is already supplied sterilized, which does not require further sterilization steps if the biomaterial is maintained and used in aseptic conditions.
- Completion of in vitro analysis of first round of NC formulations by assessing the cytotoxicity (Live/Dead assay, Alamar Blue) using HUVEC cells (D 4.1).
Due to the high surface area, high mechanical strength, biodegradability, chemical inertness, low toxicity, and the broad possibility of surface modification, the consortium aims to utilize bio-based nanomaterial ‘nanocellulose’ (NC) to manufacture the artificial lung device. The gas exchange properties of NC are tunable by modifying the nanocrystals and nanofibrils through e.g. porosity, surface area, aspect ratio, nanoparticle alignment, charge and/or aggregation. The assembly process allows its nanostructure to be controlled to generate a structure that mimics the structure of the natural lung and allows for lower shear stress in the blood coupled with high gas exchange. Counterintuitively, smaller channels reduce the blood viscosity due to the Fåhraeus and Lindqvist effect and are therefore desired. Areas up to 900m2 per gram are possible in NC aerogels which means that NC-based artificial lung devices will be at least an order of magnitude smaller than PMP-based devices. These dimensions should allow the use of purified air instead of pure oxygen as a sweep gas which would greatly expand the applicability of these devices. The device will be modular in nature allowing for it to be used for all patients regardless of size, gender or level of activity.