Periodic Reporting for period 1 - DECODE (Drug-coated balloon simulation and optimization system for the improved treatment of peripheral artery disease)
Okres sprawozdawczy: 2021-01-01 do 2022-12-31
DECODE focuses on the training of young scientists on the use of drug-eluting devices to combat the burden of peripheral artery disease (PAD). PAD affects 202 million patients worldwide and may cause disabling intermittent claudication and critical limb ischemia. The global prevalence of PAD has been increased especially in low-income and middle-income countries, exceeding 20% in persons >70 years old. The majority of patients with critical limb ischemia (CLI) have distal arterial disease located mainly below the knee. The endovascular treatment landscape encompasses a broad range of interventions, with each option having advantages and disadvantages. Bare metal stents (BMS) usually yield better outcomes compared to plain balloon angioplasty alone as they stabilize any dissection and prevent rapid elastic recoil. However, they increase local inflammation, leading to neointimal hyperplasia formation and in-stent restenosis. Also, they are associated with increased fracture rate, especially in the femoropopliteal segment.
Drug-coated balloons (DCB) and drug eluting stents (DES) have been developed to address the aforementioned disadvantages. The advantage of using paclitaxel-coated balloons is the ability to deliver the necessary drug to the affected areas without a permanent vascular prosthesis. Regarding femoropopliteal lesions, DCBs have been found to be superior than plain balloons as far as clinical improvement, target lesion revascularization and restenosis are concerned. Compared to DES, results are promising showing equal efficiency with lower cost even for long femoropopliteal lesions although data are still limited.
The overall objectives of DECODE are to provide:
-Excellent scientific training on the biomechanical properties of DCBs, integrating clinical knowledge with technological skills on materials science, engineering and numerical modelling to generate innovative insights triggering the improved understanding and treatment of PAD.
-Excellent complementary skills in personal and career development, as well as ongoing support and business training required to extend beyond scientific research.
-Exposure to both academic and non-academic environments, required to build bridges between researchers and companies, between theory and practice, which is challenging for young researchers and necessary for businesses.
-An advising network to ensure that ESRs will become well-rounded scientists, as well as well-rounded persons. This multidisciplinary training programme will be implemented by leading universities, clinical centers and non-academic partners from Europe and US.
Drug-coated balloons (DCB) and drug eluting stents (DES) have been developed to address the aforementioned disadvantages. The advantage of using paclitaxel-coated balloons is the ability to deliver the necessary drug to the affected areas without a permanent vascular prosthesis. Regarding femoropopliteal lesions, DCBs have been found to be superior than plain balloons as far as clinical improvement, target lesion revascularization and restenosis are concerned. Compared to DES, results are promising showing equal efficiency with lower cost even for long femoropopliteal lesions although data are still limited.
The overall objectives of DECODE are to provide:
-Excellent scientific training on the biomechanical properties of DCBs, integrating clinical knowledge with technological skills on materials science, engineering and numerical modelling to generate innovative insights triggering the improved understanding and treatment of PAD.
-Excellent complementary skills in personal and career development, as well as ongoing support and business training required to extend beyond scientific research.
-Exposure to both academic and non-academic environments, required to build bridges between researchers and companies, between theory and practice, which is challenging for young researchers and necessary for businesses.
-An advising network to ensure that ESRs will become well-rounded scientists, as well as well-rounded persons. This multidisciplinary training programme will be implemented by leading universities, clinical centers and non-academic partners from Europe and US.
-The 15 ESRs have been recruited and started working on their individual research projects.
-The website and social media have been created.
-All the deliverables of RP1 have been submitted on time.
-The training activities are in progress. A time plan has been prepared for the remaining training activities until the end of the project.
-The personal career development plans of the ESRs are ready. They were submitted as a deliverable in Dec. 2021 (D2.1). Their updated versions were included in D2.2.
-A workshop for DECODE was organized during the 13th HSTAM International Congress on Mechanics, Patras, 24-27 August 2022.
-The first conference papers of the ESR have been published.
-The first version of the exploitation plan and IP issues have been prepared (D1.5).
-Concerning the in vitro activities in WP3, the aim of the work within RP1 was to determine the optimal method for applying the drug to the desired surface or substrate. Besides investigating various coating methods, various polymers were also investigated as potential drug carriers.
The material behavior of the components involved during the DCB angioplasty in clinical practice was investigated, developing methods to analyze the efficacy of some parameters involved during treatment.
-Concerning the animal study (WP3), in NKUA 6/8 animal experiments and in CBSET all animal experiments have been completed. The data have been provided to the ESRs.
-In WP4 computational models at different scales have been developed:
A) Micro/nano scale computational models aim to: (i) help in interpreting the experiments (WP3) for characterizing the balloon membrane, the drug coating and the vascular tissue, (ii) mimic the interaction at micro-scale between balloon/coating system and vascular tissue, (iii) describe local drug delivery.
B) Macro/meso scale computational models aim to: (i) understand the role played by biomechanical parameters on balloon contact modalities and drug transfer to vascular tissue, (ii) simulate the various effects of the clinical procedure, such as the damage model of the wall during vessel pre-dilation with angioplasty balloons, (iii) simulate and interpret the results of in vitro experiments on DCBs (WP3), (iv) simulate the DCB angioplasties in animal studies (WP3) using 3D vessel reconstructions (WP5).
-In WP5 the architecture of the DECODE cloud platform was prepared, its modules were defined and the development of the platform is in progress.
-The ethical issues were addressed (WP6 submitted deliverables).
-The website and social media have been created.
-All the deliverables of RP1 have been submitted on time.
-The training activities are in progress. A time plan has been prepared for the remaining training activities until the end of the project.
-The personal career development plans of the ESRs are ready. They were submitted as a deliverable in Dec. 2021 (D2.1). Their updated versions were included in D2.2.
-A workshop for DECODE was organized during the 13th HSTAM International Congress on Mechanics, Patras, 24-27 August 2022.
-The first conference papers of the ESR have been published.
-The first version of the exploitation plan and IP issues have been prepared (D1.5).
-Concerning the in vitro activities in WP3, the aim of the work within RP1 was to determine the optimal method for applying the drug to the desired surface or substrate. Besides investigating various coating methods, various polymers were also investigated as potential drug carriers.
The material behavior of the components involved during the DCB angioplasty in clinical practice was investigated, developing methods to analyze the efficacy of some parameters involved during treatment.
-Concerning the animal study (WP3), in NKUA 6/8 animal experiments and in CBSET all animal experiments have been completed. The data have been provided to the ESRs.
-In WP4 computational models at different scales have been developed:
A) Micro/nano scale computational models aim to: (i) help in interpreting the experiments (WP3) for characterizing the balloon membrane, the drug coating and the vascular tissue, (ii) mimic the interaction at micro-scale between balloon/coating system and vascular tissue, (iii) describe local drug delivery.
B) Macro/meso scale computational models aim to: (i) understand the role played by biomechanical parameters on balloon contact modalities and drug transfer to vascular tissue, (ii) simulate the various effects of the clinical procedure, such as the damage model of the wall during vessel pre-dilation with angioplasty balloons, (iii) simulate and interpret the results of in vitro experiments on DCBs (WP3), (iv) simulate the DCB angioplasties in animal studies (WP3) using 3D vessel reconstructions (WP5).
-In WP5 the architecture of the DECODE cloud platform was prepared, its modules were defined and the development of the platform is in progress.
-The ethical issues were addressed (WP6 submitted deliverables).
Until the end of the project, the consortium envisions to achieve the following:
- New vessel segmentation algorithm for PAD with accuracy higher than state of the art.
- New algorithm for calcification detection.
- New method of holographic measurements with automatic path planing in the vessels.
- New algorithm for centreline generation with realtime implmentation that takes into account the bifurcation problem.
- Optimized/New drug eluting coatings for angioplasty balloons.
- Improved drug transfer to vessel wall and drug delivery to intended cells.
- Using clinical knowledge combined with research expertise to test and refine DCB deployment for PAD.
- Analyse drug transfer and downstream embolisation in human size vascular system (swine).
- Computational models for simulating various aspects of DCBs: i) simulation of the DCB angioplasty, ii) simulation of the interaction between the drug-coating and balloon membrane upon deformation, iii) simulation of the drug-coating transfer to the arterial wall during the surgical procedure.
- Novel experimental set-ups: i) to characterize the mechanical stability of the drug-coating on the polymer substrates, ii) to characterize the interaction between the drug-coating and the arterial wall and, iii) to have an ex-vivo system mimicking the in vivo environment and effectively test DCBs.
- New platform that will enhance clinical decision making incorporating various computational tools.
The potential impacts are:
- Industrial development of new devices or improvement of the existing ones.
- Improved clinical strategy and patient outcome with new devices and software.
- The use of computational models could have an economic impact as they can support the production of optimized drug-coated devices, thus potentially allowing saving drug and associated high costs.
- Reduction of chance for a secondary intervention, which is more frequently occurring in non-effective drug treatments.
- Optimisation of DCB technology and deployment technique (with impact from an interventionists point of view).
- Understanding the extent of downstream embolisation risk and establishment of research procedures to analyse downstream embolisation.
- Creation of robust and reliable experimental set up and analysis pipeline to study drug eluted devices for PAD.
- New vessel segmentation algorithm for PAD with accuracy higher than state of the art.
- New algorithm for calcification detection.
- New method of holographic measurements with automatic path planing in the vessels.
- New algorithm for centreline generation with realtime implmentation that takes into account the bifurcation problem.
- Optimized/New drug eluting coatings for angioplasty balloons.
- Improved drug transfer to vessel wall and drug delivery to intended cells.
- Using clinical knowledge combined with research expertise to test and refine DCB deployment for PAD.
- Analyse drug transfer and downstream embolisation in human size vascular system (swine).
- Computational models for simulating various aspects of DCBs: i) simulation of the DCB angioplasty, ii) simulation of the interaction between the drug-coating and balloon membrane upon deformation, iii) simulation of the drug-coating transfer to the arterial wall during the surgical procedure.
- Novel experimental set-ups: i) to characterize the mechanical stability of the drug-coating on the polymer substrates, ii) to characterize the interaction between the drug-coating and the arterial wall and, iii) to have an ex-vivo system mimicking the in vivo environment and effectively test DCBs.
- New platform that will enhance clinical decision making incorporating various computational tools.
The potential impacts are:
- Industrial development of new devices or improvement of the existing ones.
- Improved clinical strategy and patient outcome with new devices and software.
- The use of computational models could have an economic impact as they can support the production of optimized drug-coated devices, thus potentially allowing saving drug and associated high costs.
- Reduction of chance for a secondary intervention, which is more frequently occurring in non-effective drug treatments.
- Optimisation of DCB technology and deployment technique (with impact from an interventionists point of view).
- Understanding the extent of downstream embolisation risk and establishment of research procedures to analyse downstream embolisation.
- Creation of robust and reliable experimental set up and analysis pipeline to study drug eluted devices for PAD.