Periodic Reporting for period 1 - STEMCEDIF (Polymeric cell-laden vascular graft for blood vessel mimicking in tissue engineering applications)
Berichtszeitraum: 2022-09-01 bis 2024-02-29
The main goal of the project is to design and fabricate the polymer-based 3D bioprinted cell-laden vascular grafts (CLVG) with certain physical morphology (patterns), and biological properties.
The project focuses on the development of biomaterials and a method for vascular grafts fabrication that would be useful for vascular tissue engineering. Cardiovascular diseases, responsible for 17.9 million fatalities annually, constitute the leading cause of death worldwide. Bypass surgeries using autologous vessels are the preferred method to restore proper blood flow, but their availability is limited, and they may fail due to thrombosis and other complications. Allografts face rejection issues, prompting the development of synthetic grafts which are used for large artery repairs. Despite their efficacy, synthetic grafts are stiff and less effective for smaller arteries. The standard approach for the treatment of large vessels diseases like aneurysms involves the use of synthetic grafts, considered the gold standard in the treatment of adults. However, this approach is not suitable for pediatric patients due to the inability of autologous and synthetic grafts to grow and remodel, resulting in the need for multiple reoperations. Induced Pluripotent Stem Cells can overcome a limitation in vascular tissue engineering by providing patient-derived cells. Tissue engineering offers a promising solution, involving the creation of vascular grafts using biodegradable scaffolds and patient-specific cells, resulting in the formation of native-like tissue.
In order to produce scaffolds for tissue engineering, 3D printing technology is one of the most promising methods. However, the generation of biocompatible, stable and low-cost scaffolds material for tissue regeneration remains a big challenge. Naturally derived polymers, such as collagen type I or gelatin exhibit the beneficial biological properties of high biocompatibility, however poor structural stability and mechanical properties. On the other hand addition of synthetic polymers can significantly improve the stability and mechanical properties of scaffolds.
The project focuses on the development of biomaterials and a method for vascular grafts fabrication that would be useful for vascular tissue engineering. Cardiovascular diseases, responsible for 17.9 million fatalities annually, constitute the leading cause of death worldwide. Bypass surgeries using autologous vessels are the preferred method to restore proper blood flow, but their availability is limited, and they may fail due to thrombosis and other complications. Allografts face rejection issues, prompting the development of synthetic grafts which are used for large artery repairs. Despite their efficacy, synthetic grafts are stiff and less effective for smaller arteries. The standard approach for the treatment of large vessels diseases like aneurysms involves the use of synthetic grafts, considered the gold standard in the treatment of adults. However, this approach is not suitable for pediatric patients due to the inability of autologous and synthetic grafts to grow and remodel, resulting in the need for multiple reoperations. Induced Pluripotent Stem Cells can overcome a limitation in vascular tissue engineering by providing patient-derived cells. Tissue engineering offers a promising solution, involving the creation of vascular grafts using biodegradable scaffolds and patient-specific cells, resulting in the formation of native-like tissue.
In order to produce scaffolds for tissue engineering, 3D printing technology is one of the most promising methods. However, the generation of biocompatible, stable and low-cost scaffolds material for tissue regeneration remains a big challenge. Naturally derived polymers, such as collagen type I or gelatin exhibit the beneficial biological properties of high biocompatibility, however poor structural stability and mechanical properties. On the other hand addition of synthetic polymers can significantly improve the stability and mechanical properties of scaffolds.
The project delineated six core research objectives: a) design, generate and characterize patterned surfaces for target endothelial cell behavior b) design and develop biomaterial for cell-laden 3D bioprinting, c) design and produce 3D constructs and incorporate those patterned surfaces d) study cell-material interactions, e) utilize perfusion of medium through the lumen of construct and f) study CLVG properties exploring its potential implications as potential vascular grafts.
Firstly unique approaches that combine the hierarchical topography with nano-/micro-patterned cues that guide endothelial cell growth, enhance EC adhesion and migration was developed. Remarkably, patterned tubes were achieved by a combination of nanoimprint and soft lithography, which is a novel approach.
The production of 3D constructs mimicking big vessels, unique approaches that combine the highly repetitive 3D bioprinting with molding technique, together with development of a bioink that resembles mechanophysical properties of extracellular matrix, was successfully achieved.
Characterization of developed bioink and bioprinted constructs, the collaborative synergy between the Fellow, Supervisor, and collaborators from University College London and University of Valladolid, coupled with access to the NBMC AMU infrastructure, has been pivotal in the successful realization of the grant.
Obtained iPSC-CF, SMCs and iPSC-EC were successfully incorporated within 3D constructs. The overall results demonstrate high cell viability and growth of cells within the volume of the bioprint, proving the potential of the designed bioink for use in tissue engineering. No detachment of iPSC-ECs from the lumen is observed, confirming the hypothesis that the novel bioink's unique combination of designed material properties and groove pattern topographical cues protects cells from high flow rates. That data confirm the proper adjustment of the bioink in 3D bioprinting process, the novel technology of micro/nanopatterning, 3D bioprinting+molding and its potential utilization in vascular tissue engineering
This novel approach has the capacity to establish platforms for drug testing and to generate vascular grafts tailored for pediatric use, opening new prospects of personalized medicine.
During the MSCA project, the Fellow participated in scientific conferences presenting MSCA-IF results as well as many outreach and dissemination activities aimed at different target audiences, including researchers, students and school kids. Furthermore, the Fellow participated in several MSCA-focused lectures to share her experience, promote MSCA-IF in broad audience, and encourage other researchers to apply for the fellowships.
Firstly unique approaches that combine the hierarchical topography with nano-/micro-patterned cues that guide endothelial cell growth, enhance EC adhesion and migration was developed. Remarkably, patterned tubes were achieved by a combination of nanoimprint and soft lithography, which is a novel approach.
The production of 3D constructs mimicking big vessels, unique approaches that combine the highly repetitive 3D bioprinting with molding technique, together with development of a bioink that resembles mechanophysical properties of extracellular matrix, was successfully achieved.
Characterization of developed bioink and bioprinted constructs, the collaborative synergy between the Fellow, Supervisor, and collaborators from University College London and University of Valladolid, coupled with access to the NBMC AMU infrastructure, has been pivotal in the successful realization of the grant.
Obtained iPSC-CF, SMCs and iPSC-EC were successfully incorporated within 3D constructs. The overall results demonstrate high cell viability and growth of cells within the volume of the bioprint, proving the potential of the designed bioink for use in tissue engineering. No detachment of iPSC-ECs from the lumen is observed, confirming the hypothesis that the novel bioink's unique combination of designed material properties and groove pattern topographical cues protects cells from high flow rates. That data confirm the proper adjustment of the bioink in 3D bioprinting process, the novel technology of micro/nanopatterning, 3D bioprinting+molding and its potential utilization in vascular tissue engineering
This novel approach has the capacity to establish platforms for drug testing and to generate vascular grafts tailored for pediatric use, opening new prospects of personalized medicine.
During the MSCA project, the Fellow participated in scientific conferences presenting MSCA-IF results as well as many outreach and dissemination activities aimed at different target audiences, including researchers, students and school kids. Furthermore, the Fellow participated in several MSCA-focused lectures to share her experience, promote MSCA-IF in broad audience, and encourage other researchers to apply for the fellowships.
The main goal of the project led by dr Jagoda Litowczenko-Cybulska as a MSCA-IF Fellow, was to design and fabricate the polymer-based 3D bioprinted cell-laden vascular grafts (CLVG, scaffold) with certain physical morphology (patterns) and biological properties. For investigation of future clinical utility, perfusion through the tissue-engineered vascular grafts was tested. Constructs under perfusion conditions revealed the possible usage of such tissue-engineered vascular grafts. The utilization of iPSC in this study to generate iPSC-CF and iPSC-EC offers the potential to generate patient-specific iPSC-derived, non-immunogenic, and fully biocompatible personalized vascular grafts.
The MSCA fellowship has undeniably played a pivotal role in enhancing the Fellow's future career prospects. By conducting the proposed project in the dynamic scientific environment of Prof. Raya's Lab, the Fellow has successfully built a robust research profile, positioning herself for the next career step as an independent researcher. The fellowship has provided a unique opportunity to acquire expertise in novel techniques, cutting-edge high-throughput methods, obtained in UCL, Valladolid, and IDIBELL, especially in iPSC maintenance and differentiation. The results of the MSCA-IF project significantly contributed to the emerging field of biomaterials development, 3D bioprinting and vascular tissue engineering. We demonstrated a proof-of-concept for the generation of a hierarchical 3-layered vascular graft with high resemblance to native ECM and cell composition. This novel approach has the capacity to establish platforms for drug testing or to generate vascular grafts tailored for pediatric use, opening new prospects of personalized medicine.
The MSCA provided the fellow an excellent opportunity to explore new research avenues and set and lead independent research direction. Additionally, the collaborative nature of the research, both nationally and internationally, fosters innovation and aligns with European policy objectives related to advancing scientific knowledge and addressing health challenges. The work carried out during the fellowship has substantial implications for innovation and social benefits
The MSCA fellowship has undeniably played a pivotal role in enhancing the Fellow's future career prospects. By conducting the proposed project in the dynamic scientific environment of Prof. Raya's Lab, the Fellow has successfully built a robust research profile, positioning herself for the next career step as an independent researcher. The fellowship has provided a unique opportunity to acquire expertise in novel techniques, cutting-edge high-throughput methods, obtained in UCL, Valladolid, and IDIBELL, especially in iPSC maintenance and differentiation. The results of the MSCA-IF project significantly contributed to the emerging field of biomaterials development, 3D bioprinting and vascular tissue engineering. We demonstrated a proof-of-concept for the generation of a hierarchical 3-layered vascular graft with high resemblance to native ECM and cell composition. This novel approach has the capacity to establish platforms for drug testing or to generate vascular grafts tailored for pediatric use, opening new prospects of personalized medicine.
The MSCA provided the fellow an excellent opportunity to explore new research avenues and set and lead independent research direction. Additionally, the collaborative nature of the research, both nationally and internationally, fosters innovation and aligns with European policy objectives related to advancing scientific knowledge and addressing health challenges. The work carried out during the fellowship has substantial implications for innovation and social benefits