Light Sheet-based Laser Patterning Bioprinting Produces Long-term Viable Full-thickness Skin Constructs

B-BRIGHTER researchers from GUF and IBEC publish an outstanding paper in Advanced Materials Journal presenting LUMINATE (Light sheet-based Ultrafast Microscopic Non-contact And Three-dimensional Enhanced bioprinting), a method that encompasses high printing speed and high resolution while introducing a fully integrated and streamlined fluorescent light sheet microscope capable of capturing real 3D images by optical sectioning the bioprinted construct.

Recently, a great work summarizing the research advances of B-BRIGHTER project came to light and was published in the prestigious journal Advanced Materials. The work, first-authored by Levin Hafa and signed by GUF and IBEC teams, shows that B-BRIGHTER’s innovative approach lies in its ability to combine high printing speed (0.66 mm³/s) with exceptional resolution (9 µm) using light sheet-based imaging.

The methodology involves direct laser patterning and a static light sheet for confined voxel crosslinking in photocrosslinkable materials. This not only enhances the precision of the bioprinting process but also allows for real-time monitoring of hydrogel crosslinking through techniques such as fluorescent recovery after photobleaching (FRAP) and brightfield imaging.

The versatility of the integrated system is demonstrated through the encapsulation of human fibroblasts in a thiol-ene click chemistry-based hydrogel. The results show a remarkable viability of 83% ± 4.34% and functional behaviour. Additionally, the application extends to the development of full-thickness skin constructs that exhibit characteristics of both epidermal and dermal layers. Notably, these constructs remained viable for an extended period of 41 days, underlining the potential of the integrated system in long-term tissue engineering applications.

B-BRIGHTER integrated fluorescent light sheet bioprinting and imaging system represents a significant stride forward in tissue engineering technology. Its capabilities offer researchers and healthcare professionals a powerful tool for designing and fabricating complex tissue structures with unprecedented precision and efficiency. As technology continues to evolve, the future holds exciting prospects for further advancements in light-based bioprinting, ultimately shaping the landscape of biomedical research and healthcare.

Reference article: Light Sheet-based Laser Patterning Bioprinting Produces Long-term Viable Full-thickness Skin Constructs. Levin Hafa, Louise Breideband, Lucas Ramirez Posada, Núria Torras, Elena Martinez, Ernst H.K. Stelzer, Francesco Pampaloni.

B-BRIGHTER Researchers showcase the project at the European Researchers’ Night 2023

Last 29th of September, researchers from 26 European countries participated in the European Researchers’ Night 2023. Among them, Elena Martínez, Marcel Sorribas and Gustaf Mårtensson presented B-BRIGHTER and talked about the science behind the project. Additionally, B-BRIGHTER was also featured on the Catalan website of the event. 

The European Researchers’ Night is a large-scale public event that takes place at the same time across various European cities. During this event, researchers present the diverse area of science and its impact on everyday life through interactive and pleasant activities. The idea behind the event is to strengthen the connection between the public and research, stimulating interest in scientific careers and research triumphs. The event also emphasizes remarkable research initiatives spanning not only Europe but also other regions. Annually, approximately 1.5 million people participate in the event, engaging with and enjoying the world of science and research.

B-BRIGHTER took part in the event in two different activities. On the 26th of September, Elena Martínez from IBEC gave a talk about 3D Bioprinting applied to the biomedical field with the title “Bright ideas: how light allows us to create living tissues”. The audience, about 30 people from different ages, actively participated with several questions. The talk took place at the Vila Urània Civic Center, a place that brings culture at large to the society.

On the other hand, Marcel Sorribas, also from IBEC, participated in an event held the 29th of September at the CosmoCaixa Science Museum in Barcelona. The activity, called “speed-dating”, consisted in talking directly with the public to explain a research being done, and also to solve, in a very close way, all kind of questions, related with science, research and how is it like to be a researcher. In this context, Marcel focused his participation on the 3D bioprinting technique and how B-BRIGHTER new bioprinter will help to bring biomedical advances to the society, while helping to reduce animal experimentation.

Finally, Gustaf Mårtensson, B-BRIGHTER’s coordinator at Mycronic, gave talks for 9th, 10th and 12th graders at three schools.
B-BRIGHTER Project is also showcased on the Catalan website of the European Researchers’ Night, which offers information about several European projects being carried out in the region. To access this website (in English) click here.

B-BRIGHTER project at the “Advances in 3D Bioprinting” conference

The “Advances in 3D Bioprinting” conference, focused on the latest advancements in bioprinting methods and applications, counted with the presence of several B-BRIGHTER researchers from the Institute for Bioengineering of Catalonia (IBEC), who presented the last developments of the project.

From 10-12 September, lead international experts in 3D Bioprinting came together at Technion, Israel, to share their experience in various exciting topics in this field, including in situ bioprinting, bioprinting for organ-on-a-chip devices, organoid bioprinting, and bioprinting of vascularized composite tissues. B-BRIGHTER researchers from IBEC had the opportunity to present the latest advances of the project and in a very rich and fruitful scientific environment.

Elena Martínez was invited to give the talk “Development of biomimetic models of intestine tissue: guiding cellular self-organization through biofabrication technology”, where she emphasized the great possibilities of the 3D bioprinting technology to mimic this organ in the laboratory.

Additionally, to the invited talk, two posters + oral presentations showcased B-BRIGHTER at the conference. Aina Abad-Lázaro presented the work “A 3D model of the intestinal mucosa through light-based bioprinting combining organoids and stromal cells”, that aims to engineer an in vitro intestinal model more similar to the physiological condition, by bioprinting a villus-like 3D hydrogel with embedded stromal cells.

On the other hand, Nuria Torras was in charge of presenting the project overview, also with a poster and an oral presentation, entitled “3D Bioprinting by Light-Sheet Lithography: towards complex tissue constructs”. She highlighted the new bioprinting technology based on digital light-sheet illumination and using an original top-down lithography approach. To conclude this very successful participation, Nuria’s poster has received the conference best poster award. Congratulations!

Nuria Torras participates in the Youth and Science program and hosts a high school student for three weeks in the laboratory

Youth and Science program from La Pedrera Foundation in Barcelona puts together 15–16-year-old students with scientists from different fields and allow them to perform a small research project. Nuria Torras took part in this engagement activity and hosted Lola Dagà for 3 weeks at the Biomimetic systems for cell engineering group from the Institute for Bioengineering of Catalonia (IBEC).

The Catalunya La Pedrera Foundation is a private and independent foundation, led by a board of trustees comprising experts in different fields, which focus their efforts on carrying out projects that have a positive impact on people’s quality of life. Among those projects we can find the Youth and Science program, oriented to 4th year of compulsory secondary school (ESO) students. The goal of this program is to encourage student’s scientific-technological vocations offering them the opportunity to experience research firsthand and the chance of fully cultivating their skills.

For three weeks this Summer, Nuria Torras, B-BRIGHTER researcher at the Biomimetic systems for cell engineering group lead by Elena Martinez at IBEC in Barcelona, hosted a student in the frame of this program. From the 26th of June to the 14th of July, Lola Dagà could experience what it is like to be a researcher. This 15 years old student had a small research project entitled: 3D bioprinting of biological models: manufacturing and case study.

Among others, Lola learnt how to use light-based 3D bioprinting to manufacture several tissue models, by combining hydrogels and different cell lines, and how to prepare inks for bioprinting. Part of the training consisted in studying the effects of the geometry and various printing parameters in the model to optimize the results. Additionally, she could culture the manufactured samples and monitor cell behaviours through immunofluorescence and microscopy techniques (basic and confocal optical microscopy).

In addition to the practical work, Lola also learnt what is a scientific paper and how to find them in the literature, and how to present and discuss her work and results with team members, for example during the weekly meetings. This was a great experience for Lola who opened her mind to scientific research and developed a critical thinking. These kinds of engagement activities are very valuable to stimulate scientific vocations.

What is 3D bioprinting? B-BRIGHTER researchers explained that and more at the “Science Party” in Barcelona.

The 16th Science Party (“Festa de la Ciència” in Catalan) took place last 10 – 11 of June in Barcelona. Researchers from the Institute for Bioengineering of Catalonia proposed a hands-on activity to bring B-BRIGHTER project closer to the society.

One more year, the streets of Barcelona, Spain, filled with science and people interested in it. The 16th edition of the Science Party was a great success and for two days, participants had the opportunity to engage in a diverse array of actions proposed. Shows, workshops, experiments, guided tours, microtalks, games, and debates composed a total of 177 activities that attracted approximately 16,000 visitors.

Researchers Nuria Torras, Marcel Sorribas and Angela Cirulli from the Biomimetic systems for cell engineering group at the Institute for Bioengineering of Catalonia (IBEC) in Barcelona were in charge of this outreach activity in the frame of B-BRIGHTER project, entitled “3D BIOimpression: how can bioengineering help solving health problems”.

The activity began with a brief presentation in which researchers explained what is a 3D bioprinter and how it can be employed in the field of medicine and health, such as in the fabrication of organs to transplants and to reduce animal testing by substituting animals by 3d bioprinted models. Assistants could then see, in live, how a jawbone was fabricated by a conventional 3D printer while learning from the researchers how we can print live human tissues and how works a 3D Bioprinter.

Visitors could also observe under a microscope and compare samples of real human tissues with others fabricated in the laboratory by bioimpression, such as skin and intestine. They could also wear gloves and manipulate some of the materials used in the laboratory such as Petri dishes with cell cultures, tubes with nutrient solutions for cells and pipettes.

These types of outreach activities are an excellent method for bridging the gap between science and the general public, as well as for enhancing awareness of the significance of research in our daily lives and within society as a whole.

The Technion team invited to present B-BRIGHTER at the “Epithelial Differentiation and Keratinization” Gordon Research Conference

B-BRIGHTER was present at the prestigious Gordon Research Conference 2023 on “Epithelial Differentiation and Keratinization”, held last 04-09 of June in Castelldefels, Spain. The team of Ruby Shalom-Feuerstein from Technion – Israel Institute of Technology was invited to present their last advances in the research of cornea stem cells.

The Gordon Research Conference (GRC) on Epithelial Differentiation and Keratinization stands as a foremost global scientific event dedicated to propelling the boundaries of knowledge, showcasing pioneering and previously unreleased research. This year, the meeting is entitled “Novel mechanisms of regulation in epithelial biology and their implication in physiology, aging and disease”, and strives to unite distinguished speakers who are pioneers in the field of stem cell biology, cancer, regenerative medicine, immunity, aging, epigenetics, skin diseases, novel single cell molecular technologies, global genomics, and novel therapies.

In this context, Shalini Dimri, a postdoctoral researcher at Dr. Ruby Shalom-Feuerstein’s Lab at Technion, Israel, gave a talk about the work on stem cells being carried out in their laboratory in the frame of B-BRIGHTER project, under the title: “Repair of total stem cell loss: a lesson from the transparent “skin” of the eye”.

Shalini began her talk by introducing B-BRIGHTER project and technology, and afterwards she focused on the use of cornea as a robust stem cell model. She emphasized its assets as it allows tracing stem cells in live with simple microscopy, observing spatial segregation of stem cells and differentiated cells, and a robust regeneration, among other advantages. To conclude her presentation, she mentioned that differentiation is a reversible process, central cornea shows high plasticity and dedifferentiated cells display bona fide stem cell features.

The Gordon Research Conference puts a strong emphasis on encouraging discussions following each presentation and cultivating casual exchanges among scientists at every stage of their careers. The conference agenda boasts a rich array of speakers and discussion leaders hailing from institutions and entities across the globe, converging to explore the most recent advancements within the domain. For sure it has been a very fruitful event for B-BRIGHTER project. 

ASTRoLAB: a project to send B-BRIGHTER technology to the space

What would happen if we could do human tissue bioprinting under 0g? This is the key question of ASTRoLAB: Advanced Space-based Tissue Regeneration with Light-sheet Assisted Bioprinting. This side-project based on B-BRIGHTER technology has been recently submitted to the European Space Agency (ESA).

B-BRIGHTER consortium members recently presented a project in the frame of the ESA Payload Master call, with the aim to send the project’s light-sheet bioprinter to space and perform some experiments to check-out if there outcomes improve while working under 0g.

The main points of the proposal are:

– Bioprinting under 0g substantially improves the quality of the engineered tissues, by allowing a level of homogeneity of the cell-gel mixture that is not achievable in a g-field 20 µm resolution.

– We want to show that manufacturing engineered tissues in 0g offers enormous advantages compared to manufacture on Earth.

– We aim to demonstrate that the top-down bio-printing process offered by the LS-Bioprinter is much more suitable to 0g applications than the conventional extrusion methods.

The ESA Payload Masters program serves the dual role of fostering and discovering groundbreaking in-orbit experiments and cutting-edge technologies for payloads. Simultaneously, it plays a pivotal role in democratizing space exploration, making it accessible to both space and non-space industries. The main objective of the program is to enhance the competitiveness of companies by eradicating the well-known “valley of death” phenomenon and giving access to in-Orbit Demonstration and Validation (IOD/IOV).

The project winners of the call will be offered the opportunity to fly their payloads/microgravity experiments on board of Nyx for the “Mission Possible” mission. Nyx is a modular and reusable orbital vehicle that can be refuelled in orbit and serves the low Earth orbit (LEO) and lunar destinations. It will start by carrying cargo, with the growth potential to fly humans afterwards. Nyx will enable to perform microgravity experiments, in-orbit technology demonstrations, entertainment, and educational missions, but also cargo delivery to larger space infrastructures or lunar surface.

Let’s keep fingers crossed and hope ASTRoLAB will be selected!

B-BRIGHTER technology at the Connection Day 2023

The technology transfer team from the Institute for Bioengineering of Catalonia presented the B-BRIGHTER innovative 3D bioprinter at the first Connection Day in Catalonia, a networking  event designed to be a benchmark space for B2B connections in the health sector.

Last 27th of April, the Institute of Ocular Microsurgery (IMO) in Barcelona hosted the first Connection Day, coordinated by the CataloniaBio & HealthTech, an organization that represents companies in the biomedicine and health sector in Catalonia.

The technology transfer team from the Institute for Bioengineering of Catalonia was present in the event to promote their technology and innovation in the field of biomedicine and health. In this context, as partners of B-BRIGHTER, they also presented the innovative 3D bioprinting technology being developed in the project and took profit of this opportunity to do networking and pave the way for future collaborations.

Over 200 members of the CataloniaBio & HealthTech community, in addition to various ecosystem organizations, assembled to explore synergistic opportunities and collaborative avenues within their offered products, services, and solutions. Among 160 and 180 people assisted the event, and some of them get interested in knowing about B-BRIGHTER technology.
This kind of initiatives are very welcome to foster potential partnerships among companies in the health sector (biotech, medtech, pharma, digital health and services) and to promote the technology transfer from the academia to the industry, as is the case for B-BRIGHTER 3D bioprinter.

B-BRIGHTER researchers at Tübingen: project meeting and a visit to CELLENDES’s new facilities

Last 19-21 of April B-BRIGHTER members meet together at Tübingen for the 6M internal and progress meetings and a visit to the new facilities of CELLENDES.

The hotel Krone in Tübingen hosted for two days B-BRIGHTER project. On the 20th and the morning of the 21st of April, researchers met for an internal monitoring of the work done during the first six months of the project, and to discuss the following steps until the end of the year. All workpackages were presented by their coordinators and researchers could evaluate the advances until know and propose strategies and ideas to surpass obstacles.

During the afternoon of the last day, took place the progress meeting, among project members and the EIC Project Advisor and Program Manager. This was a very fruitful discussion where the project coordinator, Gustaf Mårtensson, presented the goals, the product, the development program, and the current status of the project. He highlighted the achievements during this initial phase and stressed out what is planned for the next six months.

Taking advantage of the fact that the meeting was being held in Tübingen, a visit to CELLENDES was scheduled. Researchers from B-BRIGHTER project went to the new CELLENDES facilities, in a new technological pole in the city. Helmut Wurst and Brigitte Angres explained all the space adaptations to transform in a laboratory and showed the offices and different rooms.

Two talks and two posters highlight B-BRIGHTER Project at the 3D Cell Culture Conference 2023

B-BRIGHTER project had a notable participation at the last 3D Cell Culture Conference: Models, Applications & Translation, with two talks and two posters explaining the rationale behind the project and the latest advances. The emphasis of this year’s meeting was on advanced and predictive 3D cell culture models.

Last 17-19 April, Cellendes, Goethe University Frankfurt (GUF) and the Institute of Bioengineering of Catalonia (IBEC), brought to light B-BRIGHTER project to the assistants of the 7th 3D Cell Culture Conference, held at Freiburg, Germany. The 3D Cell Culture Conference (3DCC) is an initiative of DECHEMA, a non-profit professional society which promotes scientific and technical exchange among experts from different disciplines, organizations and generations, concretely, it is organized by the working groups “Cell Culture Technology” and “Medical Biotechnology”.

The main topics of the 7th edition of the 3DCC series were the latest tendencies in development, biology and applications of organoids, the biology in microphysiological systems, new developments in the field of personalised medicine, the path from 3D cell cultures to cell-based therapies, as well as enabling technologies for standardisation and scalability.

The participation of B-BRIGHTER Project began with an oral presentation by Brigitte Angres, from Cellendes, where she talked about “Biomimetic thiol-norbonene functionalized hydrogels for photolithographic bioprinting and tissue fabrication”. The work was also presented in a poster format.

Afterwards, Levin Hafa from GUF presented a poster entitled “Bioprinting by light sheet lithography: engineering complex tissues with high resolution at high speed” explaining the project in depth and highlighting its objectives, advantages and originalities.

Finally, Nuria Torras, from IBEC talked about “A bioprinted 3D gut model with crypt-villous structures to mimic the intestinal epithelial-stromal microenvironment”, reporting a simple 3D bioprinting approach for the direct fabrication of advanced cell-laden tissue constructs by means of visible-light photopolymerization, which allows the fabrication of cell-laden structures resembling the intestinal mucosa in a single printing step.

In addition to the scientific presentations, the meeting spotlighted practical applications, products, and solutions, triggering engaging conversations among researchers, solution providers, and users.