Mimicking human skin constructs using norbornene-pullulan-based hydrogels

The demand for engineered skin tissues has surged for both in vitro and in vivo applications, and one of the key points to succeed is to choose an appropriate scaffold material. In this scenario, B-Brighter researchers at IBEC has just published a work describing a new bioink designed for engineering human skin constructs using norbornene-pullulan-based hydrogels.

Researchers from the Biomimetic Systems for Cell Engineering group at IBEC (from the left): Angela Cirulli, Núria Torras and Elena Martínez.

Engineered skin tissues have versatile applications in clinical settings, such as skin substitution and advanced wound dressings, as well as in pre-clinical scenarios to test new drugs, disease modeling, and cosmetic studies. An ideal engineered skin tissue should be easy to prepare, resistant to mechanical shear forces, and conducive to cell adhesion, growth, and vascularization, in both the epidermal and dermal compartments. It must strike a balance between elasticity and mechanical stability while providing a suitable cell microenvironment to support the different compartments of the human skin.

Recently, B-Brighter researchers at IBEC have published a work in the International Journal of Bioprinting that will help address and solve these issues. Concretely, they introduced a novel photocrosslinkable bioink designed for engineering human skin constructs, based on thiol-norbornene-pullulan (N-PLN) formulations combined with various crosslinkers. This new bioink was effectively used in a customized direct laser writing setup to mimic epithelized dermal skin constructs. The dermal compartment was formed by photocrosslinking a pre-gel solution containing human fibroblasts, while the epidermal compartment was developed by seeding human keratinocytes on the fibroblast-laden hydrogels.

Using visible light, 2.5 mm³ cell-laden hydrogels could be printed in just 10 seconds. The thiol-ene photocrosslinking chemistry employed here created a well-defined extracellular matrix with orthogonal crosslinks, maintaining high cellular viability rates for encapsulated fibroblasts.

This study proposes a promising strategy for developing an epithelized dermal human skin model using a custom-made 3D light-based bioprinting system and novel N-PLN polymers. The hydrogels formed after brief exposure to low-dose visible light exhibit the physicochemical properties necessary to support excellent cell viability, proliferation, matrix protein secretion, and elongation, which are crucial for cellular network formation. Additionally, the fibroblast-laden hydrogels support the culture of keratinocytes, enabling the formation of epithelized dermal constructs.

This method represents an optimistic starting point for developing photocrosslinkable hydrogel-based human skin constructs using thiol-ene norbornene chemistry, paving the way for the creation of complex in vitro models of human tissues. By combining visible light photopolymerization with N-PLN-based materials, this approach represents an alternative method for developing ready-to-use skin models that are easy, fast, reproducible, and cost-effective, which could be particularly beneficial for pre-clinical in vitro assays in cosmetic and pharmaceutical research.



Reference article: Mimicking human skin constructs using norbornene-pullulan-based hydrogels. Angela Cirulli, Livia Neves Borgheti-Cardoso, Núria Torras, Elena Martínez. https://doi.org/10.36922/ijb.3395

Núria Torras and Marcel Sorribas host a student in the frame of a professional observation internship

Inés Roucou, a 16-year-old student, could benefit from a 2-week stay at the Laboratory of Biomimetic Systems for Cell Engineering at IBEC in Barcelona. She learned about bioengineering and topics related to B-BRIGHTER project, guided by the researchers Núria and Marcel.

From left to right: student Inés Roucou, Núria Torras and Marcel Sorribas.

Once again, the Biomimetic Systems for Cell Engineering laboratory, led by Elena Martínez at IBEC, reinforced its commitment to educating young students and helping to inspire scientific vocations. This time, Núria Torras and Marcel Sorribas participated in a professional observation internship, developed in collaboration with the Lycée Français de Barcelona, a French school near IBEC.

This program aims to help young students choose their future careers by giving them first-hand experience of the work of professionals from different fields. In this context, Inés Roucou, who is passionate about medicine, chose Elena’s laboratory to learn about how scientific research is at the core of medical advances. She spent June 10th to 21st in the lab, gaining insight into what it’s like to be a researcher in biomedicine.

She learned about stem cells and 3D bioprinting of organs and tissues—advances that aim to reduce animal testing and have the potential to shorten transplant waiting lists in the future. She also had the opportunity to put into practice what she had learned at school about the scientific method.

In addition to the science, Núria and Marcel showed her what their day-to-day lives are like and how a laboratory operates. They also provided guidance on the studies and training needed to become a researcher.

Undoubtedly, it was a great and unforgettable experience for Inés!

B-BRIGHTER at the 1st International Conference of the Würzburg Initiative 3R (WI3R)

The Würzburg Initiative 3R celebrated its first International Conference to provide a broad communication platform to enable exchange about “3R” among researchers from the diverse sectors related with animal experimentation. It represented an effort to improve the welfare of animals in research, and Brigitte Angres and Louise Breideband were there to talk about the 3D bioprinting technology from B-BRIGHTER.

Despite their indispensability in research, animal experiments should be kept to a necessary minimum or better avoided altogether. The ethical 3Rs principle – Replace, Reduce and Refine – serves as a guideline to limit the number of experiments as well as to reduce animal suffering to an indispensable level.

The Würzburg Initiative 3R (WI3R) bundles the Bavarian activities in the field of 3R from science, regulatory authorities, and industry and networks with existing 3R centers in Germany, Europe and worldwide. In addition to the quality-assured provision of alternatives to animal experiments, the research network is also active in the field of science communication and education.

The aim of the 1st International Conference of the Würzburg Initiative 3R (WI3R) was to offer a comprehensive communication platform for a multidisciplinary community, facilitating exchange among researchers in the field of 3R research. Also, they intended to identify synergies and foster new research ideas and collaborations, focused on promoting research to develop and validate 3Rs methods to replace, reduce and refine animal tests.

From 5 to 7 June, almost 200 participants converged in Würzburg, Germany, to discuss about, among other subjects, biofabrication and 3D printing, human iPSC and organoids, emerging technologies, new approach methods, disease modeling, and regulatory acceptance. The scientific program was composed of 20 lectures and 80 posters, with researchers from all areas in the life sciences, which rely on the use of experimental animals, including pharmaceutical, cosmetics, and chemical industry, regulatory and basic sciences.

Louise Breideband from GUF presented a talk titled “Laser patterning bioprinting using a light sheet-based system equipped with light sheet imaging produces long-term viable full-thickness skin constructs”. She introduced to the audience the new B-BRIGHTER 3D bioprinter that combines live imaging of the bioprinted tissue with high resolution and high-speed capabilities.

In her talk, she highlighted that this novel light-based bioprinting technique enables fast and high-resolution biofabrication, coupled with the possibility to image cells and hydrogel before, during, and after the bioprinting procedure with light sheet fluorescence imaging. At the end of the presentation, she pointed out that producing physiologically relevant tissues helps reduce the need for animal testing in the drug discovery process, aiming ultimately to replace them

Brigitte Angres from Cellendes, on her side, presented a poster titled “Biomimetic thiol-norbornene functionalized hydrogels for photolithographic bioprinting and tissue fabrication”. Brigitte centered her participation on explaining the extent to which hydrogels are well suited for the development of tissue models to replace animal experiments.

She presented the highly versatile and controllable light-inducible biomimetic hydrogel system devoid of animal components based on the thiol-ene chemistry, developed in the frame of the project. Brigitte also underlined that this hydrogel is well applicable in bioprinting devices and microphysiological systems to yield highly diversified microarchitectures for complex tissue model fabrications.

In Brigitte’s words: “It was a very interesting meeting, exploring possibilities to apply our hydrogels for the 3R approach”.

The event was organized by the Fraunhofer, supported by some funded research clusters from the German Research Foundation (DFG) focused on i) developing new cell-based tissue models and test systems, scalable manufacture processes, prototypes and biological vascularized implants; ii) exploring the fundamentals of biofabrication and its systematic exploitation with the aim to generate functional human tissue models and iii) development of human 3D tissue models for infection research aiming to identify molecular mechanisms within the host that control the course of infectious diseases.

The conference stimulated excellent scientific discussions about novel approach methodologies as complemental or alternative methods to animal testing and experimentation, with a view to validate 3Rs methods to replace, reduce and refine animal tests. It was certainly a great scenario for creating new collaborations for B-BRIGHTER project!

Great presence of B-BRIGHTER at the third EMBL-IBEC conference

B-BRIGHTER project was present at the third edition of the EMBL-IBEC conference in Barcelona through the participation of Levin Hafa and Louise Breideband from GUF. This event, organized by the Institute for Bioengineering of Catalonia (IBEC) and the European Molecular Biology Laboratory (EMBL), has it focus on emerging and advanced therapies.

The third edition of the EMBL-IBEC Conference on Engineering Multicellular Systems took place at the

Barcelona Biomedical Research Park (PRBB) in Barcelona last 24, 25 and 26 April. This biennial conference focuses on emerging and advanced therapies and addresses the state-of-the-art advances in emerging fields of bioengineering, such as organ-on-chip, cell mechanobiology, stem cell biology, and 3D bioprinting, and how all these advances have revolutionized our ability to design and assemble multicellular living systems, from organoids to embryos.

This year, the conference featured 20 invited experts from Europe, Canada, USA, Japan and India, and brought together around 150 international experts in different fields of bioengineering, who spent three days discussing the forefront research on engineering of multicellular living systems.

In the context of this event, Louise Breideband presented a poster titled “Upgrading a Consumer Stereolithographic 3D Printer to Produce Physiologically Relevant Cancer Models”, showcasing the open-source device based on a consumer-grade 3D stereolithography apparatus (SLA) printer, developed in the frame of B-BRIGHTER project.

On the other hand, Levin Hafa presented a poster that was also selected for a short talk, titled “Laser patterning bioprinting using a light sheet-based system equipped with light sheet imaging produces long-term viable full-thickness skin constructs”. This presentation summarizes the work being done in the project as well as the main results obtained to date.

The EMBL-IBEC Conference on Engineering Multicellular Systems is being consolidated in Barcelona as an international benchmark, shedding light on the function of tissues and organs, with applications in drug modelling, disease detection and tissue engineering, and their applications in advanced therapies.

Can we repair a broken heart? Marcel Sorribas takes part in an outreach activity for senior people

In the frame of IMAB, an outreach project developed at the Institute for Bioengineering of Catalonia (IBEC) in Barcelona, Marcel Sorribas brought B-BRIGHTER project closer to over-65s.

Most science popularisation projects and outreach activities are oriented to children, families, or adults in general, leaving out an important part of the population: senior people over 65 years old. To reach this target audience, IBEC, with funding from the Spanish Foundation for Science and Technology (FECYT), developed the IMAB project: Involving the Senior Community in Advances in Bioengineering for Health and Healthy Aging (for its Spanish acronym).

The IMAB project aims to engage individuals over 65 in learning about, understanding, and expressing their opinions on the latest research in bioengineering for active aging. The objective is to bring scientific advances, gather opinions, and address the need to disseminate scientific knowledge to this age group. This initiative has been conducted in collaboration with adult education centers, community centers, associations, and university extension classes.

The materials were adapted to enhance visual and auditory comprehension. To foster discussion, fictitious patient cases were used, allowing participants to openly discuss various scenarios, and to overcome travel constraints and ensure inclusive participation, activities were held at community centers. During these workshops, participants also had the opportunity to discuss ethical issues related to organ and tissue regeneration research. It is worth highlighting that activities were designed taking into account functional diversity aspects and encouraging the participation of different sectors of society.

Several IBEC researchers took part in this initiative, covering topics from basic biological concepts to organ bioprinting, where Marcel Sorribas could take part and talk about 3D bioprinting and B-BRIGHTER project.

He talked about the regeneration of organs and tissues, mainly by 3D bioprinting. He explained what a cell is, and how can researchers construct a human organ in the laboratory. He could give details about his work on B-BRIGHTER related to synthesizing skin and intestine and stimulated interested and fruitful discussions among the public and the researchers.

Some data summarizing the whole activity

– 18 sessions were held, bringing together 295 participants with an average age of 76 (76% of them women)
– 89% would accept a heart bioprinted in the laboratory, and 97.9% would accept a dressing made from embryonic cells.
– 95.7% would agree to donate cells to a biobank, and of these, 49.1% would like to be informed about how their cells will be used.

A report with the results will be shared soon with the scientific community to provide insights into the public’s opinions and perspectives related to the senior public.

By creating educational and reflective spaces and adapting resources to individual needs, the goal of the project was not only to share knowledge but also to generate meaningful dialogue, thus contributing to a more informed and involved community in scientific issues.

Another B-BRIGHTER project meeting: this time in sunny Barcelona!

The 18M project meeting was held in Barcelona on 11 and 12 April, and researchers took the occasion to visit the premises of the Biomimetic Systems for Cell Engineering led by Elena Martínez at IBEC.

Last Thursday and Friday B-BRIGHTER researchers came together at the Institute for Bioengineering of Catalonia (IBEC) in Barcelona for another project meeting: this time 18M. They spent 2 days of very fruitful discussions to monitor the project’s evolution and define the next steps to improve the 3D bioprinter device and bring it closer to the market.

On the first day, Gustaf Mårtensson as coordinator, and Elena Martínez as host in Barcelona, opened the floor giving a brief overview of the structure of the meeting and the project’s current status. The meeting included talks from the coordinators of all 6 work packages, who exposed the advances of the ongoing work, and discussed how to solve some small technical issues. All partners highlighted the achievements made during the last 6 months from the last meeting, and defined the roadmap for the next months, focusing on bringing the commercialization of the 3D bioprinter device.

On Friday, researchers had a long and productive session to discuss use cases, and to determine the best strategy to continue developing the B-BRIGHTER device and bring it closer to the market. After that, they had the occasion to visit the Biomimetic Systems for Cell Engineering led by Elena Martínez at IBEC and see, firsthand, how the team from Barcelona develop reliable protocols for the use of the light-based bioprinter to print tissue-like constructs.

And of course, as it could not be otherwise, researchers also spent some very pleasant leisure moments!

Núria Torras and Marcel Sorribas bring B-BRIGHTER closer to students of secondary education

Students at the Secondary School Angeleta Ferrer in Barcelona had the occasion to know the B-BRIGHTER project and learn about 3D bioprinting and in vitro models.

In the context of a collaboration between the Institute for Bioengineering of Catalonia (IBEC) and the Secondary School Angeleta Ferrer in Barcelona, Núria Torras and Marcel Sorribas, participated in this educational activity and worked side by side with a group of 6 students, introducing them to the subject of 3D bioprinting and the development of tissue models with complex structures, like the intestine or skin, using a light-based bioprinter. Núria and Marcel are both B-BRIGHTER researchers at the Biomimetic Systems for Cell Engineering group at IBEC.

During February and March, the group of 12-year-old students from the Institut Angeleta Ferrer School worked closely with Núria and Marcel, developing a scientific project. Using the B-BRIGHTER project as a starting point, the students learned about the scientific method and how researchers organize their ideas and practical experiments to reach a scientifically relevant conclusion. Also, they discovered that the tissue models being developed in B-BRIGHTER project have the final aim of replacing animal testing for drug development and disease studies.

Afterwards, they applied this knowledge to different scientific topics they were studying at school, related to plant germination and how plants get the energy they need to live. Students developed a hypothesis, designed experiments to test it, obtained results, and drew some conclusions. All this work was done in close collaboration with Núria and Marcel, who went to the school and met the students online several times to fine-tune the details of their projects.

At the end of the activity, the projects were presented as scientific posters in a “mini congress,” attended by teachers, family, and friends. In addition to gaining scientific knowledge, the students had the opportunity to meet two researchers up close and learn about their careers and the day-to-day life of someone dedicated to experimental science.

Louise Breideband takes part in the EIC T2M – Innovation Discovery Training

The 6th edition of the EIC T2M – Innovation Discovery Training took place last week and Louise Breideband from GUF took the opportunity to improve her entrepreneurship skills and to learn from a science entrepreneur.

EIC T2M – Innovation Discovery Training is part of the European Innovation Council EIC Tech to Market (T2M) Entrepreneurship Programme, which covers a wide range of activities that have been improving the ability of EIC beneficiaries, preparing them to take the leap towards the market. This program aims to assist deep-tech researchers supported by the EIC Pathfinder and the EIC Transition, who have entrepreneurial aspirations, in transforming their technological solutions into marketable innovations. It seeks to accelerate their science startup projects while helping them build strong value propositions and viable business models.

In this context, the 6th edition of the EIC T2M – Innovation Discovery Training took place in two sessions of 4 hours, the first on 12th February and the second one on 16th February, with the objective to help researchers get a first idea of what it means to start a venture out of a scientific breakthrough.

In practical terms, these two half-day online training sessions consisted of collective coaching sessions designed to help deep-tech scientists learn how to effectively present their entrepreneurial ideas and gain a fundamental understanding of valuable entrepreneurship skills. They discussed and received feedback on entrepreneurial concepts from both experts and fellow attendees, on subjects such as business models, identification of customers, market sizing, Intellectual Property and funding. Concretely, exchange with market and industrial stakeholders helped participants to assess the value proposition and their product-market fit.

One important pillar of the course is giving researchers some tools and advice on effective ways to present their entrepreneurial ideas in a pitch format. In this sense, on the first day, participants got practical guidance from competent professionals and experts, among them from Jerôme Michon, who had previously participated in the program and had successfully launched his own start-up, InSpek. The testimony from someone who became an entrepreneur from the academic background added a layer of practical relevance and inspiration to the training.

The course was informative and enriching and offered helpful insights into the path from innovative ideas to market-readiness products. Also, having real-life feedback from an entrepreneur, done interactively, was a real plus.

One more year B-BRIGHTER participates in the International Day of Women and Girls in Science

B-BRIGHTER reiterates its commitment to gender equality in science and once again joins in the 11F activities. This year, Núria Torras from IBEC participated in an online talk.

Since 2015, the International Day of Women and Girls in Science, declared by the United Nations, is celebrated every year on February 11. The main objective of this global event is to eradicate gender stereotypes and established prejudices that have hindered the involvement of girls and women in science. This day is committed to providing comprehensive and unbiased opportunities for women and girls within the scientific domain. The various activities are designed to foster the empowerment of women and girls, encourage their engagement in scientific pursuits, and advance the cause of gender parity.

In this context, Nuria Torras, a researcher in the Biomimetic Systems for Cell Engineering group led by Elena Martinez at IBEC in Barcelona, participated in the 9th International Day of Women and Girls in Science. She took part in the annual event 100tifiques, organized by the Catalan Foundation for Research and Innovation (FCRI) and the Barcelona Institute of Science and Technology (BIST), an initiative that aims to bring science closer to schools and highlight female scientific talent.

Nuria gave an online talk to 25 11-year-old students from the Carles Faust school in Blanes, a city near Barcelona. She explained a bit about the work done in the B-BRIGHTER project and discussed the principles of 3D printing, the biological models, and the types of materials and cells used in the laboratory.

To conclude her participation, Nuria shared her journey to becoming a scientist, helping the students realize that a scientist is an ordinary person who also has a family, hobbies, and… can also be a woman! The students were very interested and motivated, and they took the opportunity to discuss with Nuria not only about science but also what it means to be a female scientist.

Hopefully, we will be back next year to bring science to even more girls!

Congratulations! B-BRIGHTER Technology awarded with the Goethe Innovation Prize 2023

We are very proud to share that GUF team was awarded 3rd place at the Goethe Innovation Prize Event with “Modulux3D” Project: a 3D bioprinter that revolutionizes medical research through tissue engineering. This award recognizes research projects with great innovation potential and benefits for customers or patients.

Last December 11 took place in Frankfurt a pitch competition to select the winning teams of this year’s Goethe Innovation Prize. This prize is conceded by Goethe-Unibator, the start-up center of the Goethe University Frankfurt am Main operated by the technology transfer company Innovectis. It provides students, academic staff, and alumni with active support for their start-up projects and acts as a bridge between science and business.

From a high number of applications, five projects qualified for the final and had the chance to deliver their pitches in 4 minutes in front of an audience of over 100 people. The three best teams were selected by an expert jury and won prize money and participation in the Unibator start-up program.

Louise Breideband and Levin Hafa presented the “Modulux3D” start-up, originated from B-BRIGHTER project, that aims to bring our 3D bioprinting technology to the market. They highlighted its innovative bio-printer that uses light to network biological cells and a special bio-ink. After a great and convincing pitch about the vast potential of 3Dbioprinting in the field of biomedicine, they won the third prize. Congratulations!