Optical means for stimulating and monitoring neuronal activity have provided a lot of insight in neurophysiology lately toward our understanding on how brain works. Optogenetic actuators, calcium or voltage imaging probes and other molecular tools combined with advanced microscopies allowed ‘all-optical’ readout and manipulation of neural circuits. Yet, important challenges remain to be overcome to achieve full optical neuronal control, concerning reliable delivery and expression of sensors and actuators in the same neurons, elimination of cross-talk between the imaging and manipulation channels, and achieving recording and manipulation each with single-neuron and single-action-potential precision. SLALLOM is a concerted attempt between two academic (Wavefront-Engineering Microscopy group; WEM, Neurophotonics Lab. and Lasers group, Charles Fabry Laboratory; LCF) and two industrial partners (Amplitude Systemes; AS, ALPhANOV) aiming to remedy the last two challenges. The central idea of SLALLOM is to develop a novel single-light-source ‘all-optical’ two-photon computer-generated holography (CGH) microscope using an innovative frequency-converted dual-output directly diode pumped Thulium (Tm)-doped fiber amplifier for three-dimensional (3D) multicell excitation and monitoring. The proposed laser system aims at the disruption of current laser technology used for 2-photon imaging and activation in optogenetic studies. Indeed, mature laser technologies suffer from drawbacks (e.g. lack of energy, absence of repetition rate tunability, excitation wavelength not matching the 2-photon absorption spectra peak of most molecular tools) that prevent their use for massive parallelization of neuron manipulation. We therefore propose a cutting-edge dual-branch ultrafast fiber laser system operating in the 920-975 nm wavelength range. This laser system steps away from conventional laser technologies (e.g. Ti:sapphire laser, Ytterbium fiber laser) and builds upon frequency upconversion of Tm-doped ultrafast fiber amplifiers seeded by a frequency-shifted Erbium oscillator. The two branch parameters will be optimized for their respective goal: imaging with >5 W, 40 MHz and 100 fs and photoactivation with >5 W, 10 µJ and 100 fs. A 3D-CGH microscope appropriately modified for addressing a large excitation field, will be assembled together with a 2-photon scanning system for 3D structure or functional imaging of neuronal activity, with genetic reporters. The developed laser will be used as a single-laser source for both imaging and stimulation, aiming to treat the cross-talk between these modalities by exploiting the superior temporal resolution provided by CGH in combination with highly-efficient fast-kinetic opsins. The microscope will be used to follow brain complexity in the visual cortex in vivo at high spatiotemporal resolution. The project, led with the WEM group, forerunner in developing advanced optical methods for neuronal stimulation, gathers specific and complementary skills from four partners whose expertise is recognized at international level. The WEM group has proposed about ten years ago the application of spatiotemporal light patterning with CGH and temporal focusing as a means of precisely parallel targeting cells groups, enabling photostimulation at high spatio-temporal precision. LCF is widely acknowledged as a major actor of the research in diode-pumped ultrafast lasers. ALPhANOV is a French technological center specialized in the development of innovative high-power fiber laser, especially for ultra-short pulse amplification. Finally, AS is the world leading company providing integrated, industrial-grade ultrafast laser systems, and has a long-standing collaboration with LCF through a common laboratory. SLALLOM consortium will demonstrate a reliable ground-breaking ultrafast laser source adapted to a 3D-CGH microscope to study the brain activity in vivo at high spatiotemporal resolution with scientific and industrial outcomes.

Parallel to standard Tissue Engineering, technological advances in the fields of automation, miniaturization and computer-aided design and machining have led to the development of Bioprinting. This later concept has been defined recently as the “the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies”. As compared to traditional approaches in Tissue Engineering, bioprinting represents a paradigm shift. Indeed, its principle is not more to seed cells onto a biodegradable scaffold but rather to organize the individual elements of the tissue during its fabrication step (before its maturation) through the layer-by-layer deposit of biologically relevant components. Moreover, while giving a better control on the cell distribution into 3D constructs, such automatized processes should also minimize contamination issues during tissue engineering process and should reduce the duration for manufacturing a fully functional engineered-tissue. In the framework of the project Bone printing, we will focus on the development and the evaluation of new technologies through the application of the Bioprinting principle to bone tissue engineering. Regarding basic research, the main outcome will be gaining further understanding of the influence of the local microenvironment of human mesenchymal stem cell (hMSC) on the functionality of 3D tissue-engineered constructs. This will be addressed by investigating effects of hMSC patterns and biomaterials properties such as composition and stiffness on tissue function. In this aim, CMCP will focus on the design of novel collagen-based materials through innovative cross-linking procedures. Regarding experimental developments, this project will consist in realizing the second generation of Laser-assisted Bioprinter which will permit the deposit of living cells and biomaterials in vitro, in vivo and through a safe, sterile and automatized process. As for laser-assisted technologies for biofabrication, main industrial developments concern laser sintering, photo-polymerization and, to our knowledge, no company has proposed an integrated LAB system yet. ALPhANOV and INSERM U577, in collaboration with one subcontractor (e.g. ES Technology) specialized in integrating laser machines for different kind of applications, will thus develop such a system. Regarding the preclinical aspect, we will evaluate the interest of bioprinting in vivo, what could pave the way to new perspectives in robotized surgery and medicine. The benefit of this new approach compared to the implantation of engineered tissues elaborated in vitro will be addressed in this project. To summarize, this project is related to the “tissue engineering and biomaterials” theme of TecSan 2010 program. It aims at developing new innovative technologies for bone tissue reconstruction through an original 3D laser printing technology. Bioimaging will play also a key role in this program for investigating the newly formed tissue in an experimental model of bone defect in small animal. This project includes also an automation of the bioprinting process for producing a controlled and reproducible regenerated tissue.The realization of a second generation Laser-Assisted Bioprinter should open new perspectives in regenerative medicine as well as in other biomedical area by furnishing organotypic cultures. Moreover, a spin-off (company) creation for commercialization of 3D Laser-Assisted Bioprinter, with support from the “Route des Lasers” competitiveness cluster is envisaged before the end of this project.

Today, industrial markets demand highly added value products offering new features at a low-cost. To this extent, technologies to modify surfaces instead of creating composites or applying coatings on surfaces can offer new industrial opportunities. Current state of the art identifies short pulsed(SP)/ultra-short pulsed(USP) laser-material processing as a promising technology for structuring surfaces and thus for embedding new functionalities for industrial applications. The LASER4FUN research programme pursues to go far beyond the current state through the development of new surface micro/nano-structuring/patterning methods by using emerging SP/USP laser technologies (LIPSS, DLIP, DLW & hybrid tech). The research will focus on the interaction of laser energy with several materials (metals, semiconductors, polymers, glasses & advanced materials) and on new surface functionalities like tribology, aesthetics and wettability. Moreover, LASER4FUN establishes an innovative training programme that aims at coaching a new generation of creative, entrepreneurial and innovative early stage researchers (ESRs) focused on laser surface engineering. This novel programme will contain both scientific and general skills training activities and it will benefit from training at a network (e.g. secondments). In total, 14ESRs will be enrolled, developing individual research projects within LASER4FUN programme. After 36 months of research and training, the ESRs will be PH Doctors prepared to face EU laser-engineering new challenges. LASER4FUN consortium involves 8 Academic partners (4 Universities –one of them as associated partner- and 4 RTD institutions) ensuring the progress beyond the state of the art, and 3 industrial partners guaranteeing that final solutions will be close to the market. They are from 6 different EU countries. The close cooperation among multidisciplinary partners will ensure knowledge transfer to cross the death valley between science and the market.

EU’s industry is pushed by EC‘s green deal to convert into a net-zero industry, accelerate the transEU’s industry is pushed by EC‘s green deal to convert into a net-zero industry, accelerate the transition to climate neutrality and drive its resilience. As an important part of the EU manufacturing industry, the EU’s textile sector is thus called to action and to reach the next level of disruptive innovations in sustainable textiles. BioFibreLoop is a business-driven consortium of 12 partners from small to large industry and scientific institutes and will meet these challenges by deploying a new generation of renewable, recyclable, bio-inspired materials made of lignin, cellulosic and polylactic acid at TRL 7 by 2027. The innovation addresses the outdoor/active/workwear industry and will result in circular, technical textiles made from biopolymers with innovative bio-inspired non-toxic functionalisation. BioFibreLoop will demonstrate breakthrough technologies and pave the way for market entry: (i) near to zero waste biomimetic functionalization through circularity, (ii) zero use of hazardous chemicals, (iii) satisfied consumer needs through smart functionality for hydrophobicity, oil repellency, self-cleaning, and antibacteriality. In 3 industrial demo sites (IT, DE, AT) biomimetic functionalisation and recycling of the bio-based materials will be proven at large at TRL7. These are based on processes owned by partners and brought in at TRL4 e.g. lignin-based thermoplastic coating, laser-based technology for surface structures in bio-based textiles, thermomechanical recycling of PLA and lignin-based textile materials to serve as valuable secondary raw materials. At the project’s end, a patented circular, sustainable and safe process will be validated and demonstrated at a large scale to generate brand-new renewable, recyclable and functionalised materials. By 2035, 20% of the textile industry will adopt our solution boosting ~ 950 Mio. € additional revenues.