Periodic Reporting for period 1 - Bio-HhOST (Next Generation 3D Tissue Models: Bio-Hybrid Hierarchical Organoid-Synthetic Tissues (Bio-HhOST) Comprised of Live and Artificial Cells.)
Okres sprawozdawczy: 2024-02-01 do 2025-01-31
Bio-hybrid materials and physiochemical interactions hold great promise for advancing the pharmaceutical and chemical sectors. However, current developments in these technologies are limited, with few functional options available. In this context, the EIC-funded Bio-HhOST project aims to develop a bio-hybrid material composed of living and artificial cells, enabling a wide range of interactions. The incorporation of artificial cells will facilitate the proliferation, function, and differentiation of living cells, while also possessing functional metabolisms capable of revolutionising the sector through chemical interactions. Additionally, the project employs 3D tissue models and simulations to enhance the understanding of the material and its response to diseases, thereby reducing the necessity for animal research.
Bio-HhOST is building bio-hybrid materials that comprise living & artificial cells, in dynamic communication, such that artificial cells may influence the proliferation, differentiation and function of living cells. This will be accomplished by producing precision engineered, microscale, liquid and lipid bilayer-based, chemically compartmentalised artificial cells, co-localised with live cells. This is being done by an interdisciplinary team of biologists, engineers, mathematicians and entrepreneurs. The artificial cells will contain functional metabolisms, and the ability to respond to chemical stimuli in the environment to release signalling molecules, on demand, to regulate the neighbouring living cells, as found in complex biological tissues. These new chemically programmable organoid-synthetic tissues will enable a paradigm shift, in both ability to elucidate and control the complexity of physio-chemical interactions within 3D tissues, and reduce animal use in pharmaceutical R&D.
To achieve these ambitions we have designed an integrated multistage workplan driving towards the following overarching aims:-
Aim 1. Create 3D tissues where spatial regulation of living cell differentiation is determined by co-located (chemically programmable) artificial cells.
Aim 2. Regulate and maintain such 3D tissues by dynamic communication between live and artificial cells.
Aim 3. Develop multi-level, multi-approach models of organoid-synthetic tissues behavior. These will be applied to target applications;
Aim4. Evaluating drug delivery vectors for next generation biological therapeutics.
And Aim5. generation of complex tissues formed of distinct different regions, not achievable with current organoid protocols. These exemplify our wider ambitions for the Bio-HhOST approach including to, i) understand cell behavior in increasingly realistic 3D tissue models, ii) elucidate targets for the treatment of disease, and iii) enable the reduction of animal use in pharmacuetical research.
Bio-HhOST is building bio-hybrid materials that comprise living & artificial cells, in dynamic communication, such that artificial cells may influence the proliferation, differentiation and function of living cells. This will be accomplished by producing precision engineered, microscale, liquid and lipid bilayer-based, chemically compartmentalised artificial cells, co-localised with live cells. This is being done by an interdisciplinary team of biologists, engineers, mathematicians and entrepreneurs. The artificial cells will contain functional metabolisms, and the ability to respond to chemical stimuli in the environment to release signalling molecules, on demand, to regulate the neighbouring living cells, as found in complex biological tissues. These new chemically programmable organoid-synthetic tissues will enable a paradigm shift, in both ability to elucidate and control the complexity of physio-chemical interactions within 3D tissues, and reduce animal use in pharmaceutical R&D.
To achieve these ambitions we have designed an integrated multistage workplan driving towards the following overarching aims:-
Aim 1. Create 3D tissues where spatial regulation of living cell differentiation is determined by co-located (chemically programmable) artificial cells.
Aim 2. Regulate and maintain such 3D tissues by dynamic communication between live and artificial cells.
Aim 3. Develop multi-level, multi-approach models of organoid-synthetic tissues behavior. These will be applied to target applications;
Aim4. Evaluating drug delivery vectors for next generation biological therapeutics.
And Aim5. generation of complex tissues formed of distinct different regions, not achievable with current organoid protocols. These exemplify our wider ambitions for the Bio-HhOST approach including to, i) understand cell behavior in increasingly realistic 3D tissue models, ii) elucidate targets for the treatment of disease, and iii) enable the reduction of animal use in pharmacuetical research.
In the first reporting period, the consortium has initiated interdisciplinary research between all partners towards all five aims of the Bio-HhOST project highlighted above. This includes the framework for the hybrid living materials, as well as modelling and fabrication technologies for the creation of the Bio-HhOST constructs, their maintenance and evaluation. Development of artificial cell function aligned with cell needs and response has begun development together with methods of interfacing and evaluating. Important developmental and metabolic pathways have been identified and biomolecules screened for suitability for the Bio-HhOST system, with the development of workflows for production and evaluation. We have begun development of key molecular tools for Bio-HhOST communication which will enable functional programming. Review of modelling platforms, tools and approaches has been conducted and a comprehensive review of modelling platforms, tools, and approaches relevant to the Bio-HhOST framework has been documented and delivered. Furthermore, workflows were established to facilitate seamless data exchange across collaborating sites. Working groups have been established to ensure effective and efficient interplay, collaboration and scientific information exchange between partners and workpackages allowing dynamic and responsive problem solving and translation of advances within the project towards realisation of the protype targeted exemplars for realisation of aim five.
Key results are progressing towards realisation of Bio-HhOST prototype constructs and the development of methods for their evaluation, that will also facilitate further refinement, testing and development. Development of Bio-HhOST prototype constructs is a key enabler for realisation of the outlined applications in the context and background above. These next generation 3D tissue models are anticipated to make potential impacts for use in applications spanning fundamental research, developmental biology, drug screening, drug delivery vector evaluation - in the near to medium term, with longer term prospects in clinical applications including therapeutics and diagnostics, as well as next generation functional materials. The consortium has developed an exploitation plan on order to maximise key needs and opportunities to maximise chances of success. Research will continue in the next reporting period towards meeting technical aims one to five and the production of functional demonstrators, alongside exploration of IPR training and opportunity scoping for translational impact.