DATES

Cell culture is a process highly sensitive to stimuli and interactions with the extracellular matrix (ECM). These complex, heterogeneous and highly adaptive conditions are difficult to mimic in-vitro. In this sense, biomedical research adopts a multi- and interdisciplinary character in order to accurately replicate these conditions. Novel techniques, such as computational modeling, are essential to predict optimal culture conditions, supporting the design, monitoring, and analysis of experimental results in-vitro. 

During the design of advanced biomaterials, it is essential to know the local conditions of the cells. Stimuli acting on the cells must be orchestrated to obtain the desired response. In-silico modeling offers clear advantages in defining the conditions of the cellular microenvironment, which are complex to determine experimentally. 

In this project, a dynamically adaptive multilayer scaffold loaded with drug-delivery microcapsules is proposed. These microcapsules must be able to generate the desired stimuli at the right time. This involves a thorough analysis of the conditions of factor release and matrix degradation. These parameters will depend on the composition, size, and distribution of these microcapsules in the multilayer hydrogel ECM. For the correct formulation and calibration of computational models, it is necessary to collect information on the properties and characteristics of both materials and cells. The collaborative and interactive analysis between the different groups of the project is essential for the correct development of the computational model. 

From a methodological perspective, computational modeling of spinal cord, cartilage, and multiple myeloma cells presents significant challenges. This is due to the complex conditions of the cellular environment and the heterogeneity of the cell populations. The cellular environment, composed of a dynamically adaptive multilayer microenvironment loaded with drug-delivery microcapsules, presents a high degree of complexity. The situation is further complicated when we consider multiple stimuli such as mechanical, electrical, thermal, and/or magnetic stimuli acting simultaneously. Currently, in the literature, there is no model that considers the multi-scale, multi-physics, multiphase, multi-class environment proposed in this project. By employing the proposed model, simulations can be performed in reasonable times, which allows the construction of virtual laboratories (digital twins), greatly reducing the time and material costs derived from in-vitro and in-vivo testing. 

The project covers several objectives such as: 

• Develop computational tools for the predictive analysis of key factors in the evolution of multiple myeloma and cartilage, and spinal cell growth; 
• Generate new knowledge from the development of original hypotheses and theories that can explain the in-vitro and in-vivo behavior of these cell types; 
• Exploitation and development of emerging technologies, such as active hydrogel bioreactor platforms with multilayer scaffold charged with microcapsules of factors with controlled release; 
• Analysis of the paracrine effect in multiple myeloma cells and acquisition of drug-resistant phenotypes.