On the research side, this project aims to develop experimentally guided, hybrid multiscale models and methods to study complex biological systems and problems arising in biomaterials and bioengineering (a) sprouting angiogenesis during vascularization; (b) bacterial swarming during biofilm formation. This research will have many benefits to multiscale problems and relevant applications in biomaterials, tissue regeneration and biomedical engineering, which include bioprinting technology for fabricating tissues and organs, study of cell motions, drug design and ultimately regenerative medicine. These methods can be used as hypothesis generating and testing tools for biologists and bioengineers. Through collaboration with experimentalists, the PI will develop a hybrid multiscale approach to better understand complex mechanisms in the vascularization and the biofilm growth. On the educational side, this project will not only provide multidisciplinary research training to graduate and undergraduate students, but also promote awareness and interest in computational mathematics and mathematical biology among underrepresented minority groups.
For the thrust (a), motivated by new findings in sprouting angiogenesis in bioprinting technology, the PI will integrate models for angiogenic signaling pathways with that for the mechanical motion. In particular, we employ typically coarse-grained continuum models (reaction-diffusion (RD) systems) to describe the dynamics of vascular-endothelial-growth-factor (VEGF) and nutrients/oxygen, a mechanical model for the extra-cellular matrix (ECM) based on the finite element method (FEM), and couple a discrete multicellular lattice model based on the kinetic Monte Carlo (KMC) algorithm to describe the cellular dynamics. Communication between the microscale model and the continuum ones is carried out via a suite of multiscale protocols. For the thrust (b), the PI will study several mechanisms responsible for bacterial swarming during biofilm formation, such as bacterial chemotaxis, interaction between bacteria, bacterial shapes, etc. In the proposed hybrid agent-based model, bacteria are characterized by self-propelled particles (SPP) or self-propelled rods (SPR) and the dynamics of extracellular polymeric substances (EPS) in the environment is described by continuously changing fields. The multiscale model is described by a system of ordinary and partial differential equations. The research outcomes consist of a set of hybrid multiscale models, detailed implementation of the models, and accompanying in silico analysis tools for simulating tissue formation and ultimately 3D biofabrication involving angiogenesis and vascularization. The tools can provide efficient ways to systematically test the influence of individual cellular features under a spectrum of environmental conditions and to study the collective behavior of bacterial colonies.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
