Growth & Remodeling
Predicting the Growth and Remodeling of Living Matter
Living matter is not a passive material. A blood vessel wall, a hydrogel seeded with cells, a growing tissue: all are active networks whose architecture is continuously rewritten by encapsulated cells. Cells can proliferate, collagen fibers are continuously deposited and degraded, crosslinks form and dissolve, and the mechanical state of the material feeds back onto the biological processes that shape it. The result is a material that is simultaneously a mechanical structure and a living system: one that can grow, adapt, and, under the wrong conditions, catastrophically fail.
Understanding this behavior requires more than classical mechanics. It demands a framework that can account for the continuous turnover of network constituents, the anisotropy that emerges from cell-directed fiber deposition, the coupling between mechanical stress and biological activity, and ultimately the conditions under which remodeling gives way to damage and rupture. Our research develops that framework, grounded in the statistical mechanics of transient networks.
Tissue evolution (red) in a chondrocyte (green)-laden degradable hydrogel (black)
Programming Engineered Living Matter
Engineered living materials represent a fundamentally new class of matter: living continua whose growth, form, and function can, in principle, be programmed. Realizing that potential requires digital twins: predictive computational models that can explore growth scenarios in silico before they are implemented in the lab. Taken further, this opens the possibility of reverse-engineering growth itself: decoding the biological rules that govern form, and rewriting them to produce materials with targeted architectures and functions.
A single colony of bacteria or a small tissue aggregate contains thousands to tens of thousands of cells. At this scale, individual tracking is impractical, but the collective behavior of the population can be described by smooth, continuous fields. Using a mean field approximation, the behavior of the population reflects that a representative cell: i.e. it expands, divides, pushes its neighbors, and responds to chemical and mechanical signals from its environment. This continuum picture naturally leads to a set of evolution equations that track how the density, deformation and composition of the colony change in space and time.
A key feature of cell populations is that growth is pressure-sensitive: compression inhibits cell division, while tension promotes it. Simultaneously, cells consume nutrients (oxygen, glucose) that must diffuse through the colony from its boundaries. Where nutrients are abundant and pressure is low, cells proliferate; where nutrients are depleted or compression is high, growth stalls and cells may die. It is the feedback between transport, mechanics, and reaction that gives rise to spontaneous pattern formation such as surface instabilities, fingers, buds, and other complex morphologies. The goal of our computational models is to harness these complex mechanisms, that it, to understand them well enough to tame them, and turn spontaneous pattern formation into a design tool.
Living Tissues as Remodeling Networks: From Homeostasis to Disease
Few engineering materials can match what blood vessels do routinely: sustain cyclic mechanical loading over an entire lifetime, adapt continuously to changing physiological conditions, and self-repair following injury. The wall of an artery is a living network of collagen and elastin fibers, organized into complex anisotropic architectures that are continuously maintained, remodeled, and adapted by embedded smooth muscle cells and fibroblasts. Under normal conditions, this mechano-biological feedback keeps the tissue in a state of mechanical homeostasis. Fiber deposition and degradation are balanced, and the architecture is continuously tuned to sustain the cyclic pressure imposed by blood flow. But homeostasis is not guaranteed, and when it breaks down, the consequences can be catastrophic.
Aneurysms represent one of the most dramatic examples of what happens when tissue remodeling goes wrong. Rather than appearing suddenly, an aneurysm grows through a slow, self-reinforcing process: disturbed blood flow weakens the vessel wall, which dilates, which further disturbs flow. This feedback loop can silently progress over years before culminating in rupture. Predicting which aneurysms will rupture remains one of the most pressing unsolved problems in vascular medicine.
From a modeling perspective, the difficulty lies not in any single piece of the puzzle, but in their interaction. Fluid mechanics, tissue remodeling, and cell biology are inseparable threads of the same process, yet they have traditionally been modeled in isolation, leaving the emergent instability that drives aneurysm progression largely unexplained. Our research addresses this challenge by treating the arterial wall as a living fiber network whose architecture continuously evolves under the coupled action of mechanical loading and cellular activity. In this picture, aneurysm growth is not a material failure in the classical sense. Rather, it is a dynamical instability of a living system driven out of its healthy remodeling state (or homeostasis). Understanding what triggers that transition, and what could reverse it, is the central question driving our research.
Open Questions & Current Directions
In summary, we develop bottom-up models that explicitly incorporate the feedback between tissue mechanics and cell mechanobiology to predict the growth and remodeling of engineered living materials and biological tissues alike. Below are the key questions we aim to address:
How Do Living Materials Sense, Respond, and Evolve?
Cells probe their mechanical environment, remodel the surrounding network, and alter the very state they sense. We aim to develop dynamical models that couple network mechanics and biological response to predict how architecture and properties evolve, in living tissues and engineered living materials alike.
When Does Remodeling Become Disease?
In blood vessels, pathological remodeling can silently progress toward aneurysm formation and rupture. We aim to model and identify the mechanical signatures of this degenerative process before it reaches the point of irreversible failure.
Can We Guide the Growth of Engineered Living Materials?
We develop computational models, coupling transport, mechanics, and mechano-biology, integrated with experimental data, to guide the growth of living systems. Our goal is to provide a predictive framework for tissue regeneration, disease treatment, and the design of bio-produced materials from bacteria and fungi.