Simulating a Scaffold for Bone Growth

Using a 3-D computer model, scientists have simulated stem cells growing within a scaffold to predict which combination of  properties will produce the most bone

Designing a scaffold, the internal structure that helps patients regenerate bone, is a delicate balancing act. The scaffold must be strong enough to protect the injury, porous enough to allow nutrients to pass through, and fast-dissolving enough to make room for new tissue. Now, using a 3-D computer model, scientists have simulated stem cells growing within a scaffold to predict which combination of these properties will produce the most bone.


“It’s the first 3-D computational work that takes account of stem cells” in scaffold design, says senior author Patrick J. Prendergast, PhD, a professor of bioengineering at the University of Dublin, Trinity College.


Patients rely on scaffolds to support bone regeneration after surgeries such as bone grafts, cartilage repair, or tumor removal that requires bone to be cut away. Most scaffolds are either made of gels, which tend to be weak, or stiffer materials such as coral, which may not completely dissolve. In the past, scientists evaluated scaffold materials by testing them on animals. At the same time, computational biologists devised algorithms predicting how a patient’s stem cells might differentiate into new types of tissue during healing. But until now, no one had simulated the scaffold alongside the stem cells as a way of improving scaffold design.


Granulation tissue (red), a mixture of tissue matrix and cells that develops early in wound healing, fills a bone regeneration  scaffold (green) that’s 50 percent porous. Zooming into small portions of the tissue, we see a lattice (grey) containing stem cells, which multiply and develop into new tissue (blue) that replaces the dissolving scaffold. Courtesy of Damien P. Byrne. This article was published in Biomaterials, Volume 28, Damien P. Byrne, Damien Lacroix, Josep A. Plannel, Daniel J. Kelly, Patrick J. Prendergast, “Simulation of tissue differentiation in a scaffold as a function of porosity, Young’s modulus and dissolution rate: Application of mechanobiological models in tissue engineering,” p. 5544-5554, Copyright Elsevier (2007).Prendergast’s group created a 3-D computer lattice model of a scaffold, then planted “seeds” inside the lattice to represent the patient’s stem cells. In their simulations, the cells multiplied, spread, and eventually transformed into bone, cartilage, or connective tissue depending on the strain and fluid pressure affecting each cell.


Meanwhile, the program tracked the progress of the scaffold as it slowly dissolved and became more porous, clearing room for new tissue. The scientists tried various combinations of scaffold properties and tested the system under high and low load-bearing conditions to simulate injuries in different parts of the body. A leg bone, for instance, bears more load than an arm bone and might heal differently.


The researchers found that the scaffold only works if it has the right balance of pore size and disintegration rate. If both are too high, “It won’t be long before the whole thing dissolves away,” says Prendergast. They also found that the load on the area changes how scaffolds perform, suggesting that scaffold designers should tailor their materials for specific patients and body parts. The work appears in the December 2007 issue of Biomaterials. Studying the interplay between cells and synthetic materials is promising because most people focus on only one, says Christopher Jacobs, PhD, director of the Cell and Molecular Biomechanics Laboratory at Stanford University. “I think that’s a very creative concept,” he says. The work needs to be verified with further experiments, says Jacobs, but could potentially direct the design of better scaffolds that both offer enough support and dissolve completely into the body.


Toward that end, Prendergast and his colleagues plan to simulate blood vessels growing in scaffolds, which can affect bone regeneration.


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