Ross Anderson with Harihara Baskaran, Jean Welter & Robert Brown

Modeling Oxygen Diffusion Through an Inhomogeneous Growing Cartilage Matrix

 
Once cartilage, a cushioning tissue in a joint, has failed, the mobility of the patient is significantly inhibited due to pain caused by bone-bone interaction. Cartilage lacks a vascular system, and the ability to mobilize repair cells, and thus da ma ge is cumulat ive . The current solution is to replace the joint with a plastic-metal composite prosthetic joint.  These can last up to 20 years without maintenance, but for younger patients this is not a permanent solution, and usually ends the career of athletes.  Biological cartilage repair may make it possible to delay or prevent prosthetic replacement, restore mobility, and to some degree , athletic ability.

 
This project focuses on a critical tissue engineering problem found in the artificial construction and replacement of joint cartilage. Specifically, it is currently very challenging to grow large sections of cartilage because the interior can not be properly supplied with nutrients. Two parallel approaches to this problem are to improve delivery of nutrients to the construct and to reduce the demands of the cells inside. We are studying the first approach in this project by using a combination of a biological model system and computer modeling to understand the diffusion of oxygen and nutrients into a growing cartilage disk. In the biological system, we induce stem cell differentia tion to create cartilage cells through a series of manipulations. Stem cells have much higher metabolic demands than cartilage cells. C omputer modeling of oxygen diffusion into the cartilage will help us understand the needs of the se cells during the transition from stem cells to cartilage cells. Using the finite element modeling program Femlab (Comsol, Burlington M assachusetts ), we have created a baseline model of our bioreactor system and the growing cartilage construct, illustrating diffusion through the cartilage construct as a function of time. The model is based on the Navier-Stokes e quations describing momentum balance and Fickian diffusion equation describing species transport. We intend to enhance this basic model by varying the diffusivity of the construct in the model as a function of time and space, and including functions for time dependent species consumption. Experimental verification will be accomplished by using a fiber optic oxygen sensor system to measure the concentration of oxygen at specific points in the construct.

The computer model developed in this project will define the oxygen requirements of the construct under a variety of culture conditions and will allow us to predict the effects of modifications to the bioreactor system.