Research Areas : Basic Biology

Thrust Two: Basic Biology

The general goal of Thrust 2 is to contribute biologically derived approaches to the development of biomaterials that heal so that the non-specific responses of the body, characteristic of todayÕs biomaterials, can be replaced by responses that more closely mimic those present in normal tissue. Biomaterials that heal are defined as those that achieve improved acceptance and integration when implanted in the body.

Thrust 2 investigators pursue this goal in five ways. First, they use state of the art biological methods to help develop base biomaterials that exhibit lowered interaction with the body. Second, they discover and define biomolecules that are involved in tissue response to implants, including foreign body capsule formation and blood vessel formation. Third, they define and develop biologically relevant animal model test beds for the improved biomaterials. Fourth, they work with Thrust 1 investigators to optimally immobilize the biomolecules or to deliver agents to affect the function of the biomolecules. Thrust 2 investigators also work with Thrust 3 investigators using clinically relevant human testbeds to further evaluate the materials. New efforts to make tissue engineered heart valves are also underway.

Many of the efforts under Thrust 2 are attempts to understand and alter the signal/noise ratio in implants. In the signal/noise model of the foreign body reaction, "noise" refers to reactions to inappropriate, non-specific signaling mechanisms. To the best of anyoneÕs knowledge, this noise emanates from the non-specific adsorption of proteins to the foreign material. For example, adhesion and activation signals are sent to the surrounding and invading cells by the adsorption of adhesion proteins to the surface of the foreign implant. Adsorption of adhesion proteins to normal tissue does not occur. Adhesion protein adsorption to foreign surfaces creates an aberrant, unnatural interface that is attacked by the body.

To reduce the "noise", Thrust 2 investigators have developed several materials intended to reduce non-specific protein adsorption. To raise the "signal", Thrust 2 investigators have identified a number of proteins that affect foreign body capsule and blood vessel formation around implants. A major contribution of Thrust 2 has been the use of knock out mice to identify proteins involved in controlling the foreign body reaction.