Gradient Scaffolds for Tissue Engineering

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Richard Koepsel, PhD

University of Pittsburgh

Biomaterials have been used in the medical community for various applications ranging from artificial hips, to heart valves, and skin grafts. These materials have allowed individuals to reap many benefits, from increased mobility and organ function to the purely cosmetic. There is a constant ongoing effort to improve the performance of biomaterials with respect to biological compatibility and activity.

Although the incorporation of biomaterials into the medical community has resulted in a number of benefits, many limitations still exist. For example, artificial hip implants are not permanent and are not expected to last the recipient’s lifetime but the working life of such devices continues to increase as new materials and procedures are developed. A brief look at the development of the artificial hip demonstrates a number of the issues generally encountered in the development of integrative biomaterials.

Two types of prosthetic hips are currently used the original version which are cemented in place with an adhesive and the newer cementless artificial hips which depend on bio-integration to achieve stability. Cemented hips were first introduced in 1938 and continue to be implanted today (Peltier 1998). These prosthetic devises are currently fabricated from high molecular weight polyethylene (Peltier 1998) or so called super alloys such as cobalt-chromium based alloys (Jasty 1998). These are attached directly to the hipbone and the femur by a fixation bone cement polymethyl- methacrylate (PMMA). The working life of a cemented artificial hip is about 15 years for the femoral component and 10-12 years for the acetabular part (Jasty 1998). While this is considered a good outcome there is still concern that the cemented joint does not adequately model the natural joint. The ideal for tissue integration would be a seamless, continuous transition from the natural biological material (in this case bone) and the introduced prosthetic device. This type of integration has the potential to last the lifetime of the recipient.

Cementless artificial hips were first introduced clinically in the 1980’s (Bojescui et al 2003). They differ from the cemented artificial hips in that the femoral and acetabular (hip) components are coated with a porous material to promote bone in growth. The most common coatings are sintered cobalt-chromium alloy and sintered titanium, which provide a porous surface for bone in growth (Kienapfel and Griss 1998). The cementless prosthesis thus relies on bone growth and not an adhesive to incorporate the implant into the body. A long-term clinical study on the use of the cementless hip replacements is showing encouraging results. After fifteen years, the study has shown that the average lifetime of the femoral component was 10.6 years and the acetabular component 11.0 years before surgical revisions were necessary (Bojescui et al 2003). This compares well to the cemented hips. It should be noted that this result is for the first generation cementless prosthesis and is unlikely to be the best achievable result. Advances in biomaterial integration are likely to improve results in other areas as well.

The same concept of biointegration could also be applied to medical applications in which a permanent or semi-permanent catheter is implanted in the body to assist in the transport of materials across barrier of the skin. Currently an adhesive is used to bind the skin to this percutaneous tubing. However, over time the mechanical union between the two weaken and eventually the skin pulls away from the tubing. In order to increase stability steps have been taken to increase the integration of the device with the surrounding skin. The tubing has been coated with Dacron, which acts as a support scaffold for the in growth of skin cells. While this should work in theory, because the Dacron is biologically inert, it does not allow for sufficient cellular in growth and the skin still pulls away (Bojescui et al 2003; Houel et al 1999; and Holman et al 2003).

The question to answer is, can tissue scaffolding be created which will allow for the binding of skin to percutaneous tubing in a manner analogous to the artificial hip binding to the bone? Dr. Koepsel proposes that a tissue-engineered scaffolding can be designed so that skin and tubing are united in a mechanically strong union. He will do test this hypothesis by synthesizing gradient scaffolds. These gradient scaffolds will be composed of two biomaterials, one that will rapidly degrade and another that is nearly or completely nondegradable.