The Impact of Biomaterials Research on Tissue Engineering

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The Impact of

Biomaterials Research on Tissue Engineering Charles A.Vacanti

The following article is an edited transcript of a presentation given as part of Symposium X, Frontiers of Materials Research, on November 29, 2000, at the 2000 MRS Fall Meeting. The three most important components of tissue engineering are biomaterials, cellular biology, and vascular supply. Biomaterials are needed to control the delivery of new cells into the body. In the absence of biomaterials, cells that are injected into a vein, a cavity, or tissue tend to disperse, so a sufficiently high density of cells to perform the intended function—replacement or repair of a damaged structure—is never achieved.1 A porous delivery system is needed that confines the cells to the desired location and promotes their nourishment until blood vessels grow in and new tissue is formed. Biomaterials such as plastics can provide such a porous delivery system. Over the years, scientists have used offthe-shelf products as biomaterials. For example, artificial hearts were made from a material taken from women’s girdles. Sausage casings and cellulose were used for dialysis tubing, and the same nylon that went into clothing was used for vascular grafting. This strategy, born of necessity, was employed with some success. Following suit, the first polymer scaffolding that we used successfully was made from an off-the-shelf vicryl suture material consisting of a copolymer of poly(lactic acid) (PLA) and poly(glycolic acid) (PGA).2 One end of the suture could be frayed in order to supply a large surface area on which cells could attach. Nutrients were able to diffuse through the spaces between the fibers to keep the cells alive. In one instance, we isolated cartilage cells from a cow and placed them on suture material under the skin of a nude

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(hairless) mouse. Normally, cells in a culture dish will flatten out, undesirably, into a monolayer. However, in this experiment, the cells attached in multiple layers and remained spherical, which was necessary for them to perform their differentiated functions. After several days, cells started to bridge the gaps between fibers, creating a matrix of new cartilage tissue (Figure 1). With the high porosity of this tissue, nutrients were able to diffuse through it until blood vessels could develop. Not only was the suture material biocompatible, it was also biodegradable. The scaffolding eventually dissolved, leaving behind new tissue in the shape of the implant. This was the first successful generation of cartilage tissue. We then started to explore other materials, such as alginic acid,3 a derivative of seaweed. We placed an even suspension of cells in this material; oxygen and nutrients were able to diffuse through it. When calcium was added, it became ionically cross-linked, forming a gel that works well

Figure 1. Chondrocytes seeded among fibers of polyglycolic acid generate a matrix of new cartilage tissue after three weeks.

with osteocytes. We also experimented with hydrogel pluronic, consisting of a copolymer o