Growth-Factor Delivery in Tissue Engineering
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Delivery in Tissue Engineering W. Mark Saltzman
Introduction Soluble signaling proteins called growth factors* execute critical functions during the formation of specialized tissues throughout the developing embryo. When growth factors are provided to adult animals, they often encourage regeneration or repair of organs damaged by disease or trauma: Basic fibroblast growth factor (bFGF) and transforming growth factor /3i (TGF-JSJ) encourage wound healing1-2 hematopoetic growth factors stimulate the production of blood cells/ bone morphogenetic proteins (BMPs) induce bone formation,4 nerve growth factor (NGF) enhances the survival of degenerating cholinergic neurons,5,6 and angiogenic growth factors activate new blood-vessel growth.7 Our understanding of the role of growth factors in development and regeneration should continue to expand dramatically over the next decade, inasmuch as new molecules (and new activities for known molecules) are appearing at a rapid rate. Protein growth factors may be useful in augmenting the new approaches for tissue engineering.8,9 Modern biotechnology permits the large-scale manufacture of highly purified proteins so that large quantities can be produced for use in humans. However proteins are often exceedingly difficult to administer, particularly if sustained levels are required. Most protein growth factors have short half-lives after intravenous injection, with their biological activity lasting only *The wide variety of molecules mentioned in this article belong to several important families of proteins, which can be classified according to structural homologies or biological activities. In the interest of simplicity, I refer to this large, heterogeneous group of molecules as "growth factors," intending only to indicate their potential utility in the encouragement of tissue regrowth or regeneration.
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a few minutes in the circulation, so that injection must be repeated frequently to obtain sustained blood levels (Table I). Since these molecules are large, they penetrate tissue barriers, such as the capillary wall, very slowly. In addition, growth factors are extremely potent, often possessing biological activity at a number of tissue sites throughout the body. Therefore systemic administration can lead to toxicity. In view of these difficulties, new methods for growth-factor delivery are needed. The most promising new methods involve polymers, which can be engineered to provide precisely controlled, prolonged growth-factor delivery at a localized site.
Polymer Matrices for Controlled Release Local delivery of growth factors can be accomplished by encapsulating the protein within a biocompatible polymer matrix or microsphere. The controlledrelease polymer system is then implanted at the desired tissue site where it releases the soluble factor directly into the interstitial space of the tissue (Figure la). The diffusible growth factor may influence survival or function of damaged cells within the local tissue or provide a signal that elicits cell proliferation or migration withi
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