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Regeneration of functioning tissue essentially involves recapitulating relevant aspects of organogenesis, so that the starting composite of cells, matrix, and molecular factors develops into the desired structure and physiology. A crucial aspect of development is local cell-cell communication; that is, molecular regulatory factors are more typically paracrine and autocrine than endocrine in nature. Autocrine loops were originally thought of predominantly as being involved in pathological behavior, but it is becoming increasingly clear that a large portion of normal physiological behavior-and a tremendous portion of development-is strongly regulated by autocrine factors (1). Thus, continuing progress of the field of tissue engineering will require increased understanding of how autocrine loops operate, so that they can be designed or manipulated systematically. We have made an effort in this direction, and some early experimental and modeling results can be found in the literature (2-5). In this chapter, we describe the methods we have used for creating autocrine cell loops and quantitatively assessing their operation.

Peptide growth factors and other receptor-binding cytokine ligands are of interest in contemporary molecular health care approaches in applications such as wound healing, tissue regeneration, and gene therapy. Development of effective technologies based on operation of these regulatory molecules requires an ability to deliver the ligands to target cells in a reliable and well-characterizable manner. Quantitative information concerning the fate of peptide ligands within tissues is necessary for adequate interpretation of experimental observations at the tissue level and for truly rational engineering design of ligand-based therapies. To address this need, we are undertaking efforts to elucidate effects of key molecular and cellular parameters on temporal and spatial distribution of cytokines in cell population and cell/matrix systems. In this article we summarize some of our recent findings on dynamics of growth factor depletion by cellular endocytic trafficking, growth factor transport through cellular matrices, and growth factor production and release by autocrine cell systems. (c) 1996 John Wiley & Sons, Inc.