Tissue Fabrication: Reconstitution and Remodeling in Vitro

Abstract

ABSTRACTTwo approaches to the reconstitution of tissues and organs are reviewed. The first consists of imitating the architecture of actual tissues and organs by combining cultured specialized cells with extracellular matrix components to produce a connective tissue substrate on or in which epithelial, mesothelial or endothelial cells can be plated or seeded and subsequently differentiate into mono or multilayered tissues and other structures. The second consists of providing an acellular framework of extracellular matrix constituents that can be occupied by adjacent host tissues after implantation in vivo and be remodeled by them to resemble the host tissues it is designed to replace. A paradigm for events in vivo, designed to study the process of remodeling of acellular matrices in vitro has been developed. The living skin equivalent (LSE), an example of a product fabricated using the first approach to tissue engineering, has been adapted to study events of extracellular matrix remodeling, relevent to the second approach to tissue engineering. After creating a disc shaped wound bed in an LSE, the wound is filled with a collagen matrix with or without added supplements and the process of epidermal wound closure and associated events in the dermis are followed. It is shown that fibroblast conditioned medium or a simple molecule such as ascorbic acid, added with no additional growth factors to the collagen matrix used to fill the wound bed, strongly stimulates the process of repair. Dermal fibroblasts from the adjacent tissue invade the collagen lattice that forms in the wound bed, and keratinocytes recruited from the wound edge overgrow the new dermal tissue. The applicability of the paradigm to the repair of vascular and other tissues will be discussed and approaches to optimizing the composition of acellular constructs considered.