Enterocyte transplantation using cell-polymer devices to create intestinal epithelial-lined tubes.
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ABSTRACT: The development of sufficient vascularization to maintain adequate perfusion is a primary consideration in the engineering of large tissue constructs. This research investigated the ability of aortic endothelial cells to affect the organization of vascular structures within a matrix both in vitro and in vivo. Highly porous matrices of poly(glycolic) acid (PGA) (50 mg/cc) 10 × 10 × 3 mm meshes were implanted subcutaneously (two per rat) in inbred rats, with and without syngeneic cells. Test groups (n = 8/group) were: PGA; PGA with aortic endothelial cells; PGA with aortic smooth muscle cells; PGA with skeletal muscle cells. Matrices were evaluated histologically from two rats per week at weeks 1,2,3, and 4. Scanning electron microscopy was done on matrices prior to implantation. Matrices without cells demonstrated typical ingrowth of host fibroblasts, capillaries, and macrophages/giant cells. Matrices containing skeletal muscle or aortic smooth muscle cells showed similar vascularization to matrices without cells. The implanted muscle cells demonstrated cellular growth with little organization. Matrices containing aortic endothelial cells demonstrated organized and unorganized endothelial cells within the matrix, increased numbers of capillaries, increased numbers of lymphatic-like structures, and numerous heterogeneous and unusual vascular structures which were positive for factor VIII localization including: 1) large parallel arrays of capillaries, 2) large thin sinusoidal vascular structures, and 3) layered complex vascular structures. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/63290/1/ten.1997.3.149.pdfTissue Engineering 06/1997; DOI:10.1089/ten.1997.3.149 · 4.25 Impact Factor
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ABSTRACT: A critical need in both tissue-engineering applications and basic cell culture studies is the development of synthetic extracellular matrices (ECMs) and experimental systems that reconstitute three-dimensional cell-cell interactions and control tissue formation in vitro and in vivo. We have fabricated synthetic ECMs in the form of fiber-based fabrics, highly porous sponges, and hydrogels from biodegradable polymers (e.g., polyglycolic acid) and tested their ability to regulate tissue formation. Both cell seeding onto these synthetic ECMs and subsequent culture conditions can be varied to control initial cell-cell interactions and subsequent cell growth and tissue development. Three-dimensional tissues composed of cells of interest, matrix produced by these cells, and the synthetic ECM (until it degrades) can be created with these systems. For example, smooth muscle cells can be grown on polyglycolic acid fiber-based synthetic ECMs to produce tissues with cell densities in excess of 10(8) cells/mL. These tissues contain extensive elastin and collagen, and the smooth muscle cells within the tissue express the contractile phenotype (e.g., alpha-actin staining). Similar approaches can be used to grow a number of other tissues (e.g., dental pulp) that resemble the native tissue. These engineered tissues may provide novel experimental systems to study the role of three-dimensional intercellular signaling in tissue development and may also find clinical application as replacements to lost or damaged tissues.Annals of the New York Academy of Sciences 05/1998; 842:188-94. · 4.31 Impact Factor
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ABSTRACT: Highly porous matrices of poly-L-lactide (PL) and polyglycolide (PG), 24, 50, or 95 mg/cc in the form of 10 x 10 x 3 mm wafers, were implanted subcutaneously (two per rat) in the flanks of 8-12-week-old female Lewis rats (n = 120). Matrices were harvested, two rats per week, for 15 weeks and examined histologically. At weeks 1 and 2, a thin fibrous capsule was present and matrices showed capillary beds and host-cell infiltration along the implant margins. By week 4, the PL specimens had some arterioles while the PG specimens still had only capillary beds. At week 7, PL had well developed arterioles, venules, and capillaries while PG began to show modest vascular beds of capillaries only. In terms of cellular ingrowth, PL remained unchanged from 7 to 15 weeks. Giant cell formation was observed wherever polymer was present. There was a loss of thickness and cell mass for both matrices over time (PG > PL) despite initial host-cell ingrowth. As both polymers degraded and were absorbed, the ingrown cells mass regressed. There was little remaining PG at 15 weeks, leaving no trace of cells that previously had ingrown and no evidence of scar tissue.Journal of Biomedical Materials Research 09/1998; 41(3):412-21.