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B K Mann

Publications and source records attributed to B K Mann.

4 recordsLinked to original sources

Tissue engineering in the cardiovascular system: progress toward a tissue engineered heart.

Achieving the lofty goal of developing a tissue engineered heart will likely rely on progress in engineering the various components: blood vessels, heart valves, and cardiac muscle. Advances in tissue engineered vascular grafts have shown the most progress to date. Research in tissue-engineered vascular grafts has focused on improving scaffold design, including mechanical properties and bioactivity; genetically engineering cells to improve graft performance; and optimizing tissue formation through in vitro mechanical conditioning. Some of these same approaches have been used in developing tissue engineering heart valves and cardiac muscle as well. Continued advances in scaffold technology and a greater understanding of vascular cell biology along with collaboration among engineers, scientists, and physicians will lead to further progress in the field of cardiovascular tissue engineering and ultimately the development of a tissue-engineered heart.

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Tethered-TGF-beta increases extracellular matrix production of vascular smooth muscle cells.

Biomaterials developed for tissue engineering and wound healing applications need to support robust cell adhesion, yet also need to be replaced by new tissue synthesized by those cells. In order to maintain mechanical integrity of the tissue, the cells must generate sufficient extracellular matrix before the scaffold is degraded. We have previously shown that materials containing cell adhesive ligands to promote or improve cell adhesion can decrease extracellular matrix production (Mann et al., Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. Biomaterials 1999;20:2281-6). Such decreased matrix production by cells in tissue engineering scaffolds may result in tissue failure. However, we have found that TGF-beta1 can be used in scaffolds to dramatically increase matrix production. Matrix production by vascular smooth muscle cells grown on adhesive ligand-modified glass surfaces and in PEG hydrogels containing covalently bound adhesive ligands was increased in the presence of 0.04 pmol/ml (1 ng/ml) TGF-beta1. TGF-beta1 can counteract the effect of these adhesive ligands on matrix production; matrix production could be increased even above that observed in the absence of adhesive peptides. Further, TGF-beta1 covalently immobilized to PEG retained its ability to increase matrix production. Tethering TGF-beta1 to the polymer scaffold resulted in a significant increase in matrix production over the same amount of soluble TGF-beta1.

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Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering.

Photopolymerizable polyethylene glycol (PEG) derivatives have been investigated as hydrogel tissue engineering scaffolds. These materials have been modified with bioactive peptides in order to create materials that mimic some of the properties of the natural extracellular matrix (ECM). The PEG derivatives with proteolytically degradable peptides in their backbone have been used to form hydrogels that are degraded by enzymes involved in cell migration, such as collagenase and elastase. Cell adhesive peptides, such as the peptide RGD, have been grafted into photopolymerized hydrogels to achieve biospecific cell adhesion. Cells seeded homogeneously in the hydrogels during photopolymerization remain viable, proliferate, and produce ECM proteins. Cells can also migrate through hydrogels that contain both proteolytically degradable and cell adhesive peptides. The biological activities of these materials can be tailored to meet the requirements of a given tissue engineering application by creating a mixture of various bioactive PEG derivatives prior to photopolymerization.

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Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition.

The goal of the current study was to evaluate matrix protein synthesis by cells cultured on materials that had been modified with cell adhesion ligands. We examined the effects of surface peptide density and of peptides with different affinities on the extracellular matrix production of smooth muscle cells, endothelial cells and fibroblasts. While initial adhesion was greatest on the higher density peptide surfaces, all cell types exhibited decreased matrix production on the more highly adhesive surfaces. Similarly, when different peptides were evaluated, matrix production was the lowest on the most adhesive surface and highest on the least adhesive surface. These results suggest that extracellular matrix synthesis may be regulated, to some extent, by signal transduction initiated by adhesion events. This may pose limitations for use of bioactive materials as tissue engineering scaffolds, as matrix production is an important aspect of tissue formation. However, it may be possible to increase matrix production on highly adhesive surfaces using exogenous factors. TGF-beta was shown to increase matrix production by both smooth muscle cells and endothelial cells.

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