Monday, September 21, 2009

Progress in Tissue Engineering - Delivering Life’s Blood

One reason that tissues such as skin and cartilage were among the first to be ready for human testing is that they do not require extensive internal vasculature. But most tissues do, and the difficulty of providing a blood supply has always limited the size of engineered tissues. Consequently, many scientists are focusing on designing blood vessels and incorporating them in engineered tissues. Any tissue that is more than a few 100 microns thick needs a vascular system because every cell in a tissue needs to be close enough to capillaries to absorb the oxygen and nutrients that diffuse constantly out of those tiny vessels. When deprived of these fuels, cells quickly become irreparably damaged. In the past few years a number of new approaches to building blood vessels—both outside tissues and within them—have been devised. Many techniques rely on an improved understanding of the environmental needs of endothelial cells (which form capillaries and line larger vessels), as well as an advanced ability to sculpt materials at extremely small scales. For example, when endothelial cells are laid on a bed of
scaffolding material whose surface is patterned with nanoscale grooves—1,000th the diameter of a human hair—they are encouraged to form a network of capillarylike tubes. The grooves mimic the texture of body tissues that endothelial cells rest against while forming natural blood vessels, thus providing an important environmental signal.

Microfabrication, the set of techniques used to etch microelectronics chips for computers and mobile phones, has also been employed to make capillary networks. Vacanti, with Jeffrey T. Borenstein of the Draper Laboratory in Cambridge, Mass., has generated arrays of microchannels to mimic tissue capillary networks directly within degradable polymer scaffolds, for instance. Inside these channels, endothelial cells can be cultured to form blood vessels while also acting as a natural barrier that minimizes the fouling effect of blood on the scaffold materials. An alternative is to use a membrane filter to separate the blood-carrying channels from the functional cells in a tissue construct. Another method for keeping cells and blood separate but close enough to exchange a variety of molecules is to suspend them within hydrogels, which are gelatinlike materials made from hydrated networks of polymers. Hydrogels chemically resemble the natural matrix that surrounds all cells within tissues. The functional cells can be encapsulated inside the material, and channels running through the gel can be lined with endothelial cells to engineer tissue like structures with a protovasculature.

Research from the laboratories of Laura Niklason of Yale University and Langer has shown that larger blood vessels can be generated by exposing scaffolds seeded with smooth muscle cells and endothelial cells to pulsating conditions inside a bioreactor. Arteries made in this environment, which is designed to simulate the flow of blood through vessels in the body, are mechanically robust and remain functional after being transplanted into animals. In addition to enabling tissue engineers to incorporate such vessels into larger constructs, the engineered tubes by themselves may provide grafts for bypass surgery in patients with atherosclerosis.

Although the ability to engineer capillarylike structures and larger blood vessels outside the body is a significant breakthrough, a working engineered tissue implant will have to connect quickly with the recipient’s own blood supply if the construct is to survive. Coaxing the body to form new vasculature is therefore an equally important aspect of this work. David Mooney of Harvard University, for example, has demonstrated that the controlled release of chemical growth factors from polymeric beads or from scaffold material itself can promote the formation of blood vessels that penetrate implanted tissue constructs.

Pervasis Therapeutics, with which Langer and Vacanti are affiliated, is conducting advanced clinical trials in which a variation of this principle is applied to healing a vascular injury. A three-dimensional scaffold containing smooth muscle and endothelial cells is transplanted adjacent to the site of the injury to provide growthstimulating signals and to promote natural rebuilding of the damaged blood vessel.

Despite these advances, a number of challenges still remain in making large vascularized tissues and vascular grafts, and scientists have not yet completely solved this problem. New blood vessels grow and penetrate an implanted tissue construct slowly, causing many of the construct’s cells to die for lack of a blood supply immediately after implantation. For this reason, tissue-engineering approaches that include a vascular system prefabricated within the tissue construct are very likely to be necessary for large transplants. Such prefabricated vessels may also be combined with controlled release of blood vessel–recruiting growth factors to induce further growth of the construct’s vessels. Because integrating the engineered vasculatures and those of the host is also critical, researchers need a better understanding of the cross talk between the host tissue cells and implanted cells to foster their connection. This need to decipher more of the signals that cells exchange with one another and with their environments also extends to other aspects of building a successful tissue implant, such as selecting the best biological raw materials.

Source of Information : Scientific American(2009-05)

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