Surgical treatment of vascular disease has become common, creating the need for a readily available, small-diameter vascular graft. However, the use of synthetic materials is limited to grafts larger than 5-6 mm because of the frequency of occlusion observed with smaller-diameter prosthetics. An alternative to synthetic materials would be a biomaterial that could be used in the design of a tissue-engineered graft. We demonstrate that a small-diameter (4 mm) graft constructed from a collagen biomaterial derived from the submucosa of the small intestine and type I bovine collagen has the potential to integrate into the host tissue and provide a scaffold for remodeling into a functional blood vessel. The results obtained using a rabbit arterial bypass model have shown excellent hemostasis and patency. Furthermore, within three months after implantation, the collagen grafts were remodeled into cellularized vessels that exhibited physiological activity in response to vasoactive agents.

The morphology and behavior of polymorphonuclear leukocytes (PMNs) were studied after rapid changes in the concentration of a chemotactic factor Nformylnorleucylleucylphenylalanine (f-NorleuLeuPhe) (Schiffmann et al., 1975, Proc. Natl. Acad. Scf. U. S. A . 72:1059-1062 . After an increase in peptide concentration, the cells round, form lamellipodia or ruffles over most of their surface, and stop locomotion . These changes are transient . After a delay, the cells, still in the presence of peptide, withdraw most of the ruffles and resume locomotion, forming ruffles only at their front . Cells repeat the transient generalized ruffling upon further increase in peptide concentration. The behavioral changes occur over the same dose range as binding to a saturable receptor . The duration of the transient response after a concentration increase is roughly proportional to the increase in the number ofcell receptors occupied as a result of the concentration change . Decreasing the concentration of peptide causes the cells to round transiently and form blebs before they recommence locomotion . The transient nature of these aspects of the cell's responsiveness to chemotactic factors appears to be due to adaptation by the cells . The ability to adapt to the concentration of a chemotactic factor may be important in leukocyte chemotaxis .KEY WORDS motility spreading . chemotaxis " adaptation " polymorphonuclear leukocytes Chemotaxis, the orientation of movement along a chemical gradient, is an ability exhibited by a number of cells and organisms including bacteria, slime molds, and leukocytes. Thus far, the chemotaxis by bacteria is the best understood . Bacteria have been shown to respond to changes in concentrations of chemotactic factors by transiently altering the frequency of turns in their swimming . If the concentration of a chemotactic factor is increased, the frequency of turns decreases and the bacteria tend to swim with long paths between turns . If the concentration is decreased, the frequency of turns increases and the bacteria swim J . CELL BIOLOGY

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The binding of the chemotactic peptide N-formylnorleucylleucylphenylalanine (FNLLP) to its receptor on rabbit polymorphonuclear leukocytes (PMNs) modulates the number of available peptide receptors . Incubation with FNLLP decreases subsequent binding capacity, a phenomenon that has been termed receptor down regulation . Down regulation of the chemotactic peptide receptor is concentration dependent in both the rate and extent of receptor loss. The dose response parallels that of FNLLP binding to the receptor . The time-course _ is rapid ; even at concentrations ofFNLLP as low as 3 x 10 -9 M, the new equilibrium concentration of receptors is reached within 15 min . Down regulation is temperature dependent, but does occur even at 4°C.Concomitant with down regulation, some of the peptide becomes irreversibly cell associated . At 4°C, there is a small accumulation of nondissociable peptide that rapidly reaches a plateau . At higher temperatures, accumulation of nondissociable peptide continues after the receptor number has reached equilibrium, and the amount accumulated can exceed the initial number of receptors by as much as 300%. The dose response of peptide uptake at 37°C reflects that of binding, suggesting that it is receptor mediated . This uptake may occur via a pinocytosis mechanism . Although PMNs have not been considered to be pinocytic, the addition of FNLLP causes a fourfold stimulation of the rate of pinocytosis as measured by the uptake of [3 H)sucrose .Polymorphonuclear leukocytes (PMNs) are phagocytic cells that are able to exhibit chemotaxis to a variety of agents, including denatured proteins (34), bacterial products (14), oxidized lipids (29), cell-derived factors (27, 32), serum components, particularly C5a (13, 25, 31), and small formylated peptides (23,26) . The ability of PMNs to orient and move in chemotactic gradients provides a system in which two key biological problems can be studied : the sensory detection of chemical substances, and cell movement. We have used the chemotactic peptide, N-formylnorleucylleucylphenylalanine (FNLLP), to study the first step in J . CELL BIOLOGY

Diabetic complications such as neuropathy, retinopathy, and renal and cardiovascular disease continue to pose major health risks for diabetic patients. Consequently, much effort has focused on approaches that could replace conventional insulin therapy and provide more precise regulation of blood glucose levels. The biohybrid perfused artificial pancreas was designed to incorporate islet tissue and a selectively permeable membrane that isolates this tissue from the immune system of the recipient. Biohybrid pancreas devices containing canine islet allografts were implanted in ten pancreatectomized dogs requiring 18 to 32 units of injected insulin daily. These implants resulted in good control of fasting glucose levels in six of these animals without further exogenous insulin for periods of up to 5 months.