Teruo Miyata

Collagen engineering for biomaterial use

Collagen is a typical biological macromolecule having been utilized for a long period of time as a material like cellulose. However, its application is becoming comprehensive, ranging from classical applications such as the leather, gelatine and food industries to the current one, namely, biomaterial and biotechnological uses. The diversification of collagen applications was enhanced by two factors, the accumulation of the scientific knowledge that permitted proper engineering of collagen for a biomaterial use, and the demand for new biomaterials with characteristic biological properties including interaction with cells. The collagen engineering described in this paper is designed for biomaterial use, based on the fundamental chemical and biological properties of collagen; however, it would be useful also for other applications apart from biomaterials.

Aortocoronary Bypass Grafting with Hydrophilic Small Caliber Vascular Grafts

Previous work showed that the authors vascular graft had satisfactory antithrombogenicity because of high hydrophilicity. The authors developed a small-caliber xenograft using new technology and evaluated the potential application for aortocoronary bypass grafting. Fresh sheep carotid artery with an internal diameter of 3 mm was obtained, and cross-linked with hydrophilic polyepoxy compounds. A 6 cm segment of the graft was then used between the aorta and the left circumflex coronary artery without cardiopulmonary bypass in 17 dogs. Sodium heparin was given during the surgery, but no anticoagulant was used thereafter. After the surgery, the dogs were randomly assigned to two groups according to the observation period. In 11 animals (Group 1), the observation period was up to 24 hr, at which time the grafts were evaluated; the patency rate was 72.7%. The patent grafts were clean and without thrombi. At the distal anastomotic lines of the occluded grafts, a thrombus was observed and a technical error was highly suspected. In six dogs (Group 2), angiography was performed to confirm graft patency between 2 and 3 weeks. The patency rate was 50% during the mean observation period of 17.5 days. One graft was evaluated at postoperative day 23. It was patent and soft, and the inner surface was shiny and smooth. Microscopic observation showed nice healing characteristics. These results indicate that it is possible for this new graft to be used for aortocoronary bypass grafting.

Antiadhesive Collagen Membrane with Heparin Slow Release

A collagenous antiadhesive membrane with slow heparin release was tested in animal studies and found to exhibit antiadhesion activity. The antiadhesive membrane was prepared by crosslinking protamine to purified human amnion and then ionically binding heparin to the protamine. The amount of bound heparin was proportional to the protamine content in the collagen. The heparin was found to slowly release in vivo over a period of one month. The heparinized amnion was evaluated in canines. A portion of the serous membrane was removed from the intestine and the heparinized amnion was sutured onto the site. Observations up to 687 days after surgery revealed that the heparinized amnion showed satisfactory antiadhesion efficacy. Mesothelial cell proliferation lining on the site and normal wound healing was observed with no scar formation. The amnion was incorporated into the tissue and grad ually resorbed. In contrast, all unheparinized amnion controls showed consid erable adhesion and severe scar formation with distortion of the healed in testine. Two out of the four control dogs died of intestinal obstruction.

Long-term evaluation of a growable graft

The safety of a vascular graft that can grow with the growth of its recipients was evaluated during long-term implantation in experimental animals. An acellular matrix made of human saphenous vein was cross-linked with a polyepoxy compound to give controlled biodegradability, hydrophilicity, and antithrombogenic properties. Four millimeter internal diameter (ID) grafts, enveloped with a polyester mesh tube of 10 mm ID were implanted in 15 puppies. The diameter of the graft grew to 9.5 mm after 1 year from the original 4 mm, and remained stable for 2 years and 7 months of observation. The newly formed neointima reinforced with polyester mesh was composed of smooth muscle cells covered with endothelial cells. The original vein graft was completely absorbed, and there were no degenerative changes such as calcification or aneurysmal dilatation. The graft maintained the expected size.