Takashi Teramatsu

Studies on Composites of Collagen and a Synthetic Polymer Second Report - Mode of reaction of a laminar composite with living tissue, and results of long-term implantation

We have been studying composites of synthetic polymers and proctase-treated bovine collagen (telopeptide-poor collagen). In a previous paper, it is described that one of our composites appears to have a high tissue affinity, because it was found under a scanning electron microscope, well bonding the living tissue 6 weeks after implantation in the rabbit subcutaneous tissue. In the present study, the composites were also implanted in the subcutaneous tissue in rabbits to observe the mode of its bonding to the living tissue, and at the same time the bonding force was measured at various intervals during a period of 1.5 years, to observe the degree and duration of the effect of the composition, and further to study the optimal conditions for preparation of such a composite. As a method of composition, ultraviolet radiation and glutaraldehyde treatment were also comparatively examined, besides gamma-radiation that had been employed in a previous study. As the results, it is revealed that the composite bonds to the living tissue in such a manner that a portion of the collagen part is digested and absorbed to be replaced by the invading connective tissue and a part of collagen near the surface of the synthetic polymers had escaped digestion to combine with the rabbits own collagen fiber. From these results we like to insist that the mode of reaction of our composites may be similar to real organization and be different in natur from mere encapsulation which was shown by the artificial materials hitherto in use to be considered to have a good tissue affinity. Therefor we think now the encapsulation is pseudoorganization. It is also shown that the bonding force of the composite to the living tissue and its duration depend chiefly on the degree of swelling, that is, the degree of intermolecular cross-linking, of the composed collagen part. Out of the gamma-radiated composites, those radiated 1--3 Mrads proved desirable in both tissue affinity and duration of tissue bonding, with a potent bonding force remaining effective even 1.5 years later, while the composite radiated with 5 Mrads or more proved poorer in these properties because of destruction of the collagen part, vastly varying in the properties. By ultraviolet radiation, it was easy to control the degree of swelling of collagen part with the radiation dose, however, this method gave a lower bonding force and a shorter duration of the force than gamma-radiation. The glutaraldehyde method allowed the collagen to remain over a long time, but gave the composite less tissue affinity than the other two methods.

[48] Application of immobilized enzymes for biomaterials used in surgery

Publisher Summary This chapter discusses the application of immobilized enzymes for biomaterials used in surgery. The chapter investigates the replacement of various organs with this new material experimentally and clinically, including reconstruction of the trachea, chest wall, and diaphragm in the field of thoracic surgery. With the development of techniques for binding enzymes to insoluble supports, immobilized enzymes are recently utilized in various types of medical applications, especially in clinical analysis and also in therapeutic medicine. This collagen-synthetic polymer composite material is applied as a support for the immobilization of enzymes to establish its biological functions on the surface of the material, and enzymes are successfully bound to the collagen membrane layer by activation of carboxyl groups. Trypsin and urokinase are chosen with the intention of adding proteolytic (antiinflammatory) and fibrinolytic (thromboresistant) activities, respectively, to the surface properties of the composite material. Lysozyme and a peptide antibiotic, polymyxin B, are bound onto the material for the purpose of producing bacteriolytic and antibacterial biomaterials to prevent serious problems caused by bacterial infection from occurring when artificial organs and biomaterials are implanted into the body. The chapter describes the novel method of producing this enzyme-bound collagen-synthetic polymer composite material, and discusses the enzymatic characterization and several in vivo experiments made with the material carrying immobilized enzymes.

Studies on Copolymers of Collagen and a Synthetic Polymer First Report - Experimental Study on Biocompatibility of Laminar Copolymers of Collagen and a Synthetic Polymer

To develop biomaterials for semiparmanent substitution, we are studying copolymers of collagen and a synthetic polymer. In this study, in order to test tissue compatibility, the laminar copolymers were prepared from bovine collagen treated with proctase to remove telopeptides and synthetic polymers such as polyethylene, polyvinylalcohol, silicon gum etc., by the OKAMURA-HINO metthod, namely polymerization achieved by the introduction of cross-lincages, applying plasma discharge and gamma-irradiation. These copolymers were implanted into dorsal subcutaneous tissue in rabbits and removed after 1, 2, 3, 4 and 6 weeks to be examined by light microscope and electron microscope. One or two weeks after implantation, we observed that a large number of fibroblasts gathered on the surface of the grafted collagen. After 3 or 4 weeks, bridges of collagen fibrils were observed between the copolymers and rabbit tissue. These copolymers were firmly adhered to the tissues and separable only with difficulty. These results showed that the copolymers maintain the capacity for extreme strong bonding for at least 6 weeks and possess high tissue compatibility. From that we concluded copolymers are useful as a biomedical material.

Experimental Application of Polyvinyl Alcohol-Silica for Small Artificial Vessels

Polyvinyl alcohol-silica (PVA-SiO2) composite and heparinized PVA-SiO2 were examined in vitro and in vivo as materials to coat artificial vessels to be used for the replacement of small arteries. PVA-SiO2 was observed to prolong coagulation time and on heparinized PVA-SiO2 surfaces no blood coagulation was noticed after a period of two days using the Lee-White and plasma recalcification methods. After placing non-coated and coated surfaces in contact with blood components in vitro and in vivo, the degree of blood component adhesion was greater in non-coated woven Dacron than in PVA-SiO2 coated Dacron. The degree of adhesion was even less in heparinized PVA-SiO2 coated Dacron. Furthermore, artificial vessels made of these 3 types of materials were used to replace parts of the canine abdominal aorta and were removed one and a half years later. Patency rates were as follows: non-coated 2/7, PVA-SiO2-coated 4/7, heparinized PVA-SiO2-coated 8/12. The inner surfaces of these prostheses were observed with light microscopy and scanning electron microscopy. Intima formation was thinner on the PVA-SiO2 composite surfaces than on the control surfaces. Heparin acted as a local anticoagulant and PVA-SiO2 limited intima formation. This report showed that PVA-SiO2 composite coated surfaces can be effective for small artery replacement due to good tissue affinity and anticoagulability.