Biomedical Applications - SURGERY
A huge effort has been made over the past 25 years in developing biomaterials suitable for use in surgical applications. Not only do they need to have a demanding set of physical/mechanical properties to replace hard and/or soft tissue, they also must be biocompatible. A major concern is the interaction of blood with the implanted biomaterial surfaces which are prone to thrombus formation and emboli, a life-threatening complication. Chitosan in complex with other antithrombdgenic agents and certain chitin/chitosan derivatives alone have been shown to be highly effective in producing thromboresistant surfaces.
In cardiac and major aortic surgey, life-threatening bleeding, even through modern low porosity vascular grafts, is of paramount concern. Chitosan has been shown to be very effective as a hemostatic sealant for such grafts, further avoiding the thrombogenic and antigenic disadvantages of the currently used protein-based sealants.
Hammar, et al. (1, 2) investigated and demonstrated laminar structures of chitosan and heparin which could be coated on a variety of polymers, bind effectively to produce thromboresistant surfaces and maintain their blood compatibility and efficacy for usefully long periods of time. Muzzarelli, et al. (3) reported on sulfated N-carboxymethyl chitosans which have human blood anticoagulant activity equal to heparin with no adverse effects on cellular structures owing to their reduced molecular size.
Koshino, et al. (4) and Komai, et al. (5) evaluated a series of acylated chitins as antithrombic coating materials for chemically modified natural tissues used in reconstructive surgery and found them better performing than lipopolysaccharide conjugates. Okita, et al. (6) received a US patent for a polytetrafluorethylene tubular blood vessel prosthesis with composite structures of crosslinked collagen/chitosan and the advantage of diameters 15mm that remain thromboresistant. No prior technology would allow such small diameters in a biocompatible blood vessel replacement.
In the area of hemostasis, Malette et al. (7) first reported on the efficacy of chitosan. They replaced the aorta of dogs with knit Dacron grafts treated with chitosan, observed a marked hemostatic improvement versus control and found upon autopsy that the grafts were encased in smooth muscle, with a living endothelial lining and abundant vasa-vasorum. Further study showed that the rapid and complete blood coagulation was the result of a reaction between the red blood cell membrane and the chitosan (8). From this work, Malette and Quigley received US patents for a novel method of hemostasis (9), a method for directly occluding blood vessels (10) and a method of blood clot formation that promotes tissue regeneration (11).
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