Covalent immobilization of hirudin improves the haemocompatibility of polylactide—polyglycolide in vitro

• Published in: Biomaterials 1997-11, Vol.18 (22), p.1495-1502
• Main Authors: Seifert, B., Romaniuk, P., Groth, Th
• Format: Article
• Language: English
• Subjects: Antithrombins - chemistry; Antithrombins - pharmacology; Bioassay; Biocompatibility; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biological and medical sciences; Blood; Blood Coagulation - drug effects; Drug products; haemocompatibility; hirudin immobilization; Hirudins - blood; Hirudins - chemistry; Hirudins - pharmacology; Humans; Lactic Acid - chemistry; Lactic Acid - pharmacology; Medical sciences; Microscopy, Fluorescence; Optical microscopy; Organic polymers; P-Selectin - analysis; Platelet Activation - drug effects; Platelet Adhesiveness - drug effects; Polyglycolic Acid - chemistry; Polyglycolic Acid - pharmacology; polyglycolide; Polylactic Acid-Polyglycolic Acid Copolymer; Polylactide; Polymers - chemistry; Polymers - pharmacology; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Surface treatment; Technology. Biomaterials. Equipments. Material. Instrumentation; Whole Blood Coagulation Time
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/S0142-9612(97)00079-3

A biodegradable polymer, poly( d,l-lactide- co-glycolide) RESOMER® RG756, was modified by surface immobilization of recombinant hirudin (r-Hir) with glutaraldehyde as coupling reagent to improve the blood contacting properties of the polymer. The activity of immobilized hirudin on the polymer was estimated by a chromogenic assay to about 2.5 ATU r-Hir cm −2. The improvement of the haemocompatibility of the modified RG756 was evaluated in terms of platelet adhesion/activation, whole blood clotting times and clot formation rate. Fluorescence microscopy revealed that surface modification with r-Hir resulted in decreased platelet adhesion and activation. An ELISA for P-selectin, a marker of platelet activation, was used to confirm this result. Clotting time experiments demonstrated significantly prolonged non-activated partial thromboplastin times, and a decreased clot formation rate of whole blood in contact with r-Hir modified RG756 compared with the plain polymer. Comparison of immobilized r-Hir with bound heparin yielded equivalent improvement of blood-contacting properties of the investigated polymers. These in vitro investigations indicate that the immobilization of r-Hir on RG756 is a useful method to improve the blood contacting properties of polylactides/polyglycolides and other polymers as well.