Influence of sterilization on injectable bone biomaterials

Injectable biomaterials used in bone surgery include acrylic bone cements, calcium phosphate cements, and new composite-type biomaterials with a mineral content and an organic phase dispersed or dissolved in water. Cellulose derivatives, chitosan solutions, alginates, and other polymers are studied as useful modifiers and binding agents in calcium phosphate cements. We have developed proprietary polyester copolymers including lactic acid moieties and present here results concerning the effect of sterilization on the physico-chemical properties of derived bone biomaterials. Chitosan solutions show a dramatic decrease in viscosity after 25-kGy gamma sterilization. Aqueous copolylactic solutions also show, by capillary electrophoresis, that hydrolysis occurs to liberate monomers after 25-kGy gamma sterilization. Heat sterilization also degrades chitosan solutions, and ultrafiltration is difficult because of high viscosity. However, apatite-copolylactic solids can be steam sterilized without deterioration. Gelatin has been used as a natural polymer to bind apatite particles. Gel exclusion chromatography reveals crosslinking of the chains by irradiation. Standard acrylic cements contain monomers sterilized by ultrafiltration because they do not tolerate irradiation. We have used ultrafiltration to prepare aqueous copolylactic solutions without polymer hydrolysis. Implantation of calcium phosphate cement modified by copolylactic acid in a rabbit metaphyseal model defect shows progressive substitution of the biomaterial by new bone tissue. At 3 months, a mild inflammatory reaction still remains associated with the continuing resorption of the biomaterial. These results show that interesting biological properties can be obtained with products not sterilized by irradiation. Undoubtedly, many biopolymers are fragile and, like reactive monomers, need to be sterilized by special methods if they are to be used in injectable, liquid form.