pH-stabilization of predegraded PDLLA by an admixture of water-soluble sodiumhydrogenphosphate--results of an in vitro- and in vivo-study.

Aim of the study was to examine if the addition of buffering sodiumhydrogenphosphate to poly(D,L)lactide(PDLLA) would stabilize the pH-value in the in vivo environment of implanted material and whether this improves its biocompatibility. The material was predegraded just to the point of viscous disintegration to test the PDLLA in the moment of its most aggressive effect on the surrounding tissue. Racemic amorphous PDLLA was injection-molded with or without the admixture of 1 mol NaP per 100 mol lactate, the degradation product of PDLLA (=1 mol%) to form 20mm x 3 mm x 2mm rods. Predegradation was performed by storing the rods at 55 degrees C for 14 days, just to the point of beginning dissolution. Predegraded PDLLA or PDLLA + NaP samples were used for in vitro incubation tests, as well as for the in vivo study, where the rods were implanted into the spinal muscles of 30 male Wistar rats. Repeatedly, measurements of the pH-value were made in the incubation solutions in vitro. The surrounding tissue of the implanted samples as well as the normal contralateral muscle tissue was checked for its pH-value in a group of 3 rats, respectively, anaesthesized at various time intervals after implantation. After these measurements the implants and their surrounding tissues were excised for histological examination. In Ringer's solution pH-values dropped immediately within the first week of incubation of both predegraded materials reaching -4 pH units after 4 weeks in the PDLLA containing medium, after 6 weeks in the PDLLA + NaP containing medium. Soerensen buffer slowed the pH decrease with significant differences between the material groups up to the 28th week. In vivo, the pH of the surrounding tissue was influenced by the implanted PDLLA material up to the 4th week, while the admixture of NaP resulted in a significant pH stabilization. A higher quantity of macrophages and giant cells were seen between the 2nd and 6th week after the implantation in the environment of pure PDLLA compared with PDLLA + NaP. Complete resorption of predegraded pure PDLLA or PDLLA + NaP from the extracellular space was reached 28 weeks postimplantation in vivo. Thus, sodiumhydrogenphosphate improves the biocompatibility of degrading PDLLA at the point of viscous disintegration by stabilizing the pH-value in the environment of the implants for several weeks and reducing adverse tissue reactions.