The Chronic Toxicity Of Poly-L-lactide/poly-L-lactide Grafted Nano-hydroxyapatite Bone Plates

Objective:The purpose of this study is to research the chronic toxicity of poly-L-lactide/poly-L-lactide grafted nano-hydroxyapatite bone plates during degradation.Methods:21 adult Beagle dogs were chosen, which were weighed 13-15kg, female and male at random, and that were divided into 7 groups: one month group, two months group, three months group, six months group, nine months group twelve months group and control group. There were three dogs in each group. After being anesthetized with 846 composition (0.08-0.1ml /kg.BW.i.m), fracture models were created artificially on both side of the mandible between molar teeth and premolar teeth in each dog and both sides were fixed with poly-L-lactide/poly-L-lactide (PLLA/PLLA-gHA) plates. We should observe eating, activity and wound healing of the dogs after operation. Besides, dogs of each group were sacrificed in the 1st, 2nd, 3rd, 6th, 9th and 12th months after the operation. Before sacrificing, we got the blood of every dog to make sure the biochemistry results. And then, the tissue around plates and the organs were taken out to carry out morphological observation, histopathology examination. At last, we made sure the weightloss of plates. Fibrous capsule and inflammatory cell infiltration were used to estimate implantation. Morphological and histopathology observation were used to test the general toxicity of the plates during degradation. Through these methods, we can evaluate the chronic toxicity of PLLA/ PLLA-gHA all around.Results:Viviperception: Evection was found on the mandible after operation. Eating and activity were normal. During first three days after operation, some of the mandibles have little swelling but all of them were healed with no hyperaemia and secretion in one week after operation. Compared with control group, every dog had normal information.Morphological observation: There were 18 dogs, which meant 36 mandibles in all. All the mandibles healed well except 1 mandibles of 1 dog. In the 1st, 2nd, 3rd, 6th, 9th and 12th months after the operations, organs were found normal. Besides, fibrous membrane formed around the plates.HP examination: On the first month after operation: the thick fibrous membrane formed. We also found some lymph cells. Inflammatory reaction was in grade I andâ…¡. Membrane formation was in gradeâ…¢. On the 2nd, 3rd, 6th and 9th month after operation: Inflammatory reaction and membrane formation became lighter. On the 12th month after operation: Inflammatory reaction and membrane formation were both less than grade I.The BAR of the plates: the BAR was 0.48 % after 1 month of the operation, 0.95 % after 2 months of the operations, 2.06% after 3 months of the operations, 4.31 % after 6 months of the operations, 8.69 % after 9 months of the operations and 21.54 % after 12 months of the operations.The relation between BAR and LDH: During 1st to 6th month, LDH became lower when BAR went higher. But LDH became higher between 6th to 12th month, and BAR went higher obviously.Conclusions:This new plate can control the rate of absorption suitably during 1 year of degradation. Both the tissue reaction and general toxicity are not found obvious changes during the degradation of PLLA/PLLA-gHA plates. The reliable data make addition evaluation to biosafety. It was not only safety for clinical use, but also represents the direction of the development of the materials of internal fixation.