Objective    To evaluate the biological safety of nano-hydroxyapatite and poly-amino acid (n-HA/PAA) compound.     Methods    A n-HA/PAA compound was prepared according to the ISO10993-1 standards to carry out the following experiments.      ① In vitro cytotoxicity test: L929 fibroblasts were divided into negative physiological saline group and positive phenol group. Morphologic change was observed and cytotoxicity was detected by MTT assay and flow cytometry.    ②Systemic acute toxic test: intoxication and death were observed in mice injected with a solution of nHA/PAA compound extraction and physiological saline.    ③Sensitization test: thirty mice were randomly divided into negative physiological saline group and positive dinitrofluorobenzene group. Edema and erythema were observed and scored.    ④Hemolytic test: mice were divided into negative physiological saline group and positive phenol group. Hemolytic rate of n-HA/PAA compound was calculated after anticoagulant rabbit blood was added.    ⑤Pyrogen test: 3 rabbits were injected with a solution of n-HA/PAA compound extract at the dose of 10 ml/kg. Difference in normal body temperature and temperature 3 h after injection of the solution was detected.    ⑥Genetic toxicity test: 30 mice were randomly divided into three groups and injected with physiological saline

cyclophosphamide solution

and solution of n-HA/PAA compound extract

at the dose of 100 g/kg

respectively. Bone  marrow  polychromatic erythroblasts and polychromatic erythroblasts containing micronuclei were detected and the micronuclei rate was counted.     Results    In vitro cytotoxicity test showed that n-HA/PAA compound had no obvious effect on the morphology and growth of L929 fibroblasts. MTT assay revealed that the extract of n-HA/PAA compound could not inhibit the proliferation and intoxication of L929 fibroblasts. The apoptosis of L929 fibroblasts was not obvious. Systemic acute toxic test showed that n-HA/PAA compound could not cause intoxication and death of mice. Sensitization test demonstrated no edema and erythema. The hemolytic rate of n-HA/PAA compound was 0.71% (5%). Ppyrogen test showed no obvious temperature increase. Genetic  toxicity  test displayed no micronuclei and no genetic  toxicity  of n-HA/PA compound.     Conclusion     The biological safety of n-HA/PAA compound is rather good.