ObjectiveTo observe and compare the effects of peptides on the repair of rabbit skull defects through two different binding modes of non-covalent and covalent, and the combination of carboxyl (-COOH) and amino (-NH2) groups with materials.MethodsTwenty-one 3-month-old male ordinary New Zealand white rabbits were numbered 1 to 42 on the left and right parietal bones. They were divided into 5 groups using a random number table, the control group (group A, 6 sides) and the material group 1, 2, 3, 4 (respectively group B, C, D, E, 9 sides in each group). All animals were prepared with 12-mm-diameter skull defect models, and bone morphogenetic protein 2 (BMP-2) non-covalently bound multiwalled carbon nanotubes (MWCNT)-COOH+poly (L-lactide) (PLLA), BMP-2 non-covalently bound MWCNT-NH2+PLLA, BMP-2 covalently bound MWCNT-COOH+PLLA, and BMP-2 covalently bound MWCNT-NH2+PLLA were implanted into the defects of groups B, C, D, and E, respectively. At 4, 8, and 12 weeks after operation, the samples were taken for CT scanning and three-dimensional reconstruction, the ratio of bone tissue regeneration volume to total volume and bone mineral density were measured, and the histological observation of HE staining and Masson trichrome staining were performed to quantitatively analyze the volume ratio of new bone tissue.ResultsCT scanning and three-dimensional reconstruction showed that with the extension of time, the defects in groups A-E were filled gradually, and the defect in group E was completely filled at 12 weeks after operation. HE staining and Masson trichrome staining showed that the volume of new bone tissue in each group gradually increased with time, and regenerated mature bone tissue appeared in groups D and E at 12 weeks after operation. Quantitative analysis showed that at 4, 8, and 12 weeks after operation, the ratio of bone tissue regeneration volume to total volume, bone mineral density, and the volume ratio of new bone tissue increased gradually over time; and at each time point, the above indexes increased gradually from group A to group E, and the differences between groups were significant (P<0.05).ConclusionThrough covalent binding and using -NH2 to bound peptides with materials, the best bone repair effect can be achieved.