Table 1 Data extraction and characteristics of studies included in review
Author and year of publication | Type of study | Bone structure under examination | Subject type | Number of subjects | Follow-up | Test group | Control group | Method of lactoferrin supply | Results |
|---|---|---|---|---|---|---|---|---|---|
Yoshimaki T. et al. (2014) [14] | Case – control study | Cranium, non-critical-sized calvarial defects in the parietal area | Fischer rats | 10 – in every rat 2 trepanations - one on each side of midsagittal suture | 4 weeks CT observ. and histopat. at the of study. | 3 mm collagen membrane containing 11 μl of bovine LF solution (500 mg/ml, total 5.5 mg of LF) applied intraoperatively on defect | 3 mm collagen membrane permeated with 11μl of saline solution applied intraoperatively on defect | Local administration | Newly generated bone was observed at LF sites as early as 2 weeks after surgery, but the significant differences between test and control group occurred at 3rd and 4th week of CT observation (1.70 vs. 1.13 mm3 and 2,44 vs. 1.54 mm3). The mass of new bone at sites with LF increased significantly at 4th week 1.55 vs. 1.02 mg. In histopathological examination the number of pixel covered by new bone tissue was 2 times bigger than in control site, with almost 2,5 times bigger number of osteoblast-like cells. |
Yoshimaki T et al. (2013) [15] | RCCT | Cranium, non-critical-sized calvarial defects in the parietal area | Fischer rats | 30 – 10 in every group | 4 weeks, CT observ. and histopat. at the of study. | 1. Group - 100 mg LF/kg + Collagen membrane 2. Group – 10 mg LF/kg + collagen membrane intraperitoneally injection every day, starting on the day of the operation | Collagen membrane + saline injections, intraperitoneally injection every day, starting on the day of the operation | Systemic administration | Newly generated bone was observed during CT observation 2 weeks after surgery in the LF groups, with only minimal formation of new bone in control group. The significant differences between test and control group occurred at 3rd and 4th week of study. In both test groups the collagen tissue was absorbed. In test group the fibrous tissue with osteoblasts and new bone covered the bone sites, many times more prominent in the 100 mg LF/kg. The control was filled with fibrous connective tissue; with minimal regeneration sites on defect rims. There was no Ca ions and ALP concentration differences in serum between two groups. |
Görmez et al. (2015) [16] | Case – control study | Cranium, bone defects in frontal bone area | Domestic pigs | 24 uniform bone defects in 12 pigs | 10 weeks, no intervention during the follow-up | Placement of a titanium implant + 0.3 mL inorganic bovine-derived graft + bovine lactoferrin loaded gelatin microspheres + collagen membrane (Lactoferrin group) | 1. Placement of a titanium implant + 0.3 mL inorganic bovine-derived graft + Collagen membrane; (Graft group) 2. Placement of a titanium implant + Collagen membrane; (Empty defect group) | Local administration | After 10 weeks of uneventful healing, all the implants showed successful osseointegration. Different amounts of newly formed bone defects were seen in all treatment groups. In the bovine lactoferrin group, significantly more bones around the implants were observed and bone growth above the tip of the implants was detected. Lost tissue regeneration amounted 26.9 ± 6.0% in the empty defect group, 31.8 ± 8.4% in the graft group, and 47.6± 5.0% in the lactoferrin group. In the group in which lactoferrin was used, most of the graphite was resorbed and replaced with subjects own bone. |
Paknejad et al. (2013) [17] | RCCT | Cranium, non-critical-sized calvarial defects in the parietal area | Male New Zealand rabbits | 32 bone defects in 8 rabbits | 4 weeks | Inorganic bovine-derived graft (Bio oss)+ Non-iron saturated bovine lactoferrin + Tragacanth (carrier) + collagen membrane | 1. Inorganic bovine-derived graft only 2. Inorganic bovine-derived graft + Tragacanth only 3. Inorganic bovine-derived graft + Lactoferrin only | Local administration | All groups were not scientifically different in terms of inflammation, vitality and percentage of new bone formation nor residual Bio oss material. The percentage of new bone formation in test group was 15.95 ± 2.24%, while in control groups were 1st. - 13.44 ± 2.89%; 2nd. - 14.73± 3.14%, and 3rd.-15.02 ± 1.51%. Although the mean values differ from each other, the standard deviation in all groups makes the results statistically insignificant. The results of this study are in contradiction to others investigating the effect of lactoferrin on bone regeneration rapitidy within the skull. |
Gao et al. (2018) [18] | RCCT | Cranium, critical-sized calvarial defects in the parietal area | Sprague–Dawley rats | One 5mm critical-sized defect in each of 64 subjects | 4 weeks and 12 weeks | Lactoferrin + collagen gel (10 μg/gel) | 1. No intervention 2. Collagen gel only 3. Sham surgeries (skin and periosteal incisions only) | Local administration | The bone volume fraction (BV/TV) was higher in lactoferrin-treated animals at both timepoints compared to the other groups with critical-sized defects, 16.5 ± 0.6% (4 weeks) and 21.9 ± 1.2% (12 weeks), while only 10.5 ± 1.1% and 12.2 ± 1.3% in the group without any intervention. The animals in group 4 (sham surgeries) had the highest percentage of newly formed bone compared with the other three groups at both 4 weeks (24.27 ± 2.6%) and 12 weeks (29.3 ± 0.8%). The lactoferrin treated group had greater amounts of regenerated bone at both 4 and 12 weeks. A mixture of lamellar and woven bone was observed in all critical-sized defects groups throughout the study. |