Does zinc oxide nanoparticles potentiate the regenerative effect of platelet-rich fibrin in healing of critical bone defect in rabbits?

Abstract

Background: Many encouraging studies confirmed the ability of Zinc Oxide Nanoparticles (ZnONPs) in accelerating bone growth and mineralization. The use of Platelet Rich-Fibrin (PRF) as a sole filling material for large segmental bone defects remains questionable. The objectives are to investigate the regenerative efficacy of autologous Platelet Rich-Fibrin (PRF) and Zinc Oxide Nanoparticles (ZnONPs) in repairing large segmental bone ulnar defects in a randomized controlled study in rabbits using computed tomographic interpretations. A 12 mm critical size defect was surgically induced in the ulna of 30 rabbits (n = 10/ group). In the control group, the defect was left empty. In the PRF group, the defect is filled with PRF. In the PRF/ZnONPs group, the defect is filled with PRF that was inoculated with 0.1 ml of 0.2% ZnONPs. Radiologic healing capacity was evaluated at the first, second, and third postoperative months.

Results: Statistical analysis showed significant differences in the radiologic healing scores between the groups (P = 0.000-0.0001) at all-time points (P = 0.000-0.047) during the study.

Conclusion: Rabbits in the PRF/ZnONPs group showed the highest appreciable bone quality and quantity followed by the PRF group with high quantity but low bone quality meanwhile, rabbits in the control group showed minimal quantity but medium bone quality. Interestingly, the addition of ZnONPs to PRF can accelerate the healing of ulnar critical-size defects in rabbits.

Keywords: Bone density; Bridging; Canalization; Critical bone defect; Nanoparticles; Platelet-rich fibrin; Remodeling; Zinc oxide.

Fig. 1

Graphs showing the Semi-quantitative (% of defect filling) and qualitative (scores) evaluation of newly bone formation using CBCT at the 30^th, 60^th and 90^th days

Fig. 2

Computed tomography 3D images of the ulna with CSD in control (1PO-1c), PRF (2PO-2c) and PRF/ZnONPs (3PO-3c) at the 1^st (PO), 30^th (a), 60^th (b) and 90^th (c) postoperative days showed a highly significant increase in the percent of CSD filling rate in both PRF and PRF/ZnONPs groups versus the control group

Fig. 3

Computed tomography sagittal plane images of the ulna with CSD in control (1PO-1c), PRF (2PO-2c) and PRF/ZnONPs (3PO-3c) at the 1^st, 30^th (a), 60^th (b) and 90^th (c) postoperative days showed complete bicortical bridging of the CSD in both PRF and PRF/ZnONPs groups versus unicortical bridging in the control group. Notice abundant callus formation in PRF group versus both control and PRF/ZnONPs groups

Fig. 4

Computed tomography axial plane images of the ulna with CSD in control (1PO-1c), PRF (2PO-2c) and PRF/ZnONPs (3PO-3c) at the 1^st, 30^th (a), 60^th (b) and 90^th (c) postoperative days showed recreation of the bone marrow cavity in both PRF and PRF/ZnONPs groups versus absence of canalization in the control group

Fig. 5

Computed tomography cross section images of the ulna with CSD in control (1PO-1c), PRF (2PO-2c) and PRF/ZnONPs (3PO-3c) at the 1^st, 30^th (a), 60^th (b) and 90^th (c) postoperative days showed extensive fusion between the ulna and radius with incomplete remodeling of the defect site in both PRF and control groups versus regression of the bone in the interosseous space between radius and ulna and a reduction in the callus size in the PRF/ZnONPs group indicating better remodeling

Fig. 6

Graphs showing quantitative bone densities of normal bone, new bone in-growth density (AOI density), and density of bone adjacent to the defect area (BAD density) in HU obtained by CBCT and expressed as mean ± SD at the 30^th, 60^th and 90^th days

Fig. 7

The surgical procedures for induction of 12 mm critical size ulnar defect. A 5 cm long linear incision was made over the craniolateral aspect of the mid of the antebrachium (A). The ulna was exposed by retraction of the surrounding muscles (B) where 2 drilling holes with 12 mm apart were created in the mid-diaphysis (C). The defect was left empty in the control group (D), filled with PRF clot in the PRF group (E) or ZnONPs were inoculated into the PRF clot in the PRF/ZnONPs (F)