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Comparative Study
. 2022 Mar 4;27(5):1694.
doi: 10.3390/molecules27051694.

Comparison of Hydroxyapatite/Poly(lactide-co-glycolide) and Hydroxyapatite/Polyethyleneimine Composite Scaffolds in Bone Regeneration of Swine Mandibular Critical Size Defects: In Vivo Study

Momir Stevanovic  1   2 , Dragica Selakovic  3 , Miroslav Vasovic  1 , Biljana Ljujic  4 , Suzana Zivanovic  1 , Milos Papic  1 , Marko Zivanovic  5 , Nevena Milivojevic  5 , Milica Mijovic  6 , Sasa Z Tabakovic  2 , Vukoman Jokanovic  7 , Aleksandra Arnaut  1 , Pavle Milanovic  1 , Nemanja Jovicic  8 , Gvozden Rosic  3
Affiliations
Comparative Study

Comparison of Hydroxyapatite/Poly(lactide-co-glycolide) and Hydroxyapatite/Polyethyleneimine Composite Scaffolds in Bone Regeneration of Swine Mandibular Critical Size Defects: In Vivo Study

Momir Stevanovic et al. Molecules. .

Abstract

Reconstruction of jaw bone defects present a significant problem because of specific aesthetic and functional requirements. Although widely used, the transplantation of standard autograft and allograft materials is still associated with significant constraints. Composite scaffolds, combining advantages of biodegradable polymers with bioceramics, have potential to overcome limitations of standard grafts. Polyethyleneimine could be an interesting novel biocompatible polymer for scaffold construction due to its biocompatibility and chemical structure. To date, there have been no in vivo studies assessing biological properties of hydroxyapatite bioceramics scaffold modified with polyethyleneimine. The aim of this study was to evaluate in vivo effects of composite scaffolds of hydroxyapatite ceramics and poly(lactide-co-glycolide) and novel polyethyleneimine on bone repair in swine's mandibular defects, and to compare them to conventional bone allograft (BioOss). Scaffolds were prepared using the method of polymer foam template in three steps. Pigs, 3 months old, were used and defects were made in the canine, premolar, and molar area of their mandibles. Four months following the surgical procedure, the bone was analyzed using radiological, histological, and gene expression techniques. Hydroxyapatite ceramics/polyethyleneimine composite scaffold demonstrated improved biological behavior compared to conventional allograft in treatment of swine's mandibular defects, in terms of bone density and bone tissue histological characteristics.

Keywords: composite scaffolds; hydroxyapatite ceramics; mandibular defect; poly(lactide-co-glycolide); polyethyleneimine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Radiological assessment of bone density obtained by CBCT: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 2
Figure 2
Number of cells/per bone surface: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft; representative images of H&E staining on paraffin-embedded sections (original magnification × 20): (H) BioOss graft, (I) HAP/PLGA graft, (J) HAP/PEI graft. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 3
Figure 3
Immunoreactivity to osteocalcin: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft; representative images of H&E staining on paraffin-embedded sections (original magnification × 20): (H) BioOss graft, (I) HAP/PLGA graft, (J) HAP/PEI graft. Boxes represents interquartile ranges. Thick horizontal line within a box represents a median. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 4
Figure 4
Collagen deposition in the newly formed bone tissue: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft; Representative images of H&E staining on paraffin-embedded sections (original magnification × 20): (H) BioOss graft, (I) HAP/PLGA graft, (J) HAP/PEI graft. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 5
Figure 5
Relative expression of osteocalcin gene: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 6
Figure 6
Relative expression of RANKL gene: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 7
Figure 7
Relative expression of OPG gene: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 8
Figure 8
The RANKL/OPG ratio: (A) canine area, (B) premolar area, (C) molar area, (D) whole mandibula, (E) BioOss graft, (F) HAP/PLGA graft, (G) HAP/PEI graft. The values are mean ± standard error of the mean (SEM), * denotes a significant difference p < 0.05, ** denotes a significant difference p < 0.01.
Figure 9
Figure 9
Analysis of bone density with CBCT and regions of interest (ROIs).
See this image and copyright information in PMC

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