The influence of various coatings of hydroxyapatite bone carrier on the success of bone regeneration in rabbit calvarial defects: histomorphometric and histological analysis

Sanja  Milutinović-Smiljanić; Djordje Antonijević; Milutin Mićić; Vladimir Biočanin; Nikola Sjerobabin; Božana Petrović; Vesna Danilović; Vukoman Jokanović

doi:10.2298/VSP210513072M

Sanja Milutinović-Smiljanić University of Belgrade, Faculty of Dental Medicine, Department of General and Oral Histology and Embryology, Belgrade, Serbia
Djordje Antonijević University of Belgrade, Institute for Nuclear Science “Vinča”, Laboratory for Atomic Physics, Belgrade, Serbia
Milutin Mićić University of Belgrade, Faculty of Medicine, Laboratory for Anthropology, Belgrade, Serbia
Vladimir Biočanin University of Business Academy, Faculty of Dentistry, Pančevo, Serbia
Nikola Sjerobabin University Clinical Hospital Center ‟Dr. Dragiša Mišović”, Belgrade, Serbia
Božana Petrović University of Belgrade, Institute for Nuclear Science “Vinča”, Laboratory for Atomic Physics, Belgrade, Serbia
Vesna Danilović University of Belgrade, Faculty of Dental Medicine, Department of General and Oral Histology and Embryology, Belgrade, Serbia
Vukoman Jokanović University of Belgrade, Institute for Nuclear Science “Vinča”, Laboratory for Atomic Physics, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP210513072M

Keywords: bone regeneration;, histological techniques;, materials testing;, polymers;, rabbits.

Abstract

Background/Aim. The materials used nowadays for bone replacement do not fully meet the requirements for complete regeneration, which is why new ones are being tested. Despite numerous attempts to improve bone tissue regeneration, no fulfilling material has been found yet. This study investigated the influence of poly-lactide-co-glycolide (PLGA) and polyethyleneimine (PEI) as coatings for hydroxyapatite (HAP) bone carriers on bone tissue regenerative potential in rabbits’ calvarial defect. Methods. Calvarial defects measuring 6 mm in diameter were made in 19 skeletally mature rabbits. Defects were filled with one of the following materials: PLGA coated HAP (HAP + PLGA), PEI coated HAP (HAP + PEI), and bovine HAP – Bio-Oss^® (positive control). Unfilled defects represented negative control. Histological analysis was performed in order to determine the inflammatory response of the host tissue. The formation of the new bone was evaluated using histomorphometric analysis. All analyses have been conducted in samples obtained 3, 6, and 9 weeks after implantation. Results. Three weeks post-implantation, a trend toward increased healing in the HAP + PLGA group compared to other investigated materials was noticed, with no statistically significant difference between the study groups (p > 0.05). However, after 6 and 9 weeks, significant healing was observed in favor of the HAP coated with PLGA compared to other groups (p < 0.05). Within this group, greater bone healing was observed compared to the HAP + PEI and Bio-Oss^® groups. Conclusion. PLGA demonstrated greater coating potential compared to PEI with respect to osteogenesis improvement in bone reconstructive surgery.

Author Biography

Sanja Milutinović-Smiljanić, University of Belgrade, Faculty of Dental Medicine, Department of General and Oral Histology and Embryology, Belgrade, Serbia

dr medicinskih nauka, docent

References

1. Sakkas A, Wilde F, Heufelder M, Winter K, Schramm A. Autogenous bone grafts in oral implantology-is it still a "gold standard"? A consecutive review of 279 patients with 456 clinical procedures. Int J Implant Dent 2017; 3(1): 23.

2. Howlader D, Vignesh U, Bhutia DP, Pandey R, Kumar S, Chandra T, et al. Hydroxyapatite collagen scaffold with autologous bone marrow aspirate for mandibular condylar reconstruction. J Craniomaxillofac Surg 2017; 45(9): 1566‒72.

3. Birkenfeld F, Sengebusch A, Völschow C, Möller B, Naujokat H, Wiltfang J. Scaffold implantation in the omentum majus of rabbits for new bone formation. J Craniomaxillofac Surg 2019; 47(8): 1274‒9.

4. Nezhurina EK, Karalkin PA, Komlev VS, Sviridova IK, Kirsanova VA, Akhmedova SA, et al. Physicochemical and osteoplastic characteristics of 3D printed bone grafts based on synthetic calcium phosphates and natural polymers. IOP Conf Ser Mater Sci Eng 2018; 347. doi:10.1088/1757-899X/347/1/012047.

5. Zimmerer RM, Jehn P, Kokemüller H, Abedian R, Lalk M, Tavassol F, et al. In vivo tissue engineered bone versus autologous bone: stability and structure. Int J Oral Maxillofac Surg 2017; 46(3): 385‒93.

6. Eweida A, Schulte M, Frisch O, Kneser U, Harhaus L. The impact of various scaffold components on vascularized bone constructs. J Craniomaxillofac Surg 2017; 45(6): 881‒90.

7. Kasuya S, Inui S, Kato-Kogoe N, Omori M, Yamamoto K, Inoue K, et al. Evaluation of Guided Bone Regeneration Using the Bone Substitute Bio-Oss^®and a Collagen Membrane in a Rat Cranial Bone Defect Model. J Hard Tissue Biol 2018; 27(1): 79‒84.

8. Le BQ, Rai B, Hui Lim ZX, Tan TC, Lin T, Lin Lee JJ, et al. A polycaprolactone-β-tricalcium phosphate-heparan sulphate device for cranioplasty. J Craniomaxillofac Surg 2019; 47(2): 341‒8.

9. Aludden HC, Mordenfeld A, Hallman M, Dahlin C, Jensen T. Lateral ridge augmentation with Bio-Oss alone or Bio-Oss mixed with particulate autogenous bone graft: a systematic review. Int J Oral Maxillofac Surg 2017; 46: 1030‒8.

10. Shirmohammadi A, Roshangar L, Chitsazi MT, Pourabbas R, Faramarzie M, Rahmanpour N. Comparative Study on the Efficacy of Anorganic Bovine Bone (Bio-Oss) and Nanocrystalline Hydroxyapatite (Ostim) in Maxillary Sinus Floor Augmentation. Int Sch Res Notices 2014; 2014: 967091.

11. Jokanović V, Čolović B, Marković D, Petrović M, Jokanović M, Milosavljević P, et al. In Vivo Investigation of ALBO-OS Scaffold Based on Hydroxyapatite and PLGA. J Nanomater 2016; Doi: https://doi.org/10.1155/2016/3948768.

12. Jokanović V, Čolović B, Marković D, Petrović M, Soldatović I, Antonijević Dj, et al. Extraordinary biological properties of a new calcium hydroxyapatite/poly(lactide-co-glycolide)-based scaffold confirmed by in vivo investigation. Biomed Tech (Berl) 2017; 62(3): 295–306.

13. Qiao C, Zhang K, Jin H, Miao L, Shi C, Liu X, et al. Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo. Int J Nanomedicine 2013; 8: 2985‒95.

14. Chen XA, Zhang LJ, He ZJ, Wang WW, Xu B, Zhong Q, et al. Plasmid-encapsulated polyethylene glycol grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells. Int J Nanomedicine 2011; 6: 843‒53.

15. Tierney EG, Duffy GP, Hibbitts AJ, Cryan SA, O'Brien FJ. The development of non-viral gene-activated matrices for bone regeneration using polyethyleneimine (PEI) and collagen-based scaffolds. J Control Release 2012; 158(2): 304‒11.

16. Cholas R, Kunjalukkal Padmanabhan S, Gervaso F, Udayan G, Monaco G, et al. Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix. Mater Sci Eng C Mater Biol Appl 2016; 63: 499‒505.

17. Khanam N, Mikoryak C, Draper RK, Balkus KJ Jr. Electrospun linear polyethyleneimine scaffolds for cell growth. Acta Biomaterialia 2007; 3(6): 1050‒9.

18. Al-Dosari MS, Gao X. Nonviral gene delivery: principle, limitations, and recent progress. AAPS J 2009; 11(4): 671–81.

19. Kumar S, Raj S, Sarkar K, Chatterjee K. Engineering a multi-biofunctional composite using poly(ethylenimine) decorated graphene oxide for bone tissue regeneration. Nanoscale 2016; 8(12): 6820‒36.

20. Khorsand B, Nicholson N, Do AV, Femino JE, Martin JA, Petersen E, et al. Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model. J Control Release 2017; 248: 53‒9.

21. Jang SJ, Kim SE, Han TS, Son JS, Kang SS, Choi SH. Bone Regeneration of Hydroxyapatite with Granular Form or Porous Scaffold in Canine Alveolar Sockets. In Vivo 2017; 31(3): 335–41.

22. Kubasiewicz-Ros P, Seeliger J, Kozak K, Jurczyszyn K, Gerber H, Dominiak M, et al. New nano-hydroxyapatite in bone defect regeneration: A histological study in rats. Ann Anat 2017; 213: 83‒90.

23. Xing H, Cheng L, Lu M, Liu H, Lang L, Yang T, et al. A biodegradable poly(amido amine) based on the antimicrobial polymer polyhexamethylene biguanide for efficient and safe gene delivery. Colloids Surf B Biointerfaces 2019; 182: 110355.

24. Guo X, Ding L, Kanamori K, Nakanishi K, Yang H. Functionalization of hierarchically porous silica monoliths with polyethyleneimine (PEI) for CO2 adsorption. Moc Mes Mat 2017; 245: 51‒7.

25. Liu M, Zhang L, Zhao Q, Jiang X, Wu L, Hu Y. Lower-molecular-weight chitosan-treated polyethyleneimine: a practical strategy for gene delivery to mesenchymal stem cells. Cell Physiol Biochem 2018; 50(4): 1255‒69.

26. Kunath K, von Harpe A, Fischer D, Kissel T. Galactose-PEI-DNA complexes for targeted gene delivery: degree of substitution affects complex size and transfection efficiency J Control Release 2003; 88(1): 159‒72.

27. Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T. A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm Res 1999; 16(8): 1273‒9.

28. Tachi K, Takami M, Sato H, Mochizuki A, Zhao B, Miyamoto Y, et al. Enhancement of bone morphogenetic protein-2-induced ectopic bone formation by transforming growth factor-beta1 2011. Tissue Eng Part A 2011; 17(5‒6): 597‒606.

29. Tang W, Lin D, Yu Y, Niu H, Guo H, Yuan Y, Liu C. Bioinspired trimodal macro/micro/nano-porous scaffolds loading rhBMP-2 for complete regeneration of critical size bone defect. Acta Biomater 2016; 32: 309‒23.

30. Kharkova NV, Reshetov IV, Zelianin AS, Philippov VV, Sergeeva NS, Sviridova IK, et al. Three-dimensional TCP scaffolds enriched with Erythropoietin for stimulation of vascularization and bone formation. Electron J Gen Med 2016; 16(2): em115.