Properties of Calcium Phosphate/Hydrogel Bone Grafting Composite on the Model of Diaphyseal Rat Femur’s Defect: Experimental Study
- Authors: Shcherbakov I.M.1, Klimashina E.S.1, Evdokimov P.V.1, Tikhonov A.A.1, Putlayev V.I.1, Shipunov G.A.1, Zatsepin V.A.1, Dubrov V.E.1, Danilova N.V.1, Malkov P.G.1
-
Affiliations:
- Lomonosov Moscow State University
- Issue: Vol 29, No 1 (2023)
- Pages: 25-35
- Section: Theoretical and experimental studies
- URL: https://ogarev-online.ru/2311-2905/article/view/132696
- DOI: https://doi.org/10.17816/2311-2905-2039
- ID: 132696
Cite item
Abstract
Background. The problem of bone defects replacement is relevant nowadays, that is why many scientists create new synthetic bone substitutes, but the «ideal» material has not been found so far.
The aims of the study: 1) to determine the suitability of the monocortical defect model in the rat femur diaphysis with additional prophylactic reinforcement with a bone plate for assessing the biological properties of implanted materials using the commercially available ChronOS® material as an example; 2) to assess of the osteoconductive properties of composite materials based on poly(ethylene glycol)diacrylate and octacalcium phosphate with architecture Kelvin and gyroid types on the developed model.
Methods. A prospective study, level of evidence II. A monocortical defect of the rat femoral diaphysis (length 7 mm) was produced under anaesthesia in aseptic conditions and fixed with a polyetheretherketone plate and six titanium screws. In the control group, the defect was left empty. In other groups, blocks of one of three materials were implanted — сhronOS and composites of poly(ethylene glycol)diacrylate and octacalcium phosphate with 3D-printed Kelvin and gyroid architectures. After 3 and 6 weeks, the rats were sacrificed, and histological examination of the defect zone was performed. The amount of newly formed bone tissue was histometricly assessed, followed by statistical processing of the results.
Results. All rats have reached the planned endpoint, and there were no infectious complications or loss of fixation. Histological examination of the defect zone revealed minimal bone growth in the Control group, rather slow bone formation in the Gyroid group, and statistically significantly more pronounced bone formation in the pores of the materials in the Kelvin and Chronos groups.
Conclusions. Bone defect in this model was not spontaneously filled with bone tissue and allowed us to study the biological properties of bone substitutes (the ability to biodegrade and osteoconductive properties). The osteoconductive properties of a composite material based on poly(ethylene glycol)diacrylate and octacalcium phosphate with a Kelvin architecture are higher than with a gyroid architecture and are comparable to that of the сhronOS.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Ivan M. Shcherbakov
Lomonosov Moscow State University
Author for correspondence.
Email: imscherbackov@yandex.ru
ORCID iD: 0000-0001-5487-9039
Russian Federation, Moscow
Elena S. Klimashina
Lomonosov Moscow State University
Email: alenakovaleva@gmail.com
ORCID iD: 0000-0002-7441-7381
Cand. Sci. (Chem.)
Russian Federation, MoscowPavel V. Evdokimov
Lomonosov Moscow State University
Email: pavel.evdokimov@gmail.com
ORCID iD: 0000-0003-4398-054X
Cand. Sci. (Chem.)
Russian Federation, MoscowAndrei A. Tikhonov
Lomonosov Moscow State University
Email: andytikhon94@gmail.com
ORCID iD: 0000-0003-3372-5393
Russian Federation, Moscow
Valerii I. Putlayev
Lomonosov Moscow State University
Email: valery.putlayev@gmail.com
ORCID iD: 0000-0001-7601-6787
Cand. Sci. (Chem.)
Russian Federation, MoscowGeorgii A. Shipunov
Lomonosov Moscow State University
Email: shipunovgeorge@gmail.com
ORCID iD: 0000-0003-4495-7050
Russian Federation, Moscow
Vladislav A. Zatsepin
Lomonosov Moscow State University
Email: gyglvladislav@gmail.com
ORCID iD: 0000-0001-8233-2989
Russian Federation, Moscow
Vadim E. Dubrov
Lomonosov Moscow State University
Email: vduort@gmail.com
ORCID iD: 0000-0001-5407-0432
Dr. Sci. (Med.), Professor
Russian Federation, MoscowNatal’ia V. Danilova
Lomonosov Moscow State University
Email: natalyadanilova@gmail.com
ORCID iD: 0000-0001-7848-6707
Cand. Sci. (Med.)
Russian Federation, MoscowPavel G. Malkov
Lomonosov Moscow State University
Email: malkovp@fbm.msu.ru
ORCID iD: 0000-0001-5074-3513
Cand. Sci. (Med.)
Russian Federation, MoscowReferences
- Karyakin N.N., Gorbatov R.O., Novikov A.E., Niftullaev R.M. [Surgical treatment of patients with tumors of long bones of upper limbs using tailored 3D printed bone substitute implants]. Genij Ortopedii [Orthopaedic Genius]. 2017;23(3):323-330. (In Russian). doi: 10.18019/1028-4427-2017-23-3-323-330.
- Kasyanova E.S., Kopelev P.V., Alexandrova S.A. [Analysis of the viability of bone marrow mesenchymal stromal cells cultivated on osteoreplacement material BIOSIT-SR ELCOR after surface modification bycollagen type I]. Byulleten’ innovatsionnykh tekhnologii [Bulletin of Innovative Technologies]. 2018;2(3(7)):32-37. (In Russian).
- Kryukov E.V., Brizhan’ L.K., Khominets V.V., Davydov D.V., Chirva Yu.V., Sevastianov V.I. et al. [Clinical use of scaffold-technology to manage extensive bone defects]. Genij Ortopedii [Orthopaedic Genius]. 2019;25(1):49-57. (In Russian). doi: 10.18019/1028-4427-2019-25-1-49-57.
- Khominets V.V., Vorobev K.A., Sokolova M.O., Ivanova A.K., Komarov A.V. [Allogeneic osteoplastic materials for reconstructive surgery of combat injuries]. Izvestiya Rossiiskoi Voenno-meditsinskoi akademii [Russian Military Medical Academy Reports]. 2022;41(3):309- 314. (In Russian). doi: 10.17816/rmmar109090.
- Bai X., Gao M., Syed S., Zhuang J., Xu X., Zhang X.Q. Bioactive hydrogels for bone regeneration. Bioact Mater. 2018;3(4):401-417. doi: 10.1016/j.bioactmat.2018.05.006.
- van der Heide D., Cidonio G., Stoddart M.J., D’Este M. 3D printing of inorganic-biopolymer composites for bone regeneration. Biofabrication. 2022;14(4). doi: 10.1088/1758-5090/ac8cb2.
- Wu Y., Zeng W., Xu J., Sun Y., Huang Y., Xiang D. et al. Preparation, physicochemical characterization, and in vitro and in vivo osteogenic evaluation of a bioresorbable, moldable, hydroxyapatite/poly(caprolactone-co-lactide) bone substitute. J Biomed Mater Res A. 2023;111(3):367-377. doi: 10.1002/jbm.a.37463.
- Kitamura M., Ohtsuki C., Iwasaki H., Ogata S., Tanihara M., Miyazaki T. The controlled resorption of porous alpha-tricalcium phosphate using a hydroxypropylcellulose coating. J Mater Sci Mater Med. 2004;15(10): 1153-1158. doi: 10.1023/B:JMSM.0000046399.40310.47.
- Bohner M. Resorbable biomaterials as bone graft substitutes. 2010;13(1-2):24-30. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1369702110700146. doi: 10.1016/S1369-7021(10)70014-6.
- Hing K.A. Bioceramic bone graft substitutes: influence of porosity and chemistry. Int J Appl Ceram Technol. 2005;2(3):184-199. doi: 10.1111/j.1744-7402.2005.02020.x.
- Komlev V.S., Bozo I.I., Deev R.V., Gurin A.N. Bioactivity and effect of bone formation for octacalcium phosphate ceramics. In: Octacalcium Phosphate Biomaterials. 2020. p. 85-119. doi: 10.1016/B978-0-08-102511-6.00005-4. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780081025116000054.
- Suzuki O. Octacalcium phosphate: osteoconductivity and crystal chemistry. Acta Biomater. 2010;6(9):3379-3387. doi: 10.1016/j.actbio.2010.04.002.
- Miño-Fariña N., Muñoz-Guzón F., López-Peña M., Ginebra M.P., Del Valle-Fresno S., Ayala D. et al. Quantitative analysis of the resorption and osteoconduction of a macroporous calcium phosphate bone cement for the repair of a critical size defect in the femoral condyle. Vet J. 2009;179(2):264-272. doi: 10.1016/j.tvjl.2007.09.011.
- Sutradhar A., Paulino G.H., Miller M.J., Nguyen T.H. Topological optimization for designing patient-specific large craniofacial segmental bone replacements. Proc Natl Acad Sci USA. 2010;107(30):13222-13227. doi: 10.1073/pnas.1001208107.
- Al-Tamimi A.A., Peach C., Fernandes P.R., Cseke A., Bartolo P.J.D.S. Topology Optimization to Reduce the Stress Shielding Effect for Orthopedic Applications. Procedia CIRP. 2017;65:202-206. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2212827117305425.
- Querin O.M., Victoria M., Alonso C., Ansola R., Martí P. Topology Optimization as a Digital Design Tool. In: Topology Design Methods for Structural Optimization. Elsevier; 2017. p. 93-111. doi: 10.1016/B978-0-08-100916-1.00006-4. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780081009161000064.
- Tikhonov A.A., Yevdokimov P.V., Putlyayev V.I., Safronova T.V., Filippov Ya.Yu. [On architecture of osteoconductive bioceramic implants]. Materialovedenie [Materials Science]. 2018;(8):43-48. (In Russian). doi: 10.31044/1684-579Х-2018-0-8-43-48.
- Kapfer S.C., Hyde S.T., Mecke K., Arns C.H., Schröder-Turk G.E. Minimal surface scaffold designs for tissue engineering. Biomaterials. 2011;32(29):6875-6882. doi: 10.1016/j.biomaterials.2011.06.012.
- Tikhonov A.A., Kukueva E.V., Evdokimov P.V., Klimashina E.S., Putlyaev V.I., Shcherbakov I.M. et al. [Synthesis of substituted octacalcium phosphate for filling composite implants based on polymer hydrogels produced by stereolithographic 3d printing] Neorganicheskie materialy [Inorganic Materials]. 2018;54(10):1123-1132. (In Russian). doi: 10.1134/s0002337x18100172.
- Schindelin J., Arganda-Carreras I., Frise E., Kaynig V., Longair M., Pietzsch T. et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676-682. doi: 10.1038/nmeth.2019.
- Mohiuddin O.A., Campbell B., Poche J.N., Ma M., Rogers E., Gaupp D. et al. Decellularized Adipose Tissue Hydrogel Promotes Bone Regeneration in Critical-Sized Mouse Femoral Defect Model. Front Bioeng Biotechnol. 2019;7:211. doi: 10.3389/fbioe.2019.00211.
- Dau M., Ganz C., Zaage F., Frerich B., Gerber T. Hydrogel-embedded nanocrystalline hydroxyapatite granules (Elastic blocks) based on a cross-linked polyvinylpyrrolidone as bone grafting substitute in a rat tibia model. Int J Nanomedicine. 2017;12:7393-7404.
- Frasca S., Norol F., Le Visage C., Collombet J.M., Letourneur D., Holy X. et al. Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats. J Mater Sci Mater Med. 2017;28(2):35. doi: 10.1007/s10856-016-5839-6.
- Lohmann P., Willuweit A., Neffe A.T., Geisler S., Gebauer T.P., Beer S. et al. Bone regeneration induced by a 3D architectured hydrogel in a rat critical-size calvarial defect. Biomaterials. 2017;113:158-169. doi: 10.1016/j.biomaterials.2016.10.039.
- Karalkin P.A., Sergeeva N.S., Komlev V.S., Sviridova I.K., Kirsanova V.A., Akhmedova S.A. et al. [Biocompatibility and osteoplastic properties of mineral polymer composite materials based on sodium alginate, gelatin, and calcium phosphates intended for 3d-printing of the constructions for bone replacement]. Geny i kletki [Genes and Cells]. 2016;11(3):94-101. (In Russian).
- Muraev A.A., Bonartsev A.P., Gazhva Yu.V., Riabova V.M., Volkov A.V., Zharkova I.I., et al. [Development and Preclinical Studies of Orthotopic Bone Implants Based on a Hybrid Construction from Poly(3-Hydroxybutyrate) and Sodium Alginate]. Sovremennye tehnologii v medicine [Modern Technologies in Medicine]. 2016;8(4):42. (In Russian). doi: 10.17691/stm2016.8.4.06.
- Bi S., Wang P., Hu S., Li S., Pang J., Zhou Z. et al. Construction of physical-crosslink chitosan/PVA double-network hydrogel with surface mineralization for bone repair. Carbohydr Polym. 2019;224:115176. doi: 10.1016/j.carbpol.2019.115176.
- Luneva S.N., Talashova I.A., Osipova E.V., Nakoskin A.N., Emanov A.A. [Influence of the Composition of Biocomposite Materials Implanted in Perforated Metaphyseal Defects on Reparative Regeneration and Mineralization of Bone Tissue] Byulleten’ eksperimental’noi biologii i meditsiny [Bulletin of Experimental Biology and Medicine]. 2013;156(8): 255-259. (In Russian).
- Susin C., Lee J., Fiorini T., Koo K.T., Schüpbach P., Finger Stadler A. et al. Screening of Hydroxyapatite Biomaterials for Alveolar Augmentation Using a Rat Calvaria Critical-Size Defect Model: Bone Formation/Maturation and Biomaterials Resolution. Biomolecules. 2022;12(11):1677. doi: 10.3390/biom12111677.
- Wang M., Gu Z., Li B., Zhang J., Yang L., Zheng X. et al. Bioactive Nanocomposite Microsponges for Effective Reconstruction of Critical-Sized Calvarial Defects in Rat Model. Int J Nanomedicine. 2022;17:6593-6606. doi: 10.2147/IJN.S389194.
- van der Stok J., Koolen M.K., de Maat M.P., Yavari S.A., Alblas J., Patka P. et al. Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels. Eur Cell Mater. 2015;29:141-153; discussion 153-154. doi: 10.22203/ecm.v029a11.
- Ando K., Imagama S., Kobayashi K., Ito K., Tsushima M., Morozumi M. et al. Effects of a self-assembling peptide as a scaffold on bone formation in a defect. PLoS One. 2018;13(1):e0190833. doi: 10.1371/journal.pone.0190833.
Supplementary files
