Skip to main content
Top
Published in: Journal of Orthopaedic Surgery and Research 1/2019

Open Access 01-12-2019 | Bone Defect | Research article

Surface mineralized biphasic calcium phosphate ceramics loaded with urine-derived stem cells are effective in bone regeneration

Authors: Fei Xing, Lang Li, Jiachen Sun, Guoming Liu, Xin Duan, Jialei Chen, Ming Liu, Ye Long, Zhou Xiang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

Login to get access

Abstract

Background

Segmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world. Recent developments in tissue engineering have provided a new treatment for segmental bone defects. Urine-derived stem cells (USCs) can be obtained noninvasively and might be a new kind of seed cells used in bone tissue regeneration. Therefore, the first aim of the present study was to investigate the biological characteristics of USCs. The second aim of the present study was to study the osteogenic effect of surface mineralized biphasic calcium phosphate ceramics (BCPs) loaded with USCs in vitro and in vivo.

Methods

We isolated USCs from the urine of healthy adult donors and evaluated the biological characteristics of USCs in vitro. We mineralized the surface of BCPs by simulated body fluid (SBF). Cell adhesion and proliferation of USCs on the surface mineralized BCPs were evaluated. Osteogenic proteins and genes of USCs on the surface mineralized BCPs were texted by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) assay. Critical-sized segmental bone defects model in New Zealand white rabbits were established and randomly divided into 4 groups (surface mineralized BCPs loaded with USCs, BCPs loaded with USCs, surface mineralized BCPs, and BCPs) based on the implant they received. The therapeutic efficacy of the scaffolds in a large bone defect at post-implantation was evaluated by imaging and histological examination.

Results

USCs isolated in our study expressed stem cell-specific phenotypes and had a stable proliferative capacity and multipotential differentiation capability. Surface mineralized BCPs promoted osteogenic proteins and genes expression of USCs without affecting the proliferation of USCs. After 10 weeks, the amount of new bone formation was the highest in the group of surface mineralized BCPs loaded with USCs.

Conclusion

USCs, from non-invasive sources, have good application prospects in the field of bone tissue engineering. Surface mineralized BCPs can significantly enhance osteogenic potential of USCs without changing biological characteristics of BCPs. Surface mineralized BCPs loaded with USCs are effective in repairing of critical-sized segmental bone defects in rabbits.
Literature
1.
go back to reference Sudeepta A, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815.CrossRef Sudeepta A, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815.CrossRef
2.
go back to reference Zhang Y, McNeill E, Tian H, Soker S, Andersson KE, Yoo JJ, Atala A. Urine derived cells are a potential source for urological tissue reconstruction. J Urol. 2008;180(5):2226–33.CrossRef Zhang Y, McNeill E, Tian H, Soker S, Andersson KE, Yoo JJ, Atala A. Urine derived cells are a potential source for urological tissue reconstruction. J Urol. 2008;180(5):2226–33.CrossRef
3.
go back to reference Qin D, Long T, Deng J, Zhang Y. Urine-derived stem cells for potential use in bladder repair. Stem Cell Res Ther. 2014;5(3):69.CrossRef Qin D, Long T, Deng J, Zhang Y. Urine-derived stem cells for potential use in bladder repair. Stem Cell Res Ther. 2014;5(3):69.CrossRef
4.
go back to reference Liu Y, Ma W, Liu B, Wang Y, Chu J, Xiong G, Shen L, Long C, Lin T, He D, Butnaru D, Alexey L, Zhang Y, Zhang D, Wei G. Urethral reconstruction with autologous urine-derived stem cells seeded in three-dimensional porous small intestinal submucosa in a rabbit model. Stem Cell Res Ther. 2017;8(1):63.CrossRef Liu Y, Ma W, Liu B, Wang Y, Chu J, Xiong G, Shen L, Long C, Lin T, He D, Butnaru D, Alexey L, Zhang Y, Zhang D, Wei G. Urethral reconstruction with autologous urine-derived stem cells seeded in three-dimensional porous small intestinal submucosa in a rabbit model. Stem Cell Res Ther. 2017;8(1):63.CrossRef
5.
go back to reference Bharadwaj S, Liu G, Shi Y, Markert C, Andersson KE, Atala A, Zhang Y. Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue engineering. Part A. 2011;17(15-16):2123–32.CrossRef Bharadwaj S, Liu G, Shi Y, Markert C, Andersson KE, Atala A, Zhang Y. Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue engineering. Part A. 2011;17(15-16):2123–32.CrossRef
6.
go back to reference Guan J, Zhang J, Guo S, Zhu H, Zhu Z, Li H, Wang Y, Zhang C, Chang J. Human urine-derived stem cells can be induced into osteogenic lineage by silicate bioceramics via activation of the Wnt/beta-catenin signaling pathway. Biomaterials. 2015;55:1–11.CrossRef Guan J, Zhang J, Guo S, Zhu H, Zhu Z, Li H, Wang Y, Zhang C, Chang J. Human urine-derived stem cells can be induced into osteogenic lineage by silicate bioceramics via activation of the Wnt/beta-catenin signaling pathway. Biomaterials. 2015;55:1–11.CrossRef
7.
go back to reference Franca R, Samani TD, Bayade G, Yahia L, Sacher E. Nanoscale surface characterization of biphasic calcium phosphate, with comparisons to calcium hydroxyapatite and beta-tricalcium phosphate bioceramics. Journal of colloid and interface science. 2014;420:182–8.CrossRef Franca R, Samani TD, Bayade G, Yahia L, Sacher E. Nanoscale surface characterization of biphasic calcium phosphate, with comparisons to calcium hydroxyapatite and beta-tricalcium phosphate bioceramics. Journal of colloid and interface science. 2014;420:182–8.CrossRef
8.
go back to reference Yamasaki H, Sakai H. Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs. Biomaterials. 1992;13(5):308–12.CrossRef Yamasaki H, Sakai H. Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs. Biomaterials. 1992;13(5):308–12.CrossRef
9.
go back to reference Zhang L, Hanagata N, Maeda M, Minowa T, Ikoma T, Fan H, Zhang X. Porous hydroxyapatite and biphasic calcium phosphate ceramics promote ectopic osteoblast differentiation from mesenchymal stem cells. Science and technology of advanced materials. 2009;10(2):025003.CrossRef Zhang L, Hanagata N, Maeda M, Minowa T, Ikoma T, Fan H, Zhang X. Porous hydroxyapatite and biphasic calcium phosphate ceramics promote ectopic osteoblast differentiation from mesenchymal stem cells. Science and technology of advanced materials. 2009;10(2):025003.CrossRef
10.
go back to reference Yuan H, Fernandes H, Habibovic P, de Boer J, Barradas AM, de Ruiter A, Walsh WR, van Blitterswijk CA, de Bruijn JD. Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(31):13614–9.CrossRef Yuan H, Fernandes H, Habibovic P, de Boer J, Barradas AM, de Ruiter A, Walsh WR, van Blitterswijk CA, de Bruijn JD. Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(31):13614–9.CrossRef
11.
go back to reference Yu X, Tang X, Gohil SV, Laurencin CT. Biomaterials for Bone Regenerative Engineering. Advanced Healthcare Materials. 2015;4(9):1268–85.CrossRef Yu X, Tang X, Gohil SV, Laurencin CT. Biomaterials for Bone Regenerative Engineering. Advanced Healthcare Materials. 2015;4(9):1268–85.CrossRef
12.
go back to reference Piattelli A, Scarano A, Mangano C. Clinical and histologic aspects of biphasic calcium phosphate ceramic (BCP) used in connection with implant placement. Biomaterials. 1996;17(18):1767.CrossRef Piattelli A, Scarano A, Mangano C. Clinical and histologic aspects of biphasic calcium phosphate ceramic (BCP) used in connection with implant placement. Biomaterials. 1996;17(18):1767.CrossRef
13.
go back to reference Hench LL, Thompson I. Twenty-first century challenges for biomaterials. Journal of the Royal Society, Interface. 2010;7(Suppl 4):S379–91.PubMedPubMedCentral Hench LL, Thompson I. Twenty-first century challenges for biomaterials. Journal of the Royal Society, Interface. 2010;7(Suppl 4):S379–91.PubMedPubMedCentral
14.
go back to reference Huang L, Zhou B, Wu H, Zheng L, Zhao J. Effect of apatite formation of biphasic calcium phosphate ceramic (BCP) on osteoblastogenesis using simulated body fluid (SBF) with or without bovine serum albumin (BSA), Materials science & engineering. C, Materials for biological applications. 2017;70(Pt 2):955–61.CrossRef Huang L, Zhou B, Wu H, Zheng L, Zhao J. Effect of apatite formation of biphasic calcium phosphate ceramic (BCP) on osteoblastogenesis using simulated body fluid (SBF) with or without bovine serum albumin (BSA), Materials science & engineering. C, Materials for biological applications. 2017;70(Pt 2):955–61.CrossRef
15.
go back to reference Wang J, Chen Y, Zhu X, Yuan T, Tan Y, Fan Y, Zhang X. Effect of phase composition on protein adsorption and osteoinduction of porous calcium phosphate ceramics in mice. Journal of biomedical materials research. Part A. 2014;102(12):4234–43.PubMed Wang J, Chen Y, Zhu X, Yuan T, Tan Y, Fan Y, Zhang X. Effect of phase composition on protein adsorption and osteoinduction of porous calcium phosphate ceramics in mice. Journal of biomedical materials research. Part A. 2014;102(12):4234–43.PubMed
16.
go back to reference Kokubo T, Takadama H. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials. 2006;27(15):2907–15.CrossRef Kokubo T, Takadama H. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials. 2006;27(15):2907–15.CrossRef
17.
go back to reference Patel ZS, Simon Y, Yasuhiko T, Jansen JA, Wong MEK, Mikos AG. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone. 2008;43(5):931–40.CrossRef Patel ZS, Simon Y, Yasuhiko T, Jansen JA, Wong MEK, Mikos AG. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone. 2008;43(5):931–40.CrossRef
18.
go back to reference Bharadwaj S, Liu G, Shi Y, Wu R, Yang B, He T, Fan Y, Lu X, Zhou X, Liu H, Atala A, Rohozinski J, Zhang Y. Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology, Stem cells (Dayton, Ohio). 2013;31(9):1840–56.CrossRef Bharadwaj S, Liu G, Shi Y, Wu R, Yang B, He T, Fan Y, Lu X, Zhou X, Liu H, Atala A, Rohozinski J, Zhang Y. Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology, Stem cells (Dayton, Ohio). 2013;31(9):1840–56.CrossRef
19.
go back to reference Gao P, Han P, Jiang D, Yang S, Cui Q, Li Z. Effects of the donor age on proliferation, senescence and osteogenic capacity of human urine-derived stem cells. Cytotechnology. 2017;69(5):751–63.CrossRef Gao P, Han P, Jiang D, Yang S, Cui Q, Li Z. Effects of the donor age on proliferation, senescence and osteogenic capacity of human urine-derived stem cells. Cytotechnology. 2017;69(5):751–63.CrossRef
20.
go back to reference Kawashita M, Itoh S, Miyamoto K, Takaoka GH. Apatite formation on titanium substrates by electrochemical deposition in metastable calcium phosphate solution. Journal of materials science. Materials in medicine. 2008;19(1):137–42.CrossRef Kawashita M, Itoh S, Miyamoto K, Takaoka GH. Apatite formation on titanium substrates by electrochemical deposition in metastable calcium phosphate solution. Journal of materials science. Materials in medicine. 2008;19(1):137–42.CrossRef
21.
go back to reference Borges FA, Filho Ede A, Miranda MC, Dos Santos ML, Herculano RD, Guastaldi AC. Natural rubber latex coated with calcium phosphate for biomedical application. Journal of biomaterials science. Polymer edition. 2015;26(17):1256–68.CrossRef Borges FA, Filho Ede A, Miranda MC, Dos Santos ML, Herculano RD, Guastaldi AC. Natural rubber latex coated with calcium phosphate for biomedical application. Journal of biomaterials science. Polymer edition. 2015;26(17):1256–68.CrossRef
22.
go back to reference Kokubo T, Kushitani H, Sakka S, Kitsugi T, Yamamuro T. Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. Journal of biomedical materials research. 1990;24(6):721–34.CrossRef Kokubo T, Kushitani H, Sakka S, Kitsugi T, Yamamuro T. Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. Journal of biomedical materials research. 1990;24(6):721–34.CrossRef
23.
go back to reference Pasinli A, Yuksel M, Celik E, Sener S, Tas AC. A new approach in biomimetic synthesis of calcium phosphate coatings using lactic acid-Na lactate buffered body fluid solution. Acta biomaterialia. 2010;6(6):2282–8.CrossRef Pasinli A, Yuksel M, Celik E, Sener S, Tas AC. A new approach in biomimetic synthesis of calcium phosphate coatings using lactic acid-Na lactate buffered body fluid solution. Acta biomaterialia. 2010;6(6):2282–8.CrossRef
24.
go back to reference Pan H, Zhao X, Darvell BW, Lu WW. Apatite-formation ability – Predictor of “bioactivity”? Acta Biomaterialia. 2010;6(11):4181–8.CrossRef Pan H, Zhao X, Darvell BW, Lu WW. Apatite-formation ability – Predictor of “bioactivity”? Acta Biomaterialia. 2010;6(11):4181–8.CrossRef
25.
go back to reference Shin YM, Jo SY, Park JS, Gwon HJ, Jeong SI, Lim YM. Synergistic effect of dual-functionalized fibrous scaffold with BCP and RGD containing peptide for improved osteogenic differentiation. Macromolecular bioscience. 2014;14(8):1190–8.CrossRef Shin YM, Jo SY, Park JS, Gwon HJ, Jeong SI, Lim YM. Synergistic effect of dual-functionalized fibrous scaffold with BCP and RGD containing peptide for improved osteogenic differentiation. Macromolecular bioscience. 2014;14(8):1190–8.CrossRef
26.
go back to reference Guan J, Zhang J, Zhu Z, Niu X, Guo S, Wang Y, Zhang C. Bone morphogenetic protein 2 gene transduction enhances the osteogenic potential of human urine-derived stem cells. Stem Cell Res Ther. 2015;6:5.CrossRef Guan J, Zhang J, Zhu Z, Niu X, Guo S, Wang Y, Zhang C. Bone morphogenetic protein 2 gene transduction enhances the osteogenic potential of human urine-derived stem cells. Stem Cell Res Ther. 2015;6:5.CrossRef
27.
go back to reference Müller L, Müller FA. Preparation of SBF with different content and its influence on the composition of biomimetic apatites. Acta biomaterialia. 2006;2(2):181–9.CrossRef Müller L, Müller FA. Preparation of SBF with different content and its influence on the composition of biomimetic apatites. Acta biomaterialia. 2006;2(2):181–9.CrossRef
28.
go back to reference Zhou C, Hong Y, Zhang X. Applications of nanostructured calcium phosphate in tissue engineering. Biomaterials Science. 2013;1(10):1012–28.CrossRef Zhou C, Hong Y, Zhang X. Applications of nanostructured calcium phosphate in tissue engineering. Biomaterials Science. 2013;1(10):1012–28.CrossRef
29.
go back to reference N. Jaiswal, ., S.E. Haynesworth, A.I. Caplan, S.P. Bruder, Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro, Journal of Cellular Biochemistry 64(2) (2015) 295-312.CrossRef N. Jaiswal, ., S.E. Haynesworth, A.I. Caplan, S.P. Bruder, Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro, Journal of Cellular Biochemistry 64(2) (2015) 295-312.CrossRef
30.
go back to reference Bellows CG, Reimers SM, Heersche JN. Expression of mRNAs for type-I collagen, bone sialoprotein, osteocalcin, and osteopontin at different stages of osteoblastic differentiation and their regulation by 1,25 dihydroxyvitamin D3. Cell and tissue research. 1999;297(2):249–59.CrossRef Bellows CG, Reimers SM, Heersche JN. Expression of mRNAs for type-I collagen, bone sialoprotein, osteocalcin, and osteopontin at different stages of osteoblastic differentiation and their regulation by 1,25 dihydroxyvitamin D3. Cell and tissue research. 1999;297(2):249–59.CrossRef
31.
go back to reference Bala Y, Depalle B, Farlay D, Douillard T, Meille S, Follet H, Chapurlat R, Chevalier J, Boivin G. Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. Journal of Bone & Mineral Research. 2012;27(4):825–34.CrossRef Bala Y, Depalle B, Farlay D, Douillard T, Meille S, Follet H, Chapurlat R, Chevalier J, Boivin G. Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. Journal of Bone & Mineral Research. 2012;27(4):825–34.CrossRef
Metadata
Title
Surface mineralized biphasic calcium phosphate ceramics loaded with urine-derived stem cells are effective in bone regeneration
Authors
Fei Xing
Lang Li
Jiachen Sun
Guoming Liu
Xin Duan
Jialei Chen
Ming Liu
Ye Long
Zhou Xiang
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Bone Defect
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-019-1500-7

Other articles of this Issue 1/2019

Journal of Orthopaedic Surgery and Research 1/2019 Go to the issue