Full Text:   <740>

Summary:  <191>

CLC number: R318.08

On-line Access: 2017-11-06

Received: 2016-09-29

Revision Accepted: 2017-02-20

Crosschecked: 2017-10-20

Cited: 0

Clicked: 1737

Citations:  Bibtex RefMan EndNote GB/T7714


Bing Zhang


Han Wu


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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.11 P.963-976


Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration

Author(s):  Bing Zhang, Pei-biao Zhang, Zong-liang Wang, Zhong-wen Lyu, Han Wu

Affiliation(s):  Department of Clinical Laboratory, Second Hospital of Jilin University, Changchun 130041, China; more

Corresponding email(s):   drwuhan@163.com

Key Words:  Nanocomposite, Surface modification, Bone marrow mesenchymal stem cells, Biomineralization, Bone repair

Bing Zhang, Pei-biao Zhang, Zong-liang Wang, Zhong-wen Lyu, Han Wu. Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration[J]. Journal of Zhejiang University Science B, 2017, 18(11): 963-976.

@article{title="Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration",
author="Bing Zhang, Pei-biao Zhang, Zong-liang Wang, Zhong-wen Lyu, Han Wu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration
%A Bing Zhang
%A Pei-biao Zhang
%A Zong-liang Wang
%A Zhong-wen Lyu
%A Han Wu
%J Journal of Zhejiang University SCIENCE B
%V 18
%N 11
%P 963-976
%@ 1673-1581
%D 2017
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600412

T1 - Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration
A1 - Bing Zhang
A1 - Pei-biao Zhang
A1 - Zong-liang Wang
A1 - Zhong-wen Lyu
A1 - Han Wu
J0 - Journal of Zhejiang University Science B
VL - 18
IS - 11
SP - 963
EP - 976
%@ 1673-1581
Y1 - 2017
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600412

Objective: A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapatite (g-HA)/poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. Methods: A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were observed by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. Results: After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HA/PLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HA/PLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HA/PLGA at 2–8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HA/PLGA, while only fibrous tissues formed in PLGA. Conclusions: The incorporation of g-HA mainly improved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone formation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.


方法:应用溶剂浇铸和粒子沥滤方法将PLGA和g-HA制备成复合支架g-HA/PLGA。在g-HA/PLGA支架上接种兔自体MSCs制成组织工程移植物。取宽0.3 cm长2.0 cm的上述移植物埋入兔背部肌肉内,8周后取出移植物,使用扫描式电子显微镜(SEM)检测人工骨的组织相容性(图3a),X射线能量色散谱(EDX)分析钙浓度。然后,用锯锯掉兔前肢桡骨骨干2.0 cm,取同样长度的上述移植物放置于骨缺损处(图4)。术后2、4、8周应用计算机X线摄影(CR)检测骨缺损愈合情况(图5),组织学分析愈合组织结构(图6),SEM检测人工骨与周围组织的相容性(图7),反转录聚合酶链式反应(RT-PCR)检测愈合组织Collagen I、Collagen II和Bmp-2基因的表达。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Alsberg, E., Anderson, K.W., Albeiruti, A., et al., 2001. Cell-interactive alginate hydrogels for bone tissue engineering. J. Dent. Res., 80(11):2025-2029.

[2]Bruder, S.P., Jaiswal, N., Haynesworth, S.E., 1997. Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J. Cell Biochem., 64(2):278-294.

[3]Chen, W.C., Anderson, K.W., Albeiruti, A., et al., 2011. Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type II collagen scaffold. Cytotechnology, 63(1):13-23.

[4]Ciapetti, G., Ambrosio, L., Savarino, L., et al., 2003. Osteoblast growth and function in porous poly epsilon-caprolactone matrices for bone repair: a preliminary study. Biomaterials, 24(21):3815-3824.

[5]Cleries, L., Fernandez-Pradas, J.M., Morenza, J.L., 2000. Behavior in simulated body fluid of calcium phosphate coatings obtained by laser ablation. Biomaterials, 21(18):1861-1865.

[6]Cordonnier, T., Layrolle, P., Gaillard, J., et al., 2010. 3D environment on human mesenchymal stem cells differentiation for bone tissue engineering. J. Mater. Sci. Mater. Med., 21(3):981-987.

[7]de Santis, R., Russo, A., Gloria, A., et al., 2015. Towards the design of 3D fiber-deposited poly(ε-caprolactone)/iron doped hydroxyapatite nanocomposite magnetic scaffolds for bone regeneration. J. Biomed. Nanotechnol., 11(7):1236-1246.

[8]Drosse, I., Volkmer, E., Capanna, R., et al., 2008. Tissue engineering for bone defect healing: an update on a multi-component approach. Injury, 39(Suppl. 2):S9-S20.

[9]Fuchs, J.R., Hannouche, D., Terada, S., et al., 2003. Fetal tracheal augmentation with cartilage engineered from bone marrow-derived mesenchymal progenitor cells. J. Pediatr. Surg., 38(6):984-987.

[10]Groeneveld, E.H., van den Bergh, J.P., Holzmann, P., et al., 1999. Mineralization processes in demineralized bone matrix grafts in human maxillary sinus floor elevations. J. Biomed. Mater. Res., 48(4):393-402.

[11]Hong, Z.K., Qiu, X.Y., Sun, J.R., et al., 2004. Grafting polymerization of L-lactide on the surface of hydroxyapatite nano-crystals. Polymer, 45(19):6699-6706.

[12]Hong, Z.K., Zhang, P.B., He, C.L., et al., 2005. Nano-composite of poly(L-lactide) and surface grafted hydroxyapatite: mechanical properties and biocompatibility. Biomaterials, 26(32):6296-6304.

[13]Hong, Z.K., Zhang, P.B., Liu, A.X., et al., 2007. Composites of poly(lactide-co-glycolide) and the surface modified carbonated hydroxyapatite nanoparticles. J. Biomed. Mater. Res. A, 81A(3):515-522.

[14]Huang, J., Yao, C.L., Wei, Y.H., et al., 2011. Repair of bone defect in caprine tibia using a laminated scaffold with bone marrow stromal cells loaded poly(L-lactic acid)/β-tricalcium phosphate. Artif. Organs, 35(1):49-57.

[15]Ishikawa, H., Kitoh, H., Sugiura, F., et al., 2007. The effect of recombinant human bone morphogenetic protein-2 on the osteogenic potential of rat mesenchymal stem cells after several passages. Acta Orthop., 78(2):285-292.

[16]Jeong, S.I., Ko, E.K., Yum, J., et al., 2008. Nanofibrous poly(lactic acid)/hydroxyapatite composite scaffolds for guided tissue regeneration. Macromol. Biosci., 8(4):328-338.

[17]Jie, W., Li, Y., 2004. Tissue engineering scaffold material of nano-apatite crystals and polyamide composite. J. Eur. Polym., 40(3):509-515.

[18]Jung, Y., Kim, S.S., Kim, Y.H., et al., 2005. A poly(lactic acid)/calcium metaphosphate composite for bone tissue engineering. Biomaterials, 26(32):6314-6322.

[19]Karageorgiou, V., Kaplan, D., 2005. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 26(27):5474-5491.

[20]Katsara, O., Mahaira, L.G., Iliopoulou, E.G., et al., 2011. Effects of donor age, gender, and in vitro cellular aging on the phenotypic, functional, and molecular characteristics of mouse bone marrow-derived mesenchymal stem cells. Stem Cells Dev., 20(9):1549-1561.

[21]Kim, S.S., Sun Park, M., Jeon, O., et al., 2006. Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering. Biomaterials, 27(8):1399-1409.

[22]Li, J., Hong, J., Zheng, Q., et al., 2011. Repair of rat cranial bone defects with nHAC/PLLA and BMP-2-related peptide or rhBMP-2. J. Orthop. Res., 29(11):1745-1752.

[23]Li, W.J., Tuli, R., Okafor, C., et al., 2005. A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials, 26(6):599-609.

[24]Mastrogiacomo, M., Scaglione, S., Martinetti, R., et al., 2006. Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics. Biomaterials, 27(17):3230-3237.

[25]Mokbel, N., Bou Serhal, C., Matni, G., et al., 2008. Healing patterns of critical size bony defects in rat following bone graft. Oral Maxillofac. Surg., 12(2):73-78.

[26]Nakahara, H., Goldberg, V.M., Caplan, A.I., 1992. Culture-expanded periosteum-derived cells exhibit osteochondrogenic potential in porous calcium phosphate ceramics in vivo. Clin. Orthop., 276:291-298.

[27]Nishikawa, M., Myoui, A., Ohgushi, H., et al., 2004. Bone tissue engineering using novel interconnected porous hydroxyapatite ceramics combined with marrow mesenchymal cells: quantitative and three-dimensional image analysis. Cell Transplant., 13(4):367-376.

[28]Roostaeian, J., Carlsen, B., Simhaee, D., et al., 2006. Characterization of growth and osteogenic differentiation of rabbit bone marrow stromal cells. J. Surg. Res., 133(2):76-83.

[29]Sena, L.A., Caraballo, M.M., Rossi, A.M., et al., 2009. Synthesis and characterization of biocomposites with different hydroxyapatite-collagen ratios. J. Mater. Sci. Mater. Med., 20(12):2395-2400.

[30]Stone, K.R., Steadman, J.R., Rodkey, W.G., et al., 1997. Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data. J. Bone Joint Surg. Am., 79(12):1770-1777.

[31]Sugiura, F., Kitoh, H., Ishiguro, N., 2004. Osteogenic potential of rat mesenchymal stem cells after several passages. Biochem. Biophys. Res. Commun., 316(1):233-239.

[32]Tae, S.K., Lee, S.H., Park, J.S., et al., 2006. Mesenchymal stem cells for tissue engineering and regenerative medicine. Biomed. Mater., 1(2):63-71.

[33]Tu, J., Wang, H., Li, H., et al., 2009. The in vivo bone formation by mesenchymal stem cells in zein scaffolds. Biomaterials, 30(26):4369-4376.

[34]Ueno, T., Honda, K., Hirata, A., et al., 2008. Histological comparison of bone induced from autogenously grafted periosteum with bone induced from autogenously grafted bone marrow in the rat calvarial defect model. Acta Histochem., 110(3):217-223.

[35]Vacanti, C.A., Kim, W., Upton, J., et al., 1993. Tissue-engineered growth of bone and cartilage. Transplant. Proc., 25(1 Pt 2):1019-1021.

[36]Wang, Z., Yu, Y., Wang, Y., et al., 2016. Enhanced in vitro mineralization and in vivo osteogenesis of composite scaffolds through controlled surface grafting of L-actic acid oligomer on nanohydroxyapatite. Biomacromolecules, 17(3):818-829.

[37]Zhang, P., Hong, Z., Yu, T., et al., 2009. In vivo mineralization and osteogenesis of nanocomposite scaffold of poly (lactide-co-glycolide) and hydroxyapatite surface-grafted with poly(L-lactide). Biomaterials, 30(1):58-70.

[38]Zhang, R., Ma, P.X., 1999. Poly(α-hydroxyl acids)/hydroxyapatite porous composites for bone-tissue engineering. I. Preparation and morphology. J. Biomed. Mater. Res., 44(4):446-455.

[39]Zhou, S., Greenberger, J.S., Epperly, M.W., et al., 2008. Age-related intrinsic changes in human bone-marrowderived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell, 7(3):335-343.

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