Research progress on osteochondral tissue engineering_Journal of Biomedical Engineering

Authors：

LAN Weiwei ¹ ,  CHEN Weiyi ^1,2 , HUANG Di ^1,2

1. Department of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, P.R.China;
2. Shanxi Key Laboratory of Material Strength & Structural Impact, Institute of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, P.R.China;

Corresponding author：

Keywords：

osteochondral defects; tissue-engineering; seeding cells; cytokines; scaffolds

DOI：

10.7507/1001-5515.201810001

Video：

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Osteochondral defects is a common clinical joint disease. The complexity of cartilage-bone interface and the poor self-repair capacity of cartilage are both reasons for current relatively limited clinical treatments. The introduction of tissue engineering provides a new treatment method for osteochondral repair. This paper reviews three main elements of cartilage-bone tissue engineering: seed cell source and culture method, cytokines regulation and synergistic effect, and scaffold components and type. We mainly focused on current status quo and future progress of cartilage-bone repair scaffolds. This paper provides some reference for the further development of osteochondral tissue engineering.

Citation： LAN Weiwei, CHEN Weiyi, HUANG Di. Research progress on osteochondral tissue engineering. Journal of Biomedical Engineering, 2019, 36(3): 504-510. doi: 10.7507/1001-5515.201810001 Copy

1.	Huey D J, Hu J C, Athanasiou K A. Unlike bone, cartilage regeneration remains elusive. Science, 2012, 338(6109): 917-921.
2.	张学亮, 刘舒云, 郭维民, 等. 骨软骨一体化仿生支架的研究现状与展望. 中国医药生物技术, 2017, 12(4): 350-355.
3.	Algul D, Sipahi H, Aydin A, et al. Biocompatibility of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue. International Journal of Biological Macromolecules, 2015, 79: 363-369.
4.	Levingstone T J, Matsiko A, Dickson G R, et al. A biomimetic multi-layered collagen-based scaffold for osteochondral repair. Acta Biomater, 2014, 10(5): 1996-2004.
5.	Ji Wenchen, Zhang Xiaowei, Qiu Yusheng. Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury. World Journal of Experimental Medicine, 2016, 6(3): 58-62.
6.	Yan Leping, Silva-Correia J, Oliveira M B, et al. Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: in vitro and in vivo assessment of biological performance. Acta Biomater, 2015, 12(1): 227-241.
7.	Algul D, Gokce A, Onal A, et al. In vitro release and in vivo biocompatibility studies of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue. J Biomater Sci Polym Ed, 2016, 27(5): 431-440.
8.	You Baihao, Li Qingtao, Dong Hua, et al. Bilayered HA/CS/PEGDA hydrogel with good biocompatibility and self-healing property for potential application in osteochondral defect repair. Journal of Materials Science & Technology, 2018, 34(6): 1016-1025.
9.	王永成. 一体化关节软骨细胞外基质/羟基磷灰石双相支架构建与骨软骨界面组织工程应用, 北京: 中国人民解放军医学院, 2014.
10.	张治金, 全仁夫, 岳振双, 等. 软骨组织工程中种子细胞的研究进展. 中国医药导报, 2017, 14(23): 36-39.
11.	Radhakrishnan J, Manigandan A, Chinnaswamy P, et al. Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration. Biomaterials, 2018, 162: 82-98.
12.	Zhang T, Xie J, Sun K, et al. Physiological oxygen tension modulates soluble growth factor profile after crosstalk between chondrocytes and osteoblasts. Cell Prolif, 2016, 49(1): 122-133.
13.	Nakaoka R, Hsiong S X, Mooney D J. Regulation of chondrocyte differentiation level via co-culture with osteoblasts. Tissue Eng, 2006, 12(9): 2425-2433.
14.	Ng J, Bernhard J, Vunjak-Novakovic G. Mesenchymal stem cells for osteochondral tissue engineering. Methods Mol Biol, 2016, 1416: 35-54.
15.	Yao Hang, Kang Junpei, Li Weichang, et al. Novel β-TCP/PVA bilayered hydrogels with considerable physical and bio-functional properties for osteochondral repair. Biomedical Materials, 2018, 13(1): 015012.
16.	Sartori M, Pagani S, Ferrari A, et al. A new bi-layered scaffold for osteochondral tissue regeneration: in vitro and in vivo preclinical investigations. Mater Sci Eng C Mater Biol Appl, 2017, 70(1): 101-111.
17.	Chiu L L Y, Bianco J, Giardini-Rosa R, et al. Direct and indirect co-culture of bone marrow stem cells and adipose-derived stem cells with chondrocytes in 3D scaffold-free culture. Journal of Regenerative Medicine and Tissue Engineering, 2016, 5: 1.
18.	Ehnert S, van Griensven M, Unger M A, et al. Co-culture with human osteoblasts and exposure to extremely low frequency pulsed electromagnetic fields improve osteogenic differentiation of human adipose-derived mesenchymal stem cells. International Journal of Molecular Sciences, 2018, 19(4): 994-1008.
19.	Mendes L F, Katagiri H, Tam W L, et al. Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo. Stem Cell Res Ther, 2018, 9(1): 42-56.
20.	Khorshidi S, Karkhaneh A. A review on gradient hydrogel/fiber scaffolds for osteochondral regeneration. Journal of Tissue Engineering and Regenerative Medicine, 2018, 12(4): e1974-e1990.
21.	Krishnakumar G S, Roffi A, Reale D, et al. Clinical application of bone morphogenetic proteins for bone healing: a systematic review. Int Orthop, 2017, 41(6): 1073-1083.
22.	Brigaud I, Agniel R, Leroy-Dudal J A, et al. Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto hydroxyapatite coatings: a comparative study. Acta Biomater, 2017, 55: 481-492.
23.	Sheikh Z, Javaid M A, Hamdan N, et al. Bone regeneration using bone morphogenetic proteins and various biomaterial carriers. Materials, 2015, 8(4): 1778-1816.
24.	Yao Q, Jing J, Zeng Q, et al. Bilayered BMP2 eluting coatings on graphene foam by electrophoretic deposition: electro-responsive BMP2 release and enhancement of osteogenic differentiation. ACS Appl Mater Interfaces, 2017, 9(46): 39962-39970.
25.	Han Fengxuan, Li Bin, Yang Huilin, et al. Chitosan-gelatin hydrogel/PLGA scaffold with dual-delivery of TGF-β1 and BMP-2 for osteochondral defect repair. Journal of Controlled Release, 2017, 259: e34-e35.
26.	Du Y, Liu H, Yang Q, et al. Selective laser sintering scaffold with hierarchical architecture and gradient composition for osteochondral repair in rabbits. Biomaterials, 2017, 137: 37-48.
27.	Wang Yanen, Wang Kai, Li Xinpei, et al. 3D fabrication and characterization of phosphoric acid scaffold with a HA/β-TCP weight ratio of 60: 40 for bone tissue engineering applications. PLoS One, 2017, 12(4): e0174870.
28.	Effendi M D, Gustiono D, Lukmana, et al. Comparison on mechanical properties of single layered and bilayered chitosan-gelatin coated porous hydroxyapatite scaffold prepared through freeze drying method. IOP Conference Series: Materials Science and Engineering, 2017, 172(1): 012031.
29.	Li Ang, Wei Yiyong, Hung C, et al. Chondrogenic properties of collagen type XI, a component of cartilage extracellular matrix. Biomaterials, 2018, 173: 47-57.
30.	Tamaddon M, Burrows M, Ferreira S A, et al. Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro. Scientific Reports, 2017, 7: 43519-43529.
31.	Cholas R, Padmanabhan S K, Gervaso F, et al. Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix. Mater Sci Eng: C, 2016, 63: 499-505.
32.	Lin Kaifeng, He Shu, Song Yue, et al. Low-temperature additive manufacturing of biomimic three-dimensional hydroxyapatite/collagen scaffolds for bone regeneration. ACS Appl Mater Interfaces, 2016, 8(11): 6905-6916.
33.	Seong Y J, Kang I G, Song E H, et al. Calcium phosphate-collagen scaffold with aligned pore channels for enhanced osteochondral regeneration. Advanced Healthcare Materials, 2017, 6(24): 1700966.
34.	Ruan Shiqiang, Yan Ling, Deng Jiang, et al. Preparation of a biphase composite scaffold and its application in tissue engineering for femoral osteochondral defects in rabbits. Int Orthop, 2017, 41(9): 1899-1908.
35.	Deng B, Wang F, Yin L, et al. Quantitative study on morphology of calcified cartilage zone in OARSI 0-4 cartilage from osteoarthritic knees. Current Research in Translational Medicine, 2016, 64(3): 149-154.
36.	Su Cui, Su Yunlan, Li Zhiyong, et al. In situ synthesis of bilayered gradient poly(vinylalcohol)/hydroxyapatite composite hydrogel by directional freezing-thawing and electrophoresis method. Materials Science and Engineering: C, 2017: 76-83.
37.	Chen Li, Wu Zhenxu, Zhou Yulai, et al. Biomimetic porous collagen/hydroxyapatite scaffold for bone tissue engineering. Journal of Applied Polymer Science, 2017, 134(37): 45271.
38.	Nowicki M A, Castro N J, Plesniak M W. 3D printing of novel osteochondral scaffolds with graded microstructure. Nanotechnology, 2016, 27(41): 414001.
39.	Deng C, Zhu H, Li J, et al. Bioactive scaffolds for regeneration of cartilage and subchondral bone interface. Theranostics, 2018, 8(7): 1940-1955.
40.	Perdisa F, Filardo G, Sessa A, et al. One-step treatment for patellar cartilage defects with a cell-free osteochondral scaffold. American Journal of Sports Medicine, 2017, 45(1): 1581-1588.
41.	Perdisa F, Kon E, Sessa A, et al. Treatment of knee osteochondritis dissecans with a cell-free biomimetic osteochondral scaffold clinical and imaging findings at midterm follow-up. American Journal of Sports Medicine, 2018, 46(2): 314-321.

1. Huey D J, Hu J C, Athanasiou K A. Unlike bone, cartilage regeneration remains elusive. Science, 2012, 338(6109): 917-921.
2. 张学亮, 刘舒云, 郭维民, 等. 骨软骨一体化仿生支架的研究现状与展望. 中国医药生物技术, 2017, 12(4): 350-355.
3. Algul D, Sipahi H, Aydin A, et al. Biocompatibility of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue. International Journal of Biological Macromolecules, 2015, 79: 363-369.
4. Levingstone T J, Matsiko A, Dickson G R, et al. A biomimetic multi-layered collagen-based scaffold for osteochondral repair. Acta Biomater, 2014, 10(5): 1996-2004.
5. Ji Wenchen, Zhang Xiaowei, Qiu Yusheng. Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury. World Journal of Experimental Medicine, 2016, 6(3): 58-62.
6. Yan Leping, Silva-Correia J, Oliveira M B, et al. Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: in vitro and in vivo assessment of biological performance. Acta Biomater, 2015, 12(1): 227-241.
7. Algul D, Gokce A, Onal A, et al. In vitro release and in vivo biocompatibility studies of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue. J Biomater Sci Polym Ed, 2016, 27(5): 431-440.
8. You Baihao, Li Qingtao, Dong Hua, et al. Bilayered HA/CS/PEGDA hydrogel with good biocompatibility and self-healing property for potential application in osteochondral defect repair. Journal of Materials Science & Technology, 2018, 34(6): 1016-1025.
9. 王永成. 一体化关节软骨细胞外基质/羟基磷灰石双相支架构建与骨软骨界面组织工程应用, 北京: 中国人民解放军医学院, 2014.
10. 张治金, 全仁夫, 岳振双, 等. 软骨组织工程中种子细胞的研究进展. 中国医药导报, 2017, 14(23): 36-39.
11. Radhakrishnan J, Manigandan A, Chinnaswamy P, et al. Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration. Biomaterials, 2018, 162: 82-98.
12. Zhang T, Xie J, Sun K, et al. Physiological oxygen tension modulates soluble growth factor profile after crosstalk between chondrocytes and osteoblasts. Cell Prolif, 2016, 49(1): 122-133.
13. Nakaoka R, Hsiong S X, Mooney D J. Regulation of chondrocyte differentiation level via co-culture with osteoblasts. Tissue Eng, 2006, 12(9): 2425-2433.
14. Ng J, Bernhard J, Vunjak-Novakovic G. Mesenchymal stem cells for osteochondral tissue engineering. Methods Mol Biol, 2016, 1416: 35-54.
15. Yao Hang, Kang Junpei, Li Weichang, et al. Novel β-TCP/PVA bilayered hydrogels with considerable physical and bio-functional properties for osteochondral repair. Biomedical Materials, 2018, 13(1): 015012.
16. Sartori M, Pagani S, Ferrari A, et al. A new bi-layered scaffold for osteochondral tissue regeneration: in vitro and in vivo preclinical investigations. Mater Sci Eng C Mater Biol Appl, 2017, 70(1): 101-111.
17. Chiu L L Y, Bianco J, Giardini-Rosa R, et al. Direct and indirect co-culture of bone marrow stem cells and adipose-derived stem cells with chondrocytes in 3D scaffold-free culture. Journal of Regenerative Medicine and Tissue Engineering, 2016, 5: 1.
18. Ehnert S, van Griensven M, Unger M A, et al. Co-culture with human osteoblasts and exposure to extremely low frequency pulsed electromagnetic fields improve osteogenic differentiation of human adipose-derived mesenchymal stem cells. International Journal of Molecular Sciences, 2018, 19(4): 994-1008.
19. Mendes L F, Katagiri H, Tam W L, et al. Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo. Stem Cell Res Ther, 2018, 9(1): 42-56.
20. Khorshidi S, Karkhaneh A. A review on gradient hydrogel/fiber scaffolds for osteochondral regeneration. Journal of Tissue Engineering and Regenerative Medicine, 2018, 12(4): e1974-e1990.
21. Krishnakumar G S, Roffi A, Reale D, et al. Clinical application of bone morphogenetic proteins for bone healing: a systematic review. Int Orthop, 2017, 41(6): 1073-1083.
22. Brigaud I, Agniel R, Leroy-Dudal J A, et al. Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto hydroxyapatite coatings: a comparative study. Acta Biomater, 2017, 55: 481-492.
23. Sheikh Z, Javaid M A, Hamdan N, et al. Bone regeneration using bone morphogenetic proteins and various biomaterial carriers. Materials, 2015, 8(4): 1778-1816.
24. Yao Q, Jing J, Zeng Q, et al. Bilayered BMP2 eluting coatings on graphene foam by electrophoretic deposition: electro-responsive BMP2 release and enhancement of osteogenic differentiation. ACS Appl Mater Interfaces, 2017, 9(46): 39962-39970.
25. Han Fengxuan, Li Bin, Yang Huilin, et al. Chitosan-gelatin hydrogel/PLGA scaffold with dual-delivery of TGF-β1 and BMP-2 for osteochondral defect repair. Journal of Controlled Release, 2017, 259: e34-e35.
26. Du Y, Liu H, Yang Q, et al. Selective laser sintering scaffold with hierarchical architecture and gradient composition for osteochondral repair in rabbits. Biomaterials, 2017, 137: 37-48.
27. Wang Yanen, Wang Kai, Li Xinpei, et al. 3D fabrication and characterization of phosphoric acid scaffold with a HA/β-TCP weight ratio of 60: 40 for bone tissue engineering applications. PLoS One, 2017, 12(4): e0174870.
28. Effendi M D, Gustiono D, Lukmana, et al. Comparison on mechanical properties of single layered and bilayered chitosan-gelatin coated porous hydroxyapatite scaffold prepared through freeze drying method. IOP Conference Series: Materials Science and Engineering, 2017, 172(1): 012031.
29. Li Ang, Wei Yiyong, Hung C, et al. Chondrogenic properties of collagen type XI, a component of cartilage extracellular matrix. Biomaterials, 2018, 173: 47-57.
30. Tamaddon M, Burrows M, Ferreira S A, et al. Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro. Scientific Reports, 2017, 7: 43519-43529.
31. Cholas R, Padmanabhan S K, Gervaso F, et al. Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix. Mater Sci Eng: C, 2016, 63: 499-505.
32. Lin Kaifeng, He Shu, Song Yue, et al. Low-temperature additive manufacturing of biomimic three-dimensional hydroxyapatite/collagen scaffolds for bone regeneration. ACS Appl Mater Interfaces, 2016, 8(11): 6905-6916.
33. Seong Y J, Kang I G, Song E H, et al. Calcium phosphate-collagen scaffold with aligned pore channels for enhanced osteochondral regeneration. Advanced Healthcare Materials, 2017, 6(24): 1700966.
34. Ruan Shiqiang, Yan Ling, Deng Jiang, et al. Preparation of a biphase composite scaffold and its application in tissue engineering for femoral osteochondral defects in rabbits. Int Orthop, 2017, 41(9): 1899-1908.
35. Deng B, Wang F, Yin L, et al. Quantitative study on morphology of calcified cartilage zone in OARSI 0-4 cartilage from osteoarthritic knees. Current Research in Translational Medicine, 2016, 64(3): 149-154.
36. Su Cui, Su Yunlan, Li Zhiyong, et al. In situ synthesis of bilayered gradient poly(vinylalcohol)/hydroxyapatite composite hydrogel by directional freezing-thawing and electrophoresis method. Materials Science and Engineering: C, 2017: 76-83.
37. Chen Li, Wu Zhenxu, Zhou Yulai, et al. Biomimetic porous collagen/hydroxyapatite scaffold for bone tissue engineering. Journal of Applied Polymer Science, 2017, 134(37): 45271.
38. Nowicki M A, Castro N J, Plesniak M W. 3D printing of novel osteochondral scaffolds with graded microstructure. Nanotechnology, 2016, 27(41): 414001.
39. Deng C, Zhu H, Li J, et al. Bioactive scaffolds for regeneration of cartilage and subchondral bone interface. Theranostics, 2018, 8(7): 1940-1955.
40. Perdisa F, Filardo G, Sessa A, et al. One-step treatment for patellar cartilage defects with a cell-free osteochondral scaffold. American Journal of Sports Medicine, 2017, 45(1): 1581-1588.
41. Perdisa F, Kon E, Sessa A, et al. Treatment of knee osteochondritis dissecans with a cell-free biomimetic osteochondral scaffold clinical and imaging findings at midterm follow-up. American Journal of Sports Medicine, 2018, 46(2): 314-321.

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Research progress on osteochondral tissue engineering

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