CARTILAGE REPAIR AND SUBCHONDRAL BONE RECONSTRUCTION BASED ON THREE-DIMENSIONAL PRINTING TECHNIQUE_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHANGWeijie ^1,2 ,  LIANQin ¹ , LIDichen ¹ , WANGKunzheng ² , JINZhongmin ^1,3 , BIANWeiguo ⁴ , LIUYaxiong ¹ , HEJiankang ¹ , WANGLing ¹

1. State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an Shaanxi, 710049, P. R. China;
2. the First Department of Orthopaedics, the Second Affiliated Hospital, Xi'an Jiaotong University;
3. Institute of Medical and Biological Engineering, Leeds University, UK;
4. Department of Orthopaedics, the First Affiliated Hospital, Xi'an Jiaotong University;

Corresponding author：

LIANQin, Email: lqiamt@mail.xjtu.edu.cn

Keywords：

Three-dimensional printing technique; Tissue engineered cartilage; Subchondral bone; Microstructural parameter; Cartilage repair; Rabbit

DOI：

10.7507/1002-1892.20140072

Video：

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Objective To investigate whether subchondral bone microstructural parameters are related to cartilage repair during large osteochondral defect repairing based on three-dimensional (3-D) printing technique. Methods Biomimetic biphasic osteochondral composite scaffolds were fabricated by using 3-D printing technique. The right trochlea critical sized defects (4.8 mm in diameter, 7.5 mm in depth) were created in 40 New Zealand white rabbits (aged 6 months, weighing 2.5-3.5 kg). Biomimetic biphasic osteochondral composite scaffolds were implanted into the defects in the experimental group (n=35), and no composite scaffolds implantation served as control group (n=5); the left side had no defect as sham-operation group. Animals of experimental and sham-operation groups were euthanized at 1, 2, 4, 8, 16, 24, and 52 weeks after operation, while animals of control group were sampled at 24 weeks. Subchondral bone microstructural parameters and cartilage repair were quantitatively analyzed using Micro-CT and Wayne scoring system. Correlation analysis and regression analysis were applied to reveal the relationship between subchondral bone parameters and cartilage repair. The subchondral bone parameters included bone volume fraction (BV/TV), bone surface area fraction (BSA/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular spacing (Tb.Sp). Results In the experimental group, articular cartilage repair was significantly improved at 52 weeks postoperatively, which was dominated by hyaline cartilage tissue, and tidal line formed. Wayne scores at 24 and 52 weeks were significantly higher than that at 16 weeks in the experimental group (P<0.05), but no significant difference was found between at 24 and 52 weeks (P>0.05); the scores of experimental group were significantly lower than those of sham-operation group at all time points (P<0.05). In the experimental group, new subchondral bone migrated from the surrounding defect to the centre, and subchondral bony plate formed at 24 and 52 weeks. The microstructural parameters of repaired subchondral bone followed a "twin peaks" like discipline to which BV/TV, BSA/BV, and Tb.N increased at 2 and 16 weeks, and then they returned to normal level. The Tb.Sp showed reversed discipline compared to the former 3 parameters, no significant change was found for Tb.Th during the repair process. Correlation analysis showed that BV/TV, BSA/BV, Tb.Th, Tb.N, and Tb.Sp were all related with gross appearance score and histology score of repaired cartilage. Conclusion Subchondral bone parameters are related with cartilage repair in critical size osteochondral repair in vivo. Microstructural parameters of repaired subchondral bone follow a "twin peaks" like discipline (osteoplasia-remodeling-osteoplasia-remodeling) to achieve reconstruction, 2nd week and 16th week are critical time points for subchondral bone functional restoration.

Citation： ZHANGWeijie, LIANQin, LIDichen, WANGKunzheng, JINZhongmin, BIANWeiguo, LIUYaxiong, HEJiankang, WANGLing. CARTILAGE REPAIR AND SUBCHONDRAL BONE RECONSTRUCTION BASED ON THREE-DIMENSIONAL PRINTING TECHNIQUE. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(3): 318-324. doi: 10.7507/1002-1892.20140072 Copy

1.	Teuschl AH, Nürnberger S, Redl H, et al. Articular cartilage tissue regeneration-current research strategies and outlook for the future. Eur Surg, 2013, 45(3):142-153.
2.	Huey DJ, Hu JC, Athanasiou KA. Unlike bone, cartilage regeneration remains elusive. Science, 2012, 338(6109):917-921.
3.	Mahmoudifar N, Doran PM. Chondrogenesis and cartilage tissue engineering:the longer road to technology development. Trends in Biotechnology, 2012, 30(3):166-176.
4.	Madry H, van Dijk C, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc, 2010, 18(4):419-433.
5.	Gomoll AH, Madry H, Knutsen G, et al. The subchondral bone in articular cartilage repair:current problems in the surgical management. Knee Surg Sports Traumatol Arthrosc, 2010, 18(4):434-447.
6.	National Research Council. Guide for the Care and Use of Laboratory Animals:Eighth Edition. Washington DC:National Academies Press, 2011:11-151.
7.	Bian W, Li D, Lian Q, et al. Fabrication of a bio-inspired beta-Tricalcium phosphate/collagen scaffold based on ceramic stereolithography and gel casting for osteochondral tissue engineering. Rapid Prototyping Journal, 2012, 18(1):68-80.
8.	Li X, Li D, Wang L, et al. Osteoblast cell response to beta-tricalcium phosphate scaffolds with controlled architecture in flow perfusionculture system. J Mater Sci Mater Med, 2008, 19(7):2691-2697.
9.	朱林重, 连芩, 靳忠民, 等. PEGDA 水凝胶的光固化成形工艺及其性能评价. 西安交通大学学报, 2012, 46(10):121-126.
10.	Wayne JS, McDowell CL, Shields KJ, et al. In vivo response of polylactic acid-alginate scaffolds and bone marrow-derived cells for cartilage tissueengineering. Tissue Eng, 2005, 11(5-6):953-963.
11.	Zaslav K, McAdams T, Scopp J, et al. New frontiers for cartilage repair and protection. Cartilage, 2012, 3(1 Suppl):77S-86S.
12.	Hoemann CD, Lafantaisie-Favreau CH, Lascau-Coman V, et al. The cartilage-bone interface. J Knee Surg, 2012, 25(2):85-97.
13.	Lories RJ, Luyten FP. The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol, 2010, 7(1):43-49.
14.	Orth P, Cucchiarini M, Kaul G, et al. Temporal and spatial migration pattern of the subchondral bone plate in a rabbit osteochondral defect model. Osteoarthritis Cartilage, 2012, 20(10):1161-1169.
15.	Bellido M, Lugo L, Roman-Blas JA, et al. Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritispreceded by osteoporosis. Osteoarthritis and Cartilage, 2011, 19(10):1228-1236.
16.	王富友, 杨柳, 段小军, 等. 正常膝关节软骨钙化层形态结构研究. 中国修复重建外科杂志, 2008, 27(5):524-527.
17.	付鑫, 马剑雄, 董宝康, 等. 骨微结构检测方法研究进展. 中国骨与关节外科, 2009, 2(6):509-514.
18.	徐健, 何威奇, 曾宪敏. 骨质疏松骨微结构的影像学研究进展. 华西医学, 2008, 23(3):675-676.
19.	Funck-Brentano T, Lin H, Hay E, et al. Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism. PloS One, 2012, 7(3):e33543.
20.	Cox LG, van Donkelaar CC, van Rietbergen B, et al. Alterations to the subchondral bone architecture during osteoarthritis:bone adaptation vs endochondral boneformation. Osteoarthritis Cartilage, 2013, 21(2):331-338.
21.	Vasara AI, Hyttinen MM, Lammi MJ, et al. Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats. Calcif Tissue Int, 2004, 74(1):107-114.
22.	Jackson DW, Lalor PA, Aberman HM, et al. Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study. J Bone Joint Surg (Am), 2001, 83(1):53-64.
23.	Schlichting K, Schell H, Kleemann RU, et al. Influence of scaffold stiffness on subchondral bone and subsequent cartilage regeneration in an ovine model of osteochondral defect healing. Am J Sports Med, 2008, 36(12):2379-2391.
24.	Chen H, Chevrier A, Hoemann CD, et al. Characterization of subchondral bone repair for marrow-stimulated chondral defects and its relationship to articular cartilage resurfacing. Am J Sports Med, 2011, 39(8):1731-1740.
25.	Chevrier A, Hoemann CD, Sun J, et al. Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondralbone remodeling in drilled cartilage defects. Osteoarthritis Cartilage, 2007, 15(3):316-327.
26.	Hoemann CD, Sun J, McKee MD, et al. Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondralbone in microdrilled rabbit defects. Osteoarthritis Cartilage, 2007, 15(1):78-89.
27.	Marchand C, Chen G, Tran-Khanh N, et al. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls. Tissue Eng Part A, 2012, 18(5-6):508-519.

1. Teuschl AH, Nürnberger S, Redl H, et al. Articular cartilage tissue regeneration-current research strategies and outlook for the future. Eur Surg, 2013, 45(3):142-153.
2. Huey DJ, Hu JC, Athanasiou KA. Unlike bone, cartilage regeneration remains elusive. Science, 2012, 338(6109):917-921.
3. Mahmoudifar N, Doran PM. Chondrogenesis and cartilage tissue engineering:the longer road to technology development. Trends in Biotechnology, 2012, 30(3):166-176.
4. Madry H, van Dijk C, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc, 2010, 18(4):419-433.
5. Gomoll AH, Madry H, Knutsen G, et al. The subchondral bone in articular cartilage repair:current problems in the surgical management. Knee Surg Sports Traumatol Arthrosc, 2010, 18(4):434-447.
6. National Research Council. Guide for the Care and Use of Laboratory Animals:Eighth Edition. Washington DC:National Academies Press, 2011:11-151.
7. Bian W, Li D, Lian Q, et al. Fabrication of a bio-inspired beta-Tricalcium phosphate/collagen scaffold based on ceramic stereolithography and gel casting for osteochondral tissue engineering. Rapid Prototyping Journal, 2012, 18(1):68-80.
8. Li X, Li D, Wang L, et al. Osteoblast cell response to beta-tricalcium phosphate scaffolds with controlled architecture in flow perfusionculture system. J Mater Sci Mater Med, 2008, 19(7):2691-2697.
9. 朱林重, 连芩, 靳忠民, 等. PEGDA 水凝胶的光固化成形工艺及其性能评价. 西安交通大学学报, 2012, 46(10):121-126.
10. Wayne JS, McDowell CL, Shields KJ, et al. In vivo response of polylactic acid-alginate scaffolds and bone marrow-derived cells for cartilage tissueengineering. Tissue Eng, 2005, 11(5-6):953-963.
11. Zaslav K, McAdams T, Scopp J, et al. New frontiers for cartilage repair and protection. Cartilage, 2012, 3(1 Suppl):77S-86S.
12. Hoemann CD, Lafantaisie-Favreau CH, Lascau-Coman V, et al. The cartilage-bone interface. J Knee Surg, 2012, 25(2):85-97.
13. Lories RJ, Luyten FP. The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol, 2010, 7(1):43-49.
14. Orth P, Cucchiarini M, Kaul G, et al. Temporal and spatial migration pattern of the subchondral bone plate in a rabbit osteochondral defect model. Osteoarthritis Cartilage, 2012, 20(10):1161-1169.
15. Bellido M, Lugo L, Roman-Blas JA, et al. Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritispreceded by osteoporosis. Osteoarthritis and Cartilage, 2011, 19(10):1228-1236.
16. 王富友, 杨柳, 段小军, 等. 正常膝关节软骨钙化层形态结构研究. 中国修复重建外科杂志, 2008, 27(5):524-527.
17. 付鑫, 马剑雄, 董宝康, 等. 骨微结构检测方法研究进展. 中国骨与关节外科, 2009, 2(6):509-514.
18. 徐健, 何威奇, 曾宪敏. 骨质疏松骨微结构的影像学研究进展. 华西医学, 2008, 23(3):675-676.
19. Funck-Brentano T, Lin H, Hay E, et al. Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism. PloS One, 2012, 7(3):e33543.
20. Cox LG, van Donkelaar CC, van Rietbergen B, et al. Alterations to the subchondral bone architecture during osteoarthritis:bone adaptation vs endochondral boneformation. Osteoarthritis Cartilage, 2013, 21(2):331-338.
21. Vasara AI, Hyttinen MM, Lammi MJ, et al. Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats. Calcif Tissue Int, 2004, 74(1):107-114.
22. Jackson DW, Lalor PA, Aberman HM, et al. Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study. J Bone Joint Surg (Am), 2001, 83(1):53-64.
23. Schlichting K, Schell H, Kleemann RU, et al. Influence of scaffold stiffness on subchondral bone and subsequent cartilage regeneration in an ovine model of osteochondral defect healing. Am J Sports Med, 2008, 36(12):2379-2391.
24. Chen H, Chevrier A, Hoemann CD, et al. Characterization of subchondral bone repair for marrow-stimulated chondral defects and its relationship to articular cartilage resurfacing. Am J Sports Med, 2011, 39(8):1731-1740.
25. Chevrier A, Hoemann CD, Sun J, et al. Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondralbone remodeling in drilled cartilage defects. Osteoarthritis Cartilage, 2007, 15(3):316-327.
26. Hoemann CD, Sun J, McKee MD, et al. Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondralbone in microdrilled rabbit defects. Osteoarthritis Cartilage, 2007, 15(1):78-89.
27. Marchand C, Chen G, Tran-Khanh N, et al. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls. Tissue Eng Part A, 2012, 18(5-6):508-519.

Chinese Journal of Reparative and Reconstructive Surgery

CARTILAGE REPAIR AND SUBCHONDRAL BONE RECONSTRUCTION BASED ON THREE-DIMENSIONAL PRINTING TECHNIQUE

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