Domestic porous tantalum loaded with bone morphogenetic 7 in repairing osteochondral defect in rabbits_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHANGHui ¹ , WANGQian ² , GANHongquan ³ , SHIWei ³ , LIUYongqing ³ , ZHANGDapeng ³ , LIQijia ⁴ ,  WANGZhiqiang ³

1. The 1st Department of Joint Surgery, the Second Hospital of Tangshan, Tangshan Hebei, 063000, P. R. China;
2. Department of Anatomy, Basic Medical College, North China University of Science and Technology;
3. Department of Orthopaedics, North China University of Science and Technology Affiliated Hospital;
Medical Experimental Center, North China University of Science and Technology;

Corresponding author：

WANGZhiqiang, Email: wzhqde@163.com

Keywords：

Porous tantalum; Bone morphogenetic protein 7; Cartilage defect; Subchondral bone; Repair; Rabbit

DOI：

10.7507/1002-1892.20160171

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Objective To investigate the ability to repair osteochondral defect and the biocompatibility of porous tantalum loaded with bone morphogenetic protein 7 (BMP-7) by observing the effect of porous tantalum loaded with BMP-7 in repairing articular cartilage and subchondral bone defect. Methods The cartilage defect models of medial femoral condyle were established in 48 New Zealand white rabbits, which were randomly divided into 3 groups (n=16): porous tantalum material+BMP-7 (group A) and porous tantalum material (group B) were implanted into the right side of the medial femoral condyle; and no material was implanted as control (group C). The general condition of animals was observed after operation, then the specimens were harvested for gross observation, histological observation, and scanning electron microscope (SEM) observation at 4, 8, and 16 weeks after implantation, micro-CT was used to observe the cartilage and bone ingrowth and bone formation around porous tantalum at 16 weeks after implantation. Results No animal died after operation and wound healed well. Gross observation showed that defects of groups A and B were covered with new cartilage with time, but earlier new cartilage formation and better repair were observed in group A than group B, no repair occurred at the site of bone defects, and defect surface was filled with fibrous tissue in group C. Cartilage repair gross score of group A was significantly higher than that of group B at 8 and 16 weeks (P < 0.05) but no significant difference was found between groups A and B at 4 weeks (P>0.05). SEM observation showed that the number of new cartilage and osteoblasts increased gradually with time, and the implanted material was gradually covered with the extracellular matrix, and the new bone tissue grew into the pores of the material; the neonatal bone tissue and extracellular matrix secretion of group A were significantly more than those of group B. The toluidine blue staining results showed that new cartilage and bone tissue gradually increased in the porous tantalum interface, and new bone trabecula formed and grew in the pores, the bone and the porous tantalum contact tended to close, and cartilage defect was gradually covered with cartilage like tissue, cartilage tissue and porous tantalum combined more closely in groups A and B at 4, 8 and 16 weeks. New cartilage and bone tissue of group A was more than that of group B. Micro-CT analysis indicated that the bone mineral density, trabecular thickness, trabecular number, and bone volume fraction of group A were significantly higher than those of group B at 16 weeks (P < 0.05), but the trabecular bone space was significantly lower than that of group B (P < 0.05). Conclusion The domestic porous tantalum has good biocompatibility, domestic porous tantalum loaded with BMP-7 can promote the formation of a stable connection with the host and has a good effect on cartilage and subchondral bone defect repair.

Citation： ZHANGHui, WANGQian, GANHongquan, SHIWei, LIUYongqing, ZHANGDapeng, LIQijia, WANGZhiqiang. Domestic porous tantalum loaded with bone morphogenetic 7 in repairing osteochondral defect in rabbits. Chinese Journal of Reparative and Reconstructive Surgery, 2016, 30(7): 836-842. doi: 10.7507/1002-1892.20160171 Copy

1.	Marin E, Fedrizzi L, Zagra L. Porous metallic structures for orthopaedic applications: a short review of materials and technologies. Eur Orthop Traumatol, 2010, 1(1): 103-109.
2.	Helm AT, Kerin C, Ghalayini SR, et al. Preliminary results of an uncemented trabecular metal tibial component in total knee arthroplasty. J Arthroplast, 2009, 24(6): 941-944.
3.	Cardaropoli F, Alfieri V, Caiazzo F, et al. Manufacturing of porous biomaterials for dental implant applications through selective laser melting. Adv Mater Res, 2012, 6(535-537): 1222-1229.
4.	Bobyn JD, Stackpool GJ, Hacking SA, et al. Characteristics of bone ingrowth and interface mechanics of a new porous tantalum biomatcrial. J Bone Joint Surg (Br), 1999, 81(5): 907-914.
5.	Papanna MC, Al-Hadithy N, Somanchi BV, et al. The use of bone morphogenic protein-7 (OP-1) in the management of resistant non-unions in the upper and lower limb. Injury, 2012, 43(7): 1135-1140.
6.	Zamurovic N, Cappellen D, Rohner D, et al. Coordinated activation of notch, Wnt, and transforming growth factor-beta signaling pathways in bone morphogenic protein 2-induced osteogenesis. Notch target gene Hey1 inhibits mineralization and Runx2 transcriptional activity. J Biol Chem, 2004, 279(36): 37704-37715.
7.	Chubinskaya S, Kawakami M, Rappoport L, et al. Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs. J Orthop Res, 2007, 25(4): 517-530.
8.	Papanna MC, Al-Hadithy N, Somanchi BV, et al. The use of bone morphogenic protein-7 (OP-1) in the management of resistant non-unions in the upper and lower limb. Injury, 2012, 43(7): 1135-1140.
9.	Imai Y, Miyamoto K, An HS, et al. Recombinant human osteogenic protein-1 upregulates proteoglycan metabolism of human anulus fibrosus and nucleus pulposus cells. Spine (Phila Pa 1976), 2007, 32(12): 1303-1310.
10.	Mason JM, Grande DA, Barcia M, et al. Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair. Gene Ther, 1998, 5(8): 1098-1104.
11.	张辉, 李亮, 王茜, 等.骨形成蛋白-7对多孔钽/软骨细胞复合物分泌功能以及Col-Ⅱ、AGG和Sox9基因表达的影响.北京大学学报(医学版), 2015, 47(2): 219-225.
12.	Moran ME, Kim HK, Salter RB. Biological resurfacing of full-thickness defects in patellar articular cartilage of the rabbit. Investigation of autogenous periosteal grafts subjected to continuous passive motion. J Bone Joint Surg (Br), 1992, 74(5): 659-667.
13.	Niederauer GG, Slivka MA, Leatherbury NC, et al. Evaluation of multiphase implants for repair of focal osteochondral defects in goats. Biomaterials, 2000, 21(24): 2561-2574.
14.	武垚森, 池永龙.小梁金属(多孔钽)在骨科的应用现状.中华骨科杂志, 2007, 27(12): 939-941.
15.	甘洪全, 刘鑫, 赵济华, 等.国产多孔钽材料兔竖脊肌植入组织学及生物学效应.南京医科大学学报(自然科学版), 2014, 34(5): 611-616.
16.	Sinclair SK, Konz GJ, Dawson JM, et al. Host bone response to polyetheretherketone versus porous tantalum implants for cervical spinal fusion in a goat model. Spine (Phila Pa 1976), 2012, 37(10): E571-580.
17.	Sidhu KS, Prochnow TD, Schmitt P, et al. Anterior cervical interbody fusion with rhBMP-2 and tantalum in a goat model. Spine J, 2001, 1(5): 331-340.
18.	Shapiro F, Kiode S, Glimcher MJ. Cell origin and differentiation in the repair of fullthickness defect of articular cartilage. J Bone Joint Surg (Am), 1993, 75(4): 532-553.
19.	Brittberg M, Nilsson A, Lindahl A, et al. Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin Orthop Relat Res, 1996, (326): 270-283.
20.	Lavery K, Hawley S, Swain Y, et al. New insights into BMP-7 mediated osteoblastic differentiation of primary human mesenchymal stem cells. Bone, 2009, 45(1): 27-41.
21.	Bobyn JD, Toh KK, Hacking SA, et al. Tissue response to porous tantalum acetabular cups:a canine model. J Arthroplasty, 1999, 14(3): 347-354.
22.	Duan X, Zhu X, Dong X, et al. Repair of large osteochondral defects in a beagle model with a novel type I collagen/glycosaminoglycan-porous titanium biphasic scaffold. Mater Sci Eng C Mater Biol Appl, 2013, 33(7): 3951-3957.

1. Marin E, Fedrizzi L, Zagra L. Porous metallic structures for orthopaedic applications: a short review of materials and technologies. Eur Orthop Traumatol, 2010, 1(1): 103-109.
2. Helm AT, Kerin C, Ghalayini SR, et al. Preliminary results of an uncemented trabecular metal tibial component in total knee arthroplasty. J Arthroplast, 2009, 24(6): 941-944.
3. Cardaropoli F, Alfieri V, Caiazzo F, et al. Manufacturing of porous biomaterials for dental implant applications through selective laser melting. Adv Mater Res, 2012, 6(535-537): 1222-1229.
4. Bobyn JD, Stackpool GJ, Hacking SA, et al. Characteristics of bone ingrowth and interface mechanics of a new porous tantalum biomatcrial. J Bone Joint Surg (Br), 1999, 81(5): 907-914.
5. Papanna MC, Al-Hadithy N, Somanchi BV, et al. The use of bone morphogenic protein-7 (OP-1) in the management of resistant non-unions in the upper and lower limb. Injury, 2012, 43(7): 1135-1140.
6. Zamurovic N, Cappellen D, Rohner D, et al. Coordinated activation of notch, Wnt, and transforming growth factor-beta signaling pathways in bone morphogenic protein 2-induced osteogenesis. Notch target gene Hey1 inhibits mineralization and Runx2 transcriptional activity. J Biol Chem, 2004, 279(36): 37704-37715.
7. Chubinskaya S, Kawakami M, Rappoport L, et al. Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs. J Orthop Res, 2007, 25(4): 517-530.
8. Papanna MC, Al-Hadithy N, Somanchi BV, et al. The use of bone morphogenic protein-7 (OP-1) in the management of resistant non-unions in the upper and lower limb. Injury, 2012, 43(7): 1135-1140.
9. Imai Y, Miyamoto K, An HS, et al. Recombinant human osteogenic protein-1 upregulates proteoglycan metabolism of human anulus fibrosus and nucleus pulposus cells. Spine (Phila Pa 1976), 2007, 32(12): 1303-1310.
10. Mason JM, Grande DA, Barcia M, et al. Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair. Gene Ther, 1998, 5(8): 1098-1104.
11. 张辉, 李亮, 王茜, 等.骨形成蛋白-7对多孔钽/软骨细胞复合物分泌功能以及Col-Ⅱ、AGG和Sox9基因表达的影响.北京大学学报(医学版), 2015, 47(2): 219-225.
12. Moran ME, Kim HK, Salter RB. Biological resurfacing of full-thickness defects in patellar articular cartilage of the rabbit. Investigation of autogenous periosteal grafts subjected to continuous passive motion. J Bone Joint Surg (Br), 1992, 74(5): 659-667.
13. Niederauer GG, Slivka MA, Leatherbury NC, et al. Evaluation of multiphase implants for repair of focal osteochondral defects in goats. Biomaterials, 2000, 21(24): 2561-2574.
14. 武垚森, 池永龙.小梁金属(多孔钽)在骨科的应用现状.中华骨科杂志, 2007, 27(12): 939-941.
15. 甘洪全, 刘鑫, 赵济华, 等.国产多孔钽材料兔竖脊肌植入组织学及生物学效应.南京医科大学学报(自然科学版), 2014, 34(5): 611-616.
16. Sinclair SK, Konz GJ, Dawson JM, et al. Host bone response to polyetheretherketone versus porous tantalum implants for cervical spinal fusion in a goat model. Spine (Phila Pa 1976), 2012, 37(10): E571-580.
17. Sidhu KS, Prochnow TD, Schmitt P, et al. Anterior cervical interbody fusion with rhBMP-2 and tantalum in a goat model. Spine J, 2001, 1(5): 331-340.
18. Shapiro F, Kiode S, Glimcher MJ. Cell origin and differentiation in the repair of fullthickness defect of articular cartilage. J Bone Joint Surg (Am), 1993, 75(4): 532-553.
19. Brittberg M, Nilsson A, Lindahl A, et al. Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin Orthop Relat Res, 1996, (326): 270-283.
20. Lavery K, Hawley S, Swain Y, et al. New insights into BMP-7 mediated osteoblastic differentiation of primary human mesenchymal stem cells. Bone, 2009, 45(1): 27-41.
21. Bobyn JD, Toh KK, Hacking SA, et al. Tissue response to porous tantalum acetabular cups:a canine model. J Arthroplasty, 1999, 14(3): 347-354.
22. Duan X, Zhu X, Dong X, et al. Repair of large osteochondral defects in a beagle model with a novel type I collagen/glycosaminoglycan-porous titanium biphasic scaffold. Mater Sci Eng C Mater Biol Appl, 2013, 33(7): 3951-3957.

Chinese Journal of Reparative and Reconstructive Surgery

Domestic porous tantalum loaded with bone morphogenetic 7 in repairing osteochondral defect in rabbits

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