Repair of osteochondral defect using icariin-conditioned serum combined with chitosan in rabbit knees

BMC Complementary Medicine and Therapies - Tập 20 - Trang 1-9 - 2020
Juntao Zhang1,2, Dong Ming1, Qiang Ji3, Aifeng Liu2, Chao Zhang2, Jianjie Jiao4, Man Shang4
1Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
2Department of Orthopedics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
3Tianjin University of Traditional Chinese Medicine, Tianjin, China
4Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China

Tóm tắt

Osteochondral defects caused by an acute traumatic injury or articular degeneration remains difficult to be manipulated. Repair of articular defects is still a great challenge for both tissue engineers and orthopedic surgeons. Therefore, combination of biomaterials with cartilage promotive drugs is well worth being developed to support the regeneration of both cartilage and subchondral bone. Rabbits undergoing osteochondral defect surgery were intrarticularly injected with icariin-conditioned serum (ICS), chitosan (CSSH) and combination of ICS with CSSH, respectively. Gait analysis was performed using VICON motion capture system. ICRS score and immunohistochemical (IHC) analysis including H&E, Safranin O, toluidine blue and collagen II staining was employed to evaluate macroscopic cartilage regeneration and determine the morphologic repair of cartilage. Rabbits with the treatment of ICS or CSSH alone showed mild improvement in hopping time and range of joint angles while ICS-CSSH group exhibited longer jumping time and larger range of joint angles. In addition, femoral condyle in ICS-CSSH rabbits could be seen with more native cartilage and subchondral bone regeneration in both macroscopic observation and IHC analysis. ICS combined with CSSH could promote the repair of osteochondral defect in rabbit knees. Combination of biomaterials with cartilage promotive drugs may ultimately have profound implications in the management of cartilage defect.

Tài liệu tham khảo

Fotouhi A, Maleki A, Dolati S, Aghebati-Maleki A, Aghebati-Maleki L. Platelet rich plasma, stromal vascular fraction and autologous conditioned serum in treatment of knee osteoarthritis. Biomed Pharmacother. 2018;104:652–60. Meijer H, Reinecke J, Becker C, Tholen G, Wehling P. The production of anti-inflammatory cytokines in whole blood by physico-chemical induction. Inflamm Res. 2003;52(10):404–7. Frizziero A, Giannotti E, Oliva F, Masiero S, Maffulli N. Autologous conditioned serum for the treatment of osteoarthritis and other possible applications in musculoskeletal disorders. Br Med Bull. 2013;105:169–84. Frisbie DD, Kawcak CE, Werpy NM, Park RD, McIlwraith CW. Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis. Am J Vet Res. 2007;68(3):290–6. Baltzer AW, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthr Cartil. 2009;17(2):152–60. Baselga GJ, Miguel HTP. Treatment of osteoarthritis of the knee with a combination of autologous conditioned serum and physiotherapy: a two-year observational study. PLoS One. 2015;10(12):e145551. Blazquez R, Sanchez-Margallo FM, Reinecke J, Alvarez V, Lopez E, Marinaro F, Casado JG. Conditioned serum enhances the Chondrogenic and Immunomodulatory behavior of Mesenchymal stem cells. Front Pharmacol. 2019;10:699. Zhang J, Zhang D, Wu C, Liu A, Zhang C, Jiao J, Shang M. Icariin-conditioned serum engineered with hyaluronic acid promote repair of articular cartilage defects in rabbit knees. BMC Complement Altern Med. 2019;19(1):155. Wang P, Zhang F, He Q, Wang J, Shiu HT, Shu Y, Tsang WP, Liang S, Zhao K, Wan C. Flavonoid compound Icariin activates hypoxia inducible factor-1alpha in chondrocytes and promotes articular cartilage repair. PLoS One. 2016;11(2):e148372. Wang P, Xiong X, Zhang J, Qin S, Wang W, Liu Z. Icariin increases chondrocyte vitality by promoting hypoxia-inducible factor-1alpha expression and anaerobic glycolysis. Knee. 2020;27(1):18–25. Lu TJ, Chiu FY, Chiu HY, Chang MC, Hung SC. Chondrogenic differentiation of Mesenchymal stem cells in three-dimensional chitosan film culture. Cell Transplant. 2017;26(3):417–27. Lastra ML, Molinuevo MS, Cortizo AM, Cortizo MS. Fumarate Copolymer-Chitosan Cross-Linked Scaffold Directed to Osteochondrogenic Tissue Engineering. Macromol Biosci. 2017;17(5). https://doi.org/10.1002/mabi.201600219. Epub 2016 Nov 28. Man Z, Hu X, Liu Z, Huang H, Meng Q, Zhang X, Dai L, Zhang J, Fu X, Duan X, et al. Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury. Biomaterials. 2016;108:157–67. Rodrigues MN, Oliveira MB, Costa RR, Mano JF. Chitosan/chondroitin sulfate membranes produced by polyelectrolyte Complexation for cartilage engineering. Biomacromolecules. 2016;17(6):2178–88. Wu S, Zhou Y, Yu Y, Zhou X, Du W, Wan M, Fan Y, Zhou X, Xu X, Zheng L. Evaluation of chitosan hydrogel for sustained delivery of VEGF for Odontogenic differentiation of dental pulp stem cells. Stem Cells Int. 2019;2019:1515040. Vasilyev AV, Kuznetsova VS, Bukharova TB, Zagoskin YD, Leonov GE, Grigoriev TE, Chvalun SN, Goldshtein DV, Kulakov AA. Chitosan hydrogels biocompatibility improvement with the perspective of use as a base for osteoplastic materials in dentistry. Stomatologiia (Mosk). 2019;98(6. Vyp. 2):12–8. Ni Y, Khan A, Wang B. Chitosan-Nanocellulose composites for regenerative medicine applications. Curr Med Chem. 2020. https://doi.org/10.2174/0929867327666200127152834. Online ahead of print. Erickson AE, Sun J, Lan LS, Swanson S, Chang FC, Tsao CT, Zhang M. Chitosan-based composite bilayer scaffold as an in vitro osteochondral defect regeneration model. Biomed Microdevices. 2019;21(2):34. Mohan N, Mohanan PV, Sabareeswaran A, Nair P. Chitosan-hyaluronic acid hydrogel for cartilage repair. Int J Biol Macromol. 2017;104(Pt B):1936–45. Bai Y, Li S, Li X, Han X, Li Y, Zhao J, Zhang J, Hou X, Yuan X. An injectable robust denatured albumin hydrogel formed via double equilibrium reactions. J Biomater Sci Polym Ed. 2019;30(8):662–78. Chu CR, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair. Tissue Eng Part B Rev. 2010;16(1):105–15. Srinivasan PP, McCoy SY, Jha AK, Yang W, Jia X, Farach-Carson MC, Kirn-Safran CB. Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis. Biomed Mater. 2012;7(2):24109. Aulin C, Bergman K, Jensen-Waern M, Hedenqvist P, Hilborn J, Engstrand T. In situ cross-linkable hyaluronan hydrogel enhances chondrogenesis. J Tissue Eng Regen Med. 2011;5(8):e188–96. Pauli C, Whiteside R, Heras FL, Nesic D, Koziol J, Grogan SP, Matyas J, Pritzker KP, D'Lima DD, Lotz MK. Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development. Osteoarthr Cartil. 2012;20(6):476–85. Holt K, Sorhaindo M, Coady C, Wong IH. Arthroscopic treatment of medial femoral knee Osteochondral defect using Subchondroplasty and chitosan-based scaffold. Arthrosc Tech. 2019;8(4):e413–8. Zhang X, Xu M, Song L, Wei Y, Lin Y, Liu W, Heng BC, Peng H, Wang Y, Deng X. Effects of compatibility of deproteinized antler cancellous bone with various bioactive factors on their osteogenic potential. Biomaterials. 2013;34(36):9103–14. Wei Q, He M, Chen M, Chen Z, Yang F, Wang H, Zhang J, He W. Icariin stimulates osteogenic differentiation of rat bone marrow stromal stem cells by increasing TAZ expression. Biomed Pharmacother. 2017;91:581–9. Wei Q, Zhang J, Hong G, Chen Z, Deng W, He W, Chen MH. Icariin promotes osteogenic differentiation of rat bone marrow stromal cells by activating the ERalpha-Wnt/beta-catenin signaling pathway. Biomed Pharmacother. 2016;84:931–9. Zhai Y, Ge B, Ma H, Ming L, Li Z, Cheng G, Zhou J, Chen K. Icariin promotes osteogenic differentiation of rat bone marrow stromal cells in vitro. Zhongguo Zhong Yao Za Zhi. 2010;35(23):3219–22. Chen KM, Ge BF, Liu XY, Ma PH, Lu MB, Bai MH, Wang Y. Icariin inhibits the osteoclast formation induced by RANKL and macrophage-colony stimulating factor in mouse bone marrow culture. Pharmazie. 2007;62(5):388–91. Hsieh TP, Sheu SY, Sun JS, Chen MH. Icariin inhibits osteoclast differentiation and bone resorption by suppression of MAPKs/NF-kappaB regulated HIF-1alpha and PGE (2) synthesis. Phytomedicine. 2011;18(2–3):176–85. Liu J, Ye H, Lou Y. Determination of rat urinary metabolites of icariin in vivo and estrogenic activities of its metabolites on MCF-7 cells. Pharmazie. 2005;60(2):120–5. Xu W, Zhang Y, Yang M, Shen Z, Zhang X, Zhang W, Li H. LC-MS/MS method for the simultaneous determination of icariin and its major metabolites in rat plasma. J Pharm Biomed Anal. 2007;45(4):667–72. Qin L, Han T, Zhang Q, Cao D, Nian H, Rahman K, Zheng H. Antiosteoporotic chemical constituents from Er-Xian decoction, a traditional Chinese herbal formula. J Ethnopharmacol. 2008;118(2):271–9. Dwivedi G, Chevrier A, Hoemann CD, Buschmann MD. Injectable freeze-dried chitosan-platelet-rich-plasma implants improve marrow-stimulated cartilage repair in a chronic-defect rabbit model. J Tissue Eng Regen Med. 2019;13(4):599–611. Gonshor A. Technique for producing platelet-rich plasma and platelet concentrate: background and process. Int J Periodontics Restorative Dent. 2002;22(6):547–57. Milano G, Sanna PE, Deriu L, Careddu G, Manunta L, Manunta A, Saccomanno MF, Fabbriciani C. The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: an experimental study in a sheep model. Osteoarthr Cartil. 2010;18(7):971–80.