The Evaluation of Intra-Articular Injection of Bevacizumab on the Prevention of Physeal Bar Formation in Type 4 Salter Harris Model in Rats: A Pilot Study
Abstract
Background: This study was designed to achieve a new method as a preventive treatment for complications of growth plate fractures. In this study, we investigate the effect of intra-articular injection of anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab on the repair process of articular cartilage in a type 4 Salter Harris injury model.
Methods: A Salter Harris injury was created on the proximal tibial growth plate of 14 rats by a 1.8 mm drill. The rats were randomly classified into two groups: group LD, administration of high-dose intra-articular injection of bevacizumab (250 μg), and group HD, administration of low-dose intra-articular injection of bevacizumab (50 μg) after injury. The rats were killed 2 months postoperatively and their tibia underwent micro-computed tomography (CT) analysis, histological assessment, and measurement of tibial bone length. Results: Bony bar formation was observed in 71% of the samples in the high-dose group and in 100% of the low-dose group. Relative increase in physeal cartilage thickness (P = 0.007) and decrease in bony bar formation (P = 0.029) were observed significantly in the high dose group. There was no significant difference in tibia length between the two groups (P = 0.150).
Conclusion: Intra-articular administration of bevacizumab demonstrated positive restorative effects. We suggest this method of treatment due to its potential of improving cartilage repair and capability to be used as a main or adjacent treatment in osteochondral defects.
2. Meyers AL, Marquart MJ. Pediatric physeal injuries overview. 2020. [PubMed: 32809381].
3. Flynn JM, Skaggs DL, Waters PM. Rockwood and Wilkins' fractures in children. Philadelphia, PA: Lippincott Williams & Wilkins; 2019.
4. Chung R, Xian CJ. Recent research on the growth plate: Mechanisms for growth plate injury repair and potential cell- based therapies for regeneration. J Mol Endocrinol. 2014;53(1):T45-T61. doi: 10.1530/JME-14-0062. [PubMed: 25114207].
5. Lee S, Nemeno JG, Lee JI. Repositioning bevacizumab: A promising therapeutic strategy for cartilage regeneration.Tissue Eng Part B Rev. 2016;22(5):341-57. doi: 10.1089/ten.TEB.2015.0300. [PubMed: 26905221].
6. Nagai T, Sato M, Kutsuna T, Kokubo M, Ebihara G, Ohta N, et al. Intravenous administration of anti-vascular endothelial growth factor humanized monoclonal antibody bevacizumab improves articular cartilage repair. Arthritis Res Ther. 2010;12(5):R178. doi: 10.1186/ar3142. [PubMed: 20868495]. [PubMed Central: PMC2991009].
7. Petersen W, Tsokos M, Pufe T. Expression of VEGF121 and VEGF165 in hypertrophic chondrocytes of the human growth plate and epiphyseal cartilage. J Anat. 2002;201(2):153-7. doi: 10.1046/j.1469-7580.2002.00085.x. [PubMed: 12220123]. [PubMed Central: PMC1570902].
8. Fischerauer E, Heidari N, Neumayer B, Deutsch A, Weinberg AM. The spatial and temporal expression of VEGF and its receptors 1 and 2 in post-traumatic bone bridge formation of the growth plate. J Mol Histol. 2011;42(6):513-22. doi: 10.1007/s10735-011-9359-x. [PubMed: 21928073].
9. Chung R, Xian CJ. Recent research on the growth plate: Mechanisms for growth plate injury repair and potential cell- based therapies for regeneration. J Mol Endocrinol. 2014;53(1):T45-T61.
10. Erickson CB, Shaw N, Hadley-Miller N, Riederer MS, Krebs MD, Payne KA. A rat tibial growth plate injury model to characterize repair mechanisms and evaluate growth plate regeneration strategies. J Vis Exp. 2017;(125):55571. doi: 10.3791/55571. [PubMed: 28715376]. [PubMed Central: PMC5608538].
11. Pitcher T, Sousa-Valente J, Malcangio M. The monoiodoacetate model of osteoarthritis pain in the mouse. J Vis Exp. 2016;(111):53746. doi: 10.3791/53746. [PubMed: 27214709]. [PubMed Central: PMC4942175].
12. Fouladi M, Gholami K, Ghadiri H. LOTUS-inVivo micro computed tomography system for imaging of small animals and ex-vivo biological samples. Frontiers Biomed Technol. 2020;7(2):134-7.
13. Feldkamp LA, Davis LC, Kress JW. Practical cone-beam algorithm. J Opt Soc Am. 1984;1(6):612-19.
14. Dreyer CH, Kjaergaard K, Ding M, Qin L. Vascular endothelial growth factor for in vivo bone formation: A systematic review. J Orthop Translat. 2020;24:46-57.doi: 10.1016/j.jot.2020.05.005. [PubMed: 32642428]. [PubMed Central: PMC7334443].
15. Ogden JA. Skeletal growth mechanism injury patterns. J Pediatr Orthop. 1982;2(4):371-7. doi: 10.1097/01241398- 198210000-00004. [PubMed: 7142386].
16. Rivas R, Shapiro F. Structural stages in the development of the long bones and epiphyses: A study in the New Zealand white rabbit. J Bone Joint Surg Am. 2002;84(1):85-100. doi: 10.2106/00004623-200201000-00013. [PubMed: 11792784].
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Issue | Vol 7, No 3 (2021) | |
Section | Research Articles | |
DOI | https://doi.org/10.18502/jost.v7i3.8103 | |
Keywords | ||
Salter-Harris Fractures; Growth Plate Fracture; Vascular Endothelial Growth Factors; Bevacizumab; Orthopedics |
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