Bone Marrow - Mesenchymal Stem Cell and Platelet Rich Fibrin: A Promising Step of Growth Plate Injury Treatment in Rabbit

  • Dimas Rangga Yudyanda Department of Orthopedics and Traumatology, Faculty of Medicine, Universitas Airlangga/Dr. Soetomo General Academic Hospital https://orcid.org/0009-0002-0236-6383
  • Komang Agung Irianto Department of Orthopedics and Traumatology, Faculty of Medicine, Universitas Airlanggaicine, Universitas Airlangga/Dr. Soetomo General Academic Hospital
  • Purwati Purwati Stem Cell Research and Development Center, Universitas Airlangga, 2nd Floor Institute of Tropical Disease Building, Campus C UNAIR Mulyorejo, Surabaya, East Java, Indonesia https://orcid.org/0000-0002-6144-2481
Keywords: Bone marrow, Health outcomes, Mesenchymal stem cell, Platelet-rich fibrin, Physeal injury, Tibia, Product innovation

Abstract


Background/Aim: Paediatric physeal injuries account for about 30 % of all bone injuries, often affecting growth plates. Current treatments emphasise prevention, as regenerating the damaged physis is challenging. This study aimed to analyse whether combining bone marrow mesenchymal stem-cell (BM-MSC) and platelet-rich fibrin (PRF) can regenerate physis bone.

Methods: The twenty-four New Zealand white rabbits, aged 6 weeks, were acclimatised for 1 week. BM-MSC and PRF were then prepared. A physis injury was induced in the proximal tibia of the rabbits, then divided into four groups: control, BM-MSC treatment, PRF treatment, combination of BM-MSC and PRF treatment. After 4 weeks, rabbits were sacrificed and evaluated. The bony bar diameter was measured using haematoxylin-eosin (H&E) staining, while the expression of tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) and SRY-box transcription factor 9 (SOX-9) was evaluated using immunohistochemistry (IHC). 

Results: Histology showed that the BM-MSC and PRF combination led to better regeneration than the control, BM-MSC alone, or PRF alone in terms of osteochondral union. SOX-9 indicators showed significant differences between the control vs BM-MSC groups (p = 0.099); BM-SC vs PRF groups (p = 0.032). TNF-α indicators showed no significant differences at all. VEGF indicators showed significant differences between the control vs BM-MSC and PRF groups (p = 0.008); PRF vs BM-MSC and PRF groups (p = 0.021).

Conclusion: Administration of BM-MSC, PRF or a combination of BM-MSC and PRF showed comparable effectiveness in osteochondral union based on histological outcomes. Conversely, PRF alone exhibited the highest effectiveness in IHC analysis. However, none of these results were statistically significant.

References

Eastwood DM, de Gheldere A. Physeal injuries in children. Surgery (Oxford). 2011;29(4):146–52. doi: 10.1016/j.mpsur.2011.01.003.

Salzmann GM, Niemeyer P, Hochrein A, Stoddart MJ, Angele P. Articular cartilage repair of the knee in children and adolescents. Orthop J Sports Med. 2018;6(3):232596711876019. doi: 10.1177/2325967118760190.

Vasanthan J, Gurusamy N, Rajasingh S, Sigamani V, Kirankumar S, Thomas EL, et al. Role of human mesenchymal stem cells in regenerative therapy. Cells. 2020;10(1):54. doi: 10.3390/cells10010054.

Chung R, Foster BK, Xian CJ. Preclinical studies on mesenchymal stem cell-based therapy for growth plate cartilage injury repair. Stem Cells Int. 2011;2011:1–10. doi: 10.4061/2011/570125.

Tjempakasari A, Suroto H, Santoso D. Mesenchymal stem cell senescence and osteogenesis. Medicina (B Aires). 2021;58(1):61. doi: 10.3390/medicina58010061.

Utomo DN, Widiastana IGA. The effect platelet rich plasma on mesenchymal stem cells (MSCs) differentation into chondroblast. J Orthop Traumatol Surabaya. 2019;6(2):80. doi: 10.20473/joints.v6i2.2017.80-85.

Shaw N, Erickson C, Bryant SJ, Ferguson VL, Krebs MD, Hadley-Miller N, et al. Regenerative medicine approaches for the treatment of pediatric physeal injuries. Tissue Eng Part B Rev. 2018;24(2):85–97. doi: 10.1089/ten.teb.2017.0274.

Watanabe H, Maishi N, Hoshi-Numahata M, Nishiura M, Nakanishi-Kimura A, Hida K, et al. Skeletal-vascular interactions in bone development, homeostasis, and pathological destruction. Int J Mol Sci. 2023;24(13):10912. doi: 10.3390/ijms241310912.

Hu K, Olsen BR. The roles of vascular endothelial growth factor in bone repair and regeneration. Bone. 2016;91:30–8. doi: 10.1016/j.bone.2016.06.013.

Wang X, Zhang Y, Choukroun J, Ghanaati S, Miron RJ. Effects of an injectable platelet-rich fibrin on osteoblast behavior and bone tissue formation in comparison to platelet-rich plasma. Platelets. 2018;29(1):48–55. doi: 10.1080/09537104.2017.1293807.

Yu Y, Rodriguez-Fontan F, Eckstein K, Muralidharan A, Uzcategui AC, Fuchs JR, et al. Rabbit model of physeal injury for the evaluation of regenerative medicine approaches. Tissue Eng Part C Methods. 2019;25(12):701–10. doi: 10.1089/ten.tec.2019.0180.

Yin N, Wang Y, Ding L, Yuan J, Du L, Zhu Z, et al. Platelet-rich plasma enhances the repair capacity of muscle-derived mesenchymal stem cells to large humeral bone defect in rabbits. Sci Rep. 2020;10(1):6771. doi: 10.1038/s41598-020-63496-5.

Wong KL, Zhang S, Tan SSH, Cheow YA, Lai RC, Lim SK, et al. Mesenchymal stem cell exosomes promote growth plate repair and reduce limb-length discrepancy in young rats. J Bone Joint Surg. 2022;104(12):1098–106. doi: 10.2106/JBJS.21.00789.

Guo R, Zhuang H, Chen X, Ben Y, Fan M, Wang Y, et al. Tissue engineering in growth plate cartilage regeneration: Mechanisms to therapeutic strategies. J Tissue Eng. 2023;14:20417314231187956. doi: 10.1177/20417314231187956.

Kim J, Ha Y, Kang NH. Effects of growth factors from platelet-rich fibrin on the bone regeneration. J Craniofac Surg. 2017;28(4):860–5. doi: 10.1097/SCS.0000000000003396.

Barbon S, Stocco E, Macchi V, Contran M, Grandi F, Borean A, et al. Platelet-rich fibrin scaffolds for cartilage and tendon regenerative medicine: from bench to bedside. Int J Mol Sci. 2019;20(7):1701. doi: 10.3390/ijms20071701.

Hidajat NN, Mulyadi D, Chaidir MR, Dewangga TH. Platelet-rich fibrin enhances fracture healing in tibial long bone: an experiment in rabbit. Althea Med J. 2020;7(4). doi: 10.15850/amj.v7n4.1960.

Utomo DN, Hernugrahanto KD. The role of platelet-rich fibrin facilitates the healing of gastrocnemius muscle defect: a preliminary study on animal model. (JOINTS) J Orthop Traumatol Surabaya. 2019;7(1):31. doi: 10.20473/joints.v7i1.2018.31-41.

Utomo DN, Mahyudin F, Hernugrahanto KD, Suroto H, Chilmi MZ, Rantam FA. Implantation of platelet rich fibrin and allogenic mesenchymal stem cells facilitate the healing of muscle injury: An experimental study on animal. Int J Surg Open. 2018;11:4–9. doi: 10.1016/j.ijso.2018.03.001.

Published
2025/02/28
Section
Original article