DOI QR코드

DOI QR Code

Effect of Keratin-Based Biocomposite Hydrogels as a RhBMP-2 Carrier in Calvarial Bone Defects Mouse Model

  • Jongjin, Lee (College of Veterinary Medicine, Jeonbuk National University) ;
  • Jinsu, Kang (College of Veterinary Medicine, Jeonbuk National University) ;
  • Jaewon, Seol (College of Veterinary Medicine, Jeonbuk National University) ;
  • Namsoo, Kim (College of Veterinary Medicine, Jeonbuk National University) ;
  • Suyoung, Heo (College of Veterinary Medicine, Jeonbuk National University)
  • Received : 2022.08.12
  • Accepted : 2022.11.23
  • Published : 2022.12.31

Abstract

Recently, in human medicine and veterinary medicine, interest in synthetic bone graft is increasing. Among them, bone morphogenic protein (BMP) is currently being actively researched and applied to clinical trials. However, BMP has the disadvantage of being expensive and easily absorbed into surrounding tissues. Therefore, BMP requires the use of small amounts and rhBMP (recombinant human bone morphogenetic protein)-2 carriers that can be released slowly. Hydrogel has the property of swelling a large amount of water inside when it is aqueous solution, and when it is, it consists of more than 90 percent water. Using these properties, hydrogels are often used as rhBMP-2 carrier. The scaffold used in this study is a hydrogel made from which keratin is extracted using human hair and based on it. In this study, we wanted to see the effect of bone formation in the calvarial defect model by using keratin-based hydrogel made with human hair as a scaffold. The experiment was conducted by dividing 3 groups a total of 12 mice. Calvarial bone defect is set to all 4 mm diameters. Bone formation was evaluated by using gross evaluation, micro-computed tomography (micro-CT), immunohistochemistry. Groups using keratin-based hydrogel were significantly observed compared to Group 1s, and the most bone formations were found when rhBMP-2 and hydrogel were used. This represents the superiority of the functions of the rhBMP-2 carrier by a new material, keratin-based hydrogel. Through gross evaluation, micro-CT, and immunohistochemistry, we can confirm that keratin-based hydrogel is a useful rhBMP-2 carrier.

Keywords

References

  1. Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 2012; 40: 363-408.  https://doi.org/10.1615/CritRevBiomedEng.v40.i5.10
  2. Barboza EP, Duarte ME, Geolas L, Sorensen RG, Riedel GE, Wikesjo UM. Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog. J Periodontol 2000; 71: 488-496.  https://doi.org/10.1902/jop.2000.71.3.488
  3. Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med 2008; 2: 1-13.  https://doi.org/10.1002/term.63
  4. Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med 2008; 2: 81-96.  https://doi.org/10.1002/term.74
  5. Boyne PJ, Shabahang S. An evaluation of bone induction delivery materials in conjunction with root-form implant placement. Int J Periodontics Restorative Dent 2001; 21: 333-343. 
  6. Chajra H, Rousseau CF, Cortial D, Ronziere MC, Herbage D, Mallein-Gerin F, et al. Collagen-based biomaterials and cartilage engineering. Application to osteochondral defects. Biomed Mater Eng 2008; 18(1 Suppl): S33-S45. 
  7. Choi J, Lee DH, Park SY, Seol JW. Diosmetin inhibits tumor development and block tumor angiogenesis in skin cancer. Biomed Pharmacother 2019; 117: 109091.  https://doi.org/10.1016/j.biopha.2019.109091
  8. Choi SW, Yeh YC, Zhang Y, Sung HW, Xia Y. Uniform beads with controllable pore sizes for biomedical applications. Small 2010; 6: 1492-1498.  https://doi.org/10.1002/smll.201000544
  9. Cochran DL, Schenk R, Buser D, Wozney JM, Jones AA. Recombinant human bone morphogenetic protein-2 stimulation of bone formation around endosseous dental implants. J Periodontol 1999; 70: 139-150.  https://doi.org/10.1902/jop.1999.70.2.139
  10. He C, Chen X. Transcription regulation of the vegf gene by the BMP/Smad pathway in the angioblast of zebrafish embryos. Biochem Biophys Res Commun 2005; 329: 324-330.  https://doi.org/10.1016/j.bbrc.2005.01.133
  11. Jung RE, Glauser R, Scharer P, Hammerle CH, Sailer HF, Weber FE. Effect of rhBMP-2 on guided bone regeneration in humans. Clin Oral Implants Res 2003; 14: 556-568.  https://doi.org/10.1034/j.1600-0501.2003.00921.x
  12. Kim J, Kim IS, Cho TH, Lee KB, Hwang SJ, Tae G, et al. Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials 2007; 28: 1830-1837.  https://doi.org/10.1016/j.biomaterials.2006.11.050
  13. Koempel JA, Patt BS, O'Grady K, Wozney J, Toriumi DM. The effect of recombinant human bone morphogenetic protein-2 on the integration of porous hydroxyapatite implants with bone. J Biomed Mater Res 1998; 41: 359-363.  https://doi.org/10.1002/(SICI)1097-4636(19980905)41:3<359::AID-JBM3>3.0.CO;2-B
  14. Lutolf MP, Weber FE, Schmoekel HG, Schense JC, Kohler T, Muller R, et al. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat Biotechnol 2003; 21: 513-518.  https://doi.org/10.1038/nbt818
  15. Mariner PD, Wudel JM, Miller DE, Genova EE, Streubel SO, Anseth KS. Synthetic hydrogel scaffold is an effective vehicle for delivery of INFUSE (rhBMP2) to critical-sized calvaria bone defects in rats. J Orthop Res 2013; 31: 401-406.  https://doi.org/10.1002/jor.22243
  16. Mostany R, Portera-Cailliau C. A craniotomy surgery procedure for chronic brain imaging. J Vis Exp 2008; (12): 680. 
  17. Park M, Kim BS, Shin HK, Park SJ, Kim HY. Preparation and characterization of keratin-based biocomposite hydrogels prepared by electron beam irradiation. Mater Sci Eng C Mater Biol Appl 2013; 33: 5051-5057.  https://doi.org/10.1016/j.msec.2013.08.032
  18. Park M, Shin HK, Kim BS, Kim MJ, Kim IS, Park BY, et al. Effect of discarded keratin-based biocomposite hydrogels on the wound healing process in vivo. Mater Sci Eng C Mater Biol Appl 2015; 55: 88-94.  https://doi.org/10.1016/j.msec.2015.03.033
  19. Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm (Lond) 2005; 2: 8.  https://doi.org/10.1186/1476-9255-2-8
  20. Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: state of the art and future trends. Macromol Biosci 2004; 4: 743-765.  https://doi.org/10.1002/mabi.200400026
  21. Schenk RK, Buser D, Hardwick WR, Dahlin C. Healing pattern of bone regeneration in membrane-protected defects: a histologic study in the canine mandible. Int J Oral Maxillofac Implants 1994; 9: 13-29. 
  22. Sigurdsson TJ, Nygaard L, Tatakis DN, Fu E, Turek TJ, Jin L, et al. Periodontal repair in dogs: evaluation of rhBMP-2 carriers. Int J Periodontics Restorative Dent 1996; 16: 524-537. 
  23. Wikesjo UM, Guglielmoni P, Promsudthi A, Cho KS, Trombelli L, Selvig KA, et al. Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment. J Clin Periodontol 1999; 26: 392-400.  https://doi.org/10.1034/j.1600-051X.1999.260610.x
  24. Wikesjo UM, Xiropaidis AV, Thomson RC, Cook AD, Selvig KA, Hardwick WR. Periodontal repair in dogs: space-providing ePTFE devices increase rhBMP-2/ACS-induced bone formation. J Clin Periodontol 2003; 30: 715-725.  https://doi.org/10.1034/j.1600-051X.2003.00364.x
  25. Wozney JM. The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev 1992; 32: 160-167.  https://doi.org/10.1002/mrd.1080320212
  26. Yamamoto M, Takahashi Y, Tabata Y. Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein. Biomaterials 2003; 24: 4375-4383.  https://doi.org/10.1016/S0142-9612(03)00337-5
  27. Yun J, Heo S, Lee M, Lee H. Evaluation of a poly(lactic-acid) scaffold filled with poly(lactide-co-glycolide)/hydroxyapatite nanofibres for reconstruction of a segmental bone defect in a canine model. Vet Med 2019; 64: 531-538. https://doi.org/10.17221/80/2019-VETMED