Experimental study on ectopic osteogenesis induced by bone morphogenetic protein 2-derived peptide P24 loaded chitosan-4-thio-butylamidine hydrogel_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHAN Jianfeng ¹ , LIU Xumei ² ,  YU Bo ¹

1. Department of Orthopedics & Traumatology, Zhujiang Hospital of Southern Medical University, Guangzhou Guangdong, 510282, P.R.China;
2. Department of Ultrasonic Diagnosis, Zhujiang Hospital of Southern Medical University, Guangzhou Guangdong, 510282, P.R.China;

Corresponding author：

YU Bo, Email: gzyubo@163.com

Keywords：

Chitosan-4-thio-butylamidine hydrogel; bone morphogenetic protein 2; ectopic osteogenesis; micro-CT; rat

DOI：

10.7507/1002-1892.201806086

Video：

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ObjectiveTo study the ectopic osteogenesis and biocompatibility of bone morphogenetic protein 2 (BMP-2)-derived peptide P24 loaded chitosan-4-thio-butylamidine (CS-TBA) hydrogel.MethodsFirst, the CS-TBA/hydroxyapatite (HA) solution was prepared by using chitosan, 2-iminothiolane hydrochloride, and HA. Then, the different amount of P24 peptides were added to the CS-TBA/HA to prepare the CS-TBA/5%P24/HA and CS-TBA/10%P24/HA solutions. Finally, β-glycerophosphate disodium (β-GP) was added to the CS-TBA/HA, CS-TBA/5%P24/HA, and CS-TBA/10%P24/HA to prepare the CS-TBA/HA/β-GP, CS-TBA/5%P24/HA/β-GP, and CS-TBA/10%P24/HA/β-GP hydrogels, respectively. Eighteen Sprague Dawley female rats were randomly divided into 3 groups (n=6), which were injected into the back muscle pouches with equal volume CS-TBA/HA/β-GP hydrogel (group A), CS-TBA/5%P24/HA/β-GP hydrogel (group B), and CS-TBA/10%P24/HA/β-GP hydrogel (group C). The animals were sacrificed at 4 and 8 weeks and conducted micro-CT. The ability of biodegradation and osteogenesis of hydrogl was detected by trabecular thickness (Tb.Th), trabecular number (Tb.N), bone mineral density (BMD), and histological staining (HE and Masson).ResultsAll the rats survived to the time point of the harvest. Micro-CT results showed that the new bones gradually increased in each group after operation. At the same time, the new bone formation was more obvious in groups B and C than in group A, and with the increase of P24 concentration, new bone formation in group C was much more than that in group B. The Tb.Th, Tb.N, and BMD increased gradually in 3 groups, and the differences between 4 and 8 weeks were significant (P<0.05) except the Tb.Th in group A. At different time points, the Tb.Th, Tb.N, and BMD were significantly higher in groups B and C than in group A (P<0.05), and in group C was higher than in group B (P<0.05), showing significant differences between groups. Histological staining showed that the materials of groups B and C were biodegradable, and the osteogenic effect was increased with the increase of P24 concentration.ConclusionP24 peptide can improve the ectopic osteogenesis of CS-TBA hydrogel, and the 10% concentration is more effective.

Citation： ZHAN Jianfeng, LIU Xumei, YU Bo. Experimental study on ectopic osteogenesis induced by bone morphogenetic protein 2-derived peptide P24 loaded chitosan-4-thio-butylamidine hydrogel. Chinese Journal of Reparative and Reconstructive Surgery, 2018, 32(9): 1144-1149. doi: 10.7507/1002-1892.201806086 Copy

1.	Venkatesan J, Anil S, Kim SK, et al. Chitosan as a vehicle for growth factor delivery: Various preparations and their applications in bone tissue regeneration. Int J Biol Macromol, 2017, 104(Pt B): 1383-1397.
2.	Wang J, Wang L, Yu H, et al. Recent progress on synthesis, property and application of modified chitosan: An overview. Int J Biol Macromol, 2016, 88: 333-344.
3.	Liu X, Chen Y, Huang Q, et al. A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate. Carbohydr Polym, 2014, 110: 62-69.
4.	Sarti F, Bernkop-Schnürch A. Chitosan and thiolated chitosan. Advances in Polymer Science, 2011, 243: 93-110.
5.	Park K. Chitosan-gelatin-platelet gel composite scaffold for bone regeneration. J Control Release, 2017, 254: 137-144.
6.	Fiedler J, Röderer G, Günther KP, et al. BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem, 2002, 87(3): 305-312.
7.	Inai K, Norris RA, Hoffman S, et al. BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis. Dev Biol, 2008, 315(2): 383-396.
8.	Niu X, Feng Q, Wang M, et al. Preparation and characterization of chitosan microspheres for controlled release of synthetic oligopeptide derived from BMP-2. J Microencapsul, 2009, 26(4): 297-305.
9.	Lin ZY, Duan ZX, Guo XD, et al. Bone induction by biomimetic PLGA-(PEG-ASP)n copolymer loaded with a novel synthetic BMP-2-related peptide in vitro and in vivo. J Control Release, 2010, 144(2): 190-195.
10.	Chen Y, Liu X, Liu R, et al. Zero-order controlled release of BMP2-derived peptide P24 from the chitosan scaffold by chemical grafting modification technique for promotion of osteogenesis in vitro and enhancement of bone repair in vivo. Theranostics, 2017, 7(5): 1072-1087.
11.	Ohba S. Tissue regenerative therapies based on regulatory mechanisms underlying bone and cartilage development. Clin Calcium, 2016, 26(12): 1765-1771.
12.	Fan L, Wu H, Cao M, et al. Enzymatic synthesis of collagen peptide-carboxymethylated chitosan copolymer and its characterization. React Funct Polym, 2014, 76(1): 26-31.
13.	Fan L, Wu H, Zhou X, et al. Transglutaminase-catalyzed grafting collagen on chitosan and its characterization. Carbohydr Polym, 2014, 105: 253-259.
14.	Xu B, Zheng P, Gao F, et al. A mineralized high strength and tough hydrogel for skull bone regeneration. Adv Funct Mater, 2017, 27(4): 1604327.
15.	Baker RM, Tseng LF, Iannolo MT, et al. Self-deploying shape memory polymer scaffolds for grafting and stabilizing complex bone defects: A mouse femoral segmental defect study. Biomaterials, 2016, 76: 388-398.
16.	Shi L, Wang F, Zhu W, et al. Self-healing silk fibroin-based hydrogel for bone regeneration: Dynamic metal-ligand self-assembly approach. Adv Funct Mater, 2017, 27(37): 1700591.
17.	Kim S, Kang Y, Mercado-Pagan AE, et al. In vitro evaluation of photo-crosslinkable chitosan-lactide hydrogels for bone tissue engineering. J Biomed Mater Res B Appl Biomater, 2014, 102(7): 1393-1406.
18.	Nandi SK, Kundu B, Basu D, et al. Protein growth factors loaded highly porous chitosan scaffold: a comparison of bone healing properties. Mater Sci Eng C Mater Biol Appl, 2013, 33(3): 1267-1275.
19.	Saito A, Suzuki Y, Ogata S, et al. Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope. Biochim Biophys Acta, 2003, 1651(1-2): 60-67.
20.	Li J, Hong J, Zheng Q, et al. Repair of rat cranial bone defects with nHAC/PLLA and BMP-2-related peptide or rhBMP-2. J Orthop Res, 2011, 29(11): 1745-1752.
21.	Liu X, Yu B, Huang Q, Liu R, et al. In vitro BMP-2 peptide release from thiolated chitosan based hydrogel. Int J Biol Macromol, 2016, 93(Pt A): 314-321.

1. Venkatesan J, Anil S, Kim SK, et al. Chitosan as a vehicle for growth factor delivery: Various preparations and their applications in bone tissue regeneration. Int J Biol Macromol, 2017, 104(Pt B): 1383-1397.
2. Wang J, Wang L, Yu H, et al. Recent progress on synthesis, property and application of modified chitosan: An overview. Int J Biol Macromol, 2016, 88: 333-344.
3. Liu X, Chen Y, Huang Q, et al. A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate. Carbohydr Polym, 2014, 110: 62-69.
4. Sarti F, Bernkop-Schnürch A. Chitosan and thiolated chitosan. Advances in Polymer Science, 2011, 243: 93-110.
5. Park K. Chitosan-gelatin-platelet gel composite scaffold for bone regeneration. J Control Release, 2017, 254: 137-144.
6. Fiedler J, Röderer G, Günther KP, et al. BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem, 2002, 87(3): 305-312.
7. Inai K, Norris RA, Hoffman S, et al. BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis. Dev Biol, 2008, 315(2): 383-396.
8. Niu X, Feng Q, Wang M, et al. Preparation and characterization of chitosan microspheres for controlled release of synthetic oligopeptide derived from BMP-2. J Microencapsul, 2009, 26(4): 297-305.
9. Lin ZY, Duan ZX, Guo XD, et al. Bone induction by biomimetic PLGA-(PEG-ASP)n copolymer loaded with a novel synthetic BMP-2-related peptide in vitro and in vivo. J Control Release, 2010, 144(2): 190-195.
10. Chen Y, Liu X, Liu R, et al. Zero-order controlled release of BMP2-derived peptide P24 from the chitosan scaffold by chemical grafting modification technique for promotion of osteogenesis in vitro and enhancement of bone repair in vivo. Theranostics, 2017, 7(5): 1072-1087.
11. Ohba S. Tissue regenerative therapies based on regulatory mechanisms underlying bone and cartilage development. Clin Calcium, 2016, 26(12): 1765-1771.
12. Fan L, Wu H, Cao M, et al. Enzymatic synthesis of collagen peptide-carboxymethylated chitosan copolymer and its characterization. React Funct Polym, 2014, 76(1): 26-31.
13. Fan L, Wu H, Zhou X, et al. Transglutaminase-catalyzed grafting collagen on chitosan and its characterization. Carbohydr Polym, 2014, 105: 253-259.
14. Xu B, Zheng P, Gao F, et al. A mineralized high strength and tough hydrogel for skull bone regeneration. Adv Funct Mater, 2017, 27(4): 1604327.
15. Baker RM, Tseng LF, Iannolo MT, et al. Self-deploying shape memory polymer scaffolds for grafting and stabilizing complex bone defects: A mouse femoral segmental defect study. Biomaterials, 2016, 76: 388-398.
16. Shi L, Wang F, Zhu W, et al. Self-healing silk fibroin-based hydrogel for bone regeneration: Dynamic metal-ligand self-assembly approach. Adv Funct Mater, 2017, 27(37): 1700591.
17. Kim S, Kang Y, Mercado-Pagan AE, et al. In vitro evaluation of photo-crosslinkable chitosan-lactide hydrogels for bone tissue engineering. J Biomed Mater Res B Appl Biomater, 2014, 102(7): 1393-1406.
18. Nandi SK, Kundu B, Basu D, et al. Protein growth factors loaded highly porous chitosan scaffold: a comparison of bone healing properties. Mater Sci Eng C Mater Biol Appl, 2013, 33(3): 1267-1275.
19. Saito A, Suzuki Y, Ogata S, et al. Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope. Biochim Biophys Acta, 2003, 1651(1-2): 60-67.
20. Li J, Hong J, Zheng Q, et al. Repair of rat cranial bone defects with nHAC/PLLA and BMP-2-related peptide or rhBMP-2. J Orthop Res, 2011, 29(11): 1745-1752.
21. Liu X, Yu B, Huang Q, Liu R, et al. In vitro BMP-2 peptide release from thiolated chitosan based hydrogel. Int J Biol Macromol, 2016, 93(Pt A): 314-321.

Chinese Journal of Reparative and Reconstructive Surgery

Experimental study on ectopic osteogenesis induced by bone morphogenetic protein 2-derived peptide P24 loaded chitosan-4-thio-butylamidine hydrogel

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