A Biodegradable Magnesium Phosphate Cement Incorporating Chitosan and RhBMP-2 Designed for Bone Defect Repair

Overview

Journal J Orthop Translat

Publisher Elsevier

Specialty Orthopedics

Date 2024 Nov 1

PMID 39483125

Authors

Peng He

Yanbin Zhao

Bin Wang

Guoyin Liu

Lei Zhang

Mei Li

Bin Xu

Weihua Cai

Chenglin Chu

Yu Cong

Affiliations

Soon will be listed here.

Abstract

Background: The repair of bone defects has always been a significant challenge in clinical medicine. To address this challenge, doctors often utilize autologous bone grafts, allogeneic bone grafts and artificial bone substitutes. However, the former two methods may result in additional trauma and complications, while allogeneic bone grafts carry the risks of immune rejection and disease transmission. Magnesium phosphate cement (MPC), as a artificial bone substitutes, has been a potential biomaterial for repairing bone defects, but its clinical application is limited by insufficient mechanical strength and poor osteoinductive activity.

Methods: In this study, the cement liquid phase base on rhBMP-2 and chitosan solution into MPC were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, and cellular responses and bone regeneration in response to CHI-rhBMP2 MPC were investigated in vitro and in vivo.

Results: After the chemical component modification, CHI-rhBMP2 MPC possessed controllable degradation rate, moderate setting time, appropriate cuing temperature, good injectability, and improved initial strength. In vitro tests showed that the CHIrhBMP2 MPC could promote cell proliferation and adhesion, as well as that contribute to osteoblast differentiation and mineralization. In addition, cement materials were implanted into the rabbit femoral condyles for in vivo osseointegration evaluation. The results displayed that more new bone grew around CHI-rhBMP2 MPC, verifying improved osseointegration capacity. Transcriptome analysis revealed that focal adhesion, Forkhead box O（FoxO） signaling pathway and P13K/AKT signaling pathway were may involved in CHI-rhBMP2 MPC induced new bone formation.

Conclusion: This work provides a new strategy for the rational design of potential bone repair candidate materials.

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References

Szczesny G, Kopec M, Politis D, Kowalewski Z, Lazarski A, Szolc T . A Review on Biomaterials for Orthopaedic Surgery and Traumatology: From Past to Present. Materials (Basel). 2022; 15(10). PMC: 9145924. DOI: 10.3390/ma15103622. View

Betz R . Limitations of autograft and allograft: new synthetic solutions. Orthopedics. 2002; 25(5 Suppl):s561-70. DOI: 10.3928/0147-7447-20020502-04. View

Arkin V, NarendraKumar U, Madhyastha H, Manjubala I . Characterization and Evaluations of Injectable Calcium Phosphate Cement Doped with Magnesium and Strontium. ACS Omega. 2021; 6(4):2477-2486. PMC: 7859950. DOI: 10.1021/acsomega.0c03927. View

Cui J, Yi Y, Zhang J, Chai L, Jin H . Preparation and mechanical properties analysis of porous structure for bone tissue engineering. Biomed Mater Eng. 2022; 33(6):465-476. DOI: 10.3233/BME-211377. View

Zhao S, Kong F, Jie J, Li Q, Liu H, Xu A . Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. Theranostics. 2020; 10(1):17-35. PMC: 6929615. DOI: 10.7150/thno.36930. View

Roseti L, Parisi V, Petretta M, Cavallo C, Desando G, Bartolotti I . Scaffolds for Bone Tissue Engineering: State of the art and new perspectives. Mater Sci Eng C Mater Biol Appl. 2017; 78:1246-1262. DOI: 10.1016/j.msec.2017.05.017. View

Nazira Sarian M, Iqbal N, Sotoudehbagha P, Razavi M, Ahmed Q, Sukotjo C . Potential bioactive coating system for high-performance absorbable magnesium bone implants. Bioact Mater. 2022; 12:42-63. PMC: 8777287. DOI: 10.1016/j.bioactmat.2021.10.034. View

Komori T . Functions of Osteocalcin in Bone, Pancreas, Testis, and Muscle. Int J Mol Sci. 2020; 21(20). PMC: 7589887. DOI: 10.3390/ijms21207513. View

Shan Z, Xie X, Wu X, Zhuang S, Zhang C . Development of degradable magnesium-based metal implants and their function in promoting bone metabolism (A review). J Orthop Translat. 2022; 36:184-193. PMC: 9552026. DOI: 10.1016/j.jot.2022.09.013. View

10.

Tsuji K, Bandyopadhyay A, Harfe B, Cox K, Kakar S, Gerstenfeld L . BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet. 2006; 38(12):1424-9. DOI: 10.1038/ng1916. View

11.

Baldwin P, Li D, Auston D, Mir H, Yoon R, Koval K . Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery. J Orthop Trauma. 2019; 33(4):203-213. DOI: 10.1097/BOT.0000000000001420. View

12.

Zhang W, Wang N, Yang M, Sun T, Zhang J, Zhao Y . Periosteum and development of the tissue-engineered periosteum for guided bone regeneration. J Orthop Translat. 2022; 33:41-54. PMC: 8858911. DOI: 10.1016/j.jot.2022.01.002. View

13.

Pylostomou A, Demir O, Loca D . Calcium phosphate bone cements as local drug delivery systems for bone cancer treatment. Biomater Adv. 2023; 148:213367. DOI: 10.1016/j.bioadv.2023.213367. View

14.

Ahmed M, Mohammed Ameen M, Abazari M, Badeleh S, Rostamizadeh K, Mohammed S . Chitosan-decorated and tripolyphosphate-crosslinked pH-sensitive niosomal nanogels for Controlled release of fluoropyrimidine 5-fluorouracil. Biomed Pharmacother. 2023; 164:114943. DOI: 10.1016/j.biopha.2023.114943. View

15.

Salhotra A, Shah H, Levi B, Longaker M . Mechanisms of bone development and repair. Nat Rev Mol Cell Biol. 2020; 21(11):696-711. PMC: 7699981. DOI: 10.1038/s41580-020-00279-w. View

16.

Zhang J, Liu W, Schnitzler V, Tancret F, Bouler J . Calcium phosphate cements for bone substitution: chemistry, handling and mechanical properties. Acta Biomater. 2013; 10(3):1035-49. DOI: 10.1016/j.actbio.2013.11.001. View

17.

Marupanthorn K, Tantrawatpan C, Kheolamai P, Tantikanlayaporn D, Manochantr S . Bone morphogenetic protein-2 enhances the osteogenic differentiation capacity of mesenchymal stromal cells derived from human bone marrow and umbilical cord. Int J Mol Med. 2017; 39(3):654-662. PMC: 5360390. DOI: 10.3892/ijmm.2017.2872. View

18.

Gillman C, Jayasuriya A . FDA-approved bone grafts and bone graft substitute devices in bone regeneration. Mater Sci Eng C Mater Biol Appl. 2021; 130:112466. PMC: 8555702. DOI: 10.1016/j.msec.2021.112466. View

19.

Khalili A, Ahmad M . A Review of Cell Adhesion Studies for Biomedical and Biological Applications. Int J Mol Sci. 2015; 16(8):18149-84. PMC: 4581240. DOI: 10.3390/ijms160818149. View

20.

Cui X, Huang C, Chen Z, Zhang M, Liu C, Su K . Hyaluronic acid facilitates bone repair effects of calcium phosphate cement by accelerating osteogenic expression. Bioact Mater. 2021; 6(11):3801-3811. PMC: 8058907. DOI: 10.1016/j.bioactmat.2021.03.028. View