J Biomed Mater Res A. 2021 Jul 31; doi: 10.1002/jbm.a.37283. Epub 2021 Jul 31.

Chitosan/hydroxyapatite nanocomposite scaffolds to modulate osteogenic and inflammatory response.

Journal of biomedical materials research. Part A

Alessandra Soriente, Ines Fasolino, Alejandro Gomez-Sánchez, Evgen Prokhorov, Giovanna Giuliana Buonocore, Gabriel Luna-Barcenas, Luigi Ambrosio, Maria Grazia Raucci, Iida

PMID: 34331513 DOI: 10.1002/jbm.a.37283

Abstract

Considerable attention has been given to the use of chitosan (CS)-based materials reinforced with inorganic bioactive signals such as hydroxyapatite (HA) to treat bone defects and tissue loss. It is well known that CS/HA based materials possess minimal foreign body reactions, good biocompatibility, controlled biodegradability and antibacterial property. Herein, the bioactivity of these composite systems was analyzed on in vitro bone cell models for their applications in the field of bone tissue engineering (BTE). The combination of sol-gel approach and freeze-drying technology was used to obtain CS/HA scaffolds with three-dimensional (3D) porous structure suitable for cell in-growth. Specifically, our aim was to investigate the influence of bioactive composite scaffolds on cellular behavior in terms of osteoinductivity and anti-inflammatory effects for treating bone defects. The results obtained have demonstrated that by increasing inorganic component concentration, CS/HA (60 and 70% v/v) scaffolds induced a good biological response in terms of osteogenic differentiation of human mesenchymal stem cells (hMSC) towards osteoblast phenotype. Furthermore, the scaffolds with higher concentration of inorganic fillers are able to modulate the production of pro-inflammatory (TGF-β) and anti-inflammatory (IL-4, IL-10) cytokines. Our results highlight the possibility of achieving smart CS/HA based composites able to promote a great osteogenic differentiation of hMSC by increasing the amount of HA nanoparticles used as bioactive inorganic signal. Contemporarily, these materials allow avoiding the induction of a pro-inflammatory response in bone implant site.

© 2021 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.

Keywords: 3D scaffolds; bone regeneration; chitosan; hydroxyapatite; in vitro inflammatory response

References

1. Shakir M, Jolly R, Khan MS, Iram NE, Khan HM. Nano-hydroxyapatite/chitosan-starch nanocomposite as a novel bone construct: synthesis and in vitro studies. Int J Biol Macromol. 2015;80:282-292. - PubMed
2. Wan Jeffrey B, Bahman N-T, Saeid B. Overview of hydroxyapatite-graphene nanoplatelets composite as bone graft substitute: mechanical behavior and in-vitro biofunctionality. Crit Rev Solid State. 2018;43:177-212. - PubMed
3. Szcześ A, Hołysz L, Chibowski E. Synthesis of hydroxyapatite for biomedical applications. Adv Colloid Interface Sci. 2017;249:321-330. - PubMed
4. Sultankulov B, Berillo D, Sultankulova K, Tokay T, Saparov A. Progress in the development of chitosan-based biomaterials for tissue engineering and regenerative medicine. Biomolecules. 2019;9(9):470. - PubMed
5. Xianmiao C, Yubao L, Yi Z, Li Z, Jidong L, Huanan W. Properties and in vitro biological evaluation of nanohydroxyapatite/chitosan membranes for bone guided regeneration. Mater Sci Eng C. 2009;29:29-35. - PubMed
6. Cancedda R, Giannoni P, Mastrogiacomo M. A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials. 2007;28:4240-4250. - PubMed
7. Ramakrishna S, Mayer J, Wintermantell E. Biomedical application of polymer-composite materials: a review. Compos Sci Technol. 2001;61:1189-1224. - PubMed
8. Liu X, Chen W, Zhang C, et al. Co-seeding human endothelial cells with human-induced pluripotent stem cell-derived mesenchymal stem cells on calcium phosphate scaffold enhances osteogenesis and vascularization in rats. Tissue Eng Part A. 2017;23(11-12):546-555. - PubMed
9. Soriente A, Amodio SP, Fasolino I, et al. Chitosan/PEGDA based scaffolds as bioinspired materials to control in vitro angiogenesis. Mater Sci Eng C. 2020;118:111420. - PubMed
10. Raucci MG, D'Antò V, Guarino V. Biomineralized porous composite scaffolds prepared by chemical synthesis for bone tissue regeneration. Acta Biomater. 2010;6:4090-4099. - PubMed
11. Raucci MG, Guarino V, Ambrosio L. Hybrid composite scaffolds prepared by sol-gel method for bone regeneration. Compos Sci Technol. 2010;70:1861-1868. - PubMed
12. Raucci MG, Giugliano D, Alvarez-Perez MA, Ambrosio L. Effects on growth and osteogenic differentiation of mesenchymal stem cells by the strontium-added sol-gel hydroxyapatite gel materials. J Mater Sci Mater. 2015;26(2):90. - PubMed
13. Rampersad SN. Multiple applications of Alamar blue as an indicator of metabolic function and cellular health in cell viability bioassays. Sensors. 2012;12(9):12347-12360. - PubMed
14. Zhang K, Wang S, Zhou C, et al. Advanced smart biomaterials and constructs for hard tissue engineering and regeneration. Bone Res. 2018;6:31. - PubMed
15. Atala A. Engineering organs. Curr Opin Biotechnol. 2009;20(5):575-592. - PubMed
16. Soriente A, Fasolino I, Raucci MG, et al. Effect of inorganic and organic bioactive signals decoration on the biological performance of chitosan scaffolds for bone tissue engineering. J Mater Sci Mater. 2018;7:62. - PubMed
17. Raucci MG, Fasolino I, Pastore SG, et al. Antimicrobial imidazolium ionic liquids for the development of minimal invasive calcium phosphate-based bio-nanocomposites. ACS Appl Mater Interfaces. 2018;10(49):42766-42776. - PubMed
18. Lopes DL, Martins-Cruz C, Oliveira MB, Mano JF. Bone physiology as inspiration for tissue regenerative therapies. Biomaterials. 2018;185:240-275. - PubMed
19. Raucci MG, Demitri C, Soriente A, Fasolino I, Sannino A, Ambrosio L. Gelatin/nano- hydroxyapatite hydrogel scaffold prepared by sol-gel technology as filler to repair bone defects. J Biomed Mater Res Part A. 2018;106:2007-2019. - PubMed
20. Nikolova MP, Chavali MS. Recent advances in biomaterials for 3D scaffolds: a review. Bioact Mater. 2019;4:271-292. - PubMed
21. Zhu L, Luo D, Liu Y. Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration. Int J Oral Sci. 2020;12(1):1-15. - PubMed
22. Zhang Q, Chang B, Zheng G, Du S, Li X. Quercetin stimulates osteogenic differentiation of bone marrow stromal cells through miRNA-206/connexin 43 pathway. Am J Transl Res. 2020;12(5):2062-2070. - PubMed
23. Catanzano O, Soriente A, La Gatta A, et al. Macroporous alginate foams crosslinked with strontium for bone tissue. Carbohydr Polym. 2018;202:72-83. - PubMed
24. Polo-Corrales L, Latorre-Esteves M, Ramirez-Vick JE. Scaffold design for bone regeneration. J Nanosci Nanotechnol. 2014;14(1):15-56. - PubMed
25. Gao C, Peng S, Feng P, Shuai C. Bone biomaterials and interactions with stem cells. Bone Res. 2017;5(1):1-33. - PubMed
26. Tsao YT, Huang YJ, Wu HH, Liu YA, Liu YS, Lee OK. Osteocalcin mediates biomineralization during osteogenic maturation in human mesenchymal stromal cells. Int J Mol Sci. 2017;18(1):159. - PubMed
27. Fasolino I, Raucci MG, Soriente A, et al. Osteoinductive and anti-inflammatory properties of chitosan-based scaffolds for bone regeneration. Korean J Couns Psychother. 2019;105:110046. - PubMed
28. Trindade R, Albrektsson T, Tengvall P. Foreign body reaction to biomaterials: on mechanisms for buildup and breakdown of osseointegration. Clin Implant Dent Relat Res. 2016;18(1):192-203. - PubMed
29. van der Kraan PM. Differential role of transforming growth factor-beta in an osteoarthritic or a healthy joint. J Bone Metab. 2018;25(2):65-72. - PubMed
30. Luzina IG, Keegan AD, Heller NM, Rook GA, Shea-Donohue T, Atamas SP. Regulation of inflammation by interleukin-4: a review of "alternatives". J Leukoc Biol. 2012;92(4):753-764. - PubMed
31. Burmeister AR, Marriott I. The Interleukin-10 family of cytokines and their role in the CNS. Front Cell Neurosci. 2018;12:458. - PubMed
32. Hagenacker T, Ledwig D, Büsselberg D. Feedback mechanisms in the regulation of intracellular calcium ([Ca2+]i) in the peripheral nociceptive system: role of TRPV-1 and pain related receptors. Cell Calcium. 2008;43(3):215-227. - PubMed

Publication Types

• Journal Article

Grant support

• Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional
• Consiglio Nazionale delle Ricerche