Abstract
Exploring the simple fabrication process to prepare CNC@HAp for biological tissues is still a challenging subject considering the wide applications of the composites for bio tissues. In this work, aiming for the fabrication of CNC@HAp composites via a simple and environment-friendly process and materials, we propose the neutralization titration in the presence of CNCs in the suspension. Core–shell structured composite of cellulose nanocrystal (CNC) and hydroxyapatite (HAp) (CNC@HAp) was successfully synthesized via simple aqueous neutralization titration. The method studied successfully hybridizes CNCs with a certain amount of HAps and easily controls the coating amounts of HAps from 9 wt% to 17 wt%. In particular, CNC@HAp pellets were easily prepared by simple compression molding from the powder of hybridized CNCs and HAps and the pellets showed high mechanical strength of over 500 N with a low strain of less than 5%. Both the process and the product of the study were environmental-friendly, no toxicity, simple and pure therefore the CNC@HAp can be easily applied to tissue engineering and medical purposes.
Graphic abstract

This is a preview of subscription content, access via your institution.





Abbreviations
- CNC:
-
Cellulose Nanocrystal
- HAp:
-
Hydroxyapatite
- CNC@HAp:
-
Composite of cellulose and hydroxyapatite
References
Alshehri R, Ilyas AM, Hasan A, Arnaout A, Ahmed F, Memic A (2016) Carbon nanotubes in biomedical applications: factors, mechanisms, and remedies of toxicity. J Med Chem 59:8149–8167. https://doi.org/10.1021/acs.jmedichem.5b01770
Ansari M (2019) Bone tissue regeneration: biology, strategies and interface studies. Prog Biomater 8:223–237. https://doi.org/10.1007/s40204-019-00125-z
Araki J (2013) Soft matter, electrostatic or steric? Preparations and characterizations of well-dispersed systems containing rod-like nanowhiskers of crystalline polysaccharides. Soft Matter 9:4125–4141. https://doi.org/10.1039/c3sm27514k
Araki J, Arita T (2017) Production of ultrafine dry powders of surface-intact and unmodified cellulose nanowhiskers via homogenization in nonpolar organic solvents. Chem Lett 46:1438–1441. https://doi.org/10.1216/cl.1705887
Asscher YWS, Boaretto E (2011) Variations in atomic disorder in biogenic carbonate hydroxyapatite using the infrared spectrum grinding curve method. Adv Funct Mater 21:3308–3313. https://doi.org/10.1002/adfm.201100266
Azizi Samir SA, Alloin F, Dufresne A (2005) Review of recent research into cellulosic whiskers, their properties and their application in nanocomposite field. Biomacromol 6:612–626. https://doi.org/10.1021/bm0493685
Battista OA, Smith PA (1962) Microcrystalline cellulose. Ind Eng Chem 54(9):20–29. https://doi.org/10.1021/ie50633a003
Brown RM Jr (2004) Cellulose structure and biosynthesis: what is in store for the 21st century? J Polym Sci Part A: Polym Chem 42:487–495. https://doi.org/10.1002/pola.10877
Espinosa SC, Kuhnt T, Foster EJ, Weder C (2013) Isolation of thermally stable cellulose nanocrystals by phosphoric acid hydrolysis. Biomacromol 14(4):1223–1230. https://doi.org/10.1021/bm400219u
Fujisawa S, Saito T, Isogai A (2018) All cellulose (cellulose-cellulose) green composites. Adv Green Compos. https://doi.org/10.1002/9781119323327.ch6
Halder P, Kundu S, Patel S, Parthasarathy R, Pramanik B, Paz-Ferreiro J, Shah K (2019) TGA-FTIR study on the slow pyrolysis of lignin and cellulose-rich fractions derived from imidazolium-based ionic liquid pre-treatment of sugarcane straw. Energy Convers Manage 200:112067. https://doi.org/10.1016/j.enconman.2019.112067
Hiew TN, Tian YH, Tan HM, Heng PWS (2019) A mechanistic understanding of compression damage to the dissolubility of coated pellets in tablets. Eur J Pharm Biopharm 146:93–100. https://doi.org/10.1016/j.ejpb.2019.11.006
Ifuku S, Saimoto H (2012) Chitin nanofibers: preparations, modifications, and applications. Nanoscale 4:3308–3318. https://doi.org/10.1039/c2nr30383c
Isogai A, Saito T, Fukuzumi H (2011) TEMPO-oxidized cellulose nanofibers. Nanoscale 3:71–85. https://doi.org/10.1039/c0nr00583e
Iwamoto S, Kai W, Isogai A, Iwata T (2009) Elastic modulus of single cellulose microfibrils from tunicate measured by atomic force microscopy. Biomacromol 10(9):2571–2576. https://doi.org/10.1021/bm900520n
Kandori K, Yamaguchi Y (2017) Synthesis and characterization of Mn-doped calcium hydroxyapatite particles. Phosphorus Res Bull 33:26–34. https://doi.org/10.3363/prb.33.26
Liu Y, Zhao Y, Sun B, Chen C (2013) Understanding the toxicity of carbon nanotube. Acc Chem Res 46:702–713. https://doi.org/10.1021/qr300028m
Maurer P, Pistner H, Schubert J (2006) Computer assisted chewing power in patients with segmental resection of the mandible. MKG 10:37–41. https://doi.org/10.1007/s10006-005-0656-y
Nakakubo K, Hasegawa H, Ito M, Yamazaki K, Miyaguchi M, Biswas FB, Ikaki T, Maeda K (2019) Dithiocarbamate-modified cellulose resins: a novel adsorbent for selective removal of arsenite from aqueous media. J Hazard Mater 380:120816. https://doi.org/10.1016/j.jhazmat.2019.120816
Oh SY, Yoo DI, Shin Y, Kim HC, Kim HY, Chung YS, Parkd WH, Youke JH (2005) Crystalline structure analysis of cellulose treated with sodium hydroxide and carbon dioxide by means of X-ray diffraction and FTIR spectroscopy. Carbohydr Res 340:2376–2391. https://doi.org/10.1016/j.jhazmat.2019.120816
Reyes-Gasga J, Martínez-Piñeiro EL, Rodríguez-Álvare G, Tiznado-Orozco GE, García-García R, Brès EF (2013) XRD and FTIR crystallinity indices in sound human tooth enamel and synthetic hydroxyapatite. Mater Sci Eng C 33:4568–4574. https://doi.org/10.1016/j.msec.2013.07.014
Saito T, Kuramae R, Wohlert J, Berglund LA, Isogai A (2013) An Ultrastrong nanofibrillar biomaterial: the strength of single cellulose nanofibrils revealed via sonication-induced fragmentation. Biomacromol 14:248–253. https://doi.org/10.1021/bm301674e
Sehaqui H, Allais M, Zhou Q, Berglund LA (2011) Wood cellulose biocomposites with fibrous structures at micro- and nanoscale. Compos Sci Technol 71:382–387. https://doi.org/10.1016/j.compscitech.2010.12.007
Shito K, Matsui J, Takahashi Y, Masuhara A, Arita T (2018) Proton Conductivity of poly(acrylic acid)-b-polystyrene-coated silica nanoparticles synthesized by reversible addition-fragmentation chain transfer polymerization with particles. Chem Lett 47:9–12. https://doi.org/10.1246/cl.170752
Souza Lima MM, Borsali R (2004) Rodlike Cellulose microcrystals: structure, properties, and applications. Macromol Rapid Commun 25:771–787. https://doi.org/10.1002/marc.200300268
Yin N, Chen S, Ouyang Y, Tang L, Yang J, Wang H (2011) Biomimetic mineralization synthesis of hydroxyapatite bacterial cellulose nanocomposites. Prog Nat Sci: Mater Int 21:472–477. https://doi.org/10.1016/S1002-0071(12)60085-9
Yoshida A, Miyazaki T, Ashizuka M, Ishida E (2006) Bioactivity and mechanical properties of cellulose/carbonate hydroxyapatite composites prepared in situ through mechanochemical reaction. J Biomater Appl 21:179–194. https://doi.org/10.1177/0885328206059796
Zhang L, Ruan D, Gao S (2002) Dissolution and regeneration of cellulose in NaOH/thiourea aqueous solution. J Polym Sci Part B: Polym Phys 40:1521–1529. https://doi.org/10.1002/polb.10215
Acknowledgments
This work was supported by the cooperative research program of “Network Joint Research Center for Materials and Devices” and JSPS KAKENHI No. JP18H01717.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Sato, R., Arita, T., Shimada, R. et al. Biocompatible composite of cellulose nanocrystal and hydroxyapatite with large mechanical strength. Cellulose 28, 871–879 (2021). https://doi.org/10.1007/s10570-020-03550-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10570-020-03550-7