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Vital, N.;  Ventura, C.;  Kranendonk, M.;  Silva, M.J.;  Louro, H. Production and Application of Cellulose Nanomaterials. Encyclopedia. Available online: (accessed on 17 April 2024).
Vital N,  Ventura C,  Kranendonk M,  Silva MJ,  Louro H. Production and Application of Cellulose Nanomaterials. Encyclopedia. Available at: Accessed April 17, 2024.
Vital, Nádia, Célia Ventura, Michel Kranendonk, Maria João Silva, Henriqueta Louro. "Production and Application of Cellulose Nanomaterials" Encyclopedia, (accessed April 17, 2024).
Vital, N.,  Ventura, C.,  Kranendonk, M.,  Silva, M.J., & Louro, H. (2022, October 28). Production and Application of Cellulose Nanomaterials. In Encyclopedia.
Vital, Nádia, et al. "Production and Application of Cellulose Nanomaterials." Encyclopedia. Web. 28 October, 2022.
Production and Application of Cellulose Nanomaterials

Cellulose nanomaterials (CNMs) have emerged recently as an important group of sustainable bio-based nanomaterials (NMs) with potential applications in multiple sectors, including the food, food packaging, and biomedical fields. The widening of these applications leads to increased human oral exposure to these NMs and, potentially, to adverse health outcomes. Presently, the potential hazards regarding oral exposure to CNMs are insufficiently characterised. There is a need to understand and manage the potential adverse effects that might result from the ingestion of CNMs before products using CNMs reach commercialisation.

cellulose nanomaterials cellulose nanocrystals cellulose nanofibres

1. Overview of Sources and Production of Cellulose Nanomaterials (CNMs)

Cellulose is a white, fibre-like structure consisting of a linear polysaccharide chain composed of repeated units of two D-glucopyranose rings linked together by oxygen covalently bonded to C1 of one glucose ring and C4 of the adjoining ring (β-1,4 glycosidic bond), with free hydroxyl groups (-OH) at the C-2, C-3, and C-6 atoms [1][2]. Cellulose materials can be produced at the nanoscale, and the resulting CNMs may be grouped into five main categories based on the cellulose source, extraction/production method, and surface chemistry [3][4]. These categories are cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), cellulose nanocrystals from tunicates (t-CNCs), algal cellulose (AC), and bacterial nanocellulose (BC) [3][4][5][6].
The most common sources of CNMs—particularly of CNFs and CNCs—are cellulose obtained from plants, namely, hardwood or softwood pulp. Plant cellulose can also be extracted from seed fibres, bast fibres, grasses, banana peel, oil palm, and rice straw, among others [5][7][8][9]. Cellulose is predominantly located in the plant’s secondary cell wall, which is reinforced by a matrix also consisting of lignin, hemicellulose, pectin, proteins, extractive organic substances, and trace elements [5][6][10]. Large cellulose fibres are constituted by parallel stacking of multiple cellulose chains that form the elementary fibrils and are assembled into larger microfibril bundles [5][6]. The elementary cellulose fibrils are constituted by regions of highly ordered cellulose chains (i.e., crystalline) that form the core, which alternate with disordered regions (i.e., amorphous) [5][6]. CNFs—also known as nanofibrillated cellulose, nanofibrillar cellulose, or cellulose nanofibres—are defined as “cellulose nanofibres composed of at least one elementary fibril, containing crystalline, paracrystalline and amorphous regions, with aspect ratios usually greater than 10 nm, which may contain longitudinal splits, entanglement between particles, or network-like structures” [11]. CNFs’ dimensions are typically 3–100 nm in cross-section (diameter) and up to 100 μm in length [11]. CNCs—also known as nanocrystalline cellulose, cellulose nanowhiskers, needles, spheres, or nanowires—are defined as “nanocrystals predominantly composed of cellulose with at least one elementary fibril containing predominantly crystalline and paracrystalline regions, with aspect ratio ranging from 5 to 50, not exhibiting longitudinal splits, inter-particle entanglement, or network-like structures” [11]. CNCs’ dimensions are typically 3–50 nm in cross-section and 100 nm to several μm in length, depending on the source material [11]. CNFs or CNCs are obtained by fragmentation of the cellulose hierarchical structure using different chemical, enzymatic, and/or mechanical approaches. An overview of the extraction processes for CNFs and CNCs is detailed elsewhere [10][12][13]. Briefly, the production of CNFs requires breaking the fibres into delaminated individual nanofibrils. These are mainly obtained via high-energy mechanical shearing methods, such as ultrafine grinding/microgrinding, microfluidisation, high-intensity ultrasonication, or high-pressure homogenisation, among others [10][13][14][15]. These processes are normally preceded by chemical or enzymatic hydrolysis treatments to increase the fragmentation/depolymerisation (nanofibrillation) efficiency and reduce production costs [10][12][14][15][16]. These treatments also contribute to removing non-cellulosic constituents such as lignin and hemicelluloses, producing highly purified cellulose, and can yield CNFs with modified surface chemistry [10]. Common chemical treatments leading to chemical modifications of CNFs include catalytic oxidation with 2,2,6,6-tetramethylpiperidine-1-oxyl radicals (TEMPO oxidation), whereby the primary hydroxyl groups on the C6 position of cellulose are converted to carboxylic groups [17][18][19]; carboxymethylation [20][21][22]; phosphorylation [21][22]; etc. CNCs are derived from the crystalline regions of cellulose and are commonly extracted by acid hydrolysis of cellulose pulp using mineral acids—typically sulfuric, hydrochloric, or phosphoric acid [4]. Acid hydrolysis removes non-cellulosic components and annihilates most of the amorphous regions, leaving the crystalline regions, and resulting in the formation of nanocrystal structures [4][6][13][23]. CNMs extracted from different sources via different production methods are analogous in chemical composition but have different morphologies, lengths, widths, aspect ratios, degrees of polymerisation (i.e., the number of glucose units), and crystallinity [3][6][14][24]. Different ratios of amorphous fractions and crystalline domains influence the CNMs’ physical characteristics. While CNCs have a short needle- or rod-like morphology demonstrating similar diameters and a high level of rigidity/stiffness due to their high crystallinity, entangled CNFs have fibre/fibril morphologies with a higher aspect ratio, plasticity, and flexibility [4][5].
The accessibility of hydroxyl groups on the cellulose surface and the relatively large specific surface area of CNMs offer many possibilities for their modification and functionalisation during production, resulting in different surface chemistries [3][4][15][25]. Chemical modifications can occur as a byproduct of the extraction process (e.g., sulphate half-ester formation after treatment with sulfuric acid, carboxylic acid after treatment with TEMPO, etc.) [26]. Surface functionalisation can also occur via adsorption to the surface of the particles and covalent attachment of molecules or derivatisation of the surface [26]. Molecular grafting, grafting of polymers or supramolecular units, the addition of fluorescent tags, and nanoparticles, among others, are often used to functionalise CNMs [3][22][26][27][28][29][30]. The variety of chemistries currently being used has been summarised in recent reviews [15][22][26][31][32]. The surface chemistry affects the CNMs’ hydrophilic/hydrophobic balance and its interaction with the surrounding environment, influencing CNMs’ degree of aggregation and agglomeration, dispersibility in solvents or polymers, rheology, and applicability in multiple systems [3][4][15][33][34]. Moreover, surface chemistry can also influence CNMs’ interactions with biological systems [35][36][37].

2. CNMs in Food Technology and Biomedicine

Conventional cellulose and some of its derivatives have a long history of use as additives in food and animal feed. In the European Union, several micron-sized or larger celluloses and cellulose derivatives are currently authorised as food additives in almost all food categories, at quantum satis (QS), as defined in Annex II of Regulation (EC) No 1333/2008 on food additives. They are considered safe for use as food additives, and an acceptable daily intake (ADI) has been considered unnecessary, based on their low toxicity, absence of genotoxic concerns and, if any, their negligible absorption in the human GIT [38]. Several celluloses and their derivatives are also authorised under the European Regulation (EC) No 10/2011 for plastics for food packaging, as well as for use as polymer additives, production aids, and other starting substances. Conversely, CNMs have not yet been authorised as food additives or as food contact materials in Europe. Specific assessments are required for their safety evaluation in the framework of food and feed in the European Union, as described by the European Food Safety Authority (EFSA)’s guidance on nanomaterials [39]. In the USA, celluloses have been designated “generally regarded as safe” (GRAS) by the US Food and Drug Administration (FDA) and are approved as food additives by the US Department of Agriculture’s Food Safety and Inspection Service [40][41]. No specific regulatory provisions are in place for pharmaceutical drugs or other medical products and devices using NMs in the USA, Canada, the UK, Japan, or Europe [42]. In Europe, some guidelines are available for specific NMs for applications in human medicines [43][44].
CNMs have found a multitude of potential applications in the food industry [23][45][46][47]. Three main categories of applications can be foreseen: food packaging materials, food additives, and functional foods [23][46], as depicted in Figure 1
Figure 1. Potential applications of CNMs in the food industry, including food contact materials.
There is currently a great demand for new and innovative food packaging materials driven by the policy of using fewer plastics and increasing recyclability. Replacing conventional non-renewable and practically non-biodegradable oil-based materials with CNM-based packaging materials could increase the biodegradability of food packaging and reduce packaging waste, minimising the environmental impact [1][47][48]. Several nanocomposite food packaging materials containing CNMs have been developed, showing promising results in improving the food packaging’s main functions, i.e., extending food’s stability and assuring its quality and safety for a longer shelf-life [1][8][14][45][47][48][49][50][51]. CNMs can be incorporated as reinforcing structures in different types of food packaging materials (e.g., as a filler or coating), to improve transparency or mechanical (e.g., tensile strength), thermal, and barrier (e.g., gases and water vapour) properties, as compared to conventional materials [1][46][47][50][52][53][54]. When applied as coating materials in the inner layer of food packaging materials (such as paper), CNMs can contribute to protecting packaging from water (e.g., cups for coffee) or increasing its resistance to grease/oil (e.g., in pizza/hamburger boxes) [50]. CNMs can also be added to packaging composites to increase anti-microbiological performance in various types of foods and materials [46][50][53][55][56][57]. Additionally, the quality of fruits and vegetables (e.g., strawberries, blueberries, pomegranate seeds, or pears) has been improved when coated with CNM composites (e.g., chitosan/CNMs or CNFs/nanoparticles of calcium carbonate), showing decreased weight loss and improved food preservation, or improved visual appearance [58][59][60][61]. Edible packaging materials made of CNM composites with either increased antimicrobial properties or improved mechanical strength or barrier properties have also been investigated [62][63][64].
As food additives, CNMs have been proposed as stabilisers of oil-in-water Pickering emulsions with or without antibacterial properties, to improve food’s homogeneity and stability [65][66][67][68]. CNMs or CNM composites may be used to stabilise oils or fat foams, such as cake frostings or whipped toppings, or emulsions such as salad dressings, sauces, and gravies [23]. They can also potentially be applied as rheology modifiers—for example, to improve gelling (i.e., anti-melting) and texture properties, as a fat substitute to reduce the caloric value of ice cream [69][70], or to thicken powder-based soy milk [23]. Additionally, they have been proposed as a non-caloric fat substitute in meat sausages using nanocellulose-stabilised soybean oil to retain moisture without compromising texture [71].
One of the main advantages of CNMs is their appeal to dietetic foods, due to their indigestibility by humans. The use of CNMs as functional foods has also been proposed, with their effects being studied in various aspects of the digestion process as a non-caloric fibre source (i.e., dietary fibre) to reduce the caloric density of food products [72]. They can also be used as modulating agents in the digestion and absorption of co-ingested triglycerides (i.e., fat) [73], to delay the digestion and diffusion of starch [74], or to modulate the absorption of glucose and minerals [74][75].
In addition to their uses in the food industry, CNMs have been characterised as very promising materials for biomedical and pharmaceutical applications. This is due to their supposed biocompatibility, chemical modification capabilities (vide supra), water-retaining capacity, hydrophilic properties, advantageous mechanical properties (such as high mechanical strength), and relatively inexpensive production. All of these characteristics are paired with their biodegradability, renewability, and ready availability [25][76], enabling different types of formulations, either alone or as polymer composites [76]. Multiple potential applications of CNCs or CNFs in the biomedical field have been explored in recent years, as extensively reviewed in [7][24][76][77][78][79][80][81][82][83][84][85][86]. Among many biomedical applications, CNMs have been widely investigated for the delivery of hydrophilic, hydrophobic, water-soluble, and poorly water-soluble drugs, to be applied via different routes of administration [25][79][87]. CNM-based systems using different carrier forms (for example, dry foams and films, aerogels, emulsions, or hydrogels) have been studied to mediate drug delivery (e.g., riboflavin, bendamustine, hydrochloride, naproxen and ibuprofen, furosemide, methotrexate, repaglinide) for oral administration [76][88][89][90][91][92][93][94]. These systems have been designed for sustained and targeted drug release, with decreased side effects and enhanced therapeutic efficacy over a prolonged period, and with the prospect of dose reduction [89]. Applications of CNMs in bio-adhesive films have also been sought for controlled drug delivery or local drug administration, as shown for the colon-specific delivery of methotrexate [95]. Other applications of CNMs in the biomedical field include restorative dentistry, bioprinting for tissue engineering, wound healing and tissue repair, medical implants, vascular grafts, bone tissue engineering, antimicrobial membranes, and scaffolds for human stem cell cultures, among others [24][25][76][77][81][96][97][98][99][100][101][102].


  1. Vilarinho, F.; Sanches Silva, A.; Vaz, M.F.; Farinha, J.P. Nanocellulose in green food packaging. Crit. Rev. Food Sci. Nutr. 2018, 58, 1526–1537.
  2. Endes, C.; Camarero-Espinosa, S.; Mueller, S.; Foster, E.J.; Petri-Fink, A.; Rothen-Rutishauser, B.; Weder, C.; Clift, M.J.D. A critical review of the current knowledge regarding the biological impact of nanocellulose. J. Nanobiotechnol. 2016, 14, 78.
  3. Foster, E.J.; Moon, R.J.; Agarwal, U.P.; Bortner, M.J.; Bras, J.; Camarero-Espinosa, S.; Chan, K.J.; Clift, M.J.D.; Cranston, E.D.; Eichhorn, S.J.; et al. Current characterization methods for cellulose nanomaterials. Chem. Soc. Rev. 2018, 47, 2609–2679.
  4. Moon, R.J.; Schueneman, G.T.; Simonsen, J. Overview of cellulose nanomaterials, their capabilities and applications. JOM 2016, 68, 2383–2394.
  5. Ventura, C.; Pinto, F.; Lourenço, A.F.; Ferreira, P.J.T.; Louro, H.; Silva, M.J. On the toxicity of cellulose nanocrystals and nanofibrils in animal and cellular models. Cellulose 2020, 27, 5509–5544.
  6. Moon, R.J.; Martini, A.; Nairn, J.; Simonsen, J.; Youngblood, J. Cellulose nanomaterials review: Structure, properties and nanocomposites. Chem. Soc. Rev. 2011, 40, 3941–3994.
  7. Halib, N.; Perrone, F.; Cemazar, M.; Dapas, B.; Farra, R.; Abrami, M.; Chiarappa, G.; Forte, G.; Zanconati, F.; Pozzato, G.; et al. Potential applications of nanocellulose-containing materials in the biomedical field. Materials 2017, 10, 977.
  8. Souza, E.; Gottschalk, L.; Freitas-Silva, O. Overview of nanocellulose in food packaging. Recent Pat. Food Nutr. Agric. 2019, 11, 154–167.
  9. Tibolla, H.; Pelissari, F.M.; Martins, J.T.; Lanzoni, E.M.; Vicente, A.A.; Menegalli, F.C.; Cunha, R.L. Banana starch nanocomposite with cellulose nanofibers isolated from banana peel by enzymatic treatment: In vitro cytotoxicity assessment. Carbohydr. Polym. 2019, 207, 169–179.
  10. Abdul Khalil, H.P.S.; Davoudpour, Y.; Saurabh, C.K.; Hossain, M.S.; Adnan, A.S.; Dungani, R.; Paridah, M.T.; Islam Sarker, M.Z.; Fazita, M.R.N.; Syakir, M.I.; et al. A review on nanocellulosic fibres as new material for sustainable packaging: Process and applications. Renew. Sustain. Energy Rev. 2016, 64, 823–836.
  11. ISO/TS 20477:2017; Nanotechnologies—Standard Terms and Their Definition for Cellulose Nanomaterial. ISO: Geneva, Switzerland, 2017.
  12. Michelin, M.; Gomes, D.G.; Romaní, A.; Polizeli, M.d.L.T.M.; Teixeira, J.A. Nanocellulose production: Exploring the enzymatic route and residues of pulp and paper industry. Molecules 2020, 25, 3411.
  13. Kargarzadeh, H.; Mariano, M.; Gopakumar, D.; Ahmad, I.; Thomas, S.; Dufresne, A.; Huang, J.; Lin, N. Advances in cellulose nanomaterials. Cellulose 2018, 25, 2151–2189.
  14. Klemm, D.; Cranston, E.D.; Fischer, D.; Gama, M.; Kedzior, S.A.; Kralisch, D.; Kramer, F.; Kondo, T.; Lindström, T.; Nietzsche, S.; et al. Nanocellulose as a natural source for groundbreaking applications in materials science: Today’s state. Mater. Today 2018, 21, 720–748.
  15. Abdul Khalil, H.P.S.; Davoudpour, Y.; Islam, M.N.; Mustapha, A.; Sudesh, K.; Dungani, R.; Jawaid, M. Production and modification of nanofibrillated cellulose using various mechanical processes: A review. Carbohydr. Polym. 2014, 99, 649–665.
  16. Ede, J.D.; Ong, K.J.; Goergen, M.; Rudie, A.; Pomeroy-Carter, C.A.; Shatkin, J.A. Risk analysis of cellulose nanomaterials by inhalation: Current state of science. Nanomaterials 2019, 9, 337.
  17. Gamelas, J.A.F.; Pedrosa, J.; Lourenço, A.F.; Mutjé, P.; González, I.; Chinga-Carrasco, G.; Singh, G.; Ferreira, P.J.T. On the morphology of cellulose nanofibrils obtained by TEMPO-mediated oxidation and mechanical treatment. Micron 2015, 72, 28–33.
  18. Levanič, J.; Šenk, V.P.; Nadrah, P.; Poljanšek, I.; Oven, P.; Haapala, A. Analyzing TEMPO-Oxidized cellulose fiber morphology: New insights into optimization of the oxidation process and nanocellulose dispersion quality. ACS Sustain. Chem. Eng. 2020, 8, 17752–17762.
  19. Saito, T.; Isogai, A. TEMPO-mediated oxidation of native cellulose. The effect of oxidation conditions on chemical and crystal structures of the water-insoluble fractions. Biomacromolecules 2004, 5, 1983–1989.
  20. Zhang, K.; Zhang, H.; Wang, W. Toxicological studies and some functional properties of carboxymethylated cellulose nanofibrils as potential food ingredient. Int. J. Biol. Macromol. 2021, 190, 887–893.
  21. Lopes, V.R.; Strømme, M.; Ferraz, N. In vitro biological impact of nanocellulose fibers on human gut bacteria and gastrointestinal cells. Nanomaterials 2020, 10, 1159.
  22. Rol, F.; Belgacem, M.N.; Gandini, A.; Bras, J. Recent advances in surface-modified cellulose nanofibrils. Prog. Polym. Sci. 2019, 88, 241–264.
  23. Gómez, H.C.; Serpa, A.; Velásquez-Cock, J.; Gañán, P.; Castro, C.; Vélez, L.; Zuluaga, R. Vegetable nanocellulose in food science: A review. Food Hydrocoll. 2016, 57, 178–186.
  24. Trache, D.; Tarchoun, A.F.; Derradji, M.; Hamidon, T.S.; Masruchin, N.; Brosse, N.; Hussin, M.H. Nanocellulose: From fundamentals to advanced applications. Front. Chem. 2020, 8, 392.
  25. Kupnik, K.; Primožič, M.; Kokol, V.; Leitgeb, M. Nanocellulose in drug delivery and antimicrobially active materials. Polymers 2020, 12, 2825.
  26. Shankaran, D.R. Cellulose nanocrystals for health care applications. In Applications of Nanomaterials, 1st ed.; Bhagyaraj, S.M., Oluwafemi, O.S., Kalarikkal, N., Thomas, S., Eds.; Elsevier Ltd.: Amsterdam, The Netherlands, 2018; pp. 415–459.
  27. Abitbol, T.; Palermo, A.; Moran-Mirabal, J.M.; Cranston, E.D. Fluorescent labeling and characterization of cellulose nanocrystals with varying charge contents. Biomacromolecules 2013, 14, 3278–3284.
  28. Reid, M.S.; Karlsson, M.; Abitbol, T. Fluorescently labeled cellulose nanofibrils for detection and loss analysis. Carbohydr. Polym. 2020, 250, 116943.
  29. Patel, I.; Woodcock, J.; Beams, R.; Stranick, S.J.; Nieuwendaal, R.; Gilman, J.W.; Mulenos, M.R.; Sayes, C.M.; Salari, M.; DeLoid, G.; et al. Fluorescently Labeled Cellulose Nanofibers for Environmental Health and Safety Studies. Nanomaterials 2021, 11, 1015.
  30. Salari, M.; Bitounis, D.; Bhattacharya, K.; Pyrgiotakis, G.; Zhang, Z.; Purington, E.; Gramlich, W.; Grondin, Y.; Rogers, R.; Bousfield, D.; et al. Development & characterization of fluorescently tagged nanocellulose for nanotoxicological studies. Environ. Sci. Nano 2019, 6, 1516–1526.
  31. Habibi, Y.; Lucia, L.A.; Rojas, O.J. Cellulose nanocrystals: Chemistry, self-assembly, and applications. Chem. Rev. 2010, 110, 3479–3500.
  32. Mishra, R.K.; Sabu, A.; Tiwari, S.K. Materials chemistry and the futurist eco-friendly applications of nanocellulose: Status and prospect. J. Saudi Chem. Soc. 2018, 22, 949–978.
  33. Torlopov, M.A.; Drozd, N.N.; Paderin, N.M.; Tarabukin, D.V.; Udoratina, E.V. Hemocompatibility, biodegradability and acute toxicity of acetylated cellulose nanocrystals of different types in comparison. Carbohydr. Polym. 2021, 269, 118307.
  34. Chu, Y.; Sun, Y.; Wu, W.; Xiao, H. Dispersion properties of nanocellulose: A Review. Carbohydr. Polym. 2020, 250, 116892.
  35. Aimonen, K.; Suhonen, S.; Hartikainen, M.; Lopes, V.R.; Norppa, H.; Ferraz, N.; Catalán, J. Role of surface chemistry in the in vitro lung response to nanofibrillated cellulose. Nanomaterials 2021, 11, 389.
  36. Lopes, V.R.; Sanchez-Martinez, C.; Strømme, M.; Ferraz, N. In vitro biological responses to nanofibrillated cellulose by human dermal, lung and immune cells: Surface chemistry aspect. Part. Fibre Toxicol. 2017, 14, 1.
  37. Otuechere, C.A.; Adewuyi, A.; Adebayo, O.L.; Ebigwei, I.A. In vivo hepatotoxicity of chemically modified nanocellulose in rats. Hum. Exp. Toxicol. 2019, 39, 212–223.
  38. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS); Younes, M.; Aggett, P.; Aguilar, F.; Crebelli, R.; Di Domenico, A.; Dusemund, B.; Filipič, M.; Jose Frutos, M.; Galtier, P.; et al. Re-evaluation of celluloses E 460(i), E 460(ii), E 461, E 462, E 463, E 464, E 465, E 466, E 468 and E 469 as food additives. EFSA J. 2018, 16, e05047.
  39. EFSA Scientific Committee; More, S.; Bampidis, V.; Benford, D.; Bragard, C.; Halldorsson, T.; Hernández-Jerez, A.; Hougaard Bennekou, S.; Koutsoumanis, K.; Lambré, C.; et al. Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: Human and animal health. EFSA J. 2021, 19, e06768.
  40. Deloid, G.M.; Cao, X.; Molina, R.M.; Silva, D.I.; Bhattacharya, K.; Ng, K.W.; Loo, S.C.J.; Brain, J.D.; Demokritou, P. Toxicological effects of ingested nanocellulose in: In vitro intestinal epithelium and in vivo rat models. Environ. Sci. Nano 2019, 6, 2105–2115.
  41. FDA. SCOGS (Select Committee on GRAS Substances). Available online: (accessed on 7 September 2022).
  42. Foulkes, R.; Man, E.; Thind, J.; Yeung, S.; Joy, A.; Hoskins, C. The regulation of nanomaterials and nanomedicines for clinical application: Current and future perspectives. Biomater. Sci. 2020, 8, 4653–4664.
  43. European Medicine Agency. Reflection Paper on Surface Coatings: General Issues for Consideration Regarding Parenteral Administration of Coated Nanomedicine Products. 2013. Available online: (accessed on 10 May 2022).
  44. European Medicine Agency. Reflection Paper on the Data Requirements for Intravenous Iron-Based Nano-Colloidal Products Developed with Reference to an Innovator Medicinal Product. 2015. Available online: (accessed on 10 May 2022).
  45. Ma, T.; Hu, X.; Lu, S.; Liao, X.; Song, Y.; Hu, X. Nanocellulose: A promising green treasure from food wastes to available food materials. Crit. Rev. Food Sci. Nutr. 2020, 62, 989–1002.
  46. Lu, Q.; Yu, X.; Yagoub, A.E.G.A.; Wahia, H.; Zhou, C. Application and challenge of nanocellulose in the food industry. Food Biosci. 2021, 43, 101285.
  47. Azeredo, H.M.C.; Rosa, M.F.; Mattoso, L.H.C. Nanocellulose in bio-based food packaging applications. Ind. Crops Prod. 2017, 97, 664–671.
  48. Fotie, G.; Limbo, S.; Piergiovanni, L. Manufacturing of food packaging based on nanocellulose: Current advances and challenges. Nanomaterials 2020, 10, 1726.
  49. Cazón, P.; Vázquez, M. Bacterial cellulose as a biodegradable food packaging material: A review. Food Hydrocoll. 2021, 113, 106530.
  50. Ahankari, S.S.; Subhedar, A.R.; Bhadauria, S.S.; Dufresne, A. Nanocellulose in food packaging: A review. Carbohydr. Polym. 2021, 255, 117479.
  51. Silva, F.A.G.S.; Dourado, F.; Gama, M.; Poças, F. Nanocellulose bio-based composites for food packaging. Nanomaterials 2020, 10, 2041.
  52. Seoane, I.T.; Cerrutti, P.; Vazquez, A.; Manfredi, L.B.; Cyras, V.P. Polyhydroxybutyrate-Based Nanocomposites with Cellulose Nanocrystals and Bacterial Cellulose. J. Polym. Environ. 2017, 25, 586–598.
  53. Vilela, C.; Moreirinha, C.; Domingues, E.M.; Figueiredo, F.M.L.; Almeida, A.; Freire, C.S.R. Antimicrobial and conductive nanocellulose-based films for active and intelligent food packaging. Nanomaterials 2019, 9, 980.
  54. Fotie, G.; Amoroso, L.; Muratore, G.; Piergiovanni, L. Carbon dioxide diffusion at different relative humidity through coating of cellulose nanocrystals for food packaging applications. Food Packag. Shelf Life 2018, 18, 62–70.
  55. Moreirinha, C.; Vilela, C.; Silva, N.H.C.S.; Pinto, R.J.B.; Almeida, A.; Rocha, M.A.M.; Coelho, E.; Coimbra, M.A.; Silvestre, A.J.D.; Freire, C.S.R. Antioxidant and antimicrobial films based on brewers spent grain arabinoxylans, nanocellulose and feruloylated compounds for active packaging. Food Hydrocoll. 2020, 108, 105836.
  56. Dehnad, D.; Mirzaei, H.; Emam-Djomeh, Z.; Jafari, S.M.; Dadashi, S. Thermal and antimicrobial properties of chitosan-nanocellulose films for extending shelf life of ground meat. Carbohydr. Polym. 2014, 109, 148–154.
  57. El-Wakil, N.A.; Hassan, E.A.; Abou-Zeid, R.E.; Dufresne, A. Development of wheat gluten/nanocellulose/titanium dioxide nanocomposites for active food packaging. Carbohydr. Polym. 2015, 124, 337–346.
  58. Ye, D.; Bramini, M.; Hristov, D.R.; Wan, S.; Salvati, A.; Åberg, C.; Dawson, K.A. Low uptake of silica nanoparticles in Caco-2 intestinal epithelial barriers. Beilstein J. Nanotechnol. 2017, 8, 1396–1406.
  59. Noorbakhsh-Soltani, S.M.; Zerafat, M.M.; Sabbaghi, S. A comparative study of gelatin and starch-based nano-composite films modified by nano-cellulose and chitosan for food packaging applications. Carbohydr. Polym. 2018, 189, 48–55.
  60. Dong, F.; Li, S.; Jin, C.; Liu, Z.; Zhu, K.; Zou, H.; Wang, X. Effect of nanocellulose/chitosan composite coatings on cucumber quality and shelf life. Toxicol. Environ. Chem. 2016, 98, 450–461.
  61. Deng, Z.; Jung, J.; Simonsen, J.; Zhao, Y. Cellulose nanocrystals Pickering emulsion incorporated chitosan coatings for improving storability of postharvest Bartlett pears (Pyrus communis) during long-term cold storage. Food Hydrocoll. 2018, 84, 229–237.
  62. Ma, Z.S.; Wang, Y.J.; Chen, S.S.; Zhang, N.; Sui, S.Y.; Zhang, L.P. Effects of mung bean hull nanocrystalline cellulose on the performance of whey protein concentrate edible film. Mod. Food Sci. Technol. 2016, 32, 40–45.
  63. Chen, S.; Tao, H.; Wang, Y.; Ma, Z. Process optimization of soy protein isolate-based edible films containing nanocrystalline cellulose from sunflower seed hull and chitosan. Trans. Chin. Soc. Agric. Eng. 2016, 32, 306–314.
  64. Fakhouri, F.M.; Casari, A.C.A.; Mariano, M.; Yamashita, F.; Mei, L.H.I.; Soldi, V.; Martelli, S.M. Effect of a gelatin-based edible coating containing cellulose nanocrystals (CNC) on the quality and nutrient retention of fresh strawberries during storage. IOP Conf. Ser. Mater. Sci. Eng. 2014, 64, 012024.
  65. Huang, S.; Liu, X.; Chang, C.; Wang, Y. Recent developments and prospective food-related applications of cellulose nanocrystals: A review. Cellulose 2020, 27, 2991–3011.
  66. Cunha, A.G.; Mougel, J.B.; Cathala, B.; Berglund, L.A.; Capron, I. Preparation of double Pickering emulsions stabilized by chemically tailored nanocelluloses. Langmuir 2014, 30, 9327–9335.
  67. Mikulcová, V.; Bordes, R.; Kašpárková, V. On the preparation and antibacterial activity of emulsions stabilized with nanocellulose particles. Food Hydrocoll. 2016, 61, 780–792.
  68. Hedjazi, S.; Razavi, S.H. A comparison of Canthaxanthine Pickering emulsions, stabilized with cellulose nanocrystals of different origins. Int. J. Biol. Macromol. 2018, 106, 489–497.
  69. Velásquez-Cock, J.; Serpa, A.; Vélez, L.; Gañán, P.; Gómez Hoyos, C.; Castro, C.; Duizer, L.; Goff, H.D.; Zuluaga, R. Influence of cellulose nanofibrils on the structural elements of ice cream. Food Hydrocoll. 2019, 87, 204–213.
  70. Sun, L.; Chen, W.; Liu, Y.; Li, J.; Yu, H. Soy protein isolate/cellulose nanofiber complex gels as fat substitutes: Rheological and textural properties and extent of cream imitation. Cellulose 2015, 22, 2619–2627.
  71. Qi, W.; Wu, J.; Shu, Y.; Wang, H.; Rao, W.; Xu, H.N.; Zhang, Z. Microstructure and physiochemical properties of meat sausages based on nanocellulose-stabilized emulsions. Int. J. Biol. Macromol. 2020, 152, 567–575.
  72. Andrade, D.R.M.; Mendonça, M.H.; Helm, C.V.; Magalhães, W.L.E.; de Muniz, G.I.B.; Kestur, S.G. Assessment of nano cellulose from peach palm residue as potential food additive: Part II: Preliminary studies. J. Food Sci. Technol. 2015, 52, 5641–5650.
  73. Deloid, G.M.; Sohal, I.S.; Lorente, L.R.; Molina, R.M.; Pyrgiotakis, G.; Stevanovic, A.; Zhang, R.; McClements, D.J.; Geitner, N.K.; Bousfield, D.W.; et al. Reducing intestinal digestion and absorption of fat using a nature-derived biopolymer: Interference of triglyceride hydrolysis by nanocellulose. ACS Nano 2018, 12, 6469–6479.
  74. Nsor-Atindana, J.; Douglas Goff, H.; Liu, W.; Chen, M.; Zhong, F. The resilience of nanocrystalline cellulose viscosity to simulated digestive processes and its influence on glucose diffusion. Carbohydr. Polym. 2018, 200, 436–445.
  75. Liu, L.; Kerr, W.L.; Kong, F.; Dee, D.R.; Lin, M. Influence of nano-fibrillated cellulose (NFC) on starch digestion and glucose absorption. Carbohydr. Polym. 2018, 196, 146–153.
  76. Laurén, P. Biomedical Applications of Nanofibrillar Cellulose. Ph.D. Thesis, University of Helsinki, Helsinki, Finland, 2018.
  77. Lin, N.; Dufresne, A. Nanocellulose in Biomedicine: Current status and future prospect. Eur. Polym. J. 2014, 59, 302–325.
  78. Hasan, N.; Rahman, L.; Kim, S.H.; Cao, J.; Arjuna, A.; Lallo, S.; Jhun, B.H.; Yoo, J.W. Recent advances of nanocellulose in drug delivery systems. J. Pharm. Investig. 2020, 50, 553–572.
  79. Tan, T.H.; Lee, H.V.; Yehya Dabdawb, W.A.; Hamid, S.B.B.O.A.A. A review of nanocellulose in the drug-delivery system. In Materials for Biomedical Engineering: Nanomaterials-Based Drug Delivery; Holban, A.-M., Grumezescu, A.M., Eds.; Elsevier: Amsterdam, The Netherlands, 2019; pp. 131–164.
  80. Shojaeiarani, J.; Bajwa, D.; Shirzadifar, A. A review on cellulose nanocrystals as promising biocompounds for the synthesis of nanocomposite hydrogels. Carbohydr. Polym. 2019, 216, 247–259.
  81. Khalil, H.P.S.A.; Jummaat, F.; Yahya, E.B.; Olaiya, N.G.; Adnan, A.S.; Abdat, M.; N.A.M., N.; Halim, A.S.; Kumar, U.S.U.; Bairwan, R.; et al. A Review on Micro- to Nanocellulose Biopolymer Scaffold Forming for Tissue Engineering Applications. Polymers 2020, 12, 2043.
  82. Moohan, J.; Stewart, S.A.; Espinosa, E.; Rosal, A.; Rodríguez, A.; Larrañeta, E.; Donnelly, R.F.; Domínguez-Robles, J. Cellulose Nanofibers and Other Biopolymers for Biomedical Applications. A Review. Appl. Sci. 2020, 10, 65.
  83. Subhedar, A.; Bhadauria, S.; Ahankari, S.; Kargarzadeh, H. Nanocellulose in biomedical and biosensing applications: A review. Int. J. Biol. Macromol. 2021, 166, 587–600.
  84. Gorgieva, S.; Trček, J. Bacterial cellulose: Production, modification and perspectives in biomedical applications. Nanomaterials 2019, 9, 1352.
  85. Raghav, N.; Sharma, M.R.; Kennedy, J.F. Nanocellulose: A mini-review on types and use in drug delivery systems. Carbohydr. Polym. Technol. Appl. 2021, 2, 100031.
  86. Nicu, R.; Ciolacu, F.; Ciolacu, D.E. Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications. Pharmaceutics 2021, 13, 1125.
  87. Seabra, A.B.; Bernardes, J.S.; Fávaro, W.J.; Paula, A.J.; Durán, N. Cellulose nanocrystals as carriers in medicine and their toxicities: A review. Carbohydr. Polym. 2018, 181, 514–527.
  88. Svagan, A.J.; Benjamins, J.W.; Al-Ansari, Z.; Shalom, D.B.; Müllertz, A.; Wågberg, L.; Löbmann, K. Solid cellulose nanofiber based foams—Towards facile design of sustained drug delivery systems. J. Control. Release 2016, 244, 74–82.
  89. Bhandari, J.; Mishra, H.; Mishra, P.K.; Wimmer, R.; Ahmad, F.J.; Talegaonkar, S. Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery. Int. J. Nanomed. 2017, 12, 2021–2031.
  90. Paukkonen, H.; Ukkonen, A.; Szilvay, G.; Yliperttula, M.; Laaksonen, T. Hydrophobin-nanofibrillated cellulose stabilized emulsions for encapsulation and release of BCS class II drugs. Eur. J. Pharm. Sci. 2017, 100, 238–248.
  91. Svagan, A.J.; Müllertz, A.; Löbmann, K. Floating solid cellulose nanofibre nanofoams for sustained release of the poorly soluble model drug furosemide. J. Pharm. Pharmacol. 2017, 69, 1477–1484.
  92. Ching, Y.C.; Gunathilake, T.M.S.U.; Chuah, C.H.; Ching, K.Y.; Singh, R.; Liou, N.S. Curcumin/Tween 20-incorporated cellulose nanoparticles with enhanced curcumin solubility for nano-drug delivery: Characterization and in vitro evaluation. Cellulose 2019, 26, 5467–5481.
  93. Lin, N.; Gèze, A.; Wouessidjewe, D.; Huang, J.; Dufresne, A. Biocompatible Double-Membrane Hydrogels from Cationic Cellulose Nanocrystals and Anionic Alginate as Complexing Drugs Codelivery. ACS Appl. Mater. Interfaces 2016, 8, 6880–6889.
  94. Abo-Elseoud, W.S.; Hassan, M.L.; Sabaa, M.W.; Basha, M.; Hassan, E.A.; Fadel, S.M. Chitosan nanoparticles/cellulose nanocrystals nanocomposites as a carrier system for the controlled release of repaglinide. Int. J. Biol. Macromol. 2018, 111, 604–613.
  95. Meneguin, A.B.; Ferreira Cury, B.S.; dos Santos, A.M.; Franco, D.F.; Barud, H.S.; da Silva Filho, E.C. Resistant starch/pectin free-standing films reinforced with nanocellulose intended for colonic methotrexate release. Carbohydr. Polym. 2017, 157, 1013–1023.
  96. Bacakova, L.; Pajorova, J.; Bacakova, M.; Skogberg, A.; Kallio, P.; Kolarova, K.; Svorcik, V. Versatile application of nanocellulose: From industry to skin tissue engineering and wound healing. Nanomaterials 2019, 9, 164.
  97. Silva, R.M.; Pereira, F.V.; Mota, F.A.P.; Watanabe, E.; Soares, S.M.C.S.; Santos, M.H. Dental glass ionomer cement reinforced by cellulose microfibers and cellulose nanocrystals. Mater. Sci. Eng. C 2016, 58, 389–395.
  98. Koivuniemi, R.; Hakkarainen, T.; Kiiskinen, J.; Kosonen, M.; Vuola, J.; Valtonen, J.; Luukko, K.; Kavola, H.; Yliperttula, M. Clinical Study of Nanofibrillar Cellulose Hydrogel Dressing for Skin Graft Donor Site Treatment. Adv. Wound Care 2020, 9, 199–210.
  99. Hakkarainen, T.; Koivuniemi, R.; Kosonen, M.; Escobedo-Lucea, C.; Sanz-Garcia, A.; Vuola, J.; Valtonen, J.; Tammela, P.; Mäkitie, A.; Luukko, K.; et al. Nanofibrillar cellulose wound dressing in skin graft donor site treatment. J. Control. Release 2016, 244, 292–301.
  100. Laurén, P.; Lou, Y.R.; Raki, M.; Urtti, A.; Bergström, K.; Yliperttula, M. Technetium-99m-labeled nanofibrillar cellulose hydrogel for in vivo drug release. Eur. J. Pharm. Sci. 2014, 65, 79–88.
  101. Durand, H.; Smyth, M.; Bras, J. Nanocellulose: A New Biopolymer for Biomedical Application. In Biopolymers for Biomedical and Biotechnological Applications; Rehm, B., Moradali, M.F., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2021; pp. 129–179.
  102. Jorfi, M.; Foster, E.J. Recent advances in nanocellulose for biomedical applications. J. Appl. Polym. Sci. 2015, 132, 41719.
  103. Piergiovanni, L.; Fotie, G.; Amoroso, L.; Akgun, B.; Limbo, S. Are cellulose nanocrystals “alien particles” to human experience? Packag. Technol. Sci. 2019, 32, 637–640.
  104. Shatkin, J.A.; Kim, B. Cellulose nanomaterials: Life cycle risk assessment, and environmental health and safety roadmap. Environ. Sci. Nano 2015, 2, 477–499.
  105. Amenta, V.; Aschberger, K.; Arena, M.; Bouwmeester, H.; Botelho Moniz, F.; Brandhoff, P.; Gottardo, S.; Marvin, H.J.P.; Mech, A.; Quiros Pesudo, L.; et al. Regulatory aspects of nanotechnology in the agri/feed/food sector in EU and non-EU countries. Regul. Toxicol. Pharmacol. 2015, 73, 463–476.
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