Use of Titanium Dioxide (TiO 2 ) Nanoparticles as Reinforcement Agent of Polysaccharide-Based Materials

: In recent years, a strong interest has emerged in polysaccharide-hybrid composites and their potential applications, which have interesting functional and technological properties. This review summarizes and discusses the reported advantages and limitations of the functionalization of conventional and nonconventional polysaccharides by adding TiO 2 nanoparticles as a reinforcement agent. Their e ﬀ ects on the mechanical, thermal, and UV-barrier properties as well as their water-resistance are discussed. In general, the polysaccharide–TiO 2 hybrid materials showed improved physicochemical properties in a TiO 2 content-dependent response. It showed antimicrobial activity against bacteria (gram-negative and gram-positive), yeasts, and molds with enhanced UV-protective e ﬀ ects for food and non-food packaging purposes. The reported applications of functionalized polysaccharide–TiO 2 composites include photocatalysts (dye removal from aqueous media and water puriﬁcation), biomedical (wound-healing material, drug delivery systems, biosensor, and tissue engineering), food preservation (fruits and meat), cosmetics (sunscreen and bleaching tooth treatment), textile (cotton fabric self-cleaning), and dye-sensitized solar cells. Furthermore, the polysaccharide–TiO 2 showed high biocompatibility without adverse e ﬀ ects on di ﬀ erent cell lines, indicating that their use in food, pharmaceutical, and biomedical applications is safe. However, it is necessary to evaluate the structural changes promoted by the storage conditions (time and temperature) on the physicochemical properties of polysaccharide–TiO 2 hybrid composites to guarantee their stability during a determined time.


Introduction
In recent years, the development of functional and eco-friendly materials with advanced properties as an alternative to replacing conventional nondegradable polymers has gained attention, particularly, for the polysaccharide-hybrid materials which exhibit diversified technological

Polysaccharide-TiO2 Hybrid Materials
Polysaccharides are biopolymers composed of monosaccharides connected by glycosidic bonds [3]. They are obtained from different sources (plants, animals, algae, and microbial) and exhibit a wide range of applications because they are low cost, abundant, biodegradable, edible, and biocompatible with numerous organic and inorganic compounds [3]. However, most of their potential applications are limited by their poor physical properties (high solubility, low water barrier ability, low thermal stability, poor gas permeability, and mechanical resistance). Thus, their

Starch-TiO 2 Hybrid Material
Starch is one of the most versatile polysaccharides with relevant applications. However, their hydrophilic nature limits their uses [26]. Therefore, the addition of inorganic compounds like TiO 2 into the starch matrix is a feasible strategy for development of functional starch-based materials with improved physicochemical properties for food and non-food packaging, photocatalyst, biomedical, and solar cell applications [3,40], as listed in Table 1. Table 1. Effect of TiO 2 incorporation on starch matrix properties.

Application Method/Presentation * Composition Relevant Results
Ref.
Additionally, corn starch may be combined with polyvinyl alcohol (PVA) and reinforced through TiO 2 addition to fabricate ternary-hybrid films (starch-PVA-TiO 2 ) with enhanced functional and technological properties [58]. The addition of TiO 2 in the starch/PVA matrix improved its thermal (increased) and water resistance (increased), and moisture and oxygen (reduced) permeability through hydrogen, Ti=C bonds, and attractive electrostatic forces, where nano-TiO 2 may promote the formation of a compact and dense structure, acting as an obstacle to the diffusion of water and oxygen molecules through a hybrid film without altering the starch/PVA structure [58,59].
Kochkina and Butikova [42] mentioned that the incorporation of TiO 2 into a starch/PVA film improves their physicochemical properties and extends their functionalities. The addition of TiO 2 in small quantities (0.1% w/w) into a biodegradable corn starch/PVA film did not alter its structure. However, it promotes intermolecular interaction through hydrogen-bond formation, improving its thermal stability (from 190 to 230 • C) and water vapor permeability (decrease from 12.6 to 5.39 × 10 −7 g/m h Pa) as well as improving its mechanical (tensile strength from 16.22 to 21.11 MPa) and UV-barrier properties. Similar findings were reported during evaluation of the mechanical (tensile strength increased) and physicochemical (swelling degree increased) properties in a corn starch/PVA film reinforced with TiO 2 nanoparticles [43].
Liu et al. [44] informed that incorporation of TiO 2 (0.6%) in a high-amylose starch/PVA-based membrane promoted a decrease in the optical transmittance with an increase in the mechanical (tensile strength to 9.53 MPa and elongation at break to 49.5%) properties of the film. The compatibility of high-amylose starch and TiO 2 were due to the formation of hydrogen and C-O-Ti bonds. They argued that TiO 2 could be adsorbed in the starch granule surface by the TiO 2 -amylose (changes in the intensity and profile peaks in the range of 900-1000 cm −1 of the FTIR spectra) interactions that improve the miscibility of the starch/PVA structure. Furthermore, the compatibility of the TiO 2 with a starch matrix is OH availability-dependent; however, an excessive concentration of TiO 2 (>1% w/w) in the polymeric matrix could negatively affect the physicochemical properties of the starch/PVA films. Furthermore, the hybrid membrane showed that moderate antimicrobial activity performed by an agar test diffusion assay against E. coli (inhibition zone of 12.26 mm) and S. aureus (inhibition zone of 10.22 mm), which was attributable to the ability of TiO 2 to restrain the growth of bacteria due to its photocatalytic properties. Similar trends were reported by Lin et al. [58], who informed that a starch/PVA/TiO 2 (0.03% w/w) hybrid composite exhibited bacteriostatic activity against E. coli and Listeria monocytogenes, but the effect was dependent on the strain and TiO 2 content. Likewise, Ahmed et al. [56] found that the addition of TiO 2 nanoparticles in a PVA-starch-g-C 3 -N 4 -Ag hydrogel membrane enhanced the antibacterial activity against E. coli (inhibition zone of 37.33 mm) and S. aureus (inhibition zone of 33.25 mm).
Additionally, starch obtained from nonconventional sources like wheat, rice, tapioca, cassava, potato, and sago has been functionalized with TiO 2 nanoparticles to fabricate hybrid packaging materials. However, although nano-TiO 2 can act as a physical cross-linking agent of starch-based film, the type of starch matrix will have a significant impact on the properties of hybrid films [60].
Furthermore, in a wheat starch-based film, TiO 2 acts as a physical cross-linker agent improving its thermal stability (mass loss of 50% at 289 • C), UV-barrier (blocking >99% of UV-light), mechanical (an increase of tensile strength and Young's modulus), and water-related properties with a decrease in water vapor permeability and an increase in the hydrophobicity of the hybrid material [27,45]. However, a high amount of TiO 2 negatively affects the mechanical properties of the film, and the preparation method of the wheat starch-TiO 2 hybrid material strongly influences their physicochemical properties and potential applications [46].
The functionalization of potato starch-based films adding TiO 2 nanoparticles promotes an increase in its hydrophobicity, enhancing its water-related, mechanical, thermal, and UV-barrier properties. These facts were attributable to the stable formation of hydrogen bonds between oxygen in TiO 2 and hydrogen in C-O-H of starch, which decreases the possible active sites for water molecule retention and thermal decomposition of the starch composite [19,47]. Another root vegetable starch source for making hybrid materials is the cassava [22]. Tunma [22] developed an active packaging with the cassava starch-TiO 2 composite aimed to enlarge the shelf life of bananas and tomato fruits, finding that banana (14 days) and tomatoes (21 days) packaged in the hybrid films extended their shelf life beyond that of those packaged with petroleum-based films (5 and 10 days, respectively). Furthermore, the active material showed antibacterial activity against Bacillus cereus and E. coli through bacterial membrane alteration.
Malathi and Singh [4] informed that a rice starch-based film reinforced with TiO 2 exhibited antimicrobial activity against E. coli (a reduction >90% of viable cells) under UV-light (4 h), but the effect was dose-dependent, attributed to the photocatalytic activity of TiO 2 that may promote a membrane cell alteration, affecting cell viability and cell growth. Moreover, the presence of TiO 2 in the organic matrix improved the water vapor permeability, solubility, tensile strength, and elongation. According to the authors, TiO 2 can act as a physical cross-linking agent restringing segment rotation and molecular mobility between starch chains and water molecules through hydrogen bonding or O-Ti-O and C-O-Ti bonding, enhancing the physicochemical properties of the hybrid film.
Additionally, starch has been combined with other organic matrices (pectin, kefiran, cinnamon essential oil, and poly(ε-caprolactone)) and reinforced with TiO 2 . Dash et al. [48] developed a biodegradable starch-pectin-TiO 2 film with enhanced UV-barrier properties for UV-sensible food and non-food compounds preservation (i.e., ascorbic acid). The addition of TiO 2 promotes a decrease in the moisture content, solubility, and moisture uptake with an increase in the thermal properties of the hybrid film in a dose-pendent manner. On the other hand, they reported that the mechanical properties of the hybrid film were negatively affected by the presence of nano-TiO 2 and mentioned that, at high concentrations, TiO 2 acts as an anti-plasticizer agent reducing the water molecule movement into the polymeric matrix, affecting the flexibility of the film. Goudarzi and Shahabi-Ghahfarrokhi [49] developed a photo-producible starch/kefiran-TiO 2 composite as a potential alternative for food packaging applications. They reported that enhanced physicochemical, water-related, and thermal properties of starch/kefiran by the presence of TiO 2 could be improved by the UV-radiation (345 nm) during a defined time (1 h).
Arezoo et al. [50] informed that sago starch film combined with cinnamon essential oil and TiO 2 showed antimicrobial activity against E. coli, Salmonella Typhimurium, and S. aureus. Also, their incorporation of sago starch-based film improved its mechanical, optical, and water-related properties. On the other hand, Fei et al. [32] evaluated the effects on the physicochemical properties and structure of a starch-poly(ε-caprolactone (PCL)) composite by nano-TiO 2 incorporation and reported that mechanical properties and water resistance were improved by TiO 2 addition compared with non-reinforced material, but these effects were dose-dependent with an optimum TiO 2 concentration of 6 wt%. According to the authors, the formation of intramolecular hydrogen bonds and covalent interaction (C-O-Ti bond) between starch and nano-TiO 2 promotes a decrease in the rigidity of the starch-PCL structure.
Furthermore, the functionality of starch-TiO 2 hybrid films could be enhanced by the surface modification of TiO 2 with the presence of other inorganic compounds in its network. Chueangchayaphan et al. [51] evaluated the influence of Al 2 O 3 on the properties of the starch-TiO 2 -Al 2 O 3 hybrid composite and found that physicochemical (water contact angle, hardness, and thermal stability) properties of the ternary hybrid film improved in a Al 2 O 3 -dependent concentration. Similarly, Hajizadeh et al. [52] informed that the incorporation of TiO 2 :Ag-doped nanoparticles into the starch matrix increased the water resistance of the hybrid film and significantly inhibited the growth of E. coli and S. aureus, associated with the antibacterial effect of TiO 2 .
According to the results, the incorporation of TiO 2 into starch-based materials can improve the physicochemical, thermal, mechanical, optical, and water-related properties through covalent and noncovalent interactions with the potential to develop food and non-food packaging.

Other Applications of Starch-TiO 2 Hybrid Material
Other potential applications of starch-TiO 2 , such as environmental remediation, biomedical, and dye-sensitized solar cells, have been investigated (Table 1). Yun et al. [53] prepared a starch/PVA film reinforced with TiO 2 and found that tensile strength, degree of swelling, solubility, and water vapor absorption were enhanced up to 1.14-1.52 times compared with films without nano-TiO 2 , whereas the elongation at break was negatively affected (decreased 1.60 times). Moreover, the authors reported that the starch/PVA/TiO 2 film exhibited photocatalytic activity (under UV and visible light) against bisphenol A (degree of decomposition of 0.825 and 0.534, respectively) and 2,4-dichlorophenoxyacetic acid (decomposition degree of 0.597 and 0.396, respectively) in aqueous solution (10 ppm) after 4 h of exposure. Furthermore, starch/PVA/TiO 2 has a photocatalytic degradation efficiency of 37% against methylene blue dye (10 mg/L) after 90 min of UV-light irradiation [54]. Similarly, Yun et al. [55] developed a starch/PVA film reinforced with TiO 2 and poly(methyl methacrylate-co-acrylamide) for photocatalytic purposes. They reported that hybrid films showed photocatalytic properties against methylene blue and acetaldehyde under UVA and visible light irradiation. The photocatalytic efficiency of starch-TiO 2 hybrid materials is directly proportional to the TiO 2 concentration [61]. However, it should consider that the enhanced functional properties of starch by the addition of TiO 2 could be negatively affected by a long UVA exposure time because a rupture of polysaccharide structure may occur [35].
Additionally, Ahmed et al. [56] evaluated in vivo the wound-dressing properties of a PVA-starch-g-C 3 -N 4 -Ag-TiO 2 hydrogel membrane in an open excision-type wound-healing study in adult female Albino mice. They found that hybrid membranes had better-wound healing (reduction wound area of 97%) efficiency than cotton gauze (reduction wound area of 19.5%) or untreated (reduction wound area of 7.4%) groups after seven days of evolution. Nonetheless, animals treated with the hybrid hydrogel membrane showed better re-epithelization with good anti-inflammatory response than control groups, which are parameters related to the wound-healing activity. Ujcic et al. [57] developed a biodegradable wheat starch-TiO 2 composite with a controlled drug (vancomycin) release profile and bacteriostatic properties against S. aureus without TiO 2 release from the hybrid matrix to the medium.
Khanmirzaei and Ramesh [24] fabricated a dye-sensitized solar cell using a nanocomposite polymer electrolyte formed with a rice starch-TiO 2 hybrid material. They reported that, during solar cell development, the ionic conductivity of rice starch/ionic liquid composite was enhanced by incorporating TiO 2 with an efficiency of 0.17 at 1000 W/m 2 light intensity.
In summary, the starch-TiO 2 hybrid material exhibited photocatalytic and antimicrobial activities and good ionic conductivity for potential environmental, biomedical, and dye-sensitized solar cell applications.

Environmental Applications of Sodium Alginate-TiO 2 Hybrid Material
The use of SA-TiO 2 hybrid material as a photocatalyst as an alternative to conventional catalysts has been explored [63] (Table 2). Thakur and Arobita [63], using a cross-linked SA-TiO 2 hydrogel, reported a maximum adsorption capacity of methyl violet of 1156.1 mg g −1 with an adsorption efficiency of 99.6% in comparison with SA-based film (85%), attributed to the presence of TiO 2 in the hybrid hydrogel, which acts as an anionic center that participates in the electrostatic attraction with methyl violet dye. Similarly, Reveendran and Ong [64] informed that an SA-TiO 2 hybrid film was effective for the degradation of Congo red (5 mg L −1 at pH 8) under UV-radiation (6 h) without significant losses of catalytic activity after two cycles of reuse. In general, TiO 2 favored the surface adsorption and photocatalytic degradation of dyes; however, a high dye concentration could inhibit the photocatalytic properties of TiO 2 (surface saturation) because dye molecules tend to absorb energy (light and photons), thereby reducing the generation of reactive oxygen species and hydroxyl radicals.
Dai et al. [37] developed an SA-TiO 2 hybrid aerosol as a novel oil/water separation and wastewater treatment. The hybrid aerogel showed oil/water separation efficiency of 99.7% after 60 cycles of reuse compared with sodium alginate aerogel. Furthermore, the hybrid aerogel exhibited excellent photocatalytic degradation after six repeated uses against methyl orange (>85% in 2.5 h) dye under simulated sunlight irradiation (150 min). Furthermore, Thomas et al. [65] synthesized a cross-linked SA/carboxymethyl cellulose (CMC) with nano-TiO 2 and graphene oxide (GO) composite for Congo red (30 mg L −1 ) dye degradation under direct sunlight irradiation (240 min). They reported that SA-CMC-TiO 2 -GO (1.2 g L −1 ) showed higher dye degradation (98%) compared to SA-CMC-TiO 2 (70%) or SA-CMC-GO (60%); nonetheless, the SA-CMC-TiO 2 -GO retained its degradation efficiency up to seven consecutive cycles. The enhanced photocatalytic properties of the hybrid material were attributed to the reduction of electro-hole pair recombination by the presence of TiO 2 and GO in the polymeric matrix, generating a higher concentration of hydroxyl radical.
The addition of TiO 2 into the polymeric matrix-like sodium alginate provides a major stabilization of TiO 2 , enhancing its photocatalytic and dye-removal properties.

Biomedical Applications of Sodium Alginate-TiO 2 Hybrid Material
The potential biomedical applications of the SA-TiO 2 hybrid material as a scaffold for tissue engineering, as a drug delivery system, and as a wound-healing material have been investigated [66]. Naik et al. [66] evaluated the application of TiO 2 -Hap-SA composite scaffolds as a bone implant material. In general, the hybrid material showed controlled swelling, acceptable degradation rate, excellent bio-mineralization, and biocompatibility with high cell viability in the human MG-63 cell line. Moreover, the hybrid material exhibited a controlled drug release profile of the methotrexate drug, which are suitable characteristics for biomedical applications. Furthermore, Selvi et al. [63] fabricated sodium SA-PVA-TiO 2 -curcumin patches as a wound-healing material. They found that the hybrid material reinforced with 100 µg mL −1 of TiO 2 promoted antibacterial activity (by agar test diffusion assay) against Bacillus subtilis (inhibition of 11 mm) and Klebsiella pneumonia (inhibition of 8 mm), attributed to the ability of TiO 2 to interact with the cell membrane, to increase its permeability, and to lead to cell death. Urruela-Barrios et al. [5] mentioned that an SA/gelatin hydrogel 3D printing reinforced with TiO 2 and β-tricalcium phosphate exhibited a potential use for tissue engineering application. The fabricated hybrid material by the micro-extrusion process exhibits adequate porosity and mechanical resistance. However, the authors mentioned that further studies are needed to prove the material's safety and biocompatibility. According to the evidence, incorporation of TiO 2 into sodium alginate is a viable strategy to enhance its biological properties. Table 2 lists reports on the use of the sodium alginate-TiO 2 hybrid film for food and non-food applications. Tang et al. [31] developed a degradable SA film reinforced with TiO 2 :Au for food packaging applications with advanced UV-and water-barrier properties and antimicrobial capacity. The incorporation of TiO 2 :Au nanoparticles into the SA matrix improved its water resistance, mainly attributed to the increase in the surface hydrophobicity of the hybrid film. Furthermore, it showed higher antibacterial activity against S. aureus and E. coli (95 and 90%, respectively) in UV-light presence compared with the SA-TiO 2 film (90 and 80%, respectively), which was associated with an enhanced TiO 2 :Au electron-hole recombination, improving the photocatalytic ability of the SA-TiO 2 :Au hybrid film. Additionally, the zein/sodium alginate (90:10) film functionalized with TiO 2 (0.5%) and betanin (1%) showed interesting antioxidant properties 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH, radical scavenging of 64%) without toxicity effects on endothelial cells and high antimicrobial activity (by agar test diffusion assay) against E. coli (inhibition zone of 15.4 mm) and S. aureus (inhibition zone of 16.9 mm), which exhibited potential to be used for the preservation of fresh foods [68].

Food and Non-Food Packaging Applications of Sodium Alginate-TiO 2 Hybrid Material
In general, the SA-TiO 2 hybrid material can overcome the disadvantages of conventional nano-photocatalysts, which are hard to recycle. Furthermore, the obtained hybrid composite could be a low-cost and eco-friendly alternative for the removal and degradation of dyes from aqueous solutions.

Other Applications of Sodium Alginate-TiO 2 Hybrid Material
Other investigated applications of the sodium alginate-TiO 2 hybrid composite include the separation process, dye-sensitized solar cell, and molecular electronics [30,69,70]. Premakshi et al. [30] used a cross-linked SA-based membrane with TiO 2 for dehydration of isopropanol by pervaporation. They reported that the hybrid membrane showed improved separation ability for the water-isopropanol system and suggested that the membrane exhibited high selectivity toward water molecules even with higher water concentrations in the feed (flux of 25 × 10 2 kg/m 2 h), associated with the ability of TiO 2 to form hydrogen-bonding interactions with the sodium alginate and water molecules. Furthermore, the SA-TiO 2 membrane showed enhanced mechanical and thermal properties in a dose-dependent response with an optimum concentration of TiO 2 of 10% w/w.
Uddin et al. [69] developed an SA-TiO 2 film for dye-sensitized solar cell applications to increase the ionic conductivity and to reduce the fragility of electrodes. They reported that the highest conductivity was achieved with 8% of TiO 2 (0.0472 S/m) at room temperature, which increased by 38% with an increase of the temperature (25 to 64 • C) due to nano-TiO 2 creating overlapping paths in the hybrid network which allowed the charge carriers to pass through the less resistant routes. However, at high TiO 2 concentration (>8%), electrodes were fragile and unstable. According to Peining et al. [16], the conductivity efficiency of the hybrid electrodes was improved because TiO 2 may act as a scattering center, reflecting the photons into the electrode. Furthermore, the hybrid composite showed improved mechanical and optical properties compared to a pure sodium alginate film in a dose-dependent manner, which was associated with the hydrogen-bond formation between both components and the increase in the π-conjugated system. Likewise, Padma et al. [70] prepared an SA-based membrane reinforced with TiO 2 nanoparticles for molecular electronics applications and found that the membrane-forming solution showed improved dielectric properties and ac-electrical conductivity with better thermal stability (250 • C) than the sodium alginate membrane (180 • C).
According to these data, the SA-TiO 2 hybrid material showed potential separation processes, sensitized solar cells, and molecular electronics applications.

Cellulose-TiO 2 Hybrid Material
Cellulose is an organic compound that can form intra-and intermolecular interactions with inorganic compounds [71,72]. For this reason, it is an excellent candidate for supporting nano-TiO 2 ( Table 3). Table 3. Effect of TiO 2 incorporation on cellulose-based materials properties.

Application Method/Presentation * Composition Relevant Results
Ref.

Photocatalyst Sol-gel/Composite
The TiO 2 -cellulose mass ration of 0.5 The TiO 2 -cellulose composite showed a photocatalytic reduction of Ag(I) to Ag and Au(III) to Au. [80] Photocatalyst Sol-gel/Fibers Cellulose fiber (NI), TiO 2 (0.02 mol 50 mL −1 of isopropanol) The hybrid film showed high adsorptive and photocatalytic properties against methylene blue dye under simulated sunlight. [81] Photocatalyst Cellulose/TiO 2 -polyaniline showed higher gas-ammonia sensitivity performance than cellulose-polyaniline. [89] * Material composition was based on the best-reported results. NI: no information; MFC: micro-fibrillated cellulose; CM; CMC: carboxymethyl cellulose; HCM: hydroxypropyl methylcellulose; Na-MMT: sodium montmorillonite; WPI: whey protein isolate; REO: rosemary essential oil. Table 3 lists the work on cellulose-based materials functionalized with TiO 2 for food and non-food packaging development with beneficial properties. The sol-gel method is a viable strategy to developed cellulose-TiO 2 hybrid materials [11]. In general, the incorporation of TiO 2 into the cellulose matrix improved mechanical, thermal, UV-light blocking, and water-related properties in a dose-dependent manner, attributed to the strong interactions between TiO 2 and -OH functional groups of carboxymethyl cellulose (CMM) structure. However, a high amount of TiO 2 and an inhomogeneous dispersion through films negatively affects its physicochemical (thermal, mechanical, and water-barrier) properties. Furthermore, the CMC-TiO 2 showed antimicrobial activity against E. coli and S. aureus, associated with the reactive oxygen species (ROS) generation ability of TiO 2 with cell growth inhibition properties [21,36,79].

Food and Non-Food Applications of Cellulose-TiO 2 Hybrid Material
El-Wakil et al. [73] informed that the wheat gluten-nanocellulose-TiO 2 hybrid film could be a viable alternative for the development of food active packaging materials. The hybrid film showed antimicrobial activity (reduction of viable cells of 98.5%) against Saccharomyces cerevisiae, E. coli, and S. aureus through oxidation of bacteria cell membranes. Fathi-Achacholouei and Zahedi [74] reported that a carboxymethyl cellulose-sodium montmorillonite (5%)-TiO 2 (1%) hybrid composite showed enhanced UV-light blocking (removing more than 98% of visible light), mechanical (an increase of tensile strength and elongation at break), thermal (glass transition increased from 72 to 80.3 • C), and water-related (moisture uptake reduction in 40%) properties compared with a carboxymethyl cellulose-based film.
Alizadeh-Sani et al. [75] evaluated the efficacy of a whey protein isolate-cellulose nanofiber functionalized with TiO 2 (1% w/w) and rosemary essential oil (REO, 2% w/w) in the preserving quality (microbial deterioration and sensory attributes) parameters of refrigerated meat during storage (4 • C). They reported that the lamb meat treated with the hybrid film showed acceptable microbial quality (total viable count of 4.1 log colony-forming unit (CFU) g −1 ) after six days of storage without changes in color, odor, texture, and overall acceptability. Moreover, the treated meat showed reduced lipid oxidation during storage, associated with the presence of antioxidant compounds (80% of radical scavenging by DPPH assay) into the film [76]. Additionally, the TiO 2 and REO incorporation in a whey protein isolate/cellulose nanofiber film improve mechanical and water-related properties with a decrease in its transparency. Also, the hybrid film showed remarkable antimicrobial activity against pathogenic bacteria (L. monocytogenes, E. coli O157:H7, S. enteritidis, and P. fluorescens) in a dose-dependent response, attributed to the presence of TiO 2 and bioactive compounds (polyphenol) in the REO, altering the cell membrane and finally cell death [74]. Furthermore, the authors informed that a low content of TiO 2 migrated from the polymeric matrix to the meat product but was under Food Drug Administration (FDA) limit recommendations [76].
Yu et al. [78] used a cellulose nanofibril-TiO2 hybrid composite as a reinforcement agent for the development of PVA-based packaging. The mechanical and UV-barrier properties improved in the presence of the cellulose-TiO 2 hybrid composite. Furthermore, the PVA-cellulose-TiO 2 composite did not show toxicity against cancerous (Caco-2 cell) and normal colon cells in a concentration of one mg mL -1 , whereas the cells showed epithelial integrity and viability (membranes, mitochondria, and nuclei were normal and without the presence of TiO 2 nanoparticles within the cells), associated with the strong interaction between cellulose and TiO 2 avoiding the nanoparticle release from the hybrid material to the medium. Furthermore, the hybrid material did not affect the typical intestinal bacteria (E. coli, Lactobacillus acidophilus, and Bifidobacterium animalis Bif-g cells). On the other hand, the addition of the carboxymethyl cellulose-TiO 2 hybrid composite into the PVA system could negatively affect the mechanical and barrier properties as a result of a saturation of the polymeric matrix [90].
To summarize, research-based reports support that incorporation of TiO 2 into the cellulosic matrix improved the technological (mechanical, thermal, UV-protective, and water-related) properties of cellulose-based materials with potential food and non-food packaging applications.

Environment Applications of Cellulose-TiO 2 Hybrid Material
Usage of cellulose as a supporting material of TiO 2 for removal and degradation of diverse organic and inorganic pollutants from aqueous media have been explored [70]. Miao et al. [74] fabricated a cellulose-TiO 2 mesoporous hybrid material capable of reducing Ag(I) into Ag and Au(III) to Au through photocatalytic reactions. Uddin et al. [81] prepared photoactive fibers combining cellulose and TiO 2 nanoparticles for photocatalytic purposes. They found that hybrid materials showed adsorptive and photocatalytic activities against methylene blue (0.05% w/v) and heptane-extracted bitumen fraction (0.2 w/v% of a mixture of heavy aromatic hydrocarbons) under simulated sunlight with catalytic properties even after 20 reaction cycles and without cellulose-support degradation.
Zeng et al. [82] reported that TiO 2 immobilization in a cellulose matrix is a viable alternative for removal and photocatalytic degradation of water-dye pullulans, which is low-cost and easy to be applied. They found that a macroporous hybrid structure formed among cellulose and TiO 2 (through electrostatic and hydrogen-bonding interactions) showed efficient adsorptive and photocatalytic properties against phenol dye. Furthermore, immobilized TiO 2 nanoparticles on cellulose supports have been used for Rhodamine B degradation under UV-radiation (120 min) through the de-ethylation process promoted by •OH radicals adsorbed onto the surface of hybrid material and associated with the hydrophobicity/hydrophilicity of TiO 2 -coated samples, which is pH-dependent (decreased while increased pH from 1.5 to 6) [83].
Additionally, ternary cellulose-based hybrid materials have been developed to improve the photocatalytic properties of cellulose-TiO 2 . Jo et al. [84] fabricated a cellulose/carrageenan-TiO 2 hybrid hydrogel with enhanced adsorptive and photocatalytic (removal of 115.3 mg g −1 with 85% of degradation) properties against methylene blue (60 mg L −1 ) compared with cellulose-TiO 2 (removal of 0.8 mg g −1 with 33% of degradation) and cellulose (without effect) materials under UV-radiation (254 nm) after 3 h of exposure in a carrageenan dose-dependent and its adsorptive properties.
Wang et al. [85] investigated the photocatalytic and antimicrobial activity of a cellulose fiber-based paper filled with TiO 2 :Ag (40% w/w) nanoparticles. They reported that the cellulose-TiO 2 :Ag hybrid film exhibited stable degradation rates (0.95) against methylene orange (0.02 g L −1 ) in an aqueous solution under UV-radiation (254 nm) after four hours of exposure in comparison with a cellulose-TiO 2 (0.90) film with good efficiency after three photocatalytic cycles (degradation rate of 0.95 and 0.85, respectively), but the effects were in a TiO 2 :Ag nanoparticles dose-dependent response. Furthermore, the hybrid material showed antibacterial activity against E. coli, where photocatalytic and antimicrobial activities were attributable to silver ion release.
Mohamed et al. [71] informed that a cellulose-TiO 2 :N-doped hybrid film showed remarkable photocatalytic activity under UVA (30 W at 312 nm) and visible (30 W at >420 nm) light for methylene blue (40 mg L −1 ) degradation (96 and 78%, respectively) after 360 min of exposure. They mentioned that the presence of nitrogen atoms into the TiO 2 network through hydrogen-bonding interactions (Ti-O-C) enhances the absorption energy of the hybrid film, promoting high catalytic activity.
In general, immobilization of TiO 2 onto a cellulose matrix is a feasible way to improve the adsorptive, photocatalytic, and antimicrobial properties of cellulose-based materials, which are suitable for removal of pollutants from aqueous media.

Other Applications of Cellulose-TiO 2 Hybrid Material
Other investigated applications of the cellulose-TiO 2 hybrid composite include textile (UV-protective and self-cleaning properties) and ammonia gas sensors. The introduction of TiO 2 nanoparticles in a cellulose matrix improved the UV-protective properties, associated with the optical and light scattering capability of TiO 2 [86]. Kale et al. [87] developed cotton fabric self-cleaning by coating cellulose-TiO 2 on its surface with stable properties after ten washing cycles in a dose-dependent manner. On the other hand, the self-cleaning properties of a cellulose-TiO 2 coating could be negatively affected by the surface modification of TiO 2 with SiO 2 (cellulose-TiO 2 :SiO 2 ) [88].
Pang et al. [89] developed a cellulose/TiO 2 -polyaniline (PANI) hybrid composite through P-N heterojunctions to improve ammonia-sending properties in a homemade test system at room temperature and reported that cellulose-TiO 2 -PANI showed higher gas sensitivity performance than the cellulose-PANI sensor, associated with the P-N heterojunction at the interface of PANI and TiO 2 nanoparticles.
According to the evidence, the cellulose-TiO 2 hybrid material could be used for the development of fabric cotton and biosensors with advanced properties.

Chitosan-TiO 2 Hybrid Material
Chitosan is a deacetylated form of chitin with a poly-cationic character and is nontoxic, biodegradable, and biocompatible with organic and inorganic compounds [91]. Recently, a detailed review of the chitosan-TiO 2 hybrid composite has been published [1]. It is a versatile hybrid material with enhanced physicochemical, mechanical, and barrier properties with diversified applications that include antimicrobial, environmental, biomedical, and food and non-food packaging applications [1]. Nonetheless, further studies on the chitosan-TiO 2 applications have emerged (Table 4). Table 4. Effect of TiO 2 incorporation on chitosan-based materials properties.

Environmental Applications of Chitosan-TiO 2 Hybrid Material
The Chitosan-TiO 2 hybrid composite has been used for the removal and degradation of diverse organic compounds from aqueous media under UV-light irradiation. Mahmoud et al. [92] prepared a chitosan-acrylic acid (CS-AA) hydrogel reinforced with nano-TiO 2 with enhanced swelling and adsorptive properties for methylene blue dye removal from aqueous solution (20 mg L −1 ). They informed of a remarkable change in the adsorption rate of MB (90%) using the CS-AA-TiO 2 hybrid hydrogel (0.20 g) compared with CS-AA (60%) in pH-dependent response with an optimum pH value of 10, mainly associated with the porosity and large surface area of the hybrid hydrogel. El-Ella et al. [93] investigated the carcinogenic ethidium bromide (EtBr) efficiency degradation (in aqueous media at pH 12 and aeration condition) using a chitosan-polyvinylidene-TiO 2 :Au hybrid composite under sunlight conditions (400-600 W/m 2 ). They found that the hybrid film removes 70 to 90% of the EtBr dye, where 60% of it was photodegraded in the first 60 min. According to the authors, the pH of the medium and aeration promotes •OH formation, facilitating dye adsorption and photodegradation. Additionally, Ikhlef-Taguelmimt et al. [94] immobilized TiO 2 nanoparticles into chitosan support for tetracycline (TC) degradation under UV-irradiation (360 nm at 30 W). The efficiency removal (87%) was dependent on agitation speed in the batch system and TiO 2 concentration; moreover, the efficiency was TC concentration-dependent with a decrease when increased from 30 to 40 mg L −1 after 60 min of reaction, associated with the saturation of active sites by agglomeration on the catalyst surface, decreasing light absorption capacity, and leading photocatalytic properties.
Xu et al. [95] functionalized a ceramic disk filter (CDF) with the chitosan-TiO 2 hybrid composite for bacterial removal from drinking water. They reported that CDF-chitosan-TiO 2 showed enhanced E. coli removal (99%) from contaminated water (1 × 10 6 CFU mL −1 ) compared with CDF (93%), mainly attributed to the direct interaction of bacteria (negative charge) with the chitosan-TiO 2 (positive charge) composite and the oxidative stress in cell membrane from ROS generated by TiO 2 . Moreover, they explain that the ROS generation of TiO 2 is enhanced by the presence of chitosan due to the prevention of radical recombination, inhibiting oxygen reduction and water oxidation. Furthermore, Marey [96] reported that the chitosan-TiO 2 composite is a viable strategy for removing turbidity (total solid soluble (TSS)) from wastewater because the hybrid composite showed adsorption (efficiency TSS removal of 18% nephelometric turbidity unit (NTU)) and photocatalytic (under visible light) properties in pH-dependent response, associated with the poly-cationic properties of chitosan.
In summary, chitosan-based materials functionalized with TiO 2 nanoparticles could be a viable, low-cost, and efficient alternative for water treatment.

Food and Non-Food Applications of Chitosan-TiO 2 Hybrid Material
In general, the physicochemical properties of chitosan have been improved by the incorporation of TiO 2 nanoparticles. Hussein et al. [97] reported that chitosan-TiO 2 composites via the chemical route (291 • C) showed enhanced thermal stability compared to the physically prepared (273 • C) and chitosan-based (240 • C) material. Nugraheni et al. [98] informed that the PVA-chitosan-TiO 2 hybrid membrane showed enhanced swelling properties in alkaline conditions (pH 10) compared with the acidic conditions (pH 4), associated with the protonation of an amine group from chitosan in acidic conditions. On the other hand, the physical interaction of TiO 2 :Ag with chitosan influences the properties of the hybrid film, and high amounts of TiO 2 :Ag nanoparticles could affect the plasticizing or elasticity of chitosan-based films due to the agglomeration of particles into the polymeric matrix [99]. Additionally, the chitosan-TiO 2 composite has been used for food preservation. Hosseinzadeh et al. [100] evaluated the chitosan-based film reinforced with TiO 2 (1% w/v) and Cymbopogon citratus essential oil (1.5% w/v) for preserving quality (microbial, physicochemical, and sensory) parameters of minced meat at cold storage (4 • C). They reported that minced meat treated with the hybrid film showed acceptable microbial quality (total viable count of <7 log CFU g −1 ) after 10 days of storage without significant changes in pH values (5.94 to 6.83) and organoleptic (color, odor, and taste) properties.
Evidence indicates that chitosan functionalized with TiO 2 showed enhanced physicochemical, antimicrobial, and barrier-protective properties for the development of diverse packaging materials.

Biomedical and Cosmetic Applications of Chitosan-TiO 2 Hybrid Material
The potential biomedical and cosmetic applications of the chitosan-TiO 2 hybrid composite have been explored. Hanafy et al. [101] informed that the hybrid composite formed by chitosan and TiO 2 exhibited inhibition growth against Bacillus cereus (85%), S. aureus (79%), Candida albicans (46%), Aspergillus niger (81%), and E. coli (60%). Furthermore, in an open excision-type wound-healing study in adult female rats, the hybrid film recovered faster (98% of closure after 14 days of surgery) than chitosan-based films (86% of closure after 14 days of surgery) and promoted cell growth and higher re-epithelization processes without scar formation. On the other hand, Cheng et al. [102] coated chitosan-TiO 2 -Ag nano-powder on a bendable double mattress for antibacterial purposes. According to the authors, it showed an antibacterial effect against S. aureus (inhibition of 99%), which can reduce the incidence of bedsores in patients and can reduce the frequency of mattress disinfection, decreasing cleaning costs.
Petrick et al. [103] fabricated a chitosan-TiO 2 composite as an active ingredient for the development of a multifunctional sunscreen composed of water and carboxymethyl cellulose as an emulsifier.
They reported that hybrid cream (with 10% of TiO 2 ) showed a moderate UV-protection effect (solar protection factor of 21.4); moreover, it exhibited excellent antimicrobial disinfection against E. coli (99.7%) within two hours, mainly by the photocatalytic properties of TiO 2 in visible light. Moreover, Kolsuz-Ozcetin and Surmelioglu [101] informed that an experimental 6% hydrogen peroxide hydrogel combined with the chitosan-TiO 2 composite provided effective bleaching without adverse effects on the tooth surface, which can be potentially employed for preventing dental-related problems. They argue that TiO 2 accelerates the bleaching reaction under UV-light at 385 nm.
In summary, the chitosan-TiO 2 hybrid composite exhibited enhanced antimicrobial, wound-healing, and UV-protective properties for biomedical and cosmetic applications.

Other Polysaccharides Functionalized with TiO 2
Additionally, other nonconventional polysaccharides such as gellan gum, agar, gelatin, and pullulan among others have been functionalized with TiO 2 to enhance their technological and functional properties (Table 5). Table 5. Effect of TiO 2 incorporation on nonconventional polysaccharide-based materials properties.

Hybrid biofilm promoted cell proliferation and cell migration to
accelerate the open-excision wound-healing process in an animal model. [38] Biomedical Evaporative casting/Biofilm Gellan gum (1 g 100 mL −1 ), TiO 2 (1% w/w) Hybrid biofilm is compatible with 3T3 mouse fibroblast cells and showed accelerated re-epithelialization without an inflammatory phenomenon in an animal model. [112] * Material composition was based on the best-reported results. NI: no information; BPSG: bean pod shell gum; MPEO: Mentha pulegium essential oil; PEG: polyethylene glycol; JFPS: jackfruit filum polysaccharide; SSPS: soluble soybean polysaccharide. Functionalized with TiO 2   Table 5 lists reports on the use of the chitosan-TiO 2 hybrid material for developing food and non-food packaging applications. Li et al. [105] developed hybrid agar-TiO 2 fibers through the wet spinning process with enhanced mechanical, and water-and UV-barrier properties, which were associated with the optical and hydrophilic properties of TiO 2 nanoparticles. Moreover, the mechanical, UV-barrier, and water-related properties in an agar-carrageenan film were enhanced by the addition of 1% w/v of nano-TiO 2 [34]. Similar trends were reported when TiO 2 was added in a film composed of a mixture of K-Carrageenan, xanthan gum, and gellan gum (mechanical, thermal, and water-and UV-barrier properties improved); moreover, it exhibited partial inhibition of S. aureus [17].

Food and Non-Food Applications of Nonconventional Polysaccharides
Vejdan et al. [106] studied the effect of TiO 2 incorporation in a fish gelatin/agar bilayer film. They found that the addition of TiO 2 at low levels (<0.5 g/100 mL) positively influenced the water-related, mechanical, and UV-barrier properties of the hybrid film. However, higher concentrations of TiO 2 (>0.5/100 mL) lead to a reduction of mechanical properties due to an inhomogeneous dispersion and agglomeration of inorganic particles in the polymeric matrix. Furthermore, the gelatin/agar-TiO 2 could be a viable alternative for preventing fish oil oxidation, mainly by its low light transmission through the hybrid film capability [107].
Abdel-Baky et al. [108] reported that edible guar gum-based films incorporated with nano-TiO 2 can maintain quality (soluble solids content, color, acidity, total phenol, and flavonoid compounds) attributes of some dates (Medjool and Barthy) during cold storage (for 8 weeks at 0 • C with 75% relative humidity) without microbial pollution (psychrophilic bacteria, mold, and yeast) growth. According to the authors, the hybrid film generates a low oxygen/high carbon dioxide microclimate, providing a physical barrier that decreases metabolic processes and prevents dehydration and microbial deterioration of the fruits.
Nasiri et al. [109] informed that bean pod shell gum combined with Mentha pulegium essential oil (4% w/w) and TiO 2 (2% w/w) showed antimicrobial activity against S. aureus, B. cereus, E. coli, S. typhoid, and P. aureginosa. Gram-positive bacteria were more susceptible than gram-negative bacteria, which was related to the type of bacteria (cell physiology-morphology) and attributed by the variation on their cell wall.
Jin et al. [110] prepared a hybrid film composed of jackfruit filum polysaccharides and nano-TiO2 (JFPT) using the solvent casting method for food and non-food packaging purposes. The addition of TiO 2 decreased the transparency, moisture uptake, and soluble matter of the hybrid film, and the mechanical and thermal properties were enhanced, which were ascribed to the formation of strong inter-and intramolecular interactions between the biopolymer and TiO 2 nanoparticles. Furthermore, the JFPT composite showed higher antimicrobial activity against E. coli (79%) than S. aureus (60%), which was associated with the inherent differences of each bacteria cell wall structure and the ability of TiO 2 to generate ROS to inactivate bacteria by causing cell lysis.
Salarbashi et al. [111] functionalized a soluble soybean polysaccharide with TiO 2 and found that swelling degree, water vapor permeability, and thermal and mechanical properties considerably improve in a dose-dependent response. Furthermore, the hybrid film showed antimicrobial activity against Staphylococcus epidermis (4 mg mL −1 ) and Penicillium expansum (2.5 mg mL −1 ), attributed to the catalytic properties of TiO 2, affecting the viability of the cells.
Liu et al. [20] reported that mechanical, and water-and UV-barrier characteristics of pullulan-based films were improved by the presence of TiO 2 in a dose-dependent manner, associated with the formation of intermolecular hydrogen bonds during hybrid film preparation. On the other hand, the hybrid composite formed by pectin and TiO 2 :Cu-doped nanoparticles showed methyl orange dye photodegradation from aqueous media [23].
The incorporation of TiO 2 into nonconventional polysaccharide-based materials significantly improved their physicochemical, mechanical, thermal, water-resistance, and UV-barrier properties, which are suitable characteristics for the development of food and non-food packaging materials.

Biomedical Applications of Nonconventional Polysaccharides Functionalized with TiO 2
The potential biomedical applications of nonconventional polysaccharide-based materials functionalized with TiO 2 have been investigated (Table 5). Razali et al. [33] informed that the addition of TiO 2 in gellan gum films improved their thermal stability and antimicrobial activity (by agar test diffusion assay) against S. aureus (inhibition of 10 mm), Streptococcus sp. (inhibition of 12 mm), E. coli (inhibition of 11 mm), and Pseudomonas aeruginosa (inhibition of 10 mm) without significant changes in transparency (transmittance of 94%) compared with the gellan gum-based film (without antimicrobial activity and transmittance of 100%). The improved physicochemical properties were attributed to the hydrogen-bond formation between the biopolymer and nano-TiO 2 , while the antibacterial activity of the hybrid film was attributed to the presence of TiO 2 and its ability to ROS generation, promoting a malfunction of bacteria membrane, leading to cell death. Furthermore, the biocompatibility of the gellan gum-TiO 2 hybrid film has been tested in a mouse fibroblast cell line (3T3), indicating no cytotoxic effects. Moreover, in an open-excision-type wound-healing study in adult Sprague Dawley rat, the hybrid film promoted an accelerated re-epithelialization (more than 50% on day 3 of wound operation) without inflammatory phenomenon after 14 days of evaluation in comparison with a gellan gum-based film. This phenomenon could be related to the presence of nano-TiO 2 in the polymeric matrix, which was able to promote cell growth and cell migration to accelerate open-excision wound healing, mainly by TiO 2 , which may affect protein interaction and subsequent cell adhesion and proliferation; nonetheless, the acceleration of the wound-healing process may be related to the antimicrobial properties of the hybrid film [38,112].
According to these data, nonconventional polysaccharides-based materials functionalized with TiO 2 showed interesting properties for biomedical applications. However, further studies are required to validate their safety and efficacy use.

Conclusions
Evidence indicates that the use of TiO 2 as a reinforcement agent in polysaccharide-based materials is a viable strategy that significantly enhanced their mechanical, thermal, and UV-barrier properties and water resistance. Biopolymer-TiO 2 hybrid composite is an active research area for environmental remediation and biomedical applications. Moreover, it is a low-cost and eco-friendly alternative for the development of packaging materials for food and non-food purposes based on its antimicrobial and photocatalytic properties. However, it is necessary to evaluate the possible structural changes promoted by the storage time and work temperature on the physicochemical properties of polysaccharide-TiO 2 hybrid composites to guarantee their stability and safe use during a determined time.