Nanostructured Chitosan Research Articles

Chitosan Nanoparticles for Intranasal Drug Delivery.

This manuscript explores the use of nanostructured chitosan for intranasal drug delivery, targeting improved therapeutic outcomes in neurodegenerative diseases, psychiatric care, pain management, vaccination, and diabetes treatment. Chitosan nanoparticles are shown to enhance brain delivery, improve bioavailability, and minimize systemic side effects by facilitating drug transport across the blood-brain barrier. Despite substantial advancements in targeted delivery and vaccine efficacy, challenges remain in scalability, regulatory approval, and transitioning from preclinical studies to clinical applications. The future of chitosan-based nanomedicines hinges on advancing clinical trials, fostering interdisciplinary collaboration, and innovating in nanoparticle design to overcome these hurdles and realize their therapeutic potential.

Protective immunization against Enterohemorrhagic Escherichia coli and Shigella dysenteriae Type 1 by chitosan nanoparticle loaded with recombinant chimeric antigens comprising EIT and STX1B-IpaD

Increasing evidence demonstrated that Enterohemorrhagic Escherichia coli (EHEC) and Shigella dysenteriae type 1 (S. dysenteriae1) are considered pathogens, that are connected with diarrhea and are still the greatest cause of death in children under the age of five years, worldwide. EHEC and S. dysenteriae 1 infections can be prevented and managed using a vaccination strategy against pathogen attachment stages. In this study, the chitosan nanostructures were loaded with recombinant EIT and STX1B-IpaD polypeptides. The immunogenic properties of this nano-vaccine candidate were investigated. The EIT and STX1B-IpaD recombinant proteins were heterologous expressed, purified, and confirmed by western blotting. The chitosan nanoparticles, were used to encapsulate the purified proteins. The immunogenicity of recombinant nano vaccine candidate, was examined in three groups of BalB/c mice by injection, oral delivery, and combination of oral-injection. ELISA and antibody titer, evaluated the humoral immune response. Finally, all three mice groups were challenged by two pathogens to test the ability of the nano-vaccine candidate to protect against bacterial infection. The Sereny test in guinea pigs was used to confirm the neutralizing effect of immune sera in controlling S. dysenteriae 1, infections. SDS-PAGE and western blotting, confirmed the presence and specificity of 63 and 27 kDa recombinant EIT and STX1B-IpaD, respectively. The results show that the nanoparticles containing recombinant proteins could stimulate the systemic and mucosal immune systems by producing IgG and IgA, respectively. The challenge test showed that, the candidate nano-vaccine could protect the animal model from bacterial infection. The combination of multiple recombinant proteins, carrying several epitopes and natural nanoparticles could evocate remarkable humoral and mucosal responses and improve the protection properties of synthetic antigens. Furthermore, compared with other available antigen delivery methods, using oral delivery as immune priming and injection as a booster method, could act as combinatorial methods to achieve a higher level of immunity. This approach could present an appropriate vaccine candidate against both EHEC and S. dysenteriae 1.

Zn nutrients-loaded chitosan nanocomposites and their efficacy as nanopriming agents for maize (Zea mays) seeds.

Recent breakthroughs in agro-inputs research have led to the development of nanomaterials that can promote precision agriculture and better environmental security. The agricultural sector is increasingly facing the negative impacts of changing climates due to various stress conditions. To curb this scenario, economical and low-risk practices such as decreasing fertilizer inputs and seed priming have been promoted. In the current study, the H. odoratissimum aqueous extract was used to nucleate the Zn ionic species and grow the zinc oxide nanoparticles (ZnO NPs). The developed nanocomposites and their ionic zinc precursor were then integrated into tripolyphosphate (TPP)-crosslinked chitosan (CS/TPP) nanostructures by ionic gelation. Advanced physicochemical characterization techniques (SEM, EDS, TEM, DLS, FTIR, TGA, and XPS) were exploited to report the morphology, hydrodynamic size, surface charge, and structural organization of the developed nanomaterials. These revealed positively charged particles with hydrodynamic size in the 149-257nm range. The NPs were used as priming agents for Zea mays seeds. At 0.04%, the ZnO-loaded CS/TPP NPs achieved higher root and shoot elongation in 10-day old seedlings compared to other treatments. The pristine CS/TPP NPs, Zn(II)-laden CS/TPP NPs, and ZnO-loaded CS/TPP NPs at 0.01% significantly promoted the early seedling development of seeds under salt stress. This represents the first report showing ZnO integrated chitosan nanocomposites as an auspicious nanopriming agent for stimulating the seed germination of maize. The study envisages offering perspectives on utilizing green nanotechnology to improve the early seedling development of maize. Furthermore, it has the potential to contribute towards UN SDG 2, thus addressing the threats to global food insecurity and doubling agricultural productivity by 2030.

Protonated chitosan nanostructures for enhancing ionic conductivity of solid-state electrolytes

Solid polymer electrolytes (SPEs) have aroused widespread attention for their high flexibility and good interface contact with electrode. However, the low ionic conductivity severely hinders their application in energy storage devices. Herein, a novel protonated nanostructure was synthesized through the reaction between PEO and Chitosan (Chi) and applied as fillers to form PEO/Chi composite solid-state electrolytes (PCCSEs). The fillers, which achieve nanization by the reaction with PEO, plays an important role in promoting the property of transporting Li+, due to the protonated amino (–NH3+) improving the dissociation of LiTFSI and the nanoscale size with high dispersity. Various characterizations and density functional theory (DFT) calculations were applied to reveal the enhanced Li+ transport mechanism in PCCSE. Owing to the unique design, PCCSE exhibits excellent ionic conductivity at room temperature (1.02 × 10−4 S cm−1) and the Li||SSEs||Li symmetric cells and LFP||SSEs||Li batteries with PCCSE show great cycling stability. This strategy of taking full use of the cations in protonated Chi provides effective design guidance for promoting the Li+ transport in polymer-based electrolytes.

Investigation of the Effect of Chitosan Nanoparticles Synthesis Method on Their Anticancer Activity

There has been a lot of interest in the synthesis of chitosan nanostructures for biomedical purposes. The biocompatibility, biodegradability, and cationic features of chitosan made it as a good candidate for bioprocess. This study compares chitosan nanoparticles generated by three different methods including the ionic gelation, emulsionic solvent diffusion, and reverse micellar/microemulsion techniques in terms of their physicochemical characteristics and cytotoxicity effects on the breast cancer cells. The obtained chitosan nanoparticles were specified using FTIR, UV–Vis spectroscopy, SEM, and MTT assay. Light inverted microscope distinguished the morphological differences in treated and untreated cells. Results showed that the size of chitosan nanoparticles spanned from 281[Formula: see text]nm to 420[Formula: see text]nm and ionic gelation method produced smaller and more uniform particles than two others. More positive zeta potential indicated that stable nanoparticles were synthesized by ionic gelation method. Results also indicated that nanochitosans prepared by all three methods markedly inhibited cell proliferation of MCF-7 cells with [Formula: see text] values of 0.31[Formula: see text]mg/mL, 0.74[Formula: see text]mg/mL, and 0.85[Formula: see text]mg/mL 24[Formula: see text]h after treatment, respectively. From this study, it is evident that the preparation method of nanochitosan affects its ability to inhibit breast cancer cells growth.

Facile and Scalable Synthesis and Self-Assembly of Chitosan Tartaric Sodium.

Chitosan-based nanostructures have been widely applied in biomineralization and biosensors owing to its polycationic properties. The creation of chitosan nanostructures with controllable morphology is highly desirable, but has met with limited success yet. Here, we report that nanostructured chitosan tartaric sodium (CS-TA-Na) is simply synthesized in large amounts from chitosan tartaric ester (CS-TA) hydrolyzed by NaOH solution, while the CS-TA is obtained by dehydration-caused crystallization. The structures and self-assembly properties of CS-TA-Na are carefully characterized by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), X-ray diffraction (XRD), differential scanning calorimeter (DSC), transmission electron microscopy (TEM), a scanning electron microscope (SEM) and a polarizing optical microscope (POM). As a result, the acquired nanostructured CS-TA-Na, which is dispersed in an aqueous solution 20–50 nm in length and 10–15 nm in width, shows both the features of carboxyl and amino functional groups. Moreover, morphology regulation of the CS-TA-Na nanostructures can be easily achieved by adjusting the solvent evaporation temperature. When the evaporation temperature is increased from 4 °C to 60 °C, CS-TA-Na nanorods and nanosheets are obtained on the substrates, respectively. As far as we know, this is the first report on using a simple solvent evaporation method to prepare CS-TA-Na nanocrystals with controllable morphologies.

Use of Natural Products on the Control of Aspergillus flavus and Production of Aflatoxins In Vitro and on Tomato Fruit.

Aspergillus flavus affects fresh and dry fruit and vegetable products, and its toxic metabolites, namely aflatoxins, cause serious damage in humans. The objective of this research study was to evaluate the effect of commercial natural products as well as edible and nanostructured chitosan coatings on the development of A. flavus and on the production of aflatoxins in vitro and in tomato. Treatments were as follows: chitosan 1%, chitosan coating, chitosan nanostructured coating, Citrocover 1% (citrus seed extract), Resinadher 0.5% (pine resin extract), mancozeb 2%, and water. The variables were as follows: halo inhibition, spore production, and aflatoxins content. In fruit, the following were evaluated: disease incidence, mycelial growth, and aflatoxin production. An ANOVA (Tukey: p < 0.05) was used. In vitro results showed that Citrocover and Resinadher reduced sporulation (0.2 and 0.9 × 105 spores mL−1, respectively), while chitosan inhibited the production of aflatoxins. With Resinadher and Citrocover, tomato fruit had the lowest incidence, mycelial growth, and aflatoxin production with corresponding values of 0%, 0.0 cm2, and 0.95 ppb, respectively, and 7%, 0.2 cm2, and 1.77 ppb, respectively. The use of Citrocover and Resinadher could be a viable alternative to decrease the development of A. flavus in tomato fruit.

Chitosan biopolymer, its derivatives and potential applications in nano-therapeutics: A comprehensive review

• Chitosan (CS) is a degradable and biocompatible polymer commonly exploited in drug delivery. • Different chitosan derivatives are being synthesized to enhance the surface chemistry and organ targeting efficiency. • This review focuses on different nanostructures of CS and derivatives for various routes of administration. • CS vaccine carriers are also discussed along with functionalization of CS nanostructures. • Few clinical trials are mentioned together with marketed products. Chitosan (CS) is a natural biopolymer used frequently in drug delivery because of its biodegradability and biocompatibility. Several derivatives of CS have also been synthesized to improve the mucoadhesion and solubility of the nascent CS. The nano and micro particles are reported to have enhanced drug bioavailability, solubility and permeation. Recently, there is an advancement in the active targeted drug and gene delivery using CS because of its tunable surface modifications. This review focuses on CS and its chemically modified structures along with their different nanostructures with examples from the most exploited routes of administration. Herein, the functionalization of CS nanoparticles has also been enlisted along with the use of CS in the immunotherapy as vaccine carriers. Beside, few patents, ongoing clinical trials and already marketed CS-based products are also enlisted.

The Application of Chitosan Nanostructures in Stomatology.

Chitosan (CS) is a natural polymer with a positive charge, a deacetylated derivative of chitin. Chitosan nanostructures (nano-CS) have received increasing interest due to their potential applications and remarkable properties. They offer advantages in stomatology due to their excellent biocompatibility, their antibacterial properties, and their biodegradability. Nano-CSs can be applied as drug carriers for soft tissue diseases, bone tissue engineering and dental hard tissue remineralization; furthermore, they have been used in endodontics due to their antibacterial properties; and, finally, nano-CS can improve the adhesion and mechanical properties of dental-restorative materials due to their physical blend and chemical combinations. In this review, recent developments in the application of nano-CS for stomatology are summarized, with an emphasis on nano-CS’s performance characteristics in different application fields. Moreover, the challenges posed by and the future trends in its application are assessed.

Cover Feature: Photoinduced Water Oxidation in Chitosan Nanostructures Containing Covalently Linked RuII Chromophores and Encapsulated Iridium Oxide Nanoparticles (Chem. Eur. J. 68/2021)

Fiber gels made of Ru(bpy)32+-decorated chitosan and incorporating IrO2 nanoparticles (see SEM image in the background) can effectively perform photoinduced water oxidation with better performance than isolated components. In particular, a significantly higher quantum yield for water oxidation and a better stability of the system are reported. More information can be found in the Full Paper by G. La Ganga, S. Campagna et al. (DOI: 10.1002/chem.202102032).

Photoinduced Water Oxidation in Chitosan Nanostructures Containing Covalently Linked RuII Chromophores and Encapsulated Iridium Oxide Nanoparticles.

The luminophore Ru(bpy)2(dcbpy)2+ (bpy=2,2’‐bipyridine; dcbpy=4,4’‐dicarboxy‐2,2’‐bipyridine) is covalently linked to a chitosan polymer; crosslinking by tripolyphosphate produced Ru‐decorated chitosan fibers (NS‐RuCh), with a 20 : 1 ratio between chitosan repeating units and RuII chromophores. The properties of the RuII compound are unperturbed by the chitosan structure, with NS‐RuCh exhibiting the typical metal‐to‐ligand charge‐transfer (MLCT) absorption and emission bands of RuII complexes. When crosslinks are made in the presence of IrO2 nanoparticles, such species are encapsulated within the nanofibers, thus generating the IrO2⊂NS‐RuCh system, in which both RuII photosensitizers and IrO2 water oxidation catalysts are within the nanofiber structures. NS‐RuCh and IrO2⊂NS‐RuCh have been characterized by dynamic light scattering, scanning electronic microscopy, and energy‐dispersive X‐ray analysis, which indicated a 2 : 1 ratio between RuII chromophores and IrO2 species. Photochemical water oxidation has been investigated by using IrO2⊂NS‐RuCh as the chromophore/catalyst assembly and persulfate anions as the sacrificial species: photochemical water oxidation yields O2 with a quantum yield (Φ) of 0.21, definitely higher than the Φ obtained with a similar solution containing separated Ru(bpy)3 2+ and IrO2 nanoparticles (0.05) or with respect to that obtained when using NS‐RuCh and “free” IrO2 nanoparticles (0.10). A fast hole‐scavenging process (rate constant, 7×104 s−1) involving the oxidized photosensitizer and the IrO2 catalyst within the IrO2⊂NS‐RuCh system is behind the improved photochemical quantum yield of IrO2⊂NS‐RuCh.

Selective removal of lead using nanostructured chitosan ion-imprinted polymer grafted with sodium styrene sulphonate and acrylic acid from aqueous solution

ABSTRACT Nanostructured material chitosan polymer grafted with styrenesulphonate and acrylic acid as ion-imprinted polymer have been synthesised and developed by a new method that provides control over the size and chemical structure. The utilisation of high-intensity ultrasound has been investigated for the synthesis of a nanostructured polymer that is often unavailable by conventional methods. The preparation of ion-imprinted polymer of chitosan as a backbone with grafting of sodium styrene sulphonate and acrylic acid are used for the removal of Pb2+in the presence of Zn2+ as interference ion where the maximum sorption capacities at 90 minutes and pH 4.0 are 82 and 30 mg/g, respectively. In the mean time, regeneration does not have a severe effect on the capacity of IIP. That mean the capacity decreases by 4% after 3 times regeneration.The results showed that ion imprinted polymer can be used with higher efficiency and selectivity in the presence of zinc. The kinetic studies were elaborated shows the corresponding of the theoretical and practical capacity following the models pseudo-second-order and elovich kinetic models and the results of thermodynamic parameters demonstrates that the sorption process is endothermic nature in all cases as the enthalpy equal 26.4 KJ/Mol and the free energy is −1.2 KJ/Mol. Finally, more disorder is associated with the sorption process and reflects good affinity of Pb2+ ion towards the IIP.

Tools for Nano-Enabled Agriculture: Fertilizers Based on Calcium Phosphate, Silicon, and Chitosan Nanostructures

The Green New Deal requires a profound transformation of the agricultural sector, which will have to become more sustainable and ensure universal access to healthy food. Thus, it will be essential to introduce radical technological innovations. Nanotechnologies have the potential to produce a significant boost to the improvement of the food system. Within this context, in the next years, a strong challenge will need to be faced regarding developing new and more efficient uses of nutrients in agriculture, being the nutrient use efficiency (NUE) paramount in sustaining high crop productivity without depleting biodiversity, and altering both the natural and agricultural systems. Nutrients leaching causes environmental pollution and water eutrophication, while nutrient excess favors pest and weed widespread. Therefore, it will be mandatory to improve plant nutrition efficiency without affecting agricultural productivity and economic sustainability. A promising alternative consists of the introduction of the so-called nanomaterial enhanced fertilizers and plant growth stimulators. Such innovation includes nanotechnological solutions that can improve nutrient delivery for a more finely tuned, accurate, and saving-resources distribution of nutrients. This review provides a critical view of the latest advances in nanofertilizer research, mainly referring to nano-hydroxyapatite, silica nanoparticles, and chitosan-derived nanostructures.

Nanochitosan: Commemorating the Metamorphosis of an ExoSkeletal Waste to a Versatile Nutraceutical.

Chitin (poly-N-acetyl-D-glucosamine) is the second (after cellulose) most abundant organic polymer. In its deacetylated form—chitosan—becomes a very interesting material for medical use. The chitosan nano-structures whose preparation is described in this article shows unique biomedical value. The preparation of nanochitosan, as well as the most vital biomedical applications (antitumor, drug delivery and other medical uses), have been discussed in this review. The challenges confronting the progress of nanochitosan from benchtop to bedside clinical settings have been evaluated. The need for inclusion of nano aspects into chitosan research, with improvisation from nanotechnological inputs has been prescribed for breaking down the limitations. Future perspectives of nanochitosan and the challenges facing nanochitosan applications and the areas needing research focus have been highlighted.

Development and In Vivo Characterization of Probiotic Lysate-Treated Chitosan Nanogel as a Novel Biocompatible Formulation for Wound Healing.

Wound healing is a physiological reaction to tissue injuries which plays a crucial role in replacing the destroyed tissues. Probiotics produce valuable compounds that possess antibacterial and anti-inflammatory activities, immunomodulatory effects, and angiogenesis traits leading to the promotion of wound healing. Chitosan nanostructures have versatile properties making them quickly produced into gels, scaffolds, nanoparticles, beads, and sponge structures that can be incorporated into wound healing processes. In the current study, three formulations from nanogel consisting of probiotic supernatant (Lactobacillus reuteri, Lactobacillus fermentum, and Bacillus subtilis sp. natto)-loaded chitosan nanogels were prepared from the culture of corresponding cultures. The chitosan nanogels were previously characterized by Zetasizer, FTIR, and TEM. The prepared formulations' effectiveness and dressing activity were assessed by evaluating wound closure and histological trials in Sprague-Dawley rats. The results indicated that all probiotic lysate formulations have advantages over the wound healing process. However, Bacillus subtilis natto has a better wound healing quality, which is well known in pathology examination. The favorable effects of probiotic lysate nanogels, including the reasonable wound closing rate, good wound appearance, and satisfactory histological observation via in vivo examination, suggest it as a promising nominee for wound healing purposes.

Cytotoxic Plant Extracts towards Insect Cells: Bioactivity and Nanoencapsulation Studies for Application as Biopesticides.

The potential of plant extracts as bioinsecticides has been described as a promising field of agricultural development. In this work, the extracts of Punica granatum (pomegranate), Phytolacca americana (American pokeweed), Glandora prostrata (shrubby gromwell), Ulex europaeus (gorce), Tagetes patula (French marigold), Camellia japonica red (camellia), Ruta graveolens (rue or herb-of-grace) were obtained, purified, and their activity against Spodoptera frugiperda (Sf9) insect cells was investigated. From the pool of over twenty extracts obtained, comprising different polarities and vegetable materials, less polar samples were shown to be more toxic towards the insect cell line Sf9. Among these, a dichloromethane extract of R. graveolens was capable of causing a loss of viability of over 50%, exceeding the effect of the commercial insecticide chlorpyrifos. This extract elicited chromatin condensation and the fragmentation in treated cells. Nanoencapsulation assays of the cytotoxic plant extracts in soybean liposomes and chitosan nanostructures were carried out. The nanosystems exhibited sizes lower or around 200 nm, low polydispersity, and generally high encapsulation efficiencies. Release assays showed that chitosan nanoemulsions provide a fast and total extract release, while liposome-based systems are suitable for a more delayed release. These results represent a proof-of-concept for the future development of bioinsecticide nanoformulations based on the cytotoxic plant extracts.

Chitosan-based hybrid materials as adsorbents for textile dyes–A review

Chitosan is a pseudo-natural cationic polysaccharide in nature. Because of its wide range of physical and biochemical properties, chitosan and its hybrid materials are being used in various industrial sectors. The dyes and other industrial effluents extensively compromise the plant growth and affect the food chain, these substances may also induce toxicity, mutagenicity, and carcinogenicity. Textile dyes affect the quality of water bodies, impair photosynthesis, and increase biochemical and chemical oxygen demand (BOD and COD). Removal of dyes must be performed by either physicochemical, phyto-remediation, and/or biobased methodologies. All these types of dyes degradation methodologies possess various drawbacks. Therefore, attention towards chitosan and modified chitosan-based materials has been devoted in the previous few decades due to its biocompatibility, biodegradability, less-toxic, and eco-friendly nature. However, its attractive properties rely on its ability to form linkages with the sulfonic groups of anionic dyes by the electrostatic force of attraction and adsorption of dyes effluents and other heavy metals in various capacities. This review highlights the properties and modifications of chitosan via (i) crosslinking; (ii) graft copolymerization and, (iii) surfactant impregnation for the development of chitosan-based hybrid materials with improved dye sorption properties have been described. In addition, chitosan nanostructures that are being studied for the smart degradation of textile dyes and effluents have also been discussed. This review provides an insight into the chitosan-based adsorbents and encourage researchers to use chitosan-based composites/blends for the removal of a variety of different dyes and dye-based effluents.

Quality of cold-stored cucumber as affected by nanostructured coatings of chitosan with cinnamon essential oil and cinnamaldehyde

The edible coatings (EC) of nanostructured chitosan (CNCh) and chitosan (CCh) functionalized with cinnamon essential oil (CEO) or trans-cinnamaldehyde (TCA) improve the postharvest quality of cucumber and antifungal activity against Fusarium solani. Were measured physicochemical, physiological and microbiological parameters of the fruit during storage. The morphology of nanoparticles of chitosan was observed using transmission electron microscopy (TEM), particle size distribution and Zeta potential were measured. By TEM the chitosan nanoparticles (NCh) and nanoparticles (NChCEO) had a particle size of 5 nm and 8 nm, respectively. The NCh particle size distribution showed a diameter of 4.68 nm, for NChCEO was 4.34 nm and for NChTCA was of 4.86 nm. The Zeta potential was of −1.94 mV, −1.32 mV, and −2.48 mV respectively. With the EC some changes were observed; The fruit treated with CCh and CNCh showed a weight loss of 5.49% and 8.47%. In the fruit with EC and nanoparticles, the total chlorophyll content was higher at the end of storage. The colony forming units (CFU) of fungi and yeasts were effectively inhibited with ECs. The CCh and CNCh showed the lowest severity. The EC evaluated are a technological alternative to preserve the quality of the cucumber.

Preparation and evaluation of isoniazid loaded chitosan nanostructures

The objective of this investigation was fabrication and evaluation of isoniazid loaded chitosan nanostructures. Nanostructures were fabricated by ionotropic gelation technique, and evaluated by average particle size, encapsulation efficacy, drug loading, Fourier transform infrared spectroscopy and in vitro drug release. The fabricated nanostructures were having particle size, drug loading and encapsulation efficiency ranging 234.2 to 716.8 nm, 12.70% to 17.77% and 47.7% to 79.97%, respectively. The optimized nanoformulation was found to show sustained release of drug during 24 hrs study period.

Robust and nanostructured chitosan–silica hybrids for bone repair application

In this study, chitosan-silica hybrids (CSHs) with superior mechanical strength and homogeneous dispersion of nano-sized silica particles were synthesized via a facile sol-gel method aiming for bone regeneration. The effects of varied acidic conditions of sol-gel reaction and inorganic/organic ratios on the performance of the hybrid were investigated. CSHs synthesized under weak acidic conditions (acetic acid, pH 4.0) showed a homogeneous nanostructure and robust strength (maximum compressive strength: 42.6 ± 3.3 MPa and 271 ± 31 MPa in wet and dry forms, respectively). However, those developed under the strong acidic condition (HCl, pH 4.0) and the strong acid condition plus lower pH (HCl, pH 2.8) tended to aggregate and exhibited inferior mechanical properties (compressive strength: 6.3 ± 0.3 MPa in wet form at pH 2.8). Under the latter conditions, the interactions between silica and chitosan were weak. Moreover, the mechanical properties of the CSHs could be tuned in a wide range by conveniently varying the inorganic/organic composition ratio between 50% and 70%. In vitro cytocompatibility study indicated that CSHs were non-cytotoxic. These results suggested that the weak acidic sol-gel process were essential for fabricating chitosan-silica hybrids with high mechanical strength, which had potential to be applied as a bone substitute.