J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Review

Volume 29, March 2025, pages 20-28

Structure characteristics related to biological properties and application of chitooligosaccharides: Mini-Review

Figure 3. Chitooligosaccharide binding mechanism. (a) Maillard reaction; (b) Condensation process of aldehydes and amines; (c) Electrostatic self-assembly process (Vikøren Mo et al., 2020; Wang et al., 2023; Zhang et al., 2016).

**Table 1.** Preparative methods of COS
Preparative methods	Specific techniques	Advantages	Limitations	References
Chemical methods	Acid hydrolysis	Low cost, fast reaction, scalable production	Broad molecular weight distribution, environmental pollution, potential structural damage	Einbu et al., 2007; Li et al., 2013
Oxidative degradation	Mild conditions, controllable degradation	Requires strict oxidant control, may generate byproducts	Nguyen et al., 2023
Enzymatic methods	Specific enzymes	Water barrier properties and antioxidant activity	High enzyme cost, slow reaction rate	Hellmann et al., 2025; Shinya and Fukamizo, 2017
Non-specific enzymes	Mild conditions, uniform product, eco-friendly	Low efficiency, byproduct formation	Beer et al., 2020; Poshina et al., 2020
Other methods	Physical methods (ultrasound, microwave-assisted etc.)	Eco-friendly, can be combined with other methods for higher efficiency	Limited effectiveness alone, requires parameter optimization	Li et al., 2023; Suhaimi et al., 2025; Wasikiewicz and Yeates, 2013; Yue et al., 2008

Table 1. Preparative methods of COS

Preparative methods

Specific techniques

Advantages

Limitations

References

Chemical methods

Acid hydrolysis

Low cost, fast reaction, scalable production

Broad molecular weight distribution, environmental pollution, potential structural damage

Einbu et al., 2007; Li et al., 2013

Oxidative degradation

Mild conditions, controllable degradation

Requires strict oxidant control, may generate byproducts

Nguyen et al., 2023

Enzymatic methods

Specific enzymes

Water barrier properties and antioxidant activity

High enzyme cost, slow reaction rate

Hellmann et al., 2025; Shinya and Fukamizo, 2017

Non-specific enzymes

Mild conditions, uniform product, eco-friendly

Low efficiency, byproduct formation

Beer et al., 2020; Poshina et al., 2020

Other methods

Physical methods (ultrasound, microwave-assisted etc.)

Eco-friendly, can be combined with other methods for higher efficiency

Limited effectiveness alone, requires parameter optimization

Li et al., 2023; Suhaimi et al., 2025; Wasikiewicz and Yeates, 2013; Yue et al., 2008

**Table 2.** Application of COS complex
Compound	Application	Conclusion	Reference
Yeast protein	Betanin embedding	Enhanced thermal-, light-, and metal irons (ferric and copper ions) -stabilities of betanin, protected the betanin against color fading, and realized a controlled release in simulated gastrointestinal tract.	Yang et al., 2024
Desalted duck egg white peptides (DPs)	Calcium delivery systems	These copolymers reversed the inhibition of phytic acid (PA) in calcium transport in Caco-2 cell monolayers. PA-induced calcium deficiency mice model indicated that copolymers could reverse the side effect of PA, promote calcium bioavailability, and improve gut health.	Zhao et al., 2020
Tripolyphosphate (TPP)	CPP-Ca (calciumbinding casein phosphopeptides) loaded core-shell microparticles	COS was successfully crosslinked through TPP while CPP-Ca was incorporated in it, and the calcium release and absorption studies in vitro and in vivo exhibited CPP-Ca-loaded microparticles could achieve controlled calcium release and sustained calcium uptake.	Zhu et al., 2020
Bacterial cellulose	Packaging	The composite film has good mechanical properties, COS improved the antibacterial and antioxidant properties	Yin et al., 2020
Pectin/Ca²⁺	Quercetin embedding	The drug release profile of COS-CaP-QT was pH-dependent and colon microenvironment-responsive, and COS-CaP-QT showed preferential distribution in the colon	Jing et al., 2023
Fish skin gelatin	Food packaging	The inclusion of COS significantly augmented the antibacterial and antioxidant properties of the hydrogel-based nanofiber membranes.	Liu et al., 2024
Marsupenaeus japonicus ferritin	Pickering emulsions	Emulsions stabilized by MF/COS complex at a ratio of 2:1 exhibited superior stability, evidenced by no significant creaming or demulsification during storage or heat treatment.	Gao et al., 2024
Gelatin	Safflomin/betanin embedding	Intermolecular interactions and good compatibility among gelatin, chitooligosaccharide and proper-content Safflomin/betanin promoted thethermal stability, dispersion stability and microgel particles of complexes. The complexes illustrated great oil-water interfacial adsorption behaviors and dilatational viscoelasticity for interfacial membrane, implying high elasticity and interface stability.	Wang et al., 2023
Bovine serum albumin	Improving the foaming capacity	The COS-BSA complexes have good foaming properties than BSA. The angel cake with the COS-BSA substitution rate of 25% exhibited the largest specific volume and best texture, and inhibited the microbial growth in cakes during storage.	Zhao et al., 2022
Sodium alginate/Ca²⁺	Adsorbing metal ions	The novel EDTA functionalized chitooligosaccharide/sodium alginate/Ca²⁺ physical double network hydrogel (ECSDNH) can effectively adsorb metal ions and be recycled	Yue et al., 2022
Poly(c-glutamic acid)/dopamine	Self-healing and tissue adhesive biomaterials	Through reversible ionic and p-cation interactions between the anionic c-PGA/DA conjugate and cationic COS, a physically crosslinked hydrogel was stably formed by simply mixing an aqueous solution of the c-PGA/DA conjugate with COS. The physically crosslinked c-PGA/DA/COS hydrogels exhibited excellent self-healing properties and injectability	Cheol Kim et al., 2021
Whey protein isolate-bitter melon seed oil emulsions	Loading bitter melon seed oil	With the addition of COS, the ζ-potential of the emulsion shifted from negative to positive because COS adsorb onto the surface of W-BSOE droplets. And the in vitro gastrointestinal digestion indicated that WC-BSOE droplets can release bioactive compounds that effectively treated intestinal inflammation.	Ma et al., 2024
Ovomucin	Loading and enhancing activities of Lutein	LUT-loaded nanogel (OVM-COS-LUT) was prepared by a self-assembly of ovomucin (OVM) and chitosan oligosaccharide (COS) to enhance the effective protection and bioavailability of LUT. The nanogel had excellent dispersion (PDI = 0.25) and an 89.96% LUT encapsulation rate.	Xu et al., 2024
Lysine (Lys) and glycine (Gly)	To further strengthen the antioxidant capacity of COS	Chitooligosaccharide (COS) combined with lysine or glycine via the Maillard reaction significantly enhances antioxidant activity, effectively preserving the quality and extending the shelf life of fresh-cut fruits and fruit juices during storage.	Yan et al., 2018; Yu et al., 2019

Table 2. Application of COS complex

Compound

Application

Conclusion

Reference

Yeast protein

Betanin embedding

Enhanced thermal-, light-, and metal irons (ferric and copper ions) -stabilities of betanin, protected the betanin against color fading, and realized a controlled release in simulated gastrointestinal tract.

Yang et al., 2024

Desalted duck egg white peptides (DPs)

Calcium delivery systems

These copolymers reversed the inhibition of phytic acid (PA) in calcium transport in Caco-2 cell monolayers. PA-induced calcium deficiency mice model indicated that copolymers could reverse the side effect of PA, promote calcium bioavailability, and improve gut health.

Zhao et al., 2020

Tripolyphosphate (TPP)

CPP-Ca (calciumbinding casein phosphopeptides) loaded core-shell microparticles

COS was successfully crosslinked through TPP while CPP-Ca was incorporated in it, and the calcium release and absorption studies in vitro and in vivo exhibited CPP-Ca-loaded microparticles could achieve controlled calcium release and sustained calcium uptake.

Zhu et al., 2020

Bacterial cellulose

Packaging

The composite film has good mechanical properties, COS improved the antibacterial and antioxidant properties

Yin et al., 2020

Pectin/Ca²⁺

Quercetin embedding

The drug release profile of COS-CaP-QT was pH-dependent and colon microenvironment-responsive, and COS-CaP-QT showed preferential distribution in the colon

Jing et al., 2023

Fish skin gelatin

Food packaging

The inclusion of COS significantly augmented the antibacterial and antioxidant properties of the hydrogel-based nanofiber membranes.

Liu et al., 2024

Marsupenaeus japonicus ferritin

Pickering emulsions

Emulsions stabilized by MF/COS complex at a ratio of 2:1 exhibited superior stability, evidenced by no significant creaming or demulsification during storage or heat treatment.

Gao et al., 2024

Gelatin

Safflomin/betanin embedding

Intermolecular interactions and good compatibility among gelatin, chitooligosaccharide and proper-content Safflomin/betanin promoted thethermal stability, dispersion stability and microgel particles of complexes. The complexes illustrated great oil-water interfacial adsorption behaviors and dilatational viscoelasticity for interfacial membrane, implying high elasticity and interface stability.

Wang et al., 2023

Bovine serum albumin

Improving the foaming capacity

The COS-BSA complexes have good foaming properties than BSA. The angel cake with the COS-BSA substitution rate of 25% exhibited the largest specific volume and best texture, and inhibited the microbial growth in cakes during storage.

Zhao et al., 2022

Sodium alginate/Ca²⁺

Adsorbing metal ions

The novel EDTA functionalized chitooligosaccharide/sodium alginate/Ca²⁺ physical double network hydrogel (ECSDNH) can effectively adsorb metal ions and be recycled

Yue et al., 2022

Poly(c-glutamic acid)/dopamine

Self-healing and tissue adhesive biomaterials

Through reversible ionic and p-cation interactions between the anionic c-PGA/DA conjugate and cationic COS, a physically crosslinked hydrogel was stably formed by simply mixing an aqueous solution of the c-PGA/DA conjugate with COS. The physically crosslinked c-PGA/DA/COS hydrogels exhibited excellent self-healing properties and injectability

Cheol Kim et al., 2021

Whey protein isolate-bitter melon seed oil emulsions

Loading bitter melon seed oil

With the addition of COS, the ζ-potential of the emulsion shifted from negative to positive because COS adsorb onto the surface of W-BSOE droplets. And the in vitro gastrointestinal digestion indicated that WC-BSOE droplets can release bioactive compounds that effectively treated intestinal inflammation.

Ma et al., 2024

Ovomucin

Loading and enhancing activities of Lutein

LUT-loaded nanogel (OVM-COS-LUT) was prepared by a self-assembly of ovomucin (OVM) and chitosan oligosaccharide (COS) to enhance the effective protection and bioavailability of LUT. The nanogel had excellent dispersion (PDI = 0.25) and an 89.96% LUT encapsulation rate.

Xu et al., 2024

Lysine (Lys) and glycine (Gly)

To further strengthen the antioxidant capacity of COS

Chitooligosaccharide (COS) combined with lysine or glycine via the Maillard reaction significantly enhances antioxidant activity, effectively preserving the quality and extending the shelf life of fresh-cut fruits and fruit juices during storage.

Yan et al., 2018; Yu et al., 2019