The amino group in the chitosan structure can be converted to a positively charged ammonium ion, which confers cationic properties to chitosan (Fakhri et al., 2020). The cell walls of Gram-positive bacteria are mainly composed of teichoic acid, which is negatively charged and can react with chitosan via electrostatic interactions, leading to the destruction of the bacterial cell wall, loss of cellular function, and ultimately cell death (Abd El-Hack et al., 2020). The ammonium ions in chitosan interact with the anions of lipopolysaccharides present on the outer membrane of Gram-negative bacteria, leading to a bacteriostatic effect (Ardean et al., 2021). Additionally, chitosan can cross bacterial cell membranes and interfere with the transcription and translation of genetic material, thus affecting the normal cellular function (Figure 1A) (Verlee et al., 2017). The antibacterial performance of chitosan against Staphylococcus epidermidis significantly increased when the compound was functionalized with catechol, as demonstrated by a decrease in the minimum inhibitory concentration of the polymer (Amato et al., 2018). The antibacterial properties of chitosan when formulated as hydrogels, films, sponge wound dressings make it a good wound-treatment material for the prevention and treatment of infections. A novel lignin-chitosan-PVA composite hydrogel designed as a wound dressing shows good adsorption capacity and bacteriostatic effects (Zhang Y. et al., 2019). Chitosan films containing glycerin as a strengthening agent can be used as a wound dressing to inhibit bacterial infections (Ma et al., 2017). The composite sponge prepared using hydroxybutyl chitosan and chitosan combined the hydrophilic properties of hydroxybutyl chitosan and the antibacterial properties of chitosan, highlighting its potential as a wound dressing (Hu S. et al., 2018). The successful use of these preparations in treating skin and soft tissue infections is indicative of the antibacterial effects of chitosan.

The body maintains an oxidation balance under normal physiological conditions. When the antioxidant capacity is not adequate to combat the sudden increase in free radicals, the surplus free radicals lead to cell injury, metabolic disorders of the cellular macromolecules, and the occurrence of skin and soft tissue diseases (Sztretye et al., 2019). The antioxidant properties of chitosan are attributed to the amino and hydroxyl groups in its molecular chain, which can effectively scavenge excessive free radicals in the human body (Muthu et al., 2021). The antioxidant activity of chitosan mainly depends on its relative molecular weight and the level of acetylation (Abd El-Hack et al., 2020; Cabañas-Romero et al., 2020). Chitosan shows a greater ability in scavenging free radicals having relatively low molecular weights and higher levels of acetylation (Negm et al., 2020). Chitosan derivatives obtained by chemical modification can improve the antioxidant capacity of polymers and increase their application over a range of fields (Hao et al., 2021). Chitosan composite films prepared with ascorbate have stronger DPPH radical–scavenging ability and improved ability in resisting ultraviolet-visible light and visible light (Tan et al., 2020). Chitosan derivatives containing Schiff’s base and a quaternary ammonium salt exhibit stronger antioxidant capability than chitosan due to the presence of hydroxyl and halogen groups (Wei et al., 2019). Novel chitosan derivatives containing sulfur salts have DPPH-, hydroxyl-, and superoxide radical-scavenging capacities of higher than 90%, without any associated cytotoxicity (Sun et al., 2020). Chitosan nanoparticles synthesized by doxorubicin can significantly enhance the scavenging ability of free radicals and reduce the cell viability of liver, stomach, lung, and breast cancer cells, which can be used as a potential drug carrier for tumors (Mi et al., 2021). The antioxidant capacity of chitosan can be regulated by adjusting its molecular weight, acetylation level, and the extent of chemical modification, thereby conferring tremendous application prospects in medical cosmetology and the treatment of soft tissue diseases and tumors.

Cancer is one of the most challenging conditions to cure, with surgical resection being the most efficient and effective management technique. The development of targeted drugs provides new ideas to treat cancer; however, several drugs have poor bioavailability, low selectivity, and poor stability in tumor tissues (Kandra and Kalangi, 2015). Chitosan derivatives incorporated into the nano drug-delivery systems have emerged as one of the most advanced delivery systems in the biomedical field. This technology is associated with minimum systemic toxicity and maximum cytotoxicity to the tumors and cancer cells and is the most promising targeted therapy in cancer (Verlee et al., 2017). Chitosan can directly inhibit the growth of tumor cells, induce cell necrosis and apoptosis, and enhance immunity to achieve its antitumor effect (Yu et al., 2022). The chitosan-based nanoparticles could selectively permeate cancer cells and precisely exert their effects by continuously releasing the loaded drugs while maintaining drug stability (Kamath and Sunil, 2017). N, O-carboxymethyl chitosan/multialdehyde Guar hydrogels can continuously release antitumor drug doxorubicin and possess injectable and self-healing biological properties (Pandit et al., 2021). A novel amphiphilic chitosan micelle reported to protect 75% of an anticancer drug from hydrolysis is now being used as a promising drug-delivery system (Almeida et al., 2020). The chitosan- and saline-based nanoparticles are used to deliver the pro-oxidant drug piperlongumine to prostate cancer cells due to their prostate cancer cells killing properties (Choi et al., 2019). The antitumor properties of chitosan make it a potential antitumor drug carrier for treating melanoma and sarcoma of skin and soft tissues.

Chitosan and its derivatives can stimulate phagocytes, induce natural killer cells to secrete cytokines, and activate immune-regulatory responses (Moran et al., 2018). The hydrolysate of chitosan can increase the phagocytic activity of macrophages and promote the proliferation of splenocytes and Payer’s patch lymphocytes, thereby exerting unique immunomodulatory properties (Chang et al., 2019). Polymers containing chitosan can promote the polarization of primary bone marrow–derived macrophages to anti-inflammatory activity carrying macrophages (Papadimitriou et al., 2017). Acidified chitosan can provide an immune microenvironment for osteogenic differentiation by promoting crosstalk between the immune cells and stem cells to induce angiogenesis and bone regeneration (Shu et al., 2018). Hydrogels containing chitosan can promote the wound healing capacity of the skin of diabetic rats by downregulating the pro-inflammatory factors like tumor necrosis factor-α and interleukin (IL)-1β (Chen et al., 2021). Chitosan oligosaccharides can promote the phagocytic activity of RAW264.7 cells, produce reactive oxygen species, release pro-inflammatory factors through the NF-КB pathway, and significantly enhance the immunomodulatory effect (Deng et al., 2020). Chitosan can induce and regulate immune cells by altering the microenvironment of the immune system to achieve therapeutic effects by regulating immune function in the skin and soft tissues.

In recent years, nanomaterials have gained increasing attention in the biomedical field (Zhang E. et al., 2019). Chitosan nanoparticles retain the biological properties of chitosan while improving the stability of the loaded drugs and controlling the drug-release rate (Rizeq et al., 2019). There is evidence that chitosan nanoparticles loaded with anticancer drugs could be used to target malignant tumors, thereby prolonging the drug action duration, enhancing the anticancer effect, and reducing toxicity (Assa et al., 2017). Chitosan nanoparticles are safe, biodegradable, and easy to form DNA or protein complexes for use as a potential gene delivery system (Bowman and Leong, 2006). Chitosan-coated silica nanoparticles have been shown to induce a strong immune response in vivo and can be used for oral delivery of protein vaccine (Wu et al., 2021). Chitosan nanoparticles retain the biocompatibility and biodegradability of chitosan, which is a valuable property and a promising therapeutic approach in targeted therapy when used in combination with anticancer drugs.

The chitosan-based films possess good permeability, a large surface area, and unique antibacterial properties, thus making them a potential alternative to artificial skin and an important material for wound dressings (Vivcharenko et al., 2020). The surface hydrophobicity, permeability, and sensitivity of gamma ray–irradiated chitosan films can be increased without significant changes in the original chemical structure (Salari et al., 2021). Introducing montmorillonite-copper chloride into chitosan films can increase their tensile strength and elongation at break and also confer higher antibacterial activity against foodborne pathogens, further highlighting their use as a wound dressing to combat infections (Nouri et al., 2018). Additionally, chitosan films containing human epidermal growth factors can protect against enzymatic hydrolysis and endocytosis and significantly accelerate the rate of wound healing in mice (Umar et al., 2021). These antibacterial properties and regenerative effects of chitosan make it a suitable material for wound dressing.

The porous structure, biocompatibility, and liquid-absorption properties of the chitosan sponge make it a suitable biomaterial for hemostasis (Zhang K. et al., 2020). Chitosan composite sponges can absorb water in the blood and increase blood viscosity. Moreover, they are non-toxic and biodegradable, hold antibacterial drugs, and promote blood coagulation in wounds (Hu S. et al., 2018). Chitosan composite sponges rich in andrographolide possess a large pore size and expansion rate and can effectively promote wound healing and reduce scar formation when used as a wound care material (Sanad and Abdel-Bar, 2017). Chitosan sponge provides a moist environment, allows gas exchange and blocks out microorganisms, suitable for burn wound dressing to keep away from contamination and dehydration (Jayakumar et al., 2011). Chitosan sponges have been widely used as hemostatic materials due to their porous structure and wound dressings promoting wound healing when loaded with drugs (Matica et al., 2019).

Hydrogels are hydrophilic polymers with high water content and good biocompatibility. They can be loaded with chitosan and used as wound dressings to keep the wound moist and to continuously absorb exudates (Song et al., 2021). Chitosan hydrogels loaded with metal ions can improve the imbalance in metal ions that cause delayed wound healing. Moreover, they inhibit infections and accelerate healing by regulating the expression of inflammatory factors and macrophages polarization (Xiao et al., 2021). An imbalance in metal ions can also lead to scar growth. Modulating the cation in chitosan hydrogel or adding aloe gel can lead to effective scar inhibition (Zhang N. et al., 2020). Chitosan hydrogels can also be used as hemostatic dressings. Thermal-responsive chitosan/DOPA hydrogels improve the adhesion and show a good hemostatic effect in rats (Shou et al., 2020). Chitosan sponges are often used as a hemostatic material. Hydrogels are commonly used as antibacterial dressings because their hydrophilicity and absorbability can suitably isolate infections from foreign substances and keep the wound moist.

Tissue engineering is a research hotspot in regenerative medicine. Functional scaffolds composed of natural polymers have been widely used in surgical reconstruction (Rodríguez-Vázquez et al., 2015). Collagen/chitosan scaffolds made using 3D printing technology show remarkable therapeutic effects in vivo with complete spinal cord transection, and significantly improve sensory and motor recovery (Sun et al., 2019). Chitosan scaffolds surrounded by microcellulose arranged with twisted polylactic acid can simulate the extracellular matrix of tendons, provide structural support for tendon regeneration, and facilitate tendon-cell attachment and proliferation (Nivedhitha Sundaram et al., 2019). Composite chitosan-gelatin scaffold with a double-tubular structure having large internal pores and nonporous outer layers simulate blood vessels and significantly promote the proliferation of human dermal fibroblasts after being inoculated, and can be used for angiogenesis reconstruction (Badhe et al., 2017). Nano-scaffolds made of chitosan, sulfonated chitosan, polycaprolactone, and phosphoric acid can enhance the activity and adhesion of osteoblasts, making them excellent materials for bone tissue regeneration (Ghaee et al., 2017). Chitosan scaffolds have plastic structure and the ability to promote adhesion and proliferation of tissue cells, improving soft tissue and bone tissue regeneration.

Soft tissue injury refers to laceration and contusion of the skin, subcutaneous tissue, and muscle caused by an external force, bleeding, and local swelling. Wound healing depends on the nature and degree of tissue defects, whereas age, nutritional status, and underlying diseases are systemic factors affecting wound healing (Wilkinson and Hardman, 2020). Promoting wound healing and reducing scar formation are urgent medical problems to be solved for patients with wounds and defects in body function. The antibacterial properties of chitosan and its ability to promote tissue regeneration have increased its usage in wound dressings combined with different materials, which have the overall effect of promoting wound healing (Figure 1B).

Impregnating chitosan hydrogels with silver nanoparticles can significantly improve antibacterial and antioxidant properties and enhance wound healing in vivo (Masood et al., 2019). The anti-biofilm formation ability of chitosan-immobilized ficin can inhibit S. aureus infections and promote the formation of smoother epithelial tissue (Baidamshina et al., 2020). Vaccinin-chitosan nanoparticles can promote vascular tissue production by upregulating IL-1β and PDGF-BB, thereby highlighting its potential in wound healing (Hou et al., 2020). The curcumin-loaded chitosan membranes can effectively inhibit bacterial pathogens in wounds by increasing the formation of fibrous connective tissue. Additionally, they have an obvious healing effect on wounds resulting from second-degree burns (Abbas et al., 2019). A study reports that macrophage dysfunction can lead to chronic inflammation and inhibit diabetic wound healing (Chen et al., 2021). Chitosan sulfate can improve macrophage function by inducing the polarization of M1 macrophages to M2 macrophages and promoting the production of anti-inflammatory factors, thus effectively promoting diabetic wound healing (Shen et al., 2020). Chitosan has antibacterial, antioxidant, and immunomodulatory effects that can prevent the infection of wounds and promote healing through soft tissue regeneration, making it a natural wound-dressing material.

Soft tissue infection is an inflammatory condition caused by pathogenic bacteria that invade the skin and subcutaneous tissue. Elimination of necrotic tissue and pathogenic bacteria is the cornerstone of treatment in such infections (Burnham and Kollef, 2018). The effectiveness of different wound dressings in controlling and treating infection has been clearly demonstrated, highlighting their wide use in clinical practice (Simões et al., 2018). Chitosan is an effective carrier of anti-infective drugs due to its mucous membrane dependence and the ability to prolong drug activity by retarding the biodegradation rate (Rajitha et al., 2016). The inhibitory effects of antibacterial materials based on chitosan and its derivatives on different pathogens are listed in Table 1.

Bleeding due to trauma is a serious symptom that needs immediate attention during surgical emergencies. Chitosan can promote coagulation by enhancing red blood cell agglutination and platelet adhesion and is a potential hemostatic material (Figure 1D) (Hu Z. et al., 2018). Composite sponges containing alginate/carboxymethyl chitosan/kangfuxin are biodegradable materials that accelerate blood clotting and promote wound closure (He et al., 2021). Carboxymethyl chitosan sponges grafted with marine collagen peptides can promote coagulation both in vivo and in vitro through the synergistic effect of the collagen peptide and carboxymethyl chitosan (Cheng et al., 2020). Chitosan/diatom-biosilica aerogels are associated with large surface areas and excellent water absorption capabilities and hence, show the shortest clotting time and the lowest amount of blood loss in a hemorrhage model of rats (Li J. et al., 2020). Chitosan/cellulose composite sponges with LiOH/KOH/urea solvent in the shell show better clotting ability, antibacterial effect, and good absorbability than traditional gauze and gelatin sponges (Fan et al., 2020). Different chitosan materials exhibit varying absorbability and coagulation-promoting effects and serve as convenient and effective hemostatic materials to arrest acute bleeding of the skin and soft tissues.

Soft tissue malignancy or sarcomas are tumors that originated from the mesenchymal tissue and mainly occur in the muscles, ligaments, periosteum, fat, and other sites. The efficacy of chitosan in drug-delivery systems for the targeted therapy of malignant tumors in sarcoma has been well documented (Tan et al., 2010). Methylglyoxal-conjugated chitosan nanoparticles can enhance the anticancer effect of methylglyoxal alone in tumor-bearing mice and protect it from enzymatic degradation in vivo by upregulating cytokines and surface receptors of macrophages (Chakrabarti et al., 2014; Pal et al., 2015). Thus, the immunomodulatory effects of macrophages should be activated to achieve the antitumor effect. Low-molecular-weight chitosan obtained through enzymolysis can increase the natural killing activity of tumor-bearing intestinal intraepithelial lymphocytes in mice and inhibit tumor growth by activating their intestinal immune function (Maeda and Kimura, 2004), suggesting that chitosan can achieve antitumor effects by regulating the immune system. Additionally, chitosan can reduce gastrointestinal tract injury caused by adriamycin in sarcoma-180–bearing mice without affecting the tumor-inhibition effect (Kimura et al., 2001). Chitosan can be used to prevent weight loss and spleen weight loss caused by cisplatin in tumor-bearing mice without reducing the antitumor activity of the drug (Kimura et al., 2000). Therefore, chitosan can be considered to alleviate the toxic and side effects of chemotherapy in individuals with sarcoma. Chitosan can increase the anticancer effect of drugs, reduce damage to the body, and achieve antitumor effects through immune regulation when used as a targeted drug carrier. These factors highlight its usage as a curative material in treating soft tissue tumors.