One of the key issues is that IR radiation during radiotherapy can affect the process of wound formation and healing. Wound healing during radiotherapy is more complex and complicated than in the case of typical wound healing. It is important to be aware that IR can interact with water, which constitutes 70% in the tissues of the human body, and thus produce reactive oxygen species (ROS), which are responsible for DNA damage. Overproduction of ROS leads to the development of high oxidative stress, which causes the regeneration process during healing to become longer. The presence of open wounds and a weakened immune system during the course of cancer and chemotherapy are prone to skin infections and even to cause deep tissue necrosis (Figure 3).

Simultaneously, the number of oncologic patients is increasing, in whom the administration of radiotherapy or chemotherapy can result in development of non-healing wounds. Approximately 95% of patients undergoing radiotherapy or radio chemotherapy will develop a skin condition due to the administration of high doses of ionizing radiation, known as radiodermatitis (RD) (Singh et al., 2016). The severity of radiation-induced radiodermatitis (RD) is assessed using the NCI CTCAE [National Cancer Institute-The Common Terminology Criteria for Adverse Events] grading scale and may manifest as erythema, dry desquamation, or moist desquamation. Discomfort, pain, and aesthetic concerns associated with this adverse effect can significantly impair patients’ quality of life, potentially leading to treatment interruptions or even discontinuation (Singh et al., 2016). Therefore, a more advanced wound healing management becomes imperative.

In advanced wound care management, Bonomo et al. (2019) highlight the pivotal role of topical calcium alginate dressings in patients experiencing radiation dermatitis (RD) due to radiotherapy and cetuximab treatment. Their findings suggest that early application of these dressings in cases of grade 2 and 3 RD with presence of moist desquamation significantly improved patients’ compliance, treatment tolerability, and reduced interruptions in radiation treatment. Therefore, authors recommend calcium alginate dressing in management of above-mentioned wounds.

The reports in Cao et al. (2024) indicate the positive effects of hydrogel and alginate dressings in a patient with grade 4 radiation dermatitis with head and neck cancer. The hydrogel dressing maintained a moist environment, supported autolytic debridement of necrotic tissue, and thus the process of phagocytosis, which was responsible for the removal of dead debris and bacteria. The alginate dressing allowed for the removal of excess exudate while providing optimal moisture. An additional advantage was the support of blood clotting and accelerated wound healing. Complete wound healing occurred within 20 days after 17 dressing changes. As the wound healed, the patient’s comfort improved significantly (Cao et al., 2024).

One example of preventing IR-induced skin injury is a dressing created by Zhang J. et al. (2021). Their hydrogel dressing, in which the main components were: alginate, hyaluronic acid, polylysine. Adding curcumin and (−)-epigallocatechin gallate to them allowed for a reduction in inflammation, due to antioxidant and anti-inflammatory properties (Zhang J. et al., 2021).

As another demonstration of the use of alginate-containing hydrogel as a dressing potentially supporting wound healing during radiotherapy is the product developed by Kodous et al. (2024). The researchers synthesized a hydrogel consisting of polyvinyl alcohol and sodium alginate, which was loaded with hesperidin. This flavonoid was subject to controlled release from the hydrogel. The hydrogel treatment reduced the expression of TNF-alpha, NFκB, iNOS and COX2 compared to the BJ-1 cell line stimulated with LPS (Kodous et al., 2024).

Due to the moisturizing properties of sodium alginate researchers (Hao et al., 2022) used it along with interferon-induced protein alpha 6 (IFI6) and graphene oxide to create a hydrogel that would find application in treating radiation-induced skin. Analyses conducted by the team of researchers on an animal model showed that such a designed hydrogel alleviates inflammation in the treatment of radiation-induced skin, and also induces granulation tissue formation, collagen deposition, or angiogenesis. Thanks to these changes, it was possible to close the wound more quickly.

In terms of treating infected wounds during oncological treatment, the Alinezhad et al. (2024) presented a hydrogel containing alginate, hyaluronic acid, polydopamine nanoparticles cross-linked with Zn²⁺. This type of dressing could potentially be used in photothermal therapy, because the use of near infrared (NIR) caused the generation of heat and the destruction of bacteria - E. coli and S. aureus (Alinezhad et al., 2024).

Alginates have found application in photodynamic therapy (Shu et al., 2021). This method is based on a phototoxic reaction, which occurs through the interaction of a photosensitising substance and light of the appropriate wavelength for the substance. The reaction occurs only in the presence of a photosensitiser, which is characterized by its ability to absorb quanta of energy, transmitted in the form of light. This causes a transition to the excited state and, in turn, a return to the ground state with the radiation of a portion of the energy in the form of the appropriate wavelength. The developed hydrogel is made resistant to luminescence through the incorporation of persistent luminescent materials and an immunoadjuvant (R837) into the Ca²⁺ alginate hydrogel, allowing for multiple loading of photodynamic cancer immunotherapy. The presented hydrogel showed high biocompatibility and allowed easy injection. The study confirmed a strong immune response and a synergistic effect of photodynamic immunotherapy to inhibit tumorigenesis (Shu et al., 2021).

A hydrogel comprising sodium alginate and catalase, labelled with the radioisotope ¹³¹I, was developed to alleviate hypoxia at the tumour site and destroy cancer cells using low doses of radioactivity (Chao et al., 2018). Using an injection, sodium alginate transformed into a hydrogel while binding the radioisotope and catalase at the tumour site.

Detailed information on the studies included in the text can be found in Table 2.

In oncological treatment, alginate microparticles combined with paclitaxel have been used as a carrier of cytostatic drugs (Alipour et al., 2010). Researchers used calcium alginate as a mucoadhesive polymer, and its microparticles stick to the mucosa for a long time and are therefore used as vehicles for specific drug delivery to mucosal tissues. The conducted in vitro studies showed that exposure of cells to the paclitaxel alginian carrier and pure paclitaxel inhibited cell growth in a similar way, which depended on concentration and time.

The innovative use of alginate in another study resulted in the release of immunoadjuvants during multiple sessions of chemotherapy/radiotherapy (Sun L. et al., 2021). The component of this hydrogel was sodium alginate, which was conjugated to an ATP-specific aptamer that simultaneously hybridizes to the immunoadjuvant CpG oligonucleotide. After injection, an alginate hydrogel is formed at the tumour site. Its premise was that low doses of oxaliplatin or X-rays would induce immunogenic tumour cell death, which would trigger the release of ATP, which would bind to the ATP-specific aptamer, and this would lead to the release of CpG.

Using the properties of alginate as a carrier, which has the ability to control the release of substances contained in it, Liu Q. et al. (2024) created a type of “in situ vaccine.” The researchers injected a hydrogel that formed near the tumour. It allowed the controlled release of nanoparticle paclitaxel bound to albumin, which shows better efficiency than paclitaxel itself and does not cause allergic conditions, and can also be enriched at the tumour site. Additionally, the hydrogel was attached to the immunostimulant agent R837 – Imiquimod, a TLR9 receptor agonist that promotes dendritic cell maturation, as well as migration, antigen presentation and induction of tumour-specific T lymphocytes. Elements of the immune system such as chemokines and receptors were also significantly involved. Injecting alginate near the tumour allows for a reduced dose of the drug and fewer injections, which reduces toxicity to healthy cells and tissue (Liu Q. et al., 2024).

Carriers for chemotherapeutic drugs can be created using proven and innovative 3D printing technology. Mahdizadeh et al. (2024) used niosome technology, nanocarriers consisting of cholesterol-based vesicles and non-ionic surfactants forming bilayer structures. Their main advantage is low toxicity due to the non-ionic properties of the surfactants (Mahdizadeh et al., 2024).

Detailed information on the studies included in the text can be found in Table 2.

The current treatment of wounds resulting from radiotherapy involves biological agents such as the administration of epidermal growth factor, synthetic drugs, including corticosteroids, statins, and vitamins. Their use is expensive for the patient and is burdened with side effects. This type of therapy is not precise. Wang et al. (2023) proposed a type of injectable hydrogel based on chitosan and gelatin, among others, to which epigallocatechin gallate, which captures hydroxyl radicals, was added. In cell studies and those conducted on an animal model, the hydrogel constructed in this way demonstrated an angiogenesis-promoting and anti-inflammatory effect (Wang et al., 2023).

In the field of oncology, Su et al. (2021) developed hydrogel, which is near-infrared light-responsive and applicable to peri-tumour injection. This could be used for photothermal therapy, particularly in tongue tumours. Photothermal therapy involves the use of compounds, photothermal agents and local heating of the tissue (Figure 4). The photothermal agent absorbs the laser light, resulting in the excitation of electrons and their transition from the ground state to a higher level. The energy thus supplied is given off in the form of heat instead of by photon emission. This method is characterized by high efficiency and stability, and high stability in time and space. Su et al. used biomaterial, which had a good biocompatibility and strong photothermal effect because of the formed network by negatively charged proteins, chitosan molecules and Ag₃AuS₂ nanoparticles. The researchers, through the mouse model of tongue cancer used, demonstrated that sublingual cancer cells were eliminated during a single photothermal therapy. The hydrogel system used, thanks to its low immunogenicity, reduced direct biotoxicity and improved therapeutic effects. One of the unique properties of chitosan is that it is a linear polymer with a positive charge. Combination with negatively charged carboxymethylcellulose results in the formation of a polyelectrolyte complex, in which the obtained hydrogel controls the release of substances placed in it. Zhou et al. (2025) presented a hydrogel based on these substrates with the addition of cannabidiol, the effect of which reduces oxidative stress. Studies conducted on mice confirmed and an increase in collagen synthesis.

The addition of exosomes, which have properties that promote angiogenesis in ischemic tissues and improve the activity of keratinocytes, fibroblasts, endothelial cells and components of the immune system, and their introduction into a hydrogel may bring the desired effects in the case of treatment of radiation injuries. The team of Peng et al. (2024) undertook this task and created a hydrogel based on quaternized chitosan and oxidized sodium alginate with exosomes enclosed in them, which was applied superficially to the wound to obtain a protective barrier. The synthesized hydrogel showed protective properties against microorganisms, promoted rapid re-epithelialization, angiogenesis and collagen deposition (Peng et al., 2024).

The team of Parès et al. (2024) presented a different point of view regarding chitosan hydrogel. Their area of interest was glioblastoma multiforme stage IV. In this aggressive form of cancer, healthy cells surrounding brain tissue are attacked - in them, cancer cells multiply. New reports speak of the attraction and accumulation of glioblastoma multiforme cells in a hydrogel introduced to the site of tumour resection, and then a high dose of radiotherapy is administered. The researchers prepared a macroporous hydrogel consisting of chitosan, sodium alginate, cross-linked with genipin and calcium chloride. Studies conducted on the F98 mCherry cell model distributed, accumulated and were retained throughout the gel volume (Parès et al., 2024).

Detailed information on the studies included in the text can be found in Table 2.

Chitosan hydrogels may provide a drug delivery platform for altering antitumor immunity to enhance immunotherapy. Seo et al. (2024) developed a hydrogel based on methacrylated chitosan glycol and a complex of DNA-a sodium salt extracted from salmon testes and doxorubicin. With this combination, controlled release of the DNA/DOX complex was proven to protect against tumour recurrence and metastasis and induce an antitumor response (Seo et al., 2024).

5-Fluorouracil is the most commonly prescribed drug in the treatment of solid tumours. Due to its rapid metabolism by dihydropyrimidine dehydrogenase and short half-life, limited bioavailability and high systemic toxicity, new methods are sought to target it and improve therapeutic efficacy. Chitosan as a nanocarrier has the advantage of creating a uniform particle size distribution, and the release of the substance contained in it is pH dependent. It is important to know that the pH range occurring in tumour tissues differ from the pH range in healthy tissue. Researchers have developed various methods of cross-linking chitosan so that it optimally releases the chemotherapeutic agent contained in it (Wan et al., 2024).

Reducing the side effects of chemotherapeutics is a primary concern in the design of modern drug delivery systems. Bin Jumah et al. (2024) designed a biocomposite with improved physicochemical and biological properties, consisting of a zinc-phosphate/hydroxyapatite hybrid form in core-shell nanostructure and functionalized with both chitosan and β-cyclodextrin as a 5-fluorouracil carrier. Studies on the colon cancer cell line confirmed the antitumor activity and the controlled release profile of 5-fluorouracil (Bin Jumah et al., 2024).

The idea of creating an injectable drug delivery nanosystem that would allow for better bioavailability of the target drug used in chemotherapy allowed the development of the concept by the team of Haider et al. (2024). Erlotinib is ideally suited for this type of system because it has difficulties in dissolving in water, gastrointestinal absorption and low bioavailability. In vivo studies have confirmed that intratumorally injection of the preparation causes a slowdown in tumour growth (Haider et al., 2024).

Similar conclusions were used by Daneshmehr et al. (2024), who studied the attachment of 5-fluorouracil and schionine to hydrogel nanoparticles of chitosan and pectin. They were prepared by two methods: mixing and coating. The studies carried out on cell lines for the treatment of colon cancer indicated that the mixing method showed the appropriate loading power (Daneshmehr et al., 2024).

Hydrogel based on chitosan and tannic acid was created as an antioxidant crosslinker whose goal was to control the activity of photodynamic therapy used in the treatment of cancer (Azadikhah et al., 2021). In this method, it should be mentioned that photosensitizers cause the formation of reactive oxygen species during photochemical reactions. This results in oxidative damage to cancer cells (Figure 5). The research showed that chitosan with the addition of tannic acid formed a three-dimensional structure that had good mechanical strength and antioxidant activity. The designed hydrogel effectively inhibited tumour growth and protected the dental pulp stem cells from phototoxicity.

Newly developed hydrogels containing N-carboxyethylchitosan has a pH-sensitive property, which were presented as carriers for doxorubicin (Qu et al., 2017). Analyses showed that the pH-sensitive hydrogels released more doxorubicin around/inside the tumour than in normal healthy tissue. With such carriers, it is possible to have a more effective, targeted delivery site for the anti-tumour drug, reduce side effects and protect healthy tissue not occupied by the tumour.

What’s more a biomimetic, thermosensitive hydrogel had ability to incorporate heterodimers of tegafur, protoporphyrin IX (Zhang Z. et al., 2021). The action was to combine chemotherapy with photodynamic therapy. Due to the laser effect, the concentration of reactive oxygen species increased in the tumour, and this phenomenon was important for the release of the drug. The drug injected, and released only with the laser action, reduced the disorderly effects. The researchers opted for chitosan and silk sericin. The thermosensitive properties exhibited by chitosan played an essential role in the choice of carrier.

A related case of the use of chitosan in oncology is chitosan-based hydrogel that contained albumin beads, which as a carrier are characterized by accumulation near cancer cells, and aloe vera juice, which is characterized by antibacterial and anti-inflammatory properties (Kudłacik-Kramarczyk et al., 2021). The hydrogel constructed in this way was to be used for the treatment of skin cancer or burn wounds resulting from radiation therapy. Analyses showed that the tested hydrogels were non-toxic to L929 mouse fibroblasts, and albumin beads, which are a component of the hydrogel.

A hydrogel incorporating chitosan and conjugated with porphyrins was developed to enhance the application of photodynamic therapy (Belali et al., 2018). The hydrogel designed in this way caused the excitation energy to be transferred to the porphyrin unit, and this resulted in an improved release of singlet oxygen. Cytotoxicity and phototoxicity studies of chitosan-based hydrogels highlighted the property to selectively kill cancer cells and protect healthy body cells.

Patients undergoing oncological treatment face various side effects of this therapy, one of them is ulceration of the mucous membranes. Choi et al. (2016) prepared two-layer electrospun fiber sheets that consisted of Eudraugite, chitosan and human growth hormone. Fiber sheets containing growth hormone resulted in better proliferation of human fibroblasts. Studies on an animal model proved that this type of dressing could improve the healing of mucosal ulcers.

Detailed information on the studies included in the text can be found in Table 2.

An example of creating hydrogel dressings using HA is the work of Xia et al. (2025), in which they presented a dressing that protected against radiation and at the same time had antioxidant properties. Additionally, the structure of the patch contained epidermal growth factor (EGF), which supported skin healing. The dressing designed by the researchers uses the property of releasing large amounts of free radicals, then the bonds in the structure of the dressing can be oxidized and transformed into a hydrophilic sulfone. The consequence of this action is the stretching of the hydrogel network and the release of the encapsulated EGF (Xia et al., 2025).

The use of HA cream in patients experiencing radiation dermatitis (RD) shows promise in alleviating symptoms. Preliminary data presented by Gracy et al. (2004) suggest that topical application of HA protected cultured fibroblasts from radiation damage. Chan et al. (2014) advocate for the additional use of HA to provide symptomatic relief, among other topical agents, as in vivo studies have not yet definitively established its benefits in preventing the development of RD.

Another example of using a scheme in which the primary element is the elimination of free radicals formed in wounds during radiotherapy is the creation by Shen et al. (2025) of an injectable hydrogel with Pluronic F127 diacrylate and hyaluronic acid methacryloyl, and nanoparticles of Prussian blue and resveratrol placed in them. It was proven that the hydrogel promoted the migration of fibroblasts to the site of oxidative stress A subsequent exampleis placing proteins and stem cells in hydrogels. Jin et al. (2015) created a hyaluronic acid-based hydrogel loaded with rat mesenchymal stem cells and bone morphogenetic protein-2 (BMP-2). The biomaterial was designed to affect bone healing in osteoradionecrosis of the rat mandible. Anchoring the hydrogel with stem cells and BMP-2 increased bone mineral density and bone volume.

An important aspect is the inhibition of the growth of cancer cells. Tang et al. (2019) developed a hydrogel that included hyaluronic acid, cytarabine and tyramine in its formulation. Combination therapy with radiotherapy significantly reduced 18F-FDG uptake, triggered increased apoptosis and histone H2AX phosphorylation, cell cycle arrest in the G2/M phase, and reduced the proliferation rate in tumour cells compared to monotherapy.

To mitigate the damage caused by radiotherapy, Fang et al. (2023) designed a hydrogel that included cross-linked carbohydrazide-modified gelatin and oxidized HA, polydopamine nanoparticles, and extracellular vesicles secreted by mesenchymal stem cells. In vitro studies showed enhanced cell viability, as evidenced by stimulation of proliferation and migration. Proteomic studies proved that the hydrogel alleviated the radiation-related wound microenvironment by regulating adipocyte and hypoxia-related pathways.

The advantage of hyaluronic acid as a biomaterial is that it can combine with collagen and fibronectin, i.e., matrix structures in tissues, creating a temporary scaffold. Such an organization of materials can effectively promote cell adhesion, migration and proliferation, collagen synthesis. However, its disadvantages are also noticed: poor durability in an aqueous environment, sensitivity to hyaluronidase or free radicals. Therefore, Wang et al. (2024) created a hydrogel based on hyaluronic acid and a self-assembling peptide with attached cordycipin. Hyaluronic acid was to strengthen non-covalent interactions with the peptide. The scaffold skeleton created in this way supported cell adhesion and proliferation.

Detailed information on the studies included in the text can be found in Table 2.

Hyaluronic acid has high affinity for the CD44 receptor, which is overexpressed in cancer cells. Liu et al. (2023) used this property and designed micelles in which modified hyaluronic acid served as a carrier to bind to CD44. In vivo and in vitro studies confirmed inhibition of tumour growth. And the drug delivery vehicle itself was nontoxic.

A very valuable technological achievement is the placement of drugs in hydrogel carriers. In studies by Wang et al. (2021), HA-tyramine was utilized to create a carrier for endostatin, which could be locally injected. The hydrogel prepared in this way showed longer half-life, less systemic toxic side effects. ES/HA-Tyr revealed better anti-angiogenic effect tested on cellular model and anti-tumour effect with radiotherapy tested on animal model. Intra-tumour administration allowed the drug to increase its concentration locally, thereby reducing serum endostatin levels.

Similarly, Li et al. (2016) developed redox-sensitive and intrinsically fluorescent photoclick hyaluronic acid nanogels to deliver cytochrome c to xenografted MCF-7 breast tumours in mice. The study confirmed that the production of the hyaluronic acid nanogel had high specificity. The prepared nanogel allows rapid targeting of tumour cells and rapid release of therapeutic proteins under cytoplasmic reduction conditions while providing potent anti-tumour activity. By exhibiting intrinsic fluorescence, potential use for in vivo tumour monitoring is possible.

Detailed information on the studies included in the text can be found in Table 2.

Skin changes after radiotherapy are a serious problem that occurs in patients undergoing this therapy. Hao et al. (2023) created a hydrogel with antioxidant properties, which included a heparinomimetic peptide. The created system was intended to be used in the process of repairing skin damage caused by radiation. The researchers used the K16 peptide, which had the ability to self-assemble into a hydrogel that formed a 3D mesh and thus created an environment resembling the extracellular matrix. Studies showed that this peptide also supported cell proliferation, migration, angiogenesis, well as protecting cell DNA against radiation-induced damage. The hydrogel dressing prepared in this way promoted collagen deposition and inhibited early wound degradation.

Researchers have also drawn attention to the problem of radiation-induced ototoxicity. This occurs in head and neck cancers. The mechanism of this phenomenon is not fully understood, probably radiolysis of water, which is induced by radiation, is the hotspot of cochlear cell destruction. Liu J. et al. (2024) proposed an injectable peptide hydrogel based on RADA with attached dexamethasone. Additionally, the developed peptide hydrogel reactivated the mTOR signalling pathway, which allowed protection of neuronal cells. During radiotherapy, this signalling pathway is suppressed and neuronal cells in the cochlea are destroyed.

The property of peptide hydrogels is to prolong drug retention by spatial restriction. Zhu et al. (2023) constructed a nonapeptide hydrogel with doxorubicin that responds to changing pH in the environment. The developed nonapeptide called P1 belongs to the type of self-assembling peptides, similar to surfactants. The proposed model had high efficiency of doxorubicin encapsulation, retained sensitivity in an acidic environment. Detailed information on the studies included in the text can be found in Table 2.

The team of Ye et al. (2024) had a similar assumption. In their work, they presented the IEIIIK peptide, which had the ability to surround doxorubicin and self-assemble into a hydrogel under physiological conditions, and after injection into the acidic environment of the tumour, was able to release doxorubicin and allowed its accumulation within the tumour cells.

An important challenge is to create effective peptide hydrogels as carriers of cytostatic drugs, which, thanks to their properties, can influence the change of the microenvironment inside the tumour. Jin et al. (2018) created a of melittin-RADA₃₂ hybrid peptide hydrogel, which was loaded with doxorubicin. It was designed to affect the immunosuppressive tumour microenvironments in melanoma.

This biomaterial has been shown to have the property of controlled drug release and to affect immune cells. As for subcutaneous and metastatic tumours, this hydrogel showed strong anti-tumour efficacy in their case. Raza et al. (2019) developed a FER-8 peptide hydrogel loaded with paclitaxel, which was also pH-sensitive. Analyses in an animal model showed that the peptide hydrogel, as a carrier for paclitaxel, significantly increased the amount of drug in tumour tissues, and by direct injection into the tumour, showed prolonged retention at the injection site. Due to the drug’s release property in the presence of acidic pH, prolonged delivery of the drug and thus increased tumour inhibition was possible.

In an attempt to overcome the reduced efficacy when administering combination therapy, when two or more drugs are used that would reach the target at the same time, Liu et al. (2022) were designing carriers that could release the active substances at the same time. The study showed that the peptide carrier for both drugs, when injected into the tumour site, results in a prolonged and concentrated release -gemcitabine, which is hydrophilic in nature, is released in large amounts, while paclitaxel, which is hydrophobic in nature, is released slowly, allowing for prolonged drug action and increased efficacy.

Detailed information on the studies included in the text can be found in Table 2.