Hydrogel‐Based Therapies for Photoaging: Current Advances and Future Perspectives

ABSTRACT

Background

Photoaging, caused by long‐term ultraviolet (UV) exposure, leads to wrinkles, loss of skin elasticity, pigmentation disorders, and impaired barrier function due to oxidative stress, DNA damage, and collagen breakdown. Hydrogels, with their high water content (> 90%), biocompatibility, and controlled drug release capabilities, have emerged as a powerful tool for preventing and treating skin photoaging.

Aims

To review current treatment strategies and provide an updated perspective on the treatment of photoaging.

Methods

We searched the PubMed and Web of Science library databases for eligible studies published within the past 5 years, categorizing and evaluating the effects of hydrogels with different carriers and active ingredients.

Results

A total of 21 relevant studies were included, involving Lipid‐based Hydrogels, Hyaluronic Acid‐based Hydrogels, Chitosan‐based Hydrogels, Polyacrylonitrile‐modified κ‐Carrageenan‐based Hydrogels, Gellan Gum/Sodium Alginate‐based Hydrogels, Recombinant Collagen‐based Hydrogels, and Other Polymer‐based Hydrogels.

Conclusions

The collected studies consistently demonstrate that hydrogel therapy is more effective than traditional treatments in reducing UV‐induced skin damage and promoting skin repair and regeneration. In addition to improving drug utilization efficiency, hydrogel carriers—particularly those incorporating hyaluronic acid—enhance skin hydration, slow aging, and accelerate wound healing, indicating promising therapeutic potential.

1. Introduction

Photoaging is primarily caused by UV radiation, which induces oxidative stress, DNA damage, and the degradation of collagen and elastin in the skin. Skin photoaging shows up as wrinkles, discoloration, dilated capillaries, and a dry, rough texture [1, 2], affecting both appearance and the skin's protective barrier [3, 4]. This increases the risk of inflammation and skin cancers. Traditional methods to treat the photoaging include topical creams and cosmetic surgeries [5]; however, these approaches often have their own limitations in terms of effectiveness and potential side effects. Hydrogels, with their adjustable physical and chemical properties, offer a novel and effective alternative for addressing the multifaceted issues associated with photoaging. Their ability to provide controlled drug release, improve skin hydration, and enhance the delivery of bioactive ingredients makes hydrogels a promising selection for mitigating the damage caused by UV exposure and promoting skin repair and rejuvenation.

2. Mechanism of UV‐Driven Skin Photoaging

Skin aging is divided into intrinsic aging and extrinsic aging, with the former being a physiological process influenced by factors such as genetics and hormones. UV radiation is the most important external factor, and skin aging caused by UV radiation is referred to as photoaging [6]. Based on wavelength, UVR can be divided into UVA (320 ~ 400 nm), UVB (280 ~ 320 nm), and UVC (100 ~ 280 nm). UVA can penetrate into the dermis and damage the extracellular matrix of the dermis, while UVB reaches the epidermis, inducing the generation of MMPs and leading to the degradation of dermal collagen fibers. UVC is filtered by the atmospheric ozone layer and therefore cannot reach the skin [7]. Besides the direct effects of UV radiation, the heat energy from sunlight may also contribute to photoaging [8]. Currently, it is believed that the pathogenesis of photoaging induced by UV radiation is mainly related to oxidative stress, DNA damage, inflammation, immune suppression, apoptosis, extracellular matrix degradation, mitochondrial dysfunction, and advanced glycation end products (AGEs) [9, 10].

2.1. Oxidative Stress

Cellular oxidation, coupled with an imbalance in the body's antioxidant defenses, triggers a cascade of excessive oxidative stress, culminating in the overproduction of reactive oxygen species (ROS) [11]. These highly unstable molecules wreak havoc within the cellular environment, eagerly reacting with surrounding molecules and disrupting normal function. ROS inflict direct harm on critical cellular components, including DNA, proteins, and lipids, while simultaneously driving the heightened expression of MMPs [12]. This, in turn, accelerates the degradation of collagen within the extracellular matrix, diminishing its structural integrity [13]. The cumulative effect of these intricate reactions is profound cellular dysfunction, which manifests outwardly as skin photoaging—a process characterized by increased skin laxity, the deepening of wrinkles, and a loss of youthful resilience.

2.2. DNA Damage

UV radiation can cause DNA double‐strand breaks, DNA strand breaks, removal or replacement of bases or base pairs, and also induce the formation of cyclobutane pyrimidine dimers and pyrimidine‐pyrimidone photoproducts, increasing the risk of skin inflammatory diseases and even malignant tumors [3, 4]. In addition, the ROS induced by UVA can cause secondary oxidative damage to DNA, exacerbating the carcinogenic effects of UVB [14, 15]. This ROS‐mediated damage amplifies the carcinogenic potential of UVB, as it exacerbates oxidative lesions like 8‐oxoguanine, further destabilizing the genome and accelerating the progression toward tumorigenesis [16]. Together, these synergistic effects of UVA and UVB underscore the complex role of UV radiation in driving skin pathology beyond mere photoaging, posing a substantial threat to long‐term skin health.

2.3. Inflammation and Immunosuppression

Histamine, serotonin, and kinins, along with pro‐inflammatory mediators such as TGF‐β and platelet‐derived growth factor, are the main cytokines present in skin cells that can alleviate UV‐induced damage to the dermis. These molecules contribute to tissue repair and modulate inflammatory responses, helping to restore dermal integrity following UV exposure. Moreover, TNF‐α, IL‐1, and IL‐6 indicate the immune status of photoaged skin to some extent [17]. In addition, UVB radiation induces the release of cytokines such as TNF‐α and IL‐10, further suppressing the skin's immune system [18].

2.4. Autophagy

Autophagy, a cellular recycling process, plays a key role in skin photoaging by mitigating UVR‐induced damage through the clearance of damaged organelles and proteins [19]. Autophagy can suppress excessive MMP expression by clearing ROS‐damaged signaling proteins or organelles that perpetuate inflammatory pathways, like NF‐κB, thereby indirectly preserving ECM integrity [20]. UVR‐induced DAMPs are normally cleared by autophagy to limit inflammatory signaling. When autophagy falters, persistent inflammation drives the release of cytokines such as IL‐1β and TNF‐α, exacerbating tissue damage and promoting a pro‐aging microenvironment [21]. Based on this, we conclude that chronic UV exposure synergizes with aging to dysregulate autophagy, thereby leading to the accumulation of cellular debris, heightened inflammation, and accelerated photoaging signs like wrinkles and collagen loss.

2.5. Extracellular Matrix Degradation

Matrix metalloproteinases (MMPs) can degrade various components of the extracellular matrix (ECM), especially collagen. UV radiation can upregulate the activity of MMPs, inducing the expression of MMP‐1, MMP‐3, and MMP‐9 in normal epidermis. These enzymes break down collagen fibers, leading to their progressive degradation and disorganization. As a result, the skin loses its structural integrity, strength, and elasticity, accelerating the process of photoaging and contributing to the formation of wrinkles, sagging, and other signs of premature aging [22].

2.6. Mitochondrial Dysfunction

UV radiation increases the likelihood of mtDNA mutations or deletions [23], affecting the function of the electron transport chain and ATP production, leading to mitochondrial dysfunction. These changes further result in increased cellular oxidative stress, elevated collagen‐degrading enzyme activity, and a vicious cycle that damages mitochondrial function, accelerating skin photoaging [24]. The clinical manifestations include profound wrinkle formation, irreversible loss of skin elasticity, and other characteristic signs of premature skin aging.

2.7. Ferroptosis

Ferroptosis is a novel form of iron‐dependent programmed cell death that is distinct from necrosis, autophagy, apoptosis, and other forms of cell death. UVR can induce ferroptosis in HaCaT cells, thereby exacerbating cellular aging [25]. The role of ferroptosis in skin photoaging is closely tied to its interaction with oxidative stress, a key driver of UV‐induced skin damage [26, 27]. When skin cells are exposed to UVR, it generates reactive oxygen species (ROS) that overwhelm the antioxidant defenses. This oxidative imbalance promotes lipid peroxidation, a hallmark of ferroptosis, particularly affecting polyunsaturated fatty acids in cell membranes. Iron, abundant in cells, catalyzes this process through the Fenton reaction, amplifying ROS production and pushing cells toward ferroptotic death [28]. In HaCaT cells, UVR‐induced ferroptosis disrupts normal cellular homeostasis, leading to the degradation of extracellular matrix components like collagen and elastin, which are critical for maintaining skin structure and elasticity.

2.8. Advanced Glycation End Products (AGEs)

Advanced glycation end products (AGEs) are formed from reducing sugars and macromolecules [29]. AGEs impair cell differentiation by disrupting signaling pathways essential for tissue repair and regeneration. Additionally, they upregulate the expression of MMPs, enzymes that degrade extracellular matrix components, thereby compromising structural integrity. AGEs also induce the production of reactive oxygen species (ROS), amplifying oxidative stress and triggering inflammatory responses. Collectively, these actions accelerate cellular aging, contributing to tissue dysfunction and age‐related pathologies, such as skin aging and chronic disease progression [30].

2.9. Mechanisms of Hydrogels for Skin Photoaging

Hydrogels are hydrated materials with a three‐dimensional crosslinked network structure that can absorb large amounts of water while maintaining shape stability. They are primarily composed of hydrophilic polymer chains, which form a network structure through chemical or physical crosslinking [31, 32]. The high water content (> 90%) of hydrogels allows them to mimic the skin's microenvironment, helping to alleviate dryness and barrier damage caused by UV radiation. On the other hand, hydrogels can load antioxidants or natural anti‐inflammatory ingredients to effectively combat photoaging. Additionally, hydrogels can incorporate growth factors (such as EGF, TGF‐β) to stimulate fibroblast proliferation and collagen synthesis, thereby mitigating skin aging. In recent years, there has been a more comprehensive understanding of the mechanisms by which hydrogels function in photoaging Figure 1.

FIGURE 1.

Mechanisms of hydrogels for skin photoaging.

2.10. UV Protection Effect

Hydrogels can effectively reduce UV penetration and slow down the photoaging process of the material by incorporating specific light shielding agents, such as UV absorbers, light stabilizers, and antioxidants. These composite systems operate via two synergistic mechanisms: primary protection through UV attenuation (via absorption and Rayleigh scattering) and secondary protection via ROS quenching. The combined effect significantly reduces incident UV radiation while simultaneously mitigating oxidative damage, thereby effectively retarding the photoaging process. This dual‐action preservation maintains hydrogel structural integrity by preventing both chain scission and undesirable crosslinking in the polymer network [33].

2.11. Anti‐Inflammatory Effect

Hydrogels mitigate UV‐induced inflammation by acting as biocompatible, high‐moisture carriers for anti‐inflammatory agents such as antioxidants and steroids, delivering them to damaged skin. These agents neutralize ROS and inhibit NF‐κB, reducing pro‐inflammatory cytokine expression [34]. Additionally, hydrogels' moisture‐retaining properties soothe skin barrier damage and promote inflammation resolution, aiding in photoaging prevention.

2.12. Antioxidant Ability

During the process of photoaging, oxidative stress is one of the main factors leading to material degradation. By incorporating natural or synthetic antioxidant molecules, such as vitamin E, glutathione, and certain phenolic compounds, into hydrogels, the generation of free radicals can be effectively reduced, slowing down the oxidation process and improving the hydrogel's anti‐aging properties [35].

2.13. Restoration of Skin Barrier

Owing to their high water content and flexibility, hydrogels can significantly enhance skin hydration by providing a moist environment, thereby mitigating further deterioration of barrier function [36]. Furthermore, hydrogels serve as delivery systems, encapsulating antioxidants or reparative active ingredients such as vitamin C and hyaluronic acid, effectively counteracting oxidative stress caused by photoaging while promoting epidermal cell regeneration and collagen fiber reconstruction. The physical protective layer formed by hydrogels also reduces secondary damage from external environmental factors, supporting barrier restoration.

2.14. MMPs Activity Suppression and Collagen Deposition

Hydrogels slow skin aging by inhibiting MMPs. Loaded with MMP inhibitors such as Lycium barbarum , they suppress MMP activity via localized release, inhibiting the degradation of collagen fibers in the dermis and safeguarding dermal matrix integrity [36]. Their moisturizing and barrier‐repair properties also reduce UV‐induced oxidative stress, indirectly curbing MMP overexpression and protecting against photoaging. Concurrently, by providing a moist microenvironment and encapsulating collagen‐promoting agents such as peptides or growth factors, hydrogels stimulate fibroblast activity, enhancing collagen synthesis and deposition, thereby improving the structural integrity of photoaged skin.

3. Applications of Hydrogels for Skin Photoaging

Hydrogels, prized for their superior hydration and biomimetic qualities, have been widely employed as coatings for medical devices over recent decades [37]. Their responsiveness to environmental stimuli such as pH, temperature, ultrasound, and light enhances their utility [38, 39, 40, 41, 42]. While UV‐protective and antioxidant drugs are widely studied, transdermal drug delivery—offering convenience, bypassing liver metabolism, and providing sustained release—has gained attention. Natural extracts, valued for low toxicity and biocompatibility, are ideal candidates, but their bioavailability is challenging to optimize. Combining them with hydrogels into topical composites enhances drug efficacy and photoaging treatment, making it a trending research focus Table 1.

TABLE 1.

Summary of the mechanisms by which different types of hydrogels participate in photoaging repair.

Hydrogel	Compositions	Models	Biological effect	Ref
Lipid‐based hydrogels	Rice Bran Oil	Adult male Swiss mice	Enhance the stability of rice bran oil, exhibit antioxidant, anti‐inflammatory, and anti‐edema effects	Rigo et al. [43] 2015
	Tetramethylpyrazine hydrochloride	Kunming female mice, Franz diffusion pool	Exhibit strong antioxidant effects, improve skin photoaging protection, control drug release rate	Liu et al. [44] 2022
	Octyl Methoxycinnamate	Fresh pig ear skin, Hen's Egg Test‐Chorioallantoic Membrane	Enhance UV protection, trap sunscreen molecules covalently, control drug release rate	Andreani et al. [45] 2020
	Oroxylin A	HaCaT Cells, male Kunming mice	Promote transdermal drug absorption, enhance drug stability, control drug release efficiency	Zhu et al. [46] 2022
Hyaluronic acid‐based hydrogels	Exosome‐like nanovesicles derived from Olea europaea leaves	HaCaT Cells, HDF‐α cells, male mice	Protect against UV radiation, repair photoaged skin	Wang et al. [47] 2024
	Polylactic acid	Female ICR mice	Exhibit anti‐wrinkle effects, increase collagen production	Zhao et al. [48] 2023
	Dihydrocaffeic acid and 3‐aminophenylboronic acid	L929 Fibroblasts	Control drug release rate, protect fibroblasts	Oliveira et al. [49] 2020
	Hydroxyapatite Nanoparticles	Female BALB/c nude mice	Stimulate synthesis of collagen and elastin, enhance stiffness and gel adhesiveness	Jeong et al. [50] 2017
Chitosan‐based hydrogels	Bilberry Fruit Extract, Vaccinium myrtillus	HaCaT Cells	Exhibit high antioxidant activity, inhibit hyaluronidase and tyrosinase, control release, enhance bioadhesion	Sroka et al. [51] 2024
	18β‐Glycyrrhetinic Acid	HaCaT Cells, Hairless Mice	Improve skin penetration, sustain release of active components, enhance UV protection and anti‐aging effects, recover photoaged skin	Quan et al. [52] 2023
	Ascorbyl glucoside	Franz diffusion cell with porcine skin, Guinea pig skin	Promote anti‐photoaging effects, control drug release rate	Wu et al. [53] 2023
Polyacrylonitrile‐modified κ‐carrageenan‐based hydrogels	Sulfated galactofucan Polysaccharides and alginate oligosaccharides	HaCaT Cells, Female Kunming mice	Protect against UVB‐induced photoaging, decrease inflammation, inhibit collagen degradation	Wu et al. [54] 2024
Gellan gum/sodium alginate‐based hydrogels	Oleuropein‐rich olive leaf extract	Normal human dermal fibroblasts	Exhibit effective antioxidant activity, protect against UVA‐induced photoaging	Busto et al. [55] 2023
Recombinant collagen‐based hydrogels	Adipose‐derived mesenchymal stem cells	Nude mouse, HaCaT Cells	Reduce UV‐induced skin damage, promote skin repair and regeneration	Lin et al. [56] 2025
	Recombinant collagen	Male Kunming mice	Improve crosslinking efficiency of recombinant collagen, provide high‐performance implant material for skin regeneration	Wang et al. [57] 2024
	Cysteine‐rich thrombospondin‐1 type I repeat‐like protein	L929 Mouse Fibroblasts, C57BL/6J mice	Function as waterproof coating, enhance free radical scavenging, protect against extracellular oxidative stress	Wang et al. [58] 2022
Other polymer‐based hydrogels	Selenomethionine	Epidermal stem cells, BALB/c‐nu female nude mice	Enable sustained and controlled release of Se‐Met, reduce inflammation, remodel extracellular matrix, inhibit ferroptosis	Sun et al. [59] 2024
	Autocatalytic ceria nanoparticles	L929 Cells, HaCaT Cells, Mice	Eliminate ROS, suppress MMP production, curb collagen degradation and inflammation	Kim et al. [60] 2024
	Lycium barbarum Polysaccharides	Hairless mice	Reduce UVR‐induced skin damage	Neve et al. [36] 2020
	Hesperetin	Wistar rats	Protect skin from UVA‐UVB radiation damage, enhance fluidity, improve spreadability	Andrade et al. [45] 2022
	The combination of TiO2 with mesoporous silica	Dorsal skin of one‐week‐old pigs, HaCaT Cells, BALB/c nude mice	Alleviate skin cell death and neutrophil recruitment, resist photoaging damage from UV radiation	Lin et al. [61] 2022

3.1. Plant Oils and Extracts

Long‐term sun exposure generates free radicals that cause oxidative skin damage and aging. Plant oils, which are rich in bioactive compounds, have been widely studied for their natural UV‐protective properties [62]. Rigo et al. [43] developed rice bran oil‐loaded lipid‐core nanocapsules (LNCs) that attenuated UVB‐induced skin damage in mice via NF‐κB pathway inhibition, demonstrating anti‐inflammatory and antioxidant efficacy. This hydrogel enhanced active ingredient stability and skin permeability, overcoming topical delivery limitations while enabling controlled drug release [63]. Citrus fruits contain active ingredients that can be extracted at high concentrations and have been proven to possess antioxidant, anti‐inflammatory, immunoregulatory, wound‐healing, anticancer, and neuroprotective activities [64, 65, 66]. Andrade et al. [45] formulated the ammonium acryloyldimethyltaurate/VP copolymer (AAMVPC) containing 10% hesperidin, extending its duration of action. This gel prevents skin redness and swelling, significantly reduces oxidative stress, and safeguards skin from UVA‐UVB damage, preserving structural integrity. Its semi‐solid form provides suitable rheological properties and spreadability, ensuring a pleasant application experience. Studies [67] have shown that tetramethylpyrazine hydrochloride (TMPZ) not only clears reactive oxygen species (ROS), but also inhibits the excessive secretion of inflammatory factors such as interleukins (IL), cyclooxygenase‐2 (COX‐2), and tumor necrosis factor (TNF‐α) from epidermal and dermal cells [68]. Liu et al. [44] prepared a TMPZ‐loaded liposome–hydrogel (TMPZ‐LG), which enhances its antioxidant effects. The hydrogel leverages liposomes for sustained [69] and stimulus‐responsive drug release [70], improving skin adhesion and markedly enhancing bioavailability.

3.2. Polysaccharides and Polyphenols

Seaweed polysaccharides have various biological activities, including antioxidant, anti‐inflammatory effects, and inhibition of MMPs expression [71]. Wu et al. [54] created the FACP5 multifunctional composite hydrogel using sulfated galactofucan polysaccharides and alginate oligosaccharides as active ingredients, with polyacrylonitrile‐modified κ‐carrageenan as the substrate. This hydrogel demonstrates excellent biocompatibility, antioxidant, and anti‐tyrosinase activity, reducing UVB‐induced cell mortality. Its superior water retention, ease of diffusion, and strong skin adhesion make it an ideal skin protectant against photoaging. Polyphenolic compounds scavenge free radicals and delay skin aging [72]. Busto et al. [55] developed a sustainable hydrogel film by crosslinking low‐acyl gellan gum (GG) and sodium alginate (NaALG) with tartaric acid (TA), incorporating olive leaf extract (OLE) derived from agricultural food waste. This eco‐friendly formulation effectively prevented UVA‐induced photoaging through its potent free radical scavenging activity, demonstrating the potential of circular economy principles in skincare product development. Sroka et al. [51] revealed that hydrogel anti‐hyaluronidase and anti‐tyrosinase effects depend not only on incorporated extracts but also on chitosan concentration. By optimizing the formulation with 1% cranberry acetone‐water extract and 2.5% medium molecular weight (MMW) chitosan, they achieved enhanced hydrogel viscosity, leading to superior free radical scavenging and antioxidant performance.

3.3. Advanced Hydrogels With Bioactive Compounds

Regarding the treatment of photoaging, traditional laser therapy can promote photobiomodulation (PBM) without damaging the epidermis, stimulating protein synthesis and cell proliferation, which aids in tissue repair [73, 74]. Lycium barbarum fruit extract (LBP) demonstrates photoprotective and skin‐repairing properties through its bioactive components [61]. Neves et al. [36] developed a topical hydrogel with a polysaccharide‐rich LBP fraction. In a six‐week photoaging study on hairless mice, this hydrogel, alone or combined with photobiomodulation (PBM), inhibited UVR‐induced skin thickening, reduced c‐Fos, c‐Jun, and MMP‐1, ‐2, and ‐9 expression, while increasing collagen I, III, and FGF2 levels, demonstrating significant photoaging repair. Glycyrrhizic acid (18β‐glycyrrhetinic acid, GA) offers strong antioxidant and anti‐inflammatory properties [75, 76] to combat UV damage [77]. Quan et al. [52] prepared GA nanocrystals (NGAs) via high‐pressure homogenization, then combined them with amphiphilic chitosan (ACS) at a 10:1 ratio via electrostatic adsorption to form the ANGA hydrogel. This hydrogel markedly improves GA bioavailability, alleviating UV‐induced collagen fiber damage and significantly inhibiting abnormal MMP‐1 and MMP‐3 expression. Olea europaea leaf extract (OLEX) enhances cell vitality by inhibiting fibroblast apoptosis and exerts anti‐inflammatory and anti‐aging effects via AP‐1 and NF‐κB pathways [78, 79]. Wang et al. [47] incorporated Olea europaea leaf‐derived exosome‐like nanovesicles (OLELNVs) into a crosslinked hyaluronic acid (HA) and tannic acid (TA) hydrogel. The OLELNVs@HA/TA hydrogel uses HA to boost moisture for repair and TA for excellent UV absorption, effectively reducing UV‐induced damage and promoting skin regeneration, embodying a dual “defense‐repair” strategy.

3.4. Bioactive Hydrogels Integrated With Stem Cells and Exosomes

Recent advances in hydrogel‐based delivery systems have enabled significant progress in photoaging treatment through enhanced exosome and stem cell therapies. Exosomes, serving as key mediators of intercellular communication, demonstrate improved therapeutic efficacy when encapsulated in hydrogels due to prolonged skin retention and sustained release of bioactive molecules [80]. Similarly, plant exosome‐like nanovesicles (PELNVs) benefit from hydrogel encapsulation for precise dosage control and reduced adverse effects in natural skincare applications [81, 82, 83, 84]. While stem cells show promise for photoaging treatment through their anti‐inflammatory and antioxidant properties [85, 86, 87], challenges including poor viability and unpredictable differentiation have limited their clinical application [88, 89, 90, 91]. To address these limitations, innovative hydrogel systems have been developed, such as the microfluidic‐generated recombinant human collagen hydrogel reported by Lin et al. [56] that mechanically regulates stem cell differentiation to reduce UV‐induced wrinkles while stimulating collagen production and vascularization. Complementary to this approach, Wang et al. [58] developed a novel Ca²⁺‐self‐assembled hydrogel derived from thrombospondin‐1 protein that combines waterproof coating properties with enhanced antioxidant activity, representing a significant advancement in marine biomaterial applications for skin protection. These hydrogel‐based strategies collectively offer improved solutions for overcoming current limitations in photoaging therapies.

3.5. Sunscreen and Protective Coatings

Sunscreens, divided into organic and inorganic types [92], may cause irritation with prolonged use [93]. Andreani et al. [94] developed a hydrogel with SLN‐silica particles loaded with octyl methoxycinnamate (ParsolMCX), combining organic and inorganic sunscreen benefits. This hydrogel enhances UV protection through nanoparticle scattering and covalent trapping of sunscreen molecules, enabling controlled release to reduce irritation [95]. Similarly, Lin et al. [61] incorporated TiO₂ into mesoporous silica (SBA‐15) to form a hydrogel, significantly alleviating skin cell death and neutrophil recruitment in photoaged mice, resisting UV damage via synergistic effects. Oroxylin A (OA), a flavonoid with antioxidant, anticancer, and antimicrobial properties [96, 97], was formulated by Zhu et al. [46] into OA‐nanostructured lipid carrier (OA‐NLC) hydrogels. Compared to OA solution, this hydrogel offers superior protection against UVB‐induced oxidative damage in cell models, improving transdermal absorption, drug stability, and release efficiency. Sun et al. [59] grafted Se‐Met onto UV‐responsive GelMA hydrogels via AC‐PEG‐NHS tethers. This hydrogel enhances antioxidant and UV absorption properties by inhibiting lipid peroxidation and ferroptosis while promoting GPX4 expression, significantly reducing inflammation and matrix remodeling in UV‐exposed mice.

3.6. Skin Fillers and Structural Support

Hydrogels provide structural support and actively participate in biological processes. Kim et al. [60] developed a hydrogel with cerium oxide nanoparticles (CeNPs), which effectively scavenge ROS, inhibit MMP production, and suppress collagen degradation and inflammation. Compared to simple fillers, this hydrogel enhances collagen matrix stability against enzymatic degradation, offering injectability and mechanical stability. It reduces skin oxidative stress, wrinkle count, epidermal thickness, and aging biomarkers while increasing collagen deposition. Wang et al. [57] reported the first tetrakis(hydroxymethyl) phosphonium chloride (THPC)‐crosslinked recombinant collagen hydrogel implant. Using THPC as a crosslinking agent, this hydrogel improves mechanical properties and stability, significantly enhancing crosslinking efficiency. It serves as a high‐performance implant for skin regeneration, improving dermal density and elasticity to combat photoaging. A hyaluronic acid‐hydroxyapatite nanocomposite hydrogel (HAc‐nanohap) was developed by Jeong et al. [50] through in situ precipitation. This composite showed superior stiffness and adhesiveness compared to pure HAc, leading to significant wrinkle reduction via stimulation of collagen and elastin synthesis, thereby reinforcing the dermal matrix.

3.7. Responsive Hydrogels for Controlled Release

Thermosensitive hydrogels undergo reversible phase or sol–gel transitions with temperature changes. Wu et al. [53] developed a carboxymethyl‐modified chitosan/hyaluronic acid (CMC/HA) thermosensitive hydrogel combined with ascorbyl glucoside (AA2G) liposomes. By adjusting the substitution degree, this hydrogel enhances performance, enabling gradual drug crosslinking and sustained release with temperature shifts, improving skin retention and anti‐photoaging effects. It reduces epidermal thickness, melanin deposition, and lipid oxidative damage while increasing collagen density. Hyaluronic acid (HA) hydrogel plays an important role in dermal filling. Zhao et al. [48] embedded polylactic acid (PLA) into HA using 1,4‐butanediol diglycidyl ether as a crosslinker to form an HA/PLA hydrogel. The formulation with 2 wt% PLA exhibits optimal anti‐wrinkle effects and maximal collagen production, offering high safety, injectability, and enhanced biological properties. In addition, Oliveira et al. [49] prepared a dynamic covalent hydrogel (HG) via reversible boronate ester crosslinking between HA modified with saccharide (GLU) residues and HA functionalized with 3‐aminophenylboronic acid (APBA), complexed with dihydrocaffeic acid (DHCA). The conclusion showed that at pH 7.4, this hydrogel precisely controls active substance release based on pH‐dependent dynamics, enhancing protection against UVB‐induced fibroblast death and improving drug bioavailability.

4. Conclusion and Future Perspective

Hydrogels have emerged as a transformative solution for combating photoaging, offering a multifunctional platform that addresses its complex pathological mechanisms. Their unique properties enable three key therapeutic actions: (1) physical UV shielding to prevent oxidative damage, (2) controlled delivery of antioxidants to neutralize free radicals, and (3) active promotion of dermal repair through collagen stimulation. This triple‐action approach makes hydrogels particularly valuable in both dermatological treatments and cosmetic applications. Advanced hydrogel systems provide more than just passive protection—they actively participate in skin rejuvenation by enhancing extracellular matrix remodeling and improving skin barrier function. Current research is driving the development of next‐generation formulations with improved bioactive stability, targeted delivery capabilities, and enhanced biocompatibility. These innovations promise to revolutionize photoaging management by combining preventive protection with restorative therapies, ultimately leading to more resilient, youthful‐looking skin.

The future of hydrogel‐based anti‐aging strategies lies in smart, responsive systems that can adapt to skin's changing needs, offering personalized protection and repair. This evolving technology represents a paradigm shift in dermatological care, moving beyond symptom management to comprehensive skin health preservation.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.