Shaogeng Wang
Fuchao Huang2†- 1Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China
- 2Shenzhen Baoan Clinical Medical College of Guangdong Medical University, Shenzhen, China
- 3Institute of clinical translation and regenerative medicine, People’s Hospital of Shenzhen Baoan District, Shenzhen, China
Wound repair has long been a challenging area in medical research and clinical treatment. The unique properties of MOFs(metal organic frameworks), including their highly tunable porous structures, significant specific surface area, and ease of functionalization, make them particularly useful for drug delivery applications. MOFs can efficiently load a variety of therapeutic agents, such as small molecule drugs, biomolecules, gas molecules, nanoparticles, and photosensitizers, enabling slow, controlled release and precise, targeted delivery of these substances. Moreover, MOFs can be combined with other materials to create multifunctional wound dressings. This review introduces the mechanisms and advantages of MOFs loaded with therapeutic agents and provides an overview of the latest research progress in composite materials based on MOFs loaded with effective therapeutic components for wound treatment.
1 Introduction
A wound represents a disruption of the structural integrity of skin, mucosae, or deeper organ tissues. It can be precipitated by chemical, mechanical, thermal, or radiation insults. Alternatively, it may arise secondarily to pathological states such as chronic venous or arterial insufficiency, diabetes mellitus, and immune-mediated or primary dermatological disorders (Kujath and Michelsen, 2008). The process of wound healing proceeds through four sequential phases: Haemostasis, during which platelets and coagulation factors rapidly seal the blood vessels. The second phase is inflammation, characterised by the infusion of immune cells that eliminate pathogens and secrete cytokines. The proliferation phase involves angiogenesis, granulation tissue formation, collagen deposition and re-epithelialisation to reconstruct the extracellular matrix. The final phase is remodelling, during which type III collagen is replaced by type I collagen and fibres are rearranged, ultimately restoring tissue architecture and function to near-normal levels (Tottoli et al., 2020; Soliman et al., 2018). Acute trauma often causes severe skin damage, bleeding and infection. When bacterial infections persist, they may cause chronic inflammation and abnormal angiogenesis, both of which can greatly hinder the healing process (Wang et al., 2025; Liu et al., 2025). The situation becomes even more complicated in the presence of diabetes, as it often significantly exacerbates wound severity. The unique pathological environment of diabetic ulcers involves persistent hyperglycaemia, local hypoxia and AGEs (advanced glycation end products) interacting in a way that increases susceptibility to bacterial infections, perpetuates chronic inflammation and severely impedes neurovascular regeneration (Xue et al., 2025).
Traditional drug delivery platforms are hindered by several intrinsic limitations, such as burst release, the need for frequent administration, sub-therapeutic concentrations at the lesion, poor bioavailability, systemic adverse effects, and rapid drug clearance (Mhettar et al., 2024). In recent years, nanomaterials such as liposomes, inorganic nanoparticles, and polymer nanoparticles have been widely used in the field of drug delivery to overcome these drawbacks (Zhang et al., 2025). Liposomes, despite their widespread use as drug delivery vehicles, are intrinsically limited by poor stability in physiological fluids, premature drug leakage, and modest loading capacity. Polymeric microspheres, on the other hand, may disassemble at high critical micelle concentrations, which curtails their utility as robust drug carriers (Zhao et al., 2025). Confronted with these shortcomings, the development of next-generation delivery platforms has become imperative. MOFs exhibit many ideal characteristics for use as drug carriers, including a large effective surface area, high porosity, multifunctionality, high structural tunability, adjustable drug release and so on (Chen et al., 2021; Hu et al., 2024). In addition to the aforementioned common characteristics, certain MOFs possess unique properties due to the specificity of metal ions and organic ligands. For example, although zirconium ions themselves do not exhibit significant bioactivity, some zirconium-based MOFs, such as UIO-66 and UIO-66-NH2, are promising drug carriers due to their excellent thermal stability, hydrolytic stability, and mechanical stability (Dastneshan et al., 2023). Another commonly used zinc-based MOF, ZIF-8, which is also frequently employed as a drug carrier. However, ZIF-8 has pH-responsive characteristics that enable intelligent drug release in infected wound environments (Obaid et al., 2024). Moreover, the released zinc ions exhibit antibacterial effects. Additionally, silver-based MOFs are relatively common MOFs, and their uniqueness lies in the significant antibacterial activity of the released silver ions (Wang et al., 2023). As for copper-based MOFs, the released copper ions not only have antibacterial effects but also promote collagen deposition and angiogenesis (Yao et al., 2022). Although MOF-based systems have shown great potential in the field of wound healing, their practical application still faces many challenges. One of the most concerning issues is the biosafety of MOFs. Some metal ion centers and organic linkers have potential cytotoxicity. For example, copper ions released from copper-based MOFs, silver ions released from silver-based MOFs, and 2-methylimidazole released from zinc-based MOF ZIF-8 can have toxic effects on normal cells at high concentration. Moreover, some MOFs are unstable under certain conditions. For example, some zinc-based MOFs are unstable under acidic conditions, which may lead to uncertainty in the release of drugs. However, stable MOFs like zirconium-based MOFs may pose new safety issues due to their long-term non-degradability. Therefore, it is necessary to fully understand the metabolism and degradation characteristics of MOFs in the body in the future to avoid the accumulation of MOFs in the body over a long period, which may cause cytotoxicity.
MOFs possess the ability to load a variety of substances, including antibiotics, natural extracts, hypoglycaemic drugs, anti-inflammatory drugs, growth factors, enzymes, extracellular vesicles, gas molecules, nanoparticles, and photosensitizers. They significantly enhance the stability and bioavailability of the loaded substances, while also improving the efficiency of drug delivery and targeting ability, slowly responding to release and delaying the degradation of the loaded substances. The composite materials based on MOFs loaded with active therapeutic components are able to promote wound healing through multiple mechanisms, such as antibacterial, anti-inflammatory, blood glucose control, angiogenesis, granulation tissue formation, collagen deposition, macrophage polarization, peripheral nerve regeneration, and skin appendage reconstruction, providing a more efficient solution for wound treatment. As described above, Figure 1 illustrates the various therapeutic substances that MOFs can load. The therapeutic components loaded in MOFs may overcome some of their own limitations, enhance therapeutic efficacy, and ultimately promote wound healing through multiple mechanisms.
Figure 1. Composite materials based on MOFs loaded with active therapeutic components can integrate multiple functions to promote wound healing.
This article systematically reviews the advantages of MOFs as drug carriers and provides a detailed overview of the research progress in using MOFs to load various therapeutic components for wound treatment. It is hoped that this review will serve as a reference for future studies.
2 Methods of loading therapeutic components onto MOFs and the advantages of MOFs as drug carriers
The loading of any drug into MOFs may be based on host-guest interactions, physical entrapment or covalent bonding. The loading of drugs into MOFs is governed by four complementary strategies: (1) Surface adsorption is achieved through weak forces, such as π-π stacking, van der Waals forces and hydrogen bonding; (2) Pore encapsulation involves MOFs forming tunable microporous and mesoporous structures that encapsulate drugs for the amorphous loading of poorly soluble substances; (3) Covalent anchoring using surface -OH, -COOH or -NH2 groups to form robust linkages and prevent leaching; (4) Functional molecules can be used as building blocks. Here, nucleobases, peptides, polysaccharides or amino acids are employed directly as organic linkers to co-assemble with metal nodes into bio-MOFs, achieving one-step functionalisation (Khulood et al., 2025; Khafaga et al., 2024).
MOFs have several key characteristics, including adjustable porosity, an extremely high specific surface area, a large number of active sites, and ease of functionalisation. These properties enable MOFs to encapsulate and protect unstable drugs, nucleic acids and proteins efficiently, while preventing their premature release. By rationally pairing organic linkers with metal nodes, both pore dimensions and chemical functionality of MOFs could be precisely tailored to meet specific biomedical demands. Meanwhile, the virtually limitless combinations of metal centres and ligands provide ample possibilities for surface functionalisation. Furthermore, stimulus-responsive groups enable on-demand release triggered by pH, ROS, temperature, light or biomolecular signals in the wound microenvironment. Excellent biocompatibility is fundamental to the application of some MOFs. The toxicity of MOFs primarily depends on a variety of factors, such as chemical composition and dose. Among these factors, metal ions are often the key determinants of the overall toxicity of MOFs. Therefore, MOFs are typically classified by their metal elements in terms of toxicity: MOFs with low toxicity include Zn-based MOFs, Zr-based MOFs, Mg-based MOFs, and Ca-based MOFs. In contrast, Fe-based MOFs, Co-based MOFs, and Al-based MOFs are categorized as toxic. Cu-based MOFs and Mn-based MOFs are considered highly toxic (Zhang Q. et al., 2023; Li Z. et al., 2025). Although some MOFs may have potential safety concerns, the results of short term in vivo experiments in small animals and in vitro experiments, such as those involving cells, for MOF materials currently used in wound healing all indicate that they possess good biocompatibility. Similarly, biodegradability is also a key factor influencing the application of MOFs. Numerous factors influence the stability and degradability of MOFs. Beyond metal ions and organic ligands, elements such as wound pH levels and enzymes also affect their biodegradability. Among these, Zr-based MOFs and Ag-based MOFs exhibit strong resistance to hydrolysis and acid-base attacks, demonstrating high environmental stability across diverse conditions. In contrast, Zn-based MOFs, Cu-based MOFs, and Mg-based MOFs are prone to degradation due to hydrolysis or oxidation reactions (Zhang et al., 2026). Some MOFs exhibit excellent degradability, giving them unique advantages in applications. Additionally, certain MOFs can facilitate targeted drug delivery by incorporating targeting ligands. For instance, using concanavalin A as a targeting ligand for ZIF-8 or coating ZIF-8 and UIO-66-NH2 with hyaluronic acid can both achieve targeted delivery of the loaded antibacterial drugs, thereby enhancing the antibacterial efficacy (Obaid et al., 2024; Li et al., 2024; Mansouri et al., 2025). Collectively, these merits render MOFs a superior, universal platform for drug delivery compared with conventional materials (Hu et al., 2024; Bigham et al., 2024; Tong et al., 2021; Xing et al., 2023).
3 Composite materials based on MOFs loaded with small molecule drugs for promoting wound healing
3.1 Antibiotics
Antibiotics remain the cornerstone for the prevention and treatment of infectious diseases. However, decades of indiscriminate and excessive use have fuelled the rapid evolution of antibiotic resistant and multidrug-resistant pathogens, transforming antimicrobial resistance into a formidable global public health crisis. Localized antibiotic delivery offers a powerful countermeasure by concentrating therapeutic agents at the nidus of infection, thereby reducing systemic exposure and enhancing antimicrobial efficacy. In order to achieve this objective, it is imperative to develop innovative antibiotic delivery carriers that circumvent the issues of drug burst release and rapid systemic clearance. MOFs represent an excellent choice, as these novel carriers should exhibit controllable stimulus-responsive release properties and enable precise targeting of bacteria (Dastneshan et al., 2023; Zheng et al., 2024). We have summarized several studies on composite materials based on MOFs loaded with antibiotics for promoting wound healing in Table 1.
Table 1. MOFs loaded with small molecule drugs.
The extension of the duration of antibiotic action has been demonstrated to reduce the number of doses, improve antibacterial efficacy, and prevent the development of drug-resistant bacteria. Zheng HQ et al. encapsulated the broad-spectrum cationic antibiotic CIP(ciprofloxacin) in the anionic zirconium MOF(SU-102) through an ion exchange process. CIP@SU-102 has been demonstrated to sustain release for a period of 20 days whilst maintaining its antibacterial activity (Zheng et al., 2024). In another study, Amirhossein Dastneshan et al. encapsulated CEF (cefazolin) in UIO-66-NH2 nanoparticles to achieve sustained release over several days. Compared with free CEF, the CEF-loaded nanosystem exhibited significantly greater antibacterial and anti-biofilm activity against drug-resistant Staphylococcus aureus while remaining non-cytotoxic. Following treatment with UIO-66-NH2-CEF, the formation of biofilms was reduced by approximately two to three times compared with the free form of CEF. The expression of the biofilm-related gene, icaB, in MRSA strains was also significantly reduced (Dastneshan et al., 2023). Furthermore, Mujata et al. developed a dual pH-responsive delivery platform, which was designated Doxy@CuBDC/PLGA. Doxycycline was encapsulated using two-dimensional copper-1,4-benzenedicarboxylate nanosheets and incorporated into PLGA electrospun membranes. It has been demonstrated that these membranes can sustainably release doxycycline for up to 9 days under pH 7.4 and 5.5 conditions, thus providing an effective long-acting local antibiotic strategy for the treatment of drug-resistant traumatic infections (Figure 2E) (Mujtaba et al., 2024).
Figure 2. (A) Synthesis of QCSMOF-Van; (B) Synthesis of GelMA and OSAMA; (C,D) Synthesis of QCSMOF-Van Hydrogel for Repairing Chronic Wounds and Mechanism of QCSMOF-Van Hydrogel for Repairing Chronic Wounds. Reprinted with permission from (Huang et al., 2022) Copyright 2024 American Chemical Society; (E) The synthesized structures of Doxy loaded CuBDC (Doxy@CuBDC) nanosheets were seamlessly incorporated into electrospun PLGA fibrous membrane. Reprinted under terms of the CC-BY license (Mujtaba et al., 2024). Copyright 2024, Mujata et al., published by IOP Publishing; (F) Illustrative Diagram of Fabrication and Utilization of Van/Ag/ZIF-8@HA for Killing Bacterial Cell. Reprinted with permission from (Obaid et al., 2024) Copyright 2024 American Chemical Society.
The encapsulation of antibiotics within MOFs has been shown to achieve the objectives of prolonging the duration of antibiotic action and enabling a responsive release. To further enhance the efficacy of antibiotics, the targeted delivery of antibiotics has been identified as a viable strategy. Obaid EAMS et al. developed a pH-responsive hybrid material called Van/Ag/ZIF-8@HA, wherein vancomycin is encapsulated within ZIF-8 and coated with hyaluronic acid on its surface, endowing the material with targeted bacterial delivery capability. This material combines the targeted antibacterial properties of hyaluronic acid with the pH-responsive release mechanism of ZIF-8, thereby maximizing the antibacterial efficacy of vancomycin and silver Ag+(Figure 2F) (Obaid et al., 2024). In another study, Huang K et al. synthesised a Bio-MOF using Zn2+ and curcumin, then loaded vancomycin onto the MOF and coated the Bio-MOF surface with quaternary ammonium salt chitosan, ultimately preparing a QCSMOF-Van composite hydrogel. The positively charged QCSMOF-Van has been demonstrated to be capable of actively capturing bacteria through electrostatic attraction. In comparison with conventional antimicrobial methodologies, the QCSMOF-Van composite hydrogel treatment has been shown to reduce treatment time by approximately 50%, while its antimicrobial efficacy is approximately fourfold that of vancomycin administered in isolation. Neural and vascular integration regeneration were observed in a rat wound infection model (Figures 2A–D) (Huang et al., 2022).
3.2 Natural extracts
Chronic wounds are invariably complicated by bacterial colonisation, sustained inflammation, and excessive ROS (Huang et al., 2022; Du et al., 2025). Natural extracts exhibit potent antioxidant and antibacterial activities, yet their clinical translation is hindered by poor aqueous solubility and limited physicochemical stability. Encapsulation of these phytochemicals within MOFs markedly enhances their stability, affords sustained release, and synergistically amplifies both their antimicrobial and antioxidant properties. In Table 1, you can find our summary of some research on composite materials based on MOFs loaded with natural extracts for promoting wound healing.
Curcumin (CUR) exerts potent anti-inflammatory and antioxidant bioactivities. However, its modest antibacterial efficacy, coupled with poor aqueous solubility, physical and chemical property instability, and low oral bioavailability, severely constrains clinical application. Finding the ideal drug carrier for CUR is becoming increasingly important (Wang et al., 2023; Du et al., 2025; Chen et al., 2022a). Porous-liquid (PL) technology makes ZIF-type carriers highly dispersible in physiological media and accessible to guest drugs, providing an effective platform for sustained release. Capitalising on this strategy, Weng P et al. synthesised ZIF-91-PL via surface modification and ion exchange. The resulting cationic framework exhibited potent intrinsic antibacterial activity, a notable curcumin payload and pH-responsive, prolonged release kinetics (Weng et al., 2023). And in another study, Wang F et al. developed an ABC(asymmetric bacterial cellulose) wound dressing that integrates Ag-MOFs with curcumin. In situ growth of Ag-MOFs within the ABC scaffold affords a high curcumin payload and enables prolonged, pH-sensitive release while simultaneously amplifying antioxidant capacity. The embedded Ag-MOFs also endow the dressing with potent, broad-spectrum antibacterial activity. In infected murine wounds, the patch eradicated bacteria, quelled inflammation, and hastened re-epithelialisation, angiogenesis and collagen deposition (Wang et al., 2023).
EGCG (Epigallocatechin gallate), Fu(fucoidan), AAEO (artemisia argyi essential oil), B (berberine) and ergosterol have excellent antioxidant, anti-inflammatory and antibacterial properties and are able to significantly promote wound healing (Li et al., 2022; Wan et al., 2025; Xu et al., 2025; Ai et al., 2021; Ding et al., 2025). But the presence of phenolic hydroxyl groups within the chemical structure of EGCG contributes to its suboptimal chemical stability, rendering it susceptible to isomerisation and oxidation reactions (Alam et al., 2024). To improve the stability of EGCG, Li S et al. encapsulated EGCG within the pores of the MOF Zn(BTC)4, forming the EGCG@MOF Zn(BTC)4 system. This system facilitates the sustained release of EGCG, thereby reducing its rate of degradation and extending its therapeutic efficacy. The composite markedly dampens inflammation via downregulation of Notch signalling and TNF-α, and in a murine wound model it accelerates re-epithelialisation and collagen deposition (Figure 3A) (Li et al., 2022). Similarly, AAEO’s high volatility, low water solubility, sensitivity to light and heat, and strong odor limit its practical applications. In order to address the aforementioned issues, Xu et al. loaded AAEO into ZIF-8 via a one-pot method, thereby transforming its storage from liquid to solid, while successfully avoiding its volatility and photothermal decomposition, to enhance AAEO’s stability and antibacterial efficacy. In a bacterial infected wound model, AAEO@ZIF-8 released AAEO and Zn2+ in the acidic microenvironment, exerting synergistic antibacterial effects and significantly accelerating wound healing (Xu et al., 2025). In another study, because low molecular weight Fu demonstrated significant inhibitory effects against MRSA (Wan et al., 2025), Jiang Z et al. designed a multifunctional microneedle patch, which is named HAZ@Fu MNs, to heal wounds infected with MRSA. The sulfonic acid groups in Fu form coordination bonds with zinc ions, enabling the loading of Fu onto ZIF-8 nanoparticles, which are then coated with hyaluronic acid to target MRSA. The HAZ@Fu MNs deliver these nanoparticles to the deep layers of the wound, where they continuously release active components. HAZ@Fu targets MRSA at the subcellular level via the CD44-HA receptor, thereby inhibiting its growth and exerting anti-inflammatory and reparative effects by influencing the PI3K-Akt pathway (Figure 3B) (Jiang et al., 2024). Additionally, to overcome the limitations of berberine(B) such as poor solubility, rapid metabolism, and low bioavailability (Ai et al., 2021), Mansouri A. et al. loaded it onto UiO-66-NH2(UN) and then coated with hyaluronic acid, synthesizing a novel nanomaterial UNB@H which displays pH-responsive drug release properties, bacterial targeting capabilities, and biofilm penetration ability. UNB@H has been demonstrated to reduce efflux-mediated and biofilm-related antibiotic resistance by downregulating efflux pump genes, including MexA, MexB, norA, norB, and biofilm-related genes, such as icaA, icaB, ndvB, and pelA (Mansouri et al., 2025).
Figure 3. (a) MOF Zn(BTC)4 serves as a carrier to load EGCG, forming EGCG@MOF Zn(BTC)4, which is used to promote wound healing in diabetic mouse models. Reprinted under terms of the CC-BY license (Li et al., 2022). Copyright 2022, Li et al., published by MDPI; (b) Schematic diagram of the preparation process of the HAZ@Fu MN via a template replication method, and its application encompassing both the process and mechanism of treatment for infected wounds. Reprinted under terms of the CC-BY license (Jiang et al., 2024). Copyright 2024, Jiang et al., published by BMC.
MOFs loaded with antibacterial natural extracts have been shown to significantly enhance their efficacy against both common and drug-resistant bacteria without inducing new antibiotic resistance, thus presenting a promising antibiotic-free therapeutic approach. However, the majority of these antibacterial MOFs and their composites are currently applied topically. In order to broaden the scope of applications, there is a crucial need to develop intravenously administrable MOF based materials, which may even determine whether they can replace or supplant traditional antibiotics. For this reason, Xiaoyuan Ding et al. developed a near infrared responsive nanomedicine (RBC@PB-E NPs) that is suitable for intravenous administration. Hollow PB NPs(Prussian blue nanoparticles) were prepared under acidic conditions and loaded with ergosterol via a co-solubilization method, followed by wrapping the PB-E NPs with red blood cell membranes. Following intravenous injection, the RBC@PB-E NPs accumulated at the infection site. Under NIR irradiation, PB NPs generate reactive oxygen species and heat, disrupting bacterial cell membranes and promoting ergosterol penetration into bacterial cells, thereby achieving rapid bactericidal effects (Ding et al., 2025).
3.3 Hypoglycemic drugs and RAGE (receptor for advanced glycation end products) inhibitor
Diabetic wounds are one of the most common types of chronic wounds. There are many factors that affect the healing of diabetic wounds, including high blood sugar, persistent chronic inflammation, and bacterial infections in the wound microenvironment (Burg et al., 2021). Controlling blood sugar, antibacterial, and anti-inflammatory properties are crucial for promoting wound healing in diabetes. Meng Tian et al. designed a visible-light-responsive hydrogel (Met/Ti-MOF@gel) by embedding metformin-loaded Ti-MOF within a PVA/alginate matrix. The Ti-MOF exhibits a high loading capacity of Met (metformin) and has a sustained-release characteristic. After exposure to visible light, the material could instantly generate •OH, achieving on-demand antibacterial effects. Meanwhile, metformin may correct the hyperglycemic state, polarize macrophages from the M1 type to the M2 type, and accelerate fibroblast migration, all of which collectively promote the healing of diabetic wounds (Tian et al., 2025). In another study, Liu X et al. developed a composite microneedle patch named GCM-MN-CSH. Met has been shown to coordinate with Ga3+ via its amino/imino groups, thereby embedding into Ga-carbenicillin MOFs and prolonging the in vivo retention time of Met, which would otherwise be rapidly cleared from the body. The microneedles mechanically implant GCM nanoparticles into the deep wound bed and then Ga3+ and carbenicillin synergistically eradicate pathogens, while metformin potentiates endothelial proliferation and migration, angiogenesis, collagen deposition, and M2 macrophage infiltration, collectively expediting tissue regeneration (Liu et al., 2025).
Chronic diabetes is associated with the overproduction of AGEs, which activate multiple signaling pathways, including JNK, TGF-β, MAPK/ERK, and NF-κB. These activated pathways lead to increased oxidative stress and inflammatory responses (Singh et al., 2014), which in turn significantly impair the wound healing process. To counteract advanced AGE driven pathological cues in diabetic wounds, Sun Y et al. engineered FZ@ZIF-67 by loading the RAGE inhibitor FPS-ZM1 into Co-ZIF-67. The nanocomposite releases Co2+ and FPS-ZM1 synchronously for a period exceeding 14 days. In vitro results revealed that the particles not only drive angiogenesis via Co2+ release but also liberate FPS-ZM1 to polarize macrophages toward the M2 phenotype and counteract the anti-angiogenic effects imposed by high glucose and inflammation through RAGE blockade. Animal study have demonstrated that FZ@ZIF-67 markedly accelerates re-epithelialization, collagen accumulation, and neovascularization (Sun et al., 2022). The above discussion is summarized in Table 1.
3.4 Vitamins
It is widely recognized that vitamin B12 markedly boosts the proliferation of keratinocytes and fibroblasts while simultaneously enhancing collagen production through upregulated protein synthesis and metabolism (Rembe et al., 2018). Rapid oxidation limits the systemic bioavailability of vitamins (Erem et al., 2025). To overcome this issue, Bhattacharyya et al. devised a dressing (FMOF/B12@MS) by encapsulating vitamin B12 within a carbon dot incorporated mixed-ligand Zn-MOF and overcoating with gelatin microspheres. The FMOF/B12@MS system enables sustained release of vitamin B12, which significantly accelerates the proliferation of L929 fibroblasts and promotes tissue repair. Meanwhile, the combination of Zn2+ and imidazole ligands exerts a potent synergistic bactericidal effect against Escherichia coli and Staphylococcus aureus (Figure 4) (Bhattacharyya et al., 2022). Similarly, the primary challenge in vitamin C delivery lies in maintaining its stability, as the substance is highly prone to oxidation (Caritá et al., 2020). Therefore, Moaness M et al. developed single and bi-metallic with silver-MOF based on zinc as drug carriers to address the stability issues of vitamin C during delivery. These nanocages, especially the bimetallic ZnAg variant, achieved sustained release of vitamin C over 30 days, significantly enhancing drug stability and bioavailability. This continuously delivers ascorbic acid to promote the migration of a human dermal fibroblast cell line, while Zn2+ and Ag+ exert antibacterial activity (Moaness et al., 2022). For ease of understanding, we summarize the above discussion in Table 1.
Figure 4. The vitamin B12-loaded gelatin MS accelerates wound healing. Reprinted with permission from (Bhattacharyya et al., 2022) Copyright 2022 American Chemical Society.
3.5 Other antibacterial and anti-inflammatory drugs
α-Lipoic acid (α-LA) is a powerful lipophilic antioxidant while γ-Cyclodextrin (γ-CD) possesses a hydrophobic cavity ideal for encapsulating and slowly releasing hydrophobic drugs such as α-LA. Consequently, Li Q et al. designed an injectable, self-healing hydrogel composed of chitosan, hyaluronic acid, and α-LA-loaded K-γ-CD-MOFs. The hydrophobic pockets within the K-γ-CD-MOFs stably entrap and gradually release α-LA to quench oxidative stress (Li et al., 2021). In another study, although iodine possesses broad-spectrum antimicrobial potency, its clinical use is hindered by poor aqueous solubility and poor physicochemical stability. Therefore, Chen J et al. employed a gas-solid reaction to confine iodine within a potassium iodide-cyclodextrin MOF(KI-CD-MOF), in which evenly distributed iodide ions markedly improve both solubility and stability (Chen et al., 2022b).
4 Composite materials based on MOFs loaded with biomacromolecules for promoting wound healing
Various biomolecules, such as growth factors, natural enzymes and extracellular vesicles, are able to promote wound healing via different mechanisms (Mitchell et al., 2016; Ge et al., 2023; Jung et al., 2024). Biomacromolecules are hindered by enzymatic degradation, short half-life, immunogenicity, and limited tissue penetration. Therefore, suitable carriers are required to ensure the therapeutic efficacy of these biomolecules. Commonly used biomacromolecule delivery systems fall into viral and non-viral vectors. Viral vectors suffer from poor targeting, high cost and biosafety concerns. Non-viral vectors, such as liposomes, inorganic nanoparticles, avoid these drawbacks, yet are still constrained by low encapsulation efficiency, rapid leakage, insufficient loading capacity and poor in-vivo stability, creating an urgent need for next-generation platforms. MOFs, with their tailorable porosity, ultrahigh surface areas, and readily functionalizable surfaces, can uniformly immobilize biomacromolecules, such as enzymes, proteins, antibodies, antigens, and nucleic acids within their pores, markedly improving in vivo stability, prolonging half-life, and lowering immunogenicity (Tong et al., 2021). Table 2 summarizes research on composite materials based on MOFs loaded with biomacromolecules for promoting wound healing.
Table 2. MOFs loaded with biomacromolecules.
4.1 Growth factors
Growth factors have enormous potential for application in tissue repair and regenerative medicine, but their clinical translation is still constrained by multiple limitations. It is generally accepted that natural growth factors are prone to instability, with a high propensity for degradation by proteases. This instability invariably results in a truncated half-life within the body, necessitating frequent, high-dose administrations to maintain efficacy (Mitchell et al., 2016). Secondly, the acidic, high enzyme activity, and exudate environment of the wound site further accelerates the inactivation of growth factors, causing them to be cleared before reaching the target cells, resulting in low bioavailability (Park et al., 2017). Consequently, there is an urgent need for a novel delivery system that can prolong the half-life of growth factors, facilitate precise controlled release, and reduce toxic side effects. It is submitted that this would serve to realise their therapeutic potential in treating chronic wounds caused by infection, diabetes and other conditions.
Studies indicate that NGF (nerve growth factor) accelerates cutaneous nerve regeneration and enhances wound healing (El Baassiri M et al., 2023). To delay the degradation of NGF in diabetic wounds and reduce ROS interference with skin-nerve regeneration interactions, Ji X et al. engineered NGF/Cu, a composite in which NGF is hosted within Ce-UiO-66 MOF. In vitro release assays confirmed prolonged NGF liberation in physiological saline, high-glucose, and ROS-rich environments. The platform integrates Ce-UiO-66-mediated ROS scavenging, NF-κB pathway suppression for anti-inflammation, and sustained NGF delivery for neural repair. This study serves to emphasise the potential value of integrating antioxidant and neuro-regenerative approaches as a therapeutic strategy for the management of diabetic wound (Figure 5c) (Ji et al., 2024). Additionally, promoting sensory nerve regeneration enhances skin regenerative capacity. Therefore, Zhao Q et al. developed a neuro-MOF by encapsulating MOF materials within neuroblastoma cell membranes, loading it internally with neural-associated intracellular proteins such as Wnt/Shh-activating proteins and nerve growth factor. The presence of immune evasion molecules on neuroblastoma cell membranes reduces the material’s immunogenicity, preventing clearance by the body’s immune cells. The structure is encapsulated by crosslinked hyaluronic acid methacrylate and activated by near-infrared light, enabling localized release of the internally loaded proteins to peripheral nerve regeneration and hair follicle niche formation. In a model of deep skin burns, Neuro-MOF significantly restored sensory function and induced new hair follicle formation, achieving functional skin regeneration of the burn wound (Figures 5a,b) (Zhao et al., 2023).
Figure 5. (a) The synthetic processes of Neuro-MOF microreactor; (b) Schematic illustration of the application and working principle of Neuro-MOF microreactor treating for skin burns. Reprinted with permission from (Zhao et al., 2023) Copyright 2023 American Chemical Society; (c) Preparation of NGF/CU and its application in the treatment of diabetic wounds. Reprinted under terms of the CC-BY license (Ji et al., 2024). Copyright 2024, Ji et al., published by KeAi Publishing.
Research has confirmed that rhEGF accelerates wound healing. However, its short half-life and large molecular weight pose significant challenges for transdermal delivery (Shin et al., 2023). To overcome these limitations, Li N et al. employed a one-pot method to simultaneously encapsulate cefazolin and rhEGF within ZIF-8, conjugated with concanavalin A, developing a pH-responsive ZIF-8 nanoplatform (Cef-rhEGF@ZIF-8@ConA). Concanavalin A confers bacterial targeting capabilities to the nanoplatform. This nanoplatform enables sustained release of cefazolin, rhEGF, and Zn2+ via a pH-responsive mechanism, preventing premature release in the circulatory system. Cefazolin and Zn2+ exhibit synergistic bactericidal activity, while rhEGF accelerates angiogenesis and epithelialization by upregulating the EGFR/ERK signaling pathway. In an MRSA-infected wound model, this nanocomposite selectively enriched at the infection site demonstrated significantly superior antibacterial efficacy and wound healing capacity compared to monotherapy (Li et al., 2024). Similarly, although bFGF powerfully drives tissue repair, angiogenesis, and nerve regeneration, its rapid degradation in vivo hinders clinical translation (Tu et al., 2025). To address this limitation, Wang TL et al. synthesized a CuNA(Cu-nicotinic acid MOF) via solvothermal reaction. The material’s rough surface enables high-capacity loading and sustained release of bFGF. Research has confirmed that when using CuNA-bFGF@GelMA hydrogel, the synergistic effect between bFGF and copper significantly promotes fibroblast and endothelial cell migration, while also enhancing endothelial cell tubule formation. In a mouse full-thickness wound model, this hydrogel markedly suppressed inflammatory responses, promoted neovascularization, and enhanced collagen and elastic fiber deposition (Wang et al., 2021).
4.2 Enzymes
Low bioavailability, possible immunogenicity, and poor stability under pathological conditions limit the clinical translation of natural enzymes (Mo et al., 2024). GOx (Glucose oxidase) inevitably undergoes enzyme activity inhibition during immobilization due to its fragile molecular structure and low operational stability (Ge et al., 2023). Sustaining the catalytic activity of GOx throughout wound healing remains a significant hurdle. MOFs act as protective hosts for enzymes under harsh conditions, effectively stabilizing and prolonging GOx activity. Liu et al. engineered a self-healing chitosan/DF-PEG hydrogel that embeds GOx-functionalised Co-MOF(GOx@Co-MOF). The Co-MOF preserves GOx activity while releasing H2O2 and Co2+ for long-lasting, synergistic antibacterial action (Liu et al., 2024). In the study by Yuxin Huang et al., Cu-MOF@MnO2 nanocomposites were synthesised using a hydrothermal method. GOx was then loaded onto the nanocomposites through physical adsorption, and the nanocomposites were finally encapsulated with quaternary ammonium salt chitosan to prevent premature degradation. In the wound microenvironment, GOx and Cu-MOF generate •OH through a cascade reaction, while MnO2 simultaneously generates O2, alleviating hypoxia. Q@CuMn@G significantly improved the high-glucose, hypoxic microenvironment, stimulated collagen deposition and angiogenesis (Figure 6a) (Huang et al., 2025). Likewise, SOD (superoxide dismutase) is a promising agent for scavenging excessive ROS. However, clinical translation is hindered by its potential immunogenicity, poor stability, and low utilization efficiency of the native enzyme (Rasheed, 2024). Mo F et al. engineered a multienzyme cascade platform (DSAM) by co-loading natural SOD, Au NPs and artificial DNAzyme on 2D NiCoCu-MOF. DSAM first replenishes O2 via SOD, then converts H2O2 into cytotoxic •OH via synergistic POD/GPx activities of Au NPs and DNAzyme while depleting GSH, achieving antibiotic-free eradication of resistant bacteria. The Au@NiCoCu-loaded SOD enhanced the enzyme’s activity by three times compared to natural SOD used alone (Figure 6b) (Mo et al., 2024).
Figure 6. (a) Fabrication of Q@CuMn@G and the underlying mechanisms mediating enhanced wound healing. Reprinted under terms of the CC-BY license (Huang et al., 2025). Copyright 2025, Huang et al., published by AIP Publishing; (b) Schematic illustration of multienzyme-integrated nanocatalytic probes (DSAM) for wound disinfection and healing by multienzyme activity. Reprinted with permission from (Mo et al., 2024) Copyright 2023 John Wiley and Sons.
4.3 Extracellular vesicles (EVs)
Although MSC-EVs are an effective treatment for promoting chronic wound repair, their therapeutic efficacy is reduced by their rapid diffusion and degradation (Jung et al., 2024). For this reason, Wang Pan et al. developed a novel MOF-based hydrogel (HA-U6N-EVs). The amino groups of UiO-66-NH2 bond with carboxyl groups of hyaluronic acid, forming a porous structure with internal zirconium clusters that specifically adsorb EVs via phosphate affinity. Embedding UiO-66-NH2 in the hydrogel extended EVs’ lifespan, enhancing stability and sustained release. In a rat diabetic wound model, HA-U6N-EVs significantly accelerated healing due to continuous EV release, with miRNAs involved in wound healing remaining highly abundant over 10 days (Pan et al., 2024).
5 Composite materials based on MOFs loaded with therapeutic gases for promoting wound healing
5.1 NO
Exogenous NO(nitric oxide) has demonstrated significant therapeutic potential in wound healing by enhancing angiogenesis and killing pathogens. However, the high short half-life and toxicity of NO pose significant challenges for its clinical application, particularly in achieving controlled delivery and targeted release. In addition, the limited diffusion radius of NO under physiological conditions further complicates these issues, making it difficult to achieve sustained release and deeper penetration at the wound site. Developing strategies for spatiotemporal control of NO delivery is crucial for translating NO into a viable therapeutic approach (Yao et al., 2022; Pinto et al., 2020; Chung et al., 2022). To achieve the slow release of NO, Pinto RV et al. proposed a novel NO adsorption/release mechanism via the formation of nitrites on the titanium-based MOF MIP-177. MIP-177 has a high nitric oxide storage capacity, excellent biocompatibility at therapeutic concentrations, and a slow nitric oxide release rate (Pinto et al., 2020). In another study, to achieve controlled release of NO, Chung CW et al. fixed the nitric oxide donor [Fe (μ-S-thioglycerol) (NO)2]2 onto a MOF-derived porous Fe3O4@C, which was then encapsulated in thermoresponsive PLGA microspheres to develop a magnetoresponsive nitric oxide-releasing material, MagNORM. An alternating magnetic field served as an ON/OFF trigger, enabling burst, intermittent, or sustained NO release modes and thereby affording spatiotemporal delivery precision. Continuous alternating magnetic field exposure elicited a burst of NO that effectively eradicated both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. In the absence of alternating magnetic field, MagNORM’s slow NO release still boosted collagen deposition and accelerated wound closure. In an E. coli-infected murine model, the platform demonstrated dual therapeutic efficacy magnetically activated antibacterial action and tissue repair (Chung et al., 2022). Additionally, to increase the diffusion radius of NO, Yao et al. loaded nitric oxide onto HKUST-1 particles and coated them with graphene oxide and subsequently integrated these nanoparticles (NHG) particles into polyethylene glycol dipropylamide microneedles. This material ensures precise deep delivery and photothermal-triggered release of NO to the wound site. When applied to wounds in type 1 diabetic rats, NHG-MN significantly promoted angiogenesis, tissue regeneration, and collagen deposition (Figure 7C) (Yao et al., 2022). The above discussion is summarized in Table 3.
Figure 7. (A) The schematic diagram illustrating the synthesis process of MMC; (B) The synergistic treatment of MMC with triple modes of photothermal/photodynamic/gas therapy multidrug-resistant bacterial infections; Reprinted under terms of the CC-BY license (Zou et al., 2024). Copyright 2024, Zou et al., published by AAAS; (C) Schematic diagram of the preparation and application of the porous MOF MN array. Reprinted under terms of the CC-BY license (Yao et al., 2022). Copyright 2024, Ji et al., published by WILEY.
Table 3. MOFs loaded with gas molecules,nanoparticles and photosensitizers.
5.2 CO
CO(Carbon monoxide) possesses potent bactericidal activity, and is able to penetrate biofilms freely. However, elevated doses may inflict collateral damage on healthy tissues. Consequently, a versatile delivery system capable of site-specific administration and on-demand release of CO is urgently required (Choi et al., 2022). Zou J et al. recently constructed a 2D nanotank, MMC(MXene@MOF@CORM-401), that integrates NIR-activated PTT/PDT (photothermal/photodynamic therapy) with oxidant-responsive CO gas therapy. Positively charged ZIF-8 fragments bestow MMC with bacterial-targeting ability. Upon irradiation, the photodynamic effect generates abundant ROS that promptly trigger CO liberation from CORM-401, eradicating drug-resistant bacteria and their biofilms. In an MRSA-infected diabetic mouse wound model, MMC significantly accelerated healing without inducing resistance. By enabling precise bacterial targeting and tunable CO release, the nanoplatform markedly enhances the bioavailability and safety of antibacterial agents (Figures 7A,B) (Zou et al., 2024).
6 Composite materials based on MOFs loaded with nanoparticles (NPs) for promoting wound healing
6.1 Ag NPs and Cu NPs
Ag NPs are recognized for their broad-spectrum activity against drug-resistant bacteria, yet their strong tendency to aggregate impedes sustained Ag+ release and diminishes antibacterial efficacy. Not only that, but burst release may trigger cellular uptake and DNA damage. Within the bacterial microenvironment, uncontrolled aggregation and erratic Ag+ liberation collectively result in low bioavailability and elevated systemic toxicity (Wang et al., 2023; Zhou et al., 2022; Guo et al., 2022). To address the drawbacks mentioned above, Zhou J et al. employed an in-situ immobilization strategy to anchor Ag NPs onto amine-functionalized UiO-66-NH2, yielding UiO-66-NH2-Ag nanocomposites. The MOF effectively suppresses Ag NP aggregation, markedly reducing the required dosage and enhancing biosafety. At low concentrations, the composite efficiently eradicates ampicillin-resistant E. coli and endospore-forming Bacillus subtilis (Zhou et al., 2022). In another study, to achieve controlled release of silver ions, He Y et al. fabricated a robust antibacterial platform (Ag@MOF@PDA) by templating ultrafine Ag NPs within cyclodextrin-MOFs(CD-MOFs) and further coating with polydopamine. The composite combines high aqueous stability with NIR-mediated hyperthermia, enabling on-demand acceleration of Ag+ release and synergistic photothermal chemical sterilization (He et al., 2023).
Copper has antibacterial properties and regulates angiogenesis (Näf et al., 2024). Ya Ling Fan et al. introduced a “one-nano-MOF, dual-function” strategy. Co-encapsulation of Cu NPs and curcumin within the MOF exploits synergistic Cu2+ and curcumin effects to reduce bacterial burden, downregulate the pro-inflammatory cytokine IL-1β, and simultaneously promote angiogenesis, wound contraction, and collagen deposition (Fan et al., 2024).
6.2 Au NPs,Fe NPS and Pt NPs
Chemical dynamic therapy is regarded as a promising antibiotic-free treatment option due to its ability to generate highly toxic •OH, which has been shown to kill bacteria. Au NPs, Fe NPs, and Pt NPs have been observed to exhibit peroxidase (POD)-like activity, thereby facilitating the production of •OH through catalytic reactions. These nanoparticles are frequently employed in the treatment of wound infections (Zhao et al., 2022; Lan et al., 2025; Liu et al., 2023). Although monometallic nanozymes possess bactericidal properties, their modest catalytic activity necessitates high concentrations to attain optimal antimicrobial efficacy (Liu et al., 2023). To further enhance the antibacterial efficacy of these nanoparticles, Zhao X et al. ingeniously engineered a multifunctional nanozyme (Au NCs@PCN) by in-situ anchoring Au NCs onto a zirconium-porphyrin MOF(PCN). This innovative nanozyme generates abundant ROS through synergistic CDT/PDT (chemodynamic and photodynamic therapy), and effectively eradicates bacteria via PTT at relatively mild temperatures. Moreover, the platform significantly upregulates the expression of CD31, VEGF, EGF, and bFGF, thereby accelerating angiogenesis and epithelial repair. Further mechanistic studies revealed that Au NCs@PCN accelerates wound healing by inducing cell proliferation and migration through the activation of the PI3K/AKT and CREB signaling pathways (Zhao et al., 2022). In the study by Liu C et al., a different strategy was employed that of synergistically enhancing peroxidase activity using bimetallic nanoenzymes. Concurrently, the encapsulation within MOFs addressed the issue of reduced catalytic performance caused by the instability and tendency to agglomerate of Fe3O4 NPs. They fabricated heterobimetallic cascade nanozymes (Fe3O4@MOF@Au, FMA NPs) and the MOF shell markedly improves the dispersion, stability and biosafety of Fe3O4, while Au and Fe3O4 synergistically enhance peroxidase-like activity. In vivo experiments confirmed that this low-dose, dual-enzyme cascade system significantly accelerates infected wound healing without antibiotics (Liu et al., 2023). In another study, Lan F et al. enhanced the activity of cascade nanozymes by leveraging the spatial confinement effect of MOFs. They employed a one-pot synthesis technique to confine Au NPs and Pt NPs within ZIF-8, with the outer layer modified by bacteria-targeting DNA aptamers and integrated into an injectable sodium alginate hydrogel. Au-Pt@ZIF-8 nanozymes exhibit a nanoconfinement effect, which significantly enhances the activity of cascade nanozymes, reaching 2–3 times that of single-confinement or non-confinement nanozymes. In the hyperglycemia microenvironment of infected diabetic wounds, Au nanozymes exhibit GOx-like activity, converting glucose into H2O2 and gluconic acid. Subsequently, Pt nanozymes catalyze the production of •OH from H2O2 through POD-like activity. Experimental results demonstrate that Au-Pt@ZIF-8/Apt@gel simultaneously achieves glucose consumption and targeted bacterial clearance, accelerating diabetic wound healing by promoting epithelialization and collagen deposition (Lan et al., 2025).
6.3 Mn NPS and Pd NPs
Photodynamic antimicrobial therapy based on MOFs shows great potential due to its broad-spectrum antibacterial activity, effectiveness against drug-resistant bacteria, and lack of inducing new resistance. However, it is limited by the hypoxic bacterial microenvironment. Oxygen-producing nanozymes can address both the limitations of photodynamic therapy and wound hypoxia (Li J. et al., 2025; Meng et al., 2023). Li Jiawei et al. anchored MnO2 onto copper porphyrin MOF(Cu-TCPP) via an in situ KMnO4 reduction method, synthesizing a Cu-TCPP@MnO2 cascade nanozyme that achieves triple synergistic bactericidal effects through PTT/PDT/CDT. Specifically, MnO2 catalyzes oxygen evolution from H2O2 to alleviate hypoxia and enhance PDT, while Cu2+/Mn2+ triggers a Fenton-like reaction to generate 1O2 and •OH, disrupting biofilms and depleting GSH. Experimental results demonstrate that Cu-TCPP@MnO2 achieves efficient sterilization, inflammation control, and tissue repair promotion (Li J. et al., 2025). Another study has shown that palladium nanoparticles possess remarkable photothermal conversion efficiency. Additionally, their SOD like and CAT like activities can produce oxygen, which synergistically enhances the efficacy of photodynamic therapy. Therefore, Wei Meng et al. employed an amine-assisted electrostatic adsorption and seed-mediated growth method to grow a rough Pd nanoparticles on the UiO-66-NH2 surface and then loaded the NIR-I photosensitizer IR780, forming a core-shell nanoplatform (UPI). Within the reactive oxygen species-rich microenvironment of drug-resistant infected wounds, the Pd nanoparticles convert O2• into H2O2, and catalyze endogenous or generated H2O2 to decompose into O2, thereby enhancing IR780 mediated photodynamic efficacy. The UPI achieved rapid clearance of MRSA and biofilm disruption while downregulating HIF-1α expression and alleviating inflammatory responses, ultimately promoting wound healing (Meng et al., 2023).
6.4 Ir NPS and Ce NPS
ROS exhibit dual characteristics in biological systems. While they can effectively eradicate drug-resistant bacteria, excessive and persistent ROS can cause oxidative damage to host cells (Zhou et al., 2024). By carefully modulating the balance of ROS through the coordinated actions of different nanozymes, ROS can be harnessed as antimicrobial agents while avoiding their harmful effects. Therefore, Tian J et al. engineered a core-shell nanoparticle, Ir@Cu/Zn-MOF, where the outer Cu/Zn-MOF layer initially releases Cu2+/Zn2+ to generate moderate ROS for potent antimicrobial action, while the inner Ir-PVP core is subsequently exposed upon MOF disintegration, exhibiting multi-antioxidant enzyme activities to scavenge excessive ROS and mitigate oxidative stress. This “rise-then-fall” ROS-regulation strategy demonstrated exceptional antibacterial efficacy, ROS-scavenging capacity and biocompatibility in vitro, and markedly alleviated infection, promoted neovascularization and granulation tissue formation, and accelerated wound healing in vivo (Tian et al., 2024). Similarly, Zhou X et al. developed a ROS self-balancing core-shell nanozyme (CeO2@ZIF-8/Au). The outer Au nanoparticles exhibit peroxidase-like activity to rapidly generate bactericidal ROS at the infection site, while the inner CeO2 is encapsulated by ZIF-8. Upon acid-triggered disintegration of ZIF-8, CeO2 is released and scavenges excess ROS produced by Au nanoparticles via SOD and CAT mimicking activities. This system integrates efficient sterilization, anti-inflammation, and wound-healing promotion in one platform. In vivo studies demonstrated a marked reduction in inflammation and accelerated epithelialization and collagen deposition in drug-resistant infected wounds (Zhou et al., 2024).
6.5 Other nanoparticles
The high electrical conductivity of MXene enables wound dressings to accelerate tissue repair. However, MXene tends to agglomerate, which affects its electrical properties. Zhu Y et al. developed a heart-shaped MXene@Cu-MOF(MC) nanocomposite via a one-step hydrothermal route, which efficiently prevents MXene self-aggregation while simultaneously enhancing electrical conductivity and antibacterial activity. When incorporated into polyvinyl alcohol/poly-dopamine hydrogel (PPMC), the resulting dressing can on-site disrupt bacterial biofilms and re-establish endogenous electric field pathways, significantly accelerating tissue repair (Zhu et al., 2024). Similarly, carbon dots (C-dots) exhibit enzymatic catalytic activity akin to SOD and CAT, but they are prone to aggregation. Dai S et al. encapsulated super-antioxidant nanozymes (Cu/C-dots) within ZIF-8 to fabricate ZIF-Cu/C-dots nanocomposites. The ZIF-8 prevents nanozyme aggregation and enables controlled release of Cu/C-dots and Zn2+, which synergistically scavenge ROS, eradicate bacteria, and facilitate tissue repair (Dai et al., 2024).
7 Composite materials based on MOFs loaded with photosensitizers for promoting wound healing
Upon light irradiation, a photosensitizer (PS) generates ROS for photodynamic antibacterial action. To minimize its cytotoxicity toward normal mammalian cells and tissues, encapsulating PS within host matrices or delivery systems and enabling on-demand release has emerged as a promising approach (Qian et al., 2020). The hydrophobicity and anionic nature of Ce6 may be repelled by the negatively charged cell membrane of bacteria, which may cause the reduced accumulation of ROS produced by Ce6 within the bacteria and limit its antibacterial effect. To overcome the electrostatic repulsion between hydrophobic anionic Ce6 and negatively charged bacterial membranes, Zhang et al. developed a thermosensitive Ce6@Zn-MOF hydrogel (Ce6@MOF-Gel) based on alginate and poly (propylene glycol) 407. Zn-MOF loaded with Ce6 enables acid-responsive release within the acidic environment of infected sites, while the positive charge of Zn-MOF enhances Ce6’s contact with bacteria. Concurrently, Zn2+ disrupts membrane integrity, synergizing with Ce6 induced PDT to generate potent, non-resistant bactericidal activity. This hydrogel matrix significantly enhances Ce6 stability, solubility, and photodynamic activity while mitigating inflammatory responses and promoting collagen deposition and re-epithelialization (Zhang W. et al., 2023). In another study, to effectively prevent the self-polymerization of the photosensitizer MB(methylene blue) and enhance the efficiency of PDT, Li Z et al. encapsulated MB within UiO-66(Ce) to form MB@UiO-66(Ce) nanoparticles and then embedded them into a photopolymerized sericin/gelatin hydrogel (MB@UiO-66(Ce)/PH). Upon 660 nm light irradiation, the composite generated abundant 1O2, exhibiting concentration-dependent broad-spectrum antibacterial activity. In vivo experiments demonstrated that this hydrogel could completely fill full-thickness skin defects, significantly accelerating wound healing and tissue regeneration (Li et al., 2023). Additionally, to mitigate the cytotoxicity of photosensitizers toward healthy tissues, RB (rose bengal) was one-pot encapsulated into ZIF-8 (RB@ZIF-8) and blended with PCL matrix to form composite nanofibrous membranes. Under visible light, the membranes continuously generate ROS, achieving dose and time-dependent inactivation of Staphylococcus aureus and E. coli with negligible hemolysis. In vivo studies demonstrated that the photodynamic nanofibrous mats effectively control bacterial infection and accelerate wound healing (Qian et al., 2020). Table 3 summarizes research on composite materials based on MOFs loaded with photosensitizers for promoting wound healing.
8 Conclusion and prospects
Significant progress has been made in using MOFs to deliver various effective therapeutic agents for wound treatment. In fact, we believe that the carrier function of MOFs is the basis for their therapeutic effects and those of their composites. The structure and surface properties of MOFs can be designed and optimised to efficiently load and deliver various substances, including small molecule drugs, biomolecules, gases, nanoparticles and photosensitisers. Not only do MOFs improve the stability and bioavailability of the loaded substances, they also enhance delivery efficiency and targeting, which significantly improves wound treatment outcomes and promotes wound healing. MOFs loaded with antimicrobial drugs are highly effective in preventing and treating wound infections. They can target bacteria, extend the duration of action of antimicrobial drugs, reduce the amount of antibiotics required, inhibit the growth of various bacteria effectively, and minimise the risk of drug resistance. MOFs loaded with anti-inflammatory drugs can significantly improve the water solubility and stability of the drugs, as well as enabling their controlled, slow release, thereby inhibiting the inflammatory response at the wound site. MOFs containing biomacromolecules such as growth factors can increase the half-life of drugs, slow down the body’s degradation rate, effectively promote tissue regeneration at the wound site, accelerate the wound healing process, and improve the quality of wound healing. MOFs loaded with gas molecules can achieve intelligent slow release of gas molecules, exerting the therapeutic effects of gas molecules while avoiding adverse effects on the human body. MOFs loaded with nanoparticles can prevent the aggregation of nanoparticles and the cytotoxicity caused by rapid release, enhance the activity of nanoenzymes, generate and clear ROS on demand, generate oxygen, and exert antibacterial, anti-inflammatory, and wound hypoxia relief effects. MOFs loaded with photosensitizers can avoid the toxic effects of photosensitizers on cells, enhance photodynamic activity, and thereby improve photothermal and photodynamic antibacterial effects. By designing multifunctional MOFs, it is possible to integrate multiple functions such as antibacterial, anti-inflammatory, and tissue regeneration promotion, thereby enhancing the overall efficacy of wound treatment and providing patients with more effective treatment options. Additionally, there are currently few reports on the application of metal-organic frameworks loaded with nucleic acids in wound treatment. Whether the carrier function of metal-organic frameworks can assist in gene therapy for wounds remains to be seen, and we hope that relevant research will be conducted in the future.
Although MOFs have demonstrated significant advantages in wound treatment, they still face some challenges. The stringent synthetic conditions required by most MOFs hinder their large-scale production for medical applications; process optimization and the development of efficient synthetic routes are urgently needed. Current research is mostly limited to short-term experiments on small animals, which cannot fully simulate the complex microenvironment of human wounds. Advancing to large animal experiments and clinical trials is an essential step in the process of translation. The interaction between the loaded drug and MOF may affect the therapeutic effect, but the pharmacokinetic process of MOF is complex and difficult to control drug release. At present, the mechanism of interaction between MOF and its loaded drug is still not thoroughly understood. The toxicity and biocompatibility of MOF degradation products are not yet fully understood. The long-term accumulation of certain metal ions and degradation products may cause cytotoxicity. It is necessary to understand the mechanism of MOF-induced cytotoxicity, systematically study its metabolic pathways and excretion mechanisms in vivo, assess its long-term safety, and ensure its safety for clinical application. Besides, it is also necessary to combine in vitro cell line and molecular biology research with experiments and clinical validation in animal and human models to comprehensively elucidate the molecular mechanisms by which MOFs promote wound healing. Furthermore, there is a lack of methods for real-time monitoring of the concentration of drugs released by MOFs at wound sites. This makes it difficult to achieve precise dose control on an individual basis. Developing real-time monitoring technology is an important step towards achieving precise in vivo monitoring of drug release.
Author contributions
SW: Writing – original draft, Writing – review and editing. FH: Writing – review and editing. JW: Writing – review and editing. XW: Supervision, Writing – review and editing. XP: Supervision, Writing – review and editing, Funding acquisition, Visualization.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This work was funded by Sanming Project of medicine in Shenzhen (Grant No. SZSM202106019), Shenzhen Bao’an District Medical Association (Grant No. BAYXH2023033) and 2024 High-quality Development Research Project of Shenzhen Bao’an Public Hospital (Grant No. BAGZL2024024).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Keywords: drug delivery, metal organic frameworks, MOFs, wound, wound healing
Citation: Wang S, Huang F, Wang J, Wu X and Pan X (2026) Composite materials based on metal-organic frameworks loaded with effective therapeutic components for promoting wound healing. Front. Mater. 12:1713264. doi: 10.3389/fmats.2025.1713264
Received: 25 September 2025; Accepted: 12 December 2025;
Published: 12 January 2026.
Edited by:
Lorenza Draghi, Polytechnic University of Milan, ItalyReviewed by:
Marimuthu Karunakaran, Alagappa Government Arts College, IndiaFereshte Hassanzadeh Afruzi, Iran University of Science and Technology, Iran
Copyright © 2026 Wang, Huang, Wang, Wu and Pan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xiaohua Pan, c3pweGg0MTQxQGZveG1haWwuY29t; Xiaomin Wu, eGlhb21pbnd1MDA3QDEyNi5jb20=
†These authors share first authorship