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Immunofluorescence analysis of wound healing process
Representative images of (a) M1 macrophage (TNF-α) and (b) M2 macrophage (TGF-β) immunofluorescence staining on Day 14 and statistical data of the relative intensity of (c) TNF-α and (d) TGF-β (n = 4) (**P < 0.01, ****P < 0.0001, ns: no significant difference).

Immunofluorescence analysis of wound healing process Representative images of (a) M1 macrophage (TNF-α) and (b) M2 macrophage (TGF-β) immunofluorescence staining on Day 14 and statistical data of the relative intensity of (c) TNF-α and (d) TGF-β (n = 4) (**P < 0.01, ****P < 0.0001, ns: no significant difference).

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During wound healing, oxygen availability and the anti-inflammatory microenvironment play an important role in the formation of new tissue. However, providing continuous and controllable oxygen around the injured tissue while inhibiting inflammation and realizing the synergistic effect of oxygen supply and anti-inflammation is still a major problem...

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... The cellular assays demonstrated the safe oxygenation occurred in HaCaT cells when incubated on CaO 2 @TA-loaded hydrogels, which lined up to previous studies regarding the beneficial role of low H 2 O 2 concentrations on epithelial cells, fibroblasts, and keratinocytes [117,118]. Also aiming for the management of hypoxic skin wounds, CaO 2 -loaded hydrogels based on different polysaccharides (which possess an intrinsic moisture retention ability and exert beneficial bioactivity with respect to tissue repair and regeneration, such as alginate, chitosan, hyaluronic acid) have been validated as safe dressing candidates for the uncomplicated and accelerated wound healing [106,132,133]. Using different amounts of CaO 2 nanoparticles, M.Y. ...
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The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO2@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV–Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.
... Following that, Section samples were prepared by extracting full-thickness skin tissue with a diameter of 1.5 cm from the wound center. 24 These sections were later stained using hematoxylin and eosin (H&E) as well as Masson's trichrome (MT) stains. The stained specimens were captured under a microscope, and Image J software was employed to evaluate both the thickness of the granulation tissue and collagen deposition. ...
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Purpose Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats. Methods Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition. Results Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance. Conclusion Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing.
... Recently, Li et al. [90] proposed a NIR-responsive system consisting of polydopaminehyaluronic acid (PDA-HA) hydrogel-loaded calcium peroxide-indocyanine green added to lauric acid and manganese dioxide (CaO 2 -ICG@LA@MnO 2 ) nanoparticles. In detail, a core shell, in which CaO 2 is partially linked with ICG, is covered by LA and then combined with MnO 2 . ...
... c Nanocomposite hydrogel as wound dressing. Reproduced from open access ref.[90]. ...
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Polymeric materials have found increasing use in biomedical applications in the last decades. Among them, hydrogels represent the chosen class of materials to use in this field, in particular as wound dressings. They are generally non-toxic, biocompatible, and biodegradable, and they can absorb large amounts of exudates. Moreover, hydrogels actively contribute to skin repair promoting fibroblast proliferation and keratinocyte migration, allowing oxygen to permeate, and protecting wounds from microbial invasion. As wound dressing, stimuli-responsive systems are particularly advantageous since they can be active only in response to specific environmental stimuli (such as pH, light, ROS concentration, temperature, and glucose level). In this review, we briefly resume the human skin’s structure and functions, as well as the wound healing phases; then, we present recent advances in stimuli-responsive hydrogels-based wound dressings. Lastly, we provide a bibliometric analysis of knowledge produced in the field.
... Among numerous photothermal agents, near infrared (NIR) responsive hydrogels are popular attributed to the significant tissue permeability and extremely low destructive power of NIR to biological specimens and living tissues. Polydopamine-HA hydrogel loaded with calcium peroxide-indocyanine green combined with lauric acid and manganese dioxide (CaO2-ICG@LA@MnO2) nanoparticles presented fantastic NIR irradiated photothermal property and realized the on-demand release of ROS, thus promoting the tissue regeneration (Figure 5d) [168]. In biomedical applications, hydrogels should not only exhibit biocompatibility, and response ability, but also issue adhesion, injectability, and removability. ...
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After myocardial infarction (MI), sustained ischemic events induce pathological microenvironments characterized by ischemia‐hypoxia, oxidative stress, inflammatory responses, matrix remodeling, and fibrous scarring. Conventional clinical therapies lack spatially targeted and temporally responsive modulation of the infarct microenvironment, leading to limited myocardial repair. Engineered hydrogels have a chemically programmed toolbox for minimally invasive localization of the pathological microenvironment and personalized responsive modulation over different pathological periods. Chemically programmed strategies for crosslinking interactions, interfacial binding, and topological microstructures in hydrogels enable minimally invasive implantation and in situ integration tailored to the myocardium. This enhances substance exchange and signal interactions within the infarcted microenvironment. Programmed responsive polymer networks, intelligent micro/nanoplatforms, and biological therapeutic cues contribute to the formation of microenvironment‐modulated hydrogels with precise targeting, spatiotemporal control, and on‐demand feedback. Therefore, this review summarizes the features of the MI microenvironment and chemically programmed schemes for hydrogels to conform, integrate, and modulate the cardiac pathological microenvironment. Chemically programmed strategies for oxygen‐generating, antioxidant, anti‐inflammatory, provascular, and electrointegrated hydrogels to stimulate iterative and translational cardiac tissue engineering are discussed.
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Hydrogels have emerged as a focal point of research in the biomedical field due to their applications in tissue repair. However, the majority of hydrogels lack the capability to release oxygen, constraining their therapeutic outcomes in environments with hypoxic tissues. In recent years, oxygen‐releasing hydrogels have garnered extensive attention in the field of tissue engineering, owing to their ability to modulate oxygen release and meet the diverse oxygenation requirements of various tissues. These hydrogels can enhance repair efficiency and promote tissue regeneration in hypoxic tissue environments. The design of oxygen‐releasing hydrogels primarily involves the utilization of diverse oxygen sources, such as algae, perfluorocarbons, and peroxides, to achieve optimal tissue oxygenation. This review provides a comprehensive summary of the design and fabrication strategies of oxygen‐releasing hydrogels, discusses deeply into their underlying oxygen‐releasing mechanisms, and their myriad applications in tissue repair along with the prospective challenges.