Rat Wound Model Research Articles

Rat model evaluation for healing-promoting effectiveness and antimicrobial activity of electron beam synthesized (polyvinyl alcohol-pectin)- silver doped zinc oxide hydrogel dressings enriched with lavender oil.

Ag/ZnO NPs and lavender oil (LVO) were incorporated into (polyvinyl alcohol/pectin) (PVA/Pet) dressings using electron beam irradiation technology. The Ag/ZnO NPs were prepared using the precipitation method and characterized using XRD, FTIR, and EDX techniques. TEM micrograph shows their spherical appearance with an average size of around 27.4nm. The increase in the (PVA: Pet) feed solution concentration up to 30% enhances the gel content to 92%. The swelling degree reaches 1674% using 80wt% pectin content. Meanwhile, increasing the irradiation dose up to 45kGy increases the gel fraction and negatively affects the swelling capabilities. Incorporating Ag/ZnO NPs and LVO slightly decreased the gel fraction, the swelling degree, and the dressing's porosity reached 87%. In pseudo extracellular fluids, dressings with 10% LVO demonstrate 419% swelling capacities, and their WVTR reaches 271.1g/m2h. Dressings show biocompatibility, antimicrobial potential, and excellent wound healing capacity towards the excisional wound model in rats, as confirmed by the histological and biochemical results. LVO-(PVA/Pet)-Ag/ZnO dressings may accelerate tissue granulation and remodeling by replacing lost collagen and cause the wound to constrict by upregulating markers associated with wound healing so that it can be recommended as a wound healing candidate.

Multi‐Functional Responsive Microcapsules with Sequential Release Capacity for Wound Healing

AbstractThe development of biomaterials capable of on‐demand delivery holds significant promise for wound therapy. Current research is centered on refining design precision and enhancing structural functionality to achieve effective controlled release of active agents, thereby facilitating wound healing. In this study, a coaxial microfluidic electrospray technique is employed to fabricate microcapsules comprising a black phosphorus (BP)‐laden alginate shell and a gelatin methacrylate (GelMA) core. Curcumin nanoparticles (CNPs) and vascular endothelial growth factor (VEGF) are respectively incorporated into the shell and core of the microcapsules. The photothermal performance of the microcapsules contributed to superior sterilization efficacy in the early stages of wound healing, while the growth factors in the core provided robust angiogenic effects during the later stages. These attributes enabled the microcapsules to significantly accelerate wound healing, enhance collagen deposition, and modulate inflammatory responses in a rat wound model, underscoring their potential for clinical application.

Comparative Histological Assessment of Zinc Oxide Nanoparticles and Low-Power Laser Treatment at 810nm Wavelength on the Recovery of Second-Degree Burn Wounds in Rat Models.

Background: The utilization of zinc oxide nanoparticles is thought to augment wound healing because of their antibacterial characteristics and capacity to stimulate cellular regeneration, especially in instances of minor burn injuries. On the other hand, it has been shown that tissue regeneration is aided by low-power laser therapy via photobiomodulation. Zinc oxide nanoparticles and low-power laser therapy are the two therapeutic modalities that will be compared in this study in order to assess how well they promote healing after burn injury and provide important new information on improved wound care techniques. Methods: For this investigation, thirty male Wistar rats weighing 230 ± 25 grams each were split into three groups. Every rat received general anesthesia before the experiment. A stainless-steel rod was put to the rats' skin after being heated for 20 min in a boiling water bath to cause superficial second-degree burns. The control group functioned as a reference point for comparison and did not receive any treatment intervention. Over the course of a week, zinc oxide nanoparticles were applied topically to the second group. For one week, the third group received daily therapy with a diode laser at a dosage of 10 J/cm.1 Histological and clinical exams were performed after the therapy period to evaluate the impact of the therapies. Results: The experimental groups that received low-power laser therapy (third group) and zinc oxide nanoparticles (second group) showed a substantial increase in wound contraction in relation to the control group, based on macroscopic observations. One rat from the second group showed notable indications of full wound healing on day 21. The treated rats showed the highest rate of lesion contraction, indicating that wound treatment happened at least 7 days faster in these rats than in the other groups. After 21 days, the third group's epidermis fully epithelized and formed a layer of keratinization. Furthermore, there was enhanced angiogenesis and significant fibroblast proliferation; large-scale fibrosis was also commonly seen. Conclusion: Zinc oxide nanoparticles promoted wound healing and accelerated connective tissue regeneration faster than other groups when applied to second-degree superficial burns. This research implies that the use of zinc oxide nanoparticles may be a therapeutic approach that shows promise for treating burn injuries and improving patient outcomes.

A comparative study of human amniotic membrane, tilapia skin collagen, and Centella asiatica derived gel to treat burn wound in rat model.

In the quest for an ideal wound healing material, human amniotic membrane (AM), tilapia skin collagen (TSC), and Centella asiatica (CA) have been studied separately for their healing potential. In this study, we formulated AM, TSC, and CA gel and studied their competency and wound healing efficacy in vivo. Gel was formulated using AM, TSC, CA, Carbopol 934, acrylic acid, glycerine, and triethanolamine and physicochemical properties e.g.,pH, water absorption, swelling variation, and nuclear magnetic resonance (NMR) spectroscopy were determined. Biological properties were determined by skin irritation study, brine shrimp lethality, andantibacterial activity. Wound healing potential was determined by applying gel to second-degree burnsin vivoby observing wound contracture, epithelialization period, and histological features. The gel was non-lethal to brine shrimp and had anti-bacterial activity and showed no edema or erythema after 7days of topical application. After 21days of treatment, the AM + TSC + CA group significantly (P < 0.001) accelerated wound contraction (95.75 ± 0.44%)whereasthenegative control had the lowest healing rate (40.32 ± 2.11%). Wound contraction rates of AM + TSC and TSC + CA groups were (68.12 ± 1.46%) and (82.52 ± 1.74%) respectively.Epithelialization period for AM + TSC + CA was only 22.7days whereas AM, TSC, CA, AM + TSC, AM + CA, TSC + CA, positive control, and negative control needed 29.3, 30.7, 31.3, 27.3, 26, 26.6, 25.3 and 36.6days respectively. Histological analysis showed better healing potential for AM + TSC + CA regarding epidermal regeneration, blood vessel formation, and collagen deposition. The gel was biocompatible and in vivostudies with Wistar rats exhibited better wound healing capabilities than individual components of the gel alone.

Intelligent sequential degradation hydrogels by releasing bimetal-phenolic for enhanced diabetic wound healing.

Healing of diabetic wounds is significantly impeded by a complex environment comprising biofilm formation, excessive inflammation, and compromised angiogenic capacity, leading to a disordered physiological healing process. Restoration and maintenance of a normal and orderly healing process in diabetic wounds remain unmet therapeutic objectives. Herein, an innovative bimetal-phenolic network hydrogel system is designed with a concentric circular structure, enabling dual-drug delivery with differentiated release kinetics. The outer layer, Cu@TA (tannic acid)-loaded ε-PL (poly-l-lysine)-SilMA (methacrylated silk), is engineered for an initial release to scavenge reactive oxygen species and exert antibacterial and anti-inflammatory effects. The inner layer, Zn@TA-loaded ε-PL-SilMA, is designed for sustained release to promote cell migration, modulate the immune microenvironment, and induce angiogenesis. By incorporating a polyphenolic-metal network, the Cu@TA/Zn@TA/ε-PL-SilMA hydrogel can alter its degradation rate, enabling the sequential release of Cu@TA and Zn@TA. An in vivo diabetic rat wound model, transcriptomic sequencing, and histological staining analyses revealed that the Cu@TA/Zn@TA/ε-PL-SilMA hydrogel effectively activates the Wnt/β-catenin signaling pathway, synergistically promoting wound healing by accelerating angiogenesis, effectively reducing inflammation, and promoting collagen deposition. This innovative hydrogel, with sequential degradation and release properties, is broadly applicable, ensures orderly wound healing, and holds promise for accelerating diabetic wound repair.

In Situ Forming Hypoxia‐Induced Exosome‐Loaded Hydrogel for Enhanced Diabetic Wound Healing

AbstractDiabetic wound healing presents unique challenges, including impaired angiogenesis, prolonged inflammation, and delayed re‐epithelialization. Advancements in tissue engineering offer promising solutions through cell/drug‐based therapies. Exosomes (Exo) derived from hypoxia‐preconditioned adipose‐derived stem cells (ADSCs) have gained attention for their potential to address these complex issues in diabetic wounds. Existing strategies for Exo delivery aim to overcome drawbacks associated with conventional administration methods, including rapid loss of activity, frequent dosing, and off‐target effects. However, complexities in fabrication, undesirable components within the delivery system, and unforeseen outcomes have hindered the efficacy of these approaches. Thus, an in situ formed hydrogel is engineered using click chemistry to facilitate the convenient encapsulation of hypoxia‐induced Exo. The hydrogel swiftly transitioned into a gel state upon mixing and facilitated the controlled release of Exo at various loading dosages. Through systematic screening of Exo‐hydrogel formulations, it is demonstrated that the encapsulated Exo retained their bioactivity, exhibits therapeutic efficacy in vitro via scratch and tube formation assays. Further, the optimal Exo‐hydrogel promotes accelerated wound healing while preventing scar formation in a diabetic rat wound model. The Exo‐loaded hydrogel represents a promising approach for efficient Exo delivery in wound healing applications and holds potential for broader applications in diverse medical fields.

Photothermal Nanozyme‐Encapsulating Microneedles for Synergistic Treatment of Infected Wounds

AbstractPhotothermal therapy (PTT) is widely used in wound healing because it produces heat under near‐infrared irradiation, eliminating bacterial infections. However, excessive production of reactive oxygen species (ROS) occurs during PTT, which causes oxidative stress damage. In this study, a nanozyme, PDA‐MnO2 (PM), is synthesized and encapsulated in the needle tip layer of a bi‐layer GelMA microneedle patch (PbMP), which has excellent mechanical properties and can easily penetrate the skin. In a study involving an SD rat wound model infected with S. aureus, the PbMP significantly accelerated the healing process of bacterially challenged wounds, resulting in better blood vessel growth, cell proliferation, and collagen biosynthesis than other wound dressings. The experiment shows that the PM nanoparticles in PbMP improve photothermal conversion efficiency and activate SOD and CAT, resulting in an efficient cascade enzyme reaction system to eliminate ROS during the PTT process. This study describes a highly effective nanozyme hydrogel microneedle platform with photothermal synergistic antibacterial effects on wound healing.

Neurotensin Conjugated Polymeric Porous Microparticles Suppress Inflammation and Improve Angiogenesis Aiding in Diabetic Wound Healing.

Neurotensin (NT), a bioactive tridecapeptide aids in diabetic wound healing by modulating inflammation and angiogenesis. However, its rapid degradation in peptidase-rich wound environment (plasma half-life <2 min) limits its efficacy. To address this, neurotensin-conjugated polymeric porous microparticles (NT-PMP) were developed and loaded in gelatin (hydrogel 15% w/v) for topical application, enabling sustained NT release to enhance therapeutic outcomes. NT-PMP exhibited a size range of 60 - 240 µm (mean: 120.63 ± 40.71 µm) and pore size of 5 - 16 µm (average: 10.68 ± 3.47 µm). In vitro studies demonstrated cytocompatibility of NT-PMP in fibroblasts and reduced TNF-α levels in inflammation-induced macrophages (1256 ± 167.02 pg/ml). Further NT-PMP scaffold depicted excellent cell adhesion and migration properties upon seeding of dermal fibroblasts on surface of PMPs. In vivo studies in diabetic wound rat model demonstrated effective wound management, characterized by notable regenerative and healing attributes in the presence of NT-PMP. This included complete re-epithelialization, reducing pro-inflammatory cytokine (TNF-α), and enhancing VEGF expression, ultimately leading to the development of a well-organized collagen matrix in diabetic wounds upon application of NT-PMP gel.Altogether, NT conjugated PMP loaded in hydrogel demonstrated significant regenerative and healing properties, suggesting its potential as an alternative treatment for diabetic wounds.

Exploring the wound healing potential of dietary nitrate in diabetic rat model.

The wound healing in diabetes is hindered and prolonged due to long-term inflammation, oxidative stress damage, and angiogenesis disorders induced by high glucose status. The management of such difficult-to-treat wounds continues to pose a significant challenge in clinical treatment. Dietary nitrate, commonly found in greens such as beets and spinach, acts as a nutritional supplement and is metabolized in the body through the salivary nitrate-nitrite-NO pathway. This pathway plays a crucial role in various physiological functions, including enhancing blood flow and attenuating inflammation. In this study, we established a diabetic rat wound model. Forty-eight rats were randomly divided into six groups (n = 8): the Con group, the Con + Nitrate group, the STZ group, the STZ + NaCl group, the STZ + rhEGF group, and the STZ + Nitrate group. Skin wound healing was assessed on the day of surgery and on postoperative days 3, 7, 10, and 14. Specimens were taken on days 7 and 14 post-surgery for relevant tests. We found that dietary nitrate could accelerate skin wound healing by promoting angiogenesis and increasing blood perfusion. Significantly, dietary nitrate also regulated glucose and lipid metabolism and exhibited anti-inflammatory and antioxidant properties. These findings provide a novel theoretical basis for managing wounds in diabetic individuals, indicating the broad potential of dietary nitrate in future clinical applications.

Antibiofilm carbon-wrapped copper-nickel nanoparticles loaded amorphous hydrogel accelerated healing of Pseudomonas aeruginosa infected wounds in rat model

Pseudomonas aeruginosa induced infections are becoming very common and bacterial resistance to antibiotics causes a significant challenge to health systems globally by imposing massive financial burdens. Finding antibiotics substitutes with better antibacterial activity and lower risk are highly desired. Metallic nanoparticles have been found to be very attractive antibacterial agents. In current research, Carbon-wrapped Copper-Nickel nanoparticles were prepared and characterized using Fourier Transform Infrared spectroscopy (FT-IR) and X-ray diffraction analysis. Propylene glycol, sodium alginate, and 2-phenoxy ethanol-based hydrogels were loaded with two different concentrations of Copper-Nickel nanoparticles 30 mg/ml (ALG-30) and 50 mg/ml (ALG-50). The synthesized gels were found to be cytocompatible in cell culture study using fibroblasts. Carbon-wrapped Copper-Nickel nanoparticles, ALG-30 and ALG-50 showed remarkable antibacterial activity against both Gram-positive (S. aureus and MRSA) and Gram-negative (E. coli and P. aeruginosa) bacteria. Pseudomonas aeruginosa and MRSA biofilms were significantly decreased when exposed to nanoparticles and hydrogels (ALG-30 and ALG-50) for 24 hours. In full thickness infected skin wound model in rat, Pseudomonas aeruginosa infected wound was almost 97 % healed with ALG-30 over 16 days. In ALG-30 treated group, H & E stained tissues depicted enhanced angiogenesis, reduced inflammation and stimulate re-epithelialization, while Masson trichrome stained tissues showed increased collagen deposition. Overall, Carbon-wrapped Copper-Nickel nanoparticles embedded hydrogels exhibited excellent antimicrobial activity and holds a considerable potential to alleviate the current antibiotic resistance crisis in chronically infected wounds and expected widespread use in clinical practice.

Reinforcing chitosan film with a natural nanofiller “Zein-methyl cellulose loaded curcumin” for improving its physicochemical properties and wound healing activity

Selecting the appropriate biomaterials for fabricating a wound dressing is an essential issue for accelerating the process of wound healing. The biopolymer “chitosan” attracted attention owing to its non-toxicity, biocompatibility, and biodegradability. However, chitosan showed poor mechanical, antioxidant and antibacterial properties. These limitations can be encountered by its conjugation with a nanofiller reinforcing and improving the film properties. The proposed nanofiller, derived from zein-methylcellulose loaded curcumin (ZeinMCNPs) was incorporated with different concentrations into a chitosan matrix (Ch) forming Ch/ZeinMCNPs1–3 films. Ch/ZeinMCNPs3 film showed a significant improvement in tensile strength, elongation at break% and Young's modulus over Ch film. Notably, the antibacterial and antioxidant activities of the Ch/ZeinMCNP1–3 films signified enhancement over chitosan. In wound rat model, wound healing contraction reached 96 % and 98 % for Ch/ZeinMCNPs2,3 opposite to 79 % for Ch film. In Ch/ZeinMCNPs2,3 treated wounds, H&E tissues sections revealed a reduction in inflammation, an enhancement in re-epithelization and neovascularization. Furthermore, Ch/ZeinMCNPs2,3 films boosted more collagen deposition as shown in MTC sections. Ch/ZeinMCNPs2,3 significantly increased SOD level (at day 7 and14) with a decrease in MDA level. Overall, the present study declares Ch/ZeinMCNPs nanocomposite film as a multifunctional wound dressing category covering the necessitates required for accelerating wound healing process safely.

Histone Deacetylase 7-Derived 7-Amino Acid Peptide Increases Skin Wound Healing via Regulating Epidermal Fibroblast Proliferation and Migration.

Due to the complexity of wound healing, how to achieve successful healing is a significant clinical challenge. In this study, we found that the histone deacetylase-7-derived 7-amino acid peptide (7A, MHSPGAD), especially its phosphorylated version 7Ap (MH[pSer]PGAD), increased dermal fibroblast cell HDFα proliferation and migration via elevated delta-catenin (CTNND1) serine phosphorylation-mediated beta-catenin (CTNNB) nuclear translocation and subsequent upregulation of c-Myc and cyclin D1 expression. 7Ap physically interacted with platelet-derived growth factor receptor (PDGFR) and increased PDGFR interaction with cyclin-dependent kinase 6 (CDK6). The PDGFR siRNA or CDK6 siRNA knockdown ablated 7AP-induced CTNND1 phosphorylation and subsequent c-Myc/cyclin D1 expression, indicating a novel 7Ap-PDGFR-CDK6-CTNND1/CTNNB signal pathway in regulating fibroblast proliferation and migration. Furthermore, 7Ap increased human umbilic vein endothelial cell proliferation and tube formation, suggesting an angiogenic effect. In a full-thickness excision wound rat model, the local administration of 50 ng/mL of 7Ap in hydrogel exerted a similar effect as 1 μg/mL vascular endothelial growth factor on accelerating wound healing, featured by enhanced fibroblast proliferation and migration, collagen deposition, and increased new vessel formation during the early phase of wound healing. Taken together, this study not only elicited a novel signal pathway in fibroblast proliferation but also paved an avenue to develop 7Ap as a treatment option for skin wound healing.

Mesenchymal stem cells-laden self-healing hydrogel microfiber fragments from microfluidic bubbles interrupted spinning for wound healing

Mesenchymal stem cells (MSCs) loaded hydrogels have shown positive therapeutic effects in skin wound treatment, while their application is still impractical on the wound bed. Here, we propose novel MSCs-loaded self-healing hydrogel microfiber fragments from microfluidic bubbles interrupted spinning for wound healing. The hydrogel microfibers are composed of sodium alginate, gelatin, polyvinyl alcohol, and borax, vesting them with good biocompatibility and self-healing ability. Their fragments with adjustable length are generated by introducing bubbles into microfluidic channels. We have demonstrated that the self-healing microfibers can promote the proliferation of MSCs, which are seeded alongside fragments’ surfaces to further facilitate the wound healing process. In addition, these MSCs laden self-healing hydrogel microfibers (MSG-fibers) showed obvious healing effect in rat wound model, which significantly promoted granulation tissue formation, collagen deposition and vascular construction at the wound site. Thus, we believe that our proposed MSC-laden microfiber fragments are valuable in promoting wound healing and have promising prospect in becoming new options for wound management.

Platelet Extracellular Vesicles Loaded Gelatine Hydrogels for Wound Care.

Platelet extracellular vesicles (pEVs)isolated from clinical-grade human platelet concentratesare attracting attention as a promising agent for wound healing therapies. Although pEVs have shown potential for skin regeneration, their incorporation into wound bandages has remained limitedly explored. Herein, gelatine-based hydrogel (PAH-G) foams for pEVs loading and release are formulated by crosslinking gelatine with poly(allylamine) hydrochloride (PAH) in the presence of glutaraldehyde and sodium bicarbonate. The optimized PAH-G hydrogel foam, PAH0.24G37, displayed an elastic modulus G' = 8.5 kPa at 37°C and retained a rubbery state at elevated temperatures. The excellent swelling properties of PAH0.24G37 allowed to easily absorb pEVs at high concentration (1×1011 particles mL-1). The therapeutic effect of pEVs was evaluated in vivo on a chronic wound rat model. These studies demonstrated full wound closure after 14 days upon treatment with PAH0.24G37@pEVs. The maintenance of a reduced-inflammatory environment from the onset of treatment promoted a quicker transition to skin remodeling. Promotion of follicle activation and angiogenesis as well as M1-M2 macrophage modulation are evidenced. Altogether, the multifunctional properties of PAH0.24G37@pEVs addressed the complex challenges associated with chronic diabetic wounds, representing a significant advance toward personalized treatment regimens for these conditions.

Histomorphometric analysis of excisional cutaneous wounds with different diameters in an animal model.

The skin wound model in rats is a fundamental stage in preclinical trials, but there is a lack of standardization in these trials regarding the initial wound area, making analysis and comparison between studies difficult. Therefore, this study evaluates the healing progression of excisional skin lesions of varying diameters in Wistar rats, aiming to identify the optimal wound size for monitoring treatment effects on wound healing. Excisions of 0.8, 1.5, 2.0 and 3.0 cm in diameter were made on the back of the animals. Thirty animals were used per treatment and evaluated on days 3, 7, 10, 14 and 21 after surgery. The lesions were cleaned daily with saline solution until they were completely closed. The 0.8 cm group showed complete repair on D14, while in the other groups, the wounds persisted until day 21, with a reddened surface and no complete epidermal coverage, but with greater keratinization and presence of appendages in the 1.5 cm lesions. Therefore, as a standardization model for creating skin wounds, we suggest using 1.5 or 2.0 cm excisions, considering that 0.8 cm wounds close very early and 3.0 cm wounds, although behaving similarly to 2.0 cm wounds, are more invasive for the animals. The 1.5 cm model proved to be suitable for closure within 21 days. When evaluating a product intended to accelerate wound healing, 2.0 cm lesions are recommended to assess the effectiveness of the treatment.

Stretchable wireless optoelectronic synergistic patches for effective wound healing

Physiotherapies play a crucial role in noninvasive tissue engineering for wound healing. However, challenges such as the implementation of complex interventions and unsatisfactory treatment outcomes impede widespread application. Here, we proposed a stretchable and wirelessly-powered optoelectronic synergistic patch with a dual-layer serpentine wireless receiver circuit to drive the optoelectronic modulation component. Optimized structure and impedance matching enable the patch to seamlessly attach to irregular skin surfaces and operate robustly over a 30% tensile strain range. Based on Sprague-Dawley rat wound model. The wound closure rate of the optoelectronic synergistic group significantly outperformed both monointervention and blank control groups. Mechanistically, optoelectronic synergistic intervention enhances the secretion of vascular endothelial marker proteins and growth factors, and stabilizes mitochondrial function during oxidative stress. Overall, the scalable amalgamation of flexible electronics, wireless transmission, and synergistic interventions promise to improve wound care.

Curcumin-loaded gold nanoparticles with enhanced antibacterial efficacy and wound healing properties in diabetic rats

Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV–Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis of AuNPs. The optimal formulation (F2) exhibited the smallest particle size (41.77 ± 6.8 nm), reasonable PDI (0.59 ± 0.17), high %EE (94.43 ± 0.25 %), a moderate zeta potential (−8.44 ± 1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin’s antibacterial efficacy by lowering the minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.

Multifunctional Photothermal Nanorods for Targeted Treatment of Drug-Resistant Bacteria-Induced Wound Healing.

The challenge of drug-resistant bacteria-induced wound healing in clinical and public healthcare settings is significant due to the negative impacts on surrounding tissues and difficulties in monitoring the healing progress. We developed photothermal antibacterial nanorods (AuNRs-PU) with the aim of selectively targeting and combating drug-resistant Pseudomonas aeruginosa (P. aeruginosa). The AuNRs-PU were engineered with a bacterial-specific targeting polypeptide (UBI29-41) and a bacterial adhesive carbohydrate polymer composed of galactose and phenylboronic acid. The objective was to facilitate sutureless wound closure by specially distinguishing between bacteria and nontarget cells and subsequently employing photothermal methods to eradicate the bacteria. AuNRs-PU demonstrated high photothermal conversion efficiency in 808 nm laser and effectively caused physical harm to drug-resistant P. aeruginosa. By integrating the multifunctional bacterial targeting copolymer onto AuNRs, AuNRs-PU showed rapid and efficient bacterial targeting and aggregation in the presence of bacteria and cells, consequently shielding cells from bacterial harm. In a diabetic rat wound model, AuNRs-PU played a crucial role in enhancing healing by markedly decreasing inflammation and expediting epidermis formation, collagen deposition, and neovascularization levels. Consequently, the multifunctional photothermal therapy shows promise in addressing the complexities associated with managing drug-resistant infected wound healing.

A Skin Stress Shielding Platform Based on Body Temperature-Induced Shrinking of Hydrogel for Promoting Scar-Less Wound Healing.

Stress concentration surrounding wounds drives fibroblasts into a state of high mechanical tension, leading to the delay of wound healing, exacerbating pathological fibrosis, and even causing tissue dysfunction. Here, an innovative skin stress-shielding hydrogel wound dressing is reported that makes the wound sites shrink as a response to body temperature and then remolds the stress micro-environment of wound sites to reduce the formation of skin scars. Composed of a modified natural temperature-sensitive polymer cross-linked with polyacrylic acid networks, this hydrogel wound dressing has demonstrated a substantial decrease in scar area for full-thickness wounds in rat models. The physical forces exerted by the wound dressing are instrumental in attenuating the activation and transduction of fibroblasts within the wound sites, thereby mitigating the excessive deposition of the extracellular matrix (ECM). Notably, the wound dressing significantly down-regulates the expression of transforming growth factor-β1(TGF-β1) and collagen I, while concurrently exerting a dramatic inhibitory effect on the integrin-focal adhesion kinase (FAK)/phosphorylated-FAK (p-FAK) signaling pathway. Collectively, the fabrication of functional hydrogels with a stress-shielding profile is a new route for achieving scar-less wound healing, thus offering immense potential for improving clinical outcomes and restoring tissue integrity.

The effect of liposomal composition with encapsulated potassium orotate on the macrophage link of immunity in the treatment of wounds

In veterinary medicine, treatment of wounds is one of the most important areas. A possible way to solve the problem of wound treatment is to activate the body's own protective reserves, primarily the immune system. Various immunostimulants and immunomodulators are widely used to activate the immune system. Known immunostimulants are derivatives of pyrimidine bases, in particular, potassium orotate (potassium salt of orotic acid). Orotic acid is found in milk and colostrum of animals. The use of orotic acid or its salts as immunostimulants is difficult due to their low bioavailability determined by their solubility in water. It is possible to increase the effectiveness of immunostimulators based on potassium orotate by including it in liposomes. Liposomes with encapsulated potassium orotate were obtained by shaking. The aim of the research was to study the activation of immunity macrophage link by liposomes with encapsulated potassium orotate. Evaluation of the effectiveness of the liposomal drug was carried out on rat wound models and on post-castration wounds of suckling pigs. Animal experiments were conducted according to bioethical norms. Complete wound healing in rats with the use of liposomal gel occurred on day 2, earlier than in the control with the use of Monclavit-1, while in the experimental group, compared with the control group, the content of leukocytes, lymphocytes, monocytes, platelets and granulocytes was significantly higher. The healing of surgical wounds in piglets after castration with the use of liposomal gel occurred 2 days earlier than with the use of the drug "Monclavit-1". There were no complications in both groups. Based on the analysis of literature data and the results of our own research, a scheme of the mechanism of action of a liposomal drug was proposed. The hypothesis about the mechanism of influence of liposomal composition on the macrophage link of immunity has been presented.