A wound dressing releasing essential oils, vitamins and oxygen for chronic wound treatment applications

Abstract

The invention relates to an anti-inflammatory and anti-bacterial wound dressing that simultaneously and continuously releases and distributes oxygen, essential oils, and vitamins within the same biomaterial, and to a production method of said wound dressing.

Description

[0001] DESCRIPTION

[0002] A WOUND DRESSING RELEASING ESSENTIAL OILS, VITAMINS AND OXYGEN FOR CHRONIC WOUND TREATMENT APPLICATIONS

[0003] Technical Field

[0004] The invention relates to an anti-inflammatory and anti-bacterial wound dressing that simultaneously and continuously releases and distributes oxygen, essential oils, and vitamins within the same biomaterial, and to a production method of said wound dressing.

[0005] State of the Art

[0006] Wound dressings are medical materials that protect the injured tissue from external factors, support the healing process, and reduce the risk of infection. The most common traditional wound dressings used in wound care are gauze, cotton, and bandages. Although these materials have been used to protect the wound site from external factors, stop bleeding, and provide a basic physical barrier, they have significant shortcomings in terms of critical factors such as moisture balance, infection control, non-adhesion, and biocompatibility. For example, gauze can cause the wound to dry out due to its inability to maintain moisture balance, while adhesion problems can delay healing and damage tissue. In addition, since gauze has high germ permeability, it increases the risk of infection and is inefficient in exudate management. Cotton, on the other hand, can dry the wound site excessively by absorbing excess fluid, increase the risk of infection due to its fibers sticking to the wound surface, and cause irritation. Bandages may cause skin irritation due to their low air permeability and may delay healing by disrupting blood circulation when tightened too tightly. All these shortcomings highlight the need for the development of modern biomaterials and smart wound dressings.

[0007] Wound dressings in the present art are quite insufficient in simultaneously solving problems such as bacterial infections, chronic inflammation, and severe hypoxia in the wound, which negatively affect the healing process of the wound. More specifically, bacterial infections in particular delay healing by causing microorganisms to multiply around and within the wound. In addition, chronic inflammation, which is persistent anduncontrolled inflammation, can disrupt the body's normal healing mechanisms and prevent tissue regeneration. Severe hypoxia resulting from tissues in the area of the wound not receiving enough oxygen reduces cellular energy production, slowing down healing.

[0008] In the state of the art, optimization of the simultaneous controlled release of oxygen, vitamins, drug molecules, and essential oils is very challenging. Failure to adjust these optimization processes can lead to prolonged, too fast or too slow release of components into the cell. Fast release causes rapid depletion of the active components, making it unable to meet the need for long-term treatment. Slow release, on the other hand, delays the onset of therapeutic effects and negatively affects the healing process. Moreover, homogeneous distribution of these components in biomaterials is very difficult. Concentration gradients may occur during release, resulting in uneven effects in the areas to be treated. In addition, insufficient biocompatibility and biodegradation rates also limit the effectiveness of these systems. The rapid and high-dose release of said components increases the risk of toxicity by causing a sudden and intense exposure of cells in the application area to these substances. This can disrupt the normal biological functions of cells and even lead to cell death. Uncontrolled release of such reagents, especially in sensitive tissues, leads to increased inflammation and further complicates the wound healing process. In addition, the rapid depletion of reagents leads to reduced efficacy of the wound dressing and therefore frequent changing. There is a high risk of damage to the newly formed tissue during wound dressing changing procedures. Frequent interventions, especially during the formation phase of granulation tissue, disrupt the integrity of this delicate structure and delay the healing process. However, frequent changing procedures require the use of more medical equipment, leading to increased treatment costs.

[0009] Document no. US2012225102A1 in the state of the art relates to a perfluorocarbon gel composition having a plurality of uses, including medical and cosmetic uses, and production methods thereof. In said document, oxygen is supplied to the tissue for up to 24 hours. Exposure to high amounts of oxygen, which can be toxic for cell survival and wound healing, cannot be prevented.Document no. CN108837086A in another state of the art relates to a traditional Chinese medicine film agent for skin protection and damage repair and a preparation method thereof. Said film material in question is intended for skin protection and damage repair. However, the oxygen supply provided by oxygen-carrying microbubbles appears to be short-lived and the release of oxygen is uncontrolled. The rapid release of oxygen can provide oxygen for a short period of time, and in treatments with prolonged oxygen requirements, such as chronic wounds, this oxygen supply can be rapidly depleted, leading to interruptions in the treatment process and delayed wound healing.

[0010] Document no. CN117482280A in another state of the art relates to a production method and application of a blood cell active hydrogel for wound repair. In said document, it is stated that the hydrogel increases the oxygen level rapidly, however the oxygen level drops after about 12 hours. The irregular and sudden distribution of oxygen can cause cells to be momentarily exposed to excessive oxygen and cause oxidative stress, leading to toxic effects on healthy cells. Furthermore, rapid increase in oxygen level and its decrease in a short period of time may cause hypoxic conditions to reoccur and negatively affect wound healing.

[0011] In order to overcome the disadvantages mentioned in the state of the art and above, it is necessary to develop new wound dressings that provide continuous oxygen and controlled pH-dependent co-distribution of anti-inflammatory and anti-bacterial essential oils and vitamins within the same biomaterial.

[0012] Summary of the Invention

[0013] The present invention, in order to overcome the disadvantages mentioned above and to provide new advantages in the related technical field, relates to an anti-inflammatory and anti-bacterial wound dressing that simultaneously and continuously releases and distributes oxygen, essential oils, and vitamins within the same biomaterial, and to a production method of said wound dressing.

[0014] The invention relates to wound dressings in the form of gels, wound dressings, or hydrogels which can carry oxygen, vitamins and essential oils and which, due to the synergistic effect of this combination, can be used in the treatment of chronic woundssuch as skin cancer, burns, diabetic ulcers, pressure sores, venous wounds, etc. Hypoxia, inflammation, and infection have an interdependent relationship. Hypoxia causes inflammation to become chronic, and chronic inflammation and infection cause hypoxia to increase and persist. Increasing and chronic hypoxia, inflammation, and infection cause delayed wound healing and even non-healing. The invention contains oxygen, vitamins, and essential oils, and the synergistic effect of this combination, along with the combined use of antibacterial and anti-inflammatory agents, reduces hypoxia and subsequently prevents the chronicity of inflammation and infection, promoting faster wound healing.

[0015] The invention provides a continuous oxygen and pH-controlled co-distribution of vitamins and essential oils. Thanks to the effect of the simultaneous release of oxygen, vitamins and essential oils, it is used especially in the treatment of inflammation, cancer, burns, diabetic ulcers, infections which are pathological conditions triggered by hypoxia and acidic pH or in which they are active, as well as in oxygen and natural drug therapies. It also promotes healthy cell viability and proliferation, allowing chronic wounds and damaged tissues to heal faster. The invention inhibits bacterial growth on and around the wound and also inhibits inflammation, cancer and infection in hypoxic and acidic conditions.

[0016] The invention is a single system that combines essential oil, oxygen, and vitamin carrying unit on the same nanoparticle (biomaterial). Therefore, it prolongs the release of biomolecules and, since the number of biomolecules released is spread over time, it reduces the direct effect of oxygen, vitamins, and essential oils, which can be harmful in high amounts, on healthy cells and ensures that the anti-inflammatory and antibacterial effects of these biomolecules are long-lasting. The invention eliminates the problem of frequent changes of wound dressings due to high release rates, reducing damage to the healing wound layer and impairment of patient comfort. This helps to reduce treatment costs and expenses.

[0017] The invention relates to an EDTA-functionalized GelMA hydrogel with anti-inflammatory and anti-bacterial properties, comprising perfluorocarbon based PMOFs and essential oil that carry vitamins and deliver oxygen, and this structure it contains provides pH dependent vitamin release and continuous oxygen release (7-15 days). By providing pH-dependent anti-inflammatory vitamin release, it releases higher levels of anti-inflammatory and anti-bacterial vitamins into more acidic wound tissue and can reduce vitamin release depending on wound healing. The invention provides long-term release of oxygen and essential oils, preventing cells from being exposed to high amounts of oxygen and essential oils that may be toxic, and providing a slow but long-lasting (7-15 days) release of oxygen necessary for their survival and wound healing. Additionally, the EDTA it contains provides antibacterial and anti-inflammatory effects, preventing bacterial growth, infection, and inflammation on the wound for an extended period.

[0018]

[0019] Fig. 1 . A graphical view showing the release of tea tree oil with a hydrogel (alginate) containing tea tree oil and a hydrogel containing PMOF and tea tree oil.

[0020] Fig. 2. A graphical view of alginate and alginate containing PMOF showing oxygen release in hypoxic environment.

[0021] Fig. 3. A graphical view showing the viability of fibroblast cells in the presence of Mixture 1 , Mixture 2, Mixture 3, Mixture 4, and Mixture 5 and after 5 days of incubation in hypoxic medium.

[0022] Fig. 4. A graphical view showing the effect of tea tree oil in different ratios in Mixture 2 and Mixture 4 on E. coliand S. aureus bacteria.

[0023] Fig. 5. 1 H-NMR spectrum view of GelMA and GelMA-EDTA mixture.

[0024] Fig. 6. A graphical view showing fibroblast cell viability after one day incubation of Plate (control), GelMA, GelMA-EDTA, and GelMA-EDTA-PMOF in hypoxia medium. Fig. 7. A graphical view of Plate, GelMA, GelMA-EDTA, and GelMA-EDTA-PMOF showing ROS production after one day of incubation in hypoxia medium.

[0025] Detailed Description of the Invention

[0026] The example embodiments are described in more detail below with reference to the accompanying descriptions. Furthermore, the embodiments can be established in different forms and should not be interpreted as being limited to the embodiments specified herein. Rather, these example embodiments are provided so that this description will be thorough, and will fully convey the scope to those skilled in the art.

[0027] The invention relates to a wound dressing comprising hydrogel (with anti-inflammatory and antibacterial properties) structures functionalized with perfluorocarbon (O2 carryingstructure) periodic mesoporous organosilica (pH sensitive structure capable of encapsulating hydrophobic and hydrophilic biomolecules) and EDTA (ethylene diamine tetraacetic acid), which enables the controlled continuous co-distribution of essential oils (vegetable and volatile oils) and vitamins with anti-inflammatory and antibacterial properties within the same biomaterial, depending on oxygen and pH.

[0028] In an embodiment of the invention, the wound dressing comprises a perfluorocarbon-based oxygen-carrying periodic mesoporous organosilica (PMOF), alginate, laponite (lithium magnesium sodium silicate), vitamins, essential oils, and EDTA-functionalized gelatin methacrylate (GelMA).

[0029] More specifically, the wound dressing comprises:

[0030] - perfluorocarbon-based oxygen carrier periodic mesoporous organosilica (PMOF) in the range of 0.01-0.1 wt. %,

[0031] - alginate in the range of 3-8 wt. %,

[0032] - laponite in the range of 1-3 wt. %,

[0033] - vitamin in the range of 0.01-0.03 wt. %,

[0034] - essential oil in the range of 3-10 wt. %,

[0035] EDTA-functionalized GelMA in the range of 50-80 wt. %.

[0036] In another embodiment, the wound dressing comprises:

[0037] - perfluorocarbon-based oxygen carrier periodic mesoporous organosilica (PMOF) at a rate of 0.01 wt. %,

[0038] - alginate at a rate of 7 wt. %,

[0039] - laponite at a rate of 3 wt. %,

[0040] - vitamin at a rate of 0.03 wt. %,

[0041] - essential oil at a rate of 10 wt. %,

[0042] - EDTA-functionalized GelMA at a rate of 79.96 wt. %.

[0043] In different embodiments of the wound dressing, it may contain PMOF, alginate, laponite, vitamins, essential oil, EDTA, and GelMA components individually or in combinations at specified weight ratios. The fact that the wound dressing contains components in specified weight ratios in the invention was discovered as a result of the work carried out within the scope of the invention. A wound dressing thatsimultaneously and continuously releases and distributes oxygen, essential oils and vitamins is obtained with the components with said weight ratios.

[0044] The vitamins used in the wound dressing subject to the invention are Vitamin A and / or Vitamin B and / or Vitamin C and / or Vitamin D and / or Vitamin E and / or Vitamin K, but the embodiment is not limited thereto. These vitamins provide antioxidant, antibacterial, and anti-inflammatory properties.

[0045] The essential oil used in the wound dressing subject to the invention is tea tree oil and / or lavender oil and / or thyme oil and / or peppermint oil and / or cinnamon oil and / or St. John's wort oil. Said essential oils are vegetable and volatile oils with antiinflammatory and anti-bacterial properties. Thus, the advanced technical effect is achieved due to its antioxidant, anti-bacterial, and anti-inflammatory properties.

[0046] The laponite contained in the wound dressing subject to the invention makes the hydrogel more fluid and improves its injectability. It also enables the printing of wound dressings tailored to the patient's needs through advanced 3D printing applications.

[0047] The invention relates to a production method of said wound dressing and comprises the following process steps:

[0048] i. dissolving cetyltrimethyl ammonium bromide (CTAB) in a solution containing water, ethanol, and ammonia,

[0049] ii. adding 1 ,2-bis(trimethoxysilyl)ethane (BTME) and 1H,1H,2H,2H- perfluorooctyltriethoxysilane (POTS) into the mixture and stirring,

[0050] iii. stirring the mixture in an ethanol solution containing hydrochloric acid solution and obtaining periodic mesoporous organosilica (PMOF) and washing the obtained PMOF with ethanol and drying,

[0051] iv. suspending PMOF in water and mixing with vitamin and centrifuging the mixture, washing with water, and drying,

[0052] v. mixing gelatin methacrylate (GelMA)-water solution with 1 -ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC) - N-Hydroxysuccinimide (NHS) solution, then adding EDTA into the mixture and continuing mixing,

[0053] vi. dialyzing and then lyophilizing the mixture,

[0054] vii. mixing the lyophilized mixture with phosphate buffered saline (PBS) solution containing eosin Y, triethanolamine (TEA), and vinyl caprolactam (VC),viii. mixing the mixture with the dried mixture obtained in step (iv.) and subjecting it to sonication,

[0055] ix. adding alginate and laponite into the sonicated mixture and mixing,

[0056] x. cross-linking by using visible light and with calcium chloride (CaCl2), and then lyophilizing,

[0057] xi. adding essential oil to the lyophilized mixture.

[0058] The solution mentioned in process step (i.) of the method steps subject to the invention comprises 90 ml water, 33 ml ethanol, and 28 wt. % ammonia. Said 28 wt. % ammonia is 0.075 g in an embodiment of the invention, but the embodiment is not limited thereto. Said step ensures the hydrolysis of the silica source.

[0059] In process step (ii.) of the method steps subject to the invention, 1.27 g BTME and 0.59 g POTS are added into said mixture. It is then stirred for 48 hours at a room temperature in the temperature range of 20-24°C With said step, the hydrolyzed silica source is polymerized to form nanoparticles.

[0060] In process step (iii.) of the method of the method steps subject to the invention, the mixture is stirred for 6 hours at 50°C in an ethanol solution containing aqueous hydrochloric acid (HCI) solution at a rate of 36 wt. %. In a preferred embodiment of the invention, the mixture is stirred in a 50 ml ethanol solution containing 1.5 g of aqueous hydrochloric acid (HCI) solution for 6 hours at 50°C The mixture is then centrifuged to obtain PMOF in solid form. Then the PMOF is washed 1-2 times with ethanol and dried in vacuum at 60°C With said step, CTAP is removed and the porous structure of PMOF is obtained.

[0061] In the process step (iv.) of the method steps subject to the invention, PMOF is suspended in 1 ml of water and mixed with vitamin in the range of 0.01-0.03 wt. % at room temperature between the temperature range of 20-24°C for 1 day. In another embodiment of the invention, 5 mg of vitamin is added. In addition, 100 mg PMOF is used. Said step ensures that the vitamin is loaded onto the surface and pores of the PMOF. The vitamins mentioned in this step are Vitamin A and / or Vitamin B and / or Vitamin C and / or Vitamin D and / or Vitamin E and / or Vitamin K. The mixture mixed with the vitamin is first centrifuged at 6000 rpm for 15 minutes and then washed twice withwater. After the washing process, it is dried for 1 day at a room temperature in the range of 20-24°C With said step, PMOF is obtained in dry form.

[0062] In process step (v.) of the method subject to the invention, a GelMA-water solution at a rate of 3% weight / volume (w / v) is first mixed with a mixture of 1 -ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) - N-Hydroxysuccinimide (NHS) at a concentration of 0.2 M for 1 hour. EDTA at a concentration of 0.1 M is then added to this solution and stirred for 24 hours at room temperature in the range 20-24°C Said step enables the functionalization of GelMa with EDTA. The GelMA mentioned in this step is synthesized by known methods in accordance with the literature. For said synthesis, gelatin (20 g) is first dissolved in PBS (600 mL) at 60°C for 1 hour with stirring. Then, methacrylic anhydride (16 mL) is added dropwise to the mixture and stirred continuously. The entire mixture is then transferred to a dialysis membrane (12-14 kDa) and kept in autoclaved deionized water at 50°Cfor 7 days to remove unreacted methacrylic anhydride. Water is replaced daily with fresh, preheated water. After 7 days, the solution is filtered through a vacuum filter (110 mm pore size) and then lyophilized to obtain a dried GelMA foam.

[0063] The mixture mentioned in process step (vi.) of the method subject to the invention is dialyzed against deionized water for 3 days. After the dialysis process, it is subjected to lyophilization at (-60)°C for 1 day. With said step, it is ensured that the unreacted chemicals are removed.

[0064] The lyophilized mixture mentioned in process step (vi.) of the method subject to the invention is mixed in phosphate buffered saline (PBS) with eosin Y at a concentration of 0.1 M as photoinitiator, triethanolamine (TEA) at a rate of 1.3% w / v as co-initiator and vinyl caprolactam (VC) at a rate of 1.0% w / v as co-monomer. In an exemplary embodiment of the invention, the lyophilized mixture is mixed with eosin Y at a concentration of 0.1 M, 133 pL triethanolamine (TEA), and 0.1 g vinyl caprolactam (VC) in 10 mL PBS. The lyophilized mixture mentioned here is used in said embodiments at a rate of 10% w / v or 1 g. After the mixing process, it is kept at 80°Cfor 10 minutes to dissolve GelMA-EDTA in solid form. With said step, GelMA-EDTA to be cross-linked with light is obtained.In process step (viii.) of the method subject to the invention, the mixture kept at 80°Cas mentioned in process step (vii.) is mixed with the mixture centrifuged, washed with water and dried as mentioned in process step (iv.), i.e., PMOF obtained in dry form. Said mixing process takes an average of 20 minutes. In an embodiment of the invention, the PMOF obtained in dry form, 1.0 mg / mL is used, but the embodiment is not limited thereto. After the mixing process, the mixture is subjected to sonication for 20 minutes.

[0065] In the process step (ix.) of the method subject to the invention, 70 mg / mL alginate and 30 mg / mL laponite are added into the mixture subjected to sonication and mixed. In an example embodiment, laponite at a rate of 3 wt. % and alginate at a rate of 7 wt. % are added and mixed. In another exemplary embodiment of the invention, the process step (ix.) of adding alginate and laponite to the mixture subjected to sonification and mixing it includes a process step of transferring the mixture into a syringe and printing it on a template on a 3D (3-D) printer. More specifically, in the process step (ix.), alginate and laponite are added to the mixture subjected to sonification, mixed and transferred into a syringe and printed on a 3D printer on a square template. This procedure uses a 3-cc syringe barrel and a 0.41 mm needle. Grid square structures, each side measuring 10 mm and 1.5 mm in height, are produced using a 3D printer. The syringe speed is set at 80 mm / s and the injection head speed at 10 mm / s. Extrusion pressure levels of 40 kPa and temperatures of 25 °C are used. It is then cross-linked with calcium chloride (CaCI2) using visible light with process steps (x.) and (xi.), in other words by following these process steps, and then lyophilized. Finally, essential oil is added.

[0066] In the process step (x.) of the method subject to the invention, it is cross-linked by using visible light at 450-550 nm with an intensity of 100 mW / cm2at room temperature in the range of 20-24°C for 60-180 seconds range, followed with calcium chloride (CaCI2) at a concentration of 0.1 M for 15 minutes. It is then subjected to lyophilization for 24 hours. More specifically, it is kept at -80°C for 24 hours and then freeze-dried for 24 hours, i.e., lyophilized, to obtain wound dressing scaffolds.

[0067] In the process step (xi.) of the method subject to the invention, essential oil is added at the rate of 10 wt. % after the lyophilization process. Said essential oil is tea tree oil and / or lavender oil and / or thyme oil and / or peppermint oil and / or cinnamon oil and / or St. John's wort oil.The method steps of the invention provide a wound dressing or preferably a wound dressing in hydrogel form. Various experiments were carried out for the wound dressing subject to the invention. Firstly, only alginate (hydrogel) (Mixture 1), hydrogel containing tea tree oil (Mixture 2), hydrogel containing PMOF (Mixture 3), hydrogel containing PMOF and tea tree oil (Mixture 4) were prepared. Mixture 4 is a single system combining tea tree oil and nanoparticle containing the oxygen carrying unit (PMOF) in the same hydrogel (Alg-Alginate). Mixture 4 can release about 5% more oil compared to Mixture 2. This shows that PMOF can adsorb and release more oil over time with its large surface area. Said results are shown in the graph in Figure 1. Figure 2, which shows the oxygen release property, shows that Mixture 3, which contains the oxygen carrying unit, releases oxygen continuously and for a longer period of time under hypoxic (1%-02) conditions compared to Mixture 1. The O2 level of Mixture 3 increased continuously during the 15-day period and after 15 days of incubation, the O2 level of the medium containing Mixture 3 was approximately 11.5%. These results show that PMOF, the 02-carrying nanomaterial, can provide continuous O2 release from the alginate web to the medium.

[0068] Cell experiments for the invention were performed using healthy human primary dermal fibroblast cells. In the presence of Mixture 1, Mixture 2, Mixture 3, Mixture 4 and Mixture 5 containing only tea tree, it was carried out under hypoxic conditions at 37°C for 5 days. Cells in the culture plate were used as controls. While a decrease in fibroblast cell viability was observed in the presence of Mixture 5 and Mixture 2, cell viability in Mixture 4 remained as in the control group. This result, shown in Figure 3, indicates that cell viability was maintained in hypoxic medium with the use of oxygen and tea tree oil alone, and that tea tree oil and oxygen had no toxic effect on cell viability for 5 days. Mixture 2 and Mixture 4 were also exposed to E. coli and S. aureus bacteria for 24 hours. The graph showing the relevant results is given in Figure 4, and said results show that low concentrations of tea tree oil (0 and 3 pl) were not effective in suppressing E. coli and S. aureus. At these concentrations, an increase in the viability of E. coli in Mixture 2 and Mixture 4 was observed compared to the control (plate). Additionally, the fact that Mixture 4 is more effective than Mixture 2 indicates that PMOF's O2release can produce reactive oxygen species, an additional parameter that acts as an antibacterial agent to inhibit bacterial growth, but is not sufficient on its own to inhibit bacteria. It is therefore necessary to use Mixture 3 in combination with tea tree oil to ensure effective inhibition of bacteria. In addition, the experimentconducted shows that the most effective concentration of tea tree oil is 5 l and it completely inhibits E. coliand S. aureus in an interaction duration of 24 hours.

[0069] In addition, the invention is functionalized as a wound dressing by using GelMA and EDTA, which has anti-inflammatory and antioxidant properties, instead of using a hydrogel containing only PMOF and tea tree oil (Mixture 4). 1H-NMR spectra of only GelMA (Mixture A) and GelMA-EDTA (Mixture B) are shown in Figure 5. As can be seen in Figure 5, the 1H-NMR spectrum shows two peaks at 3.27 ppm and 3.00 ppm belonging to protons in the acetate-methylene and backbone-methylene positions, respectively. Then, the effects of anti-inflammatory EDTA and EDTA and O2 on fibroblast cell viability under hypoxic conditions were examined. Said percent cell viability results for Mixture A, Mixture B, Mixture C (PMOF- GelMA-EDTA containing hydrogel) are shown in Figure 6. The results showed that Mixture B increased fibroblast cell viability and decreased reactive oxygen levels (ROS) compared to Mixture A. In addition, the simultaneous use of Mixture A and PMOF with Mixture C was more effective on cell viability and further reduced ROS (Figure 7). Said experimental study demonstrates the successful effect of using only EDTA and O2simultaneously on fibroblast cell viability under hypoxic conditions. A multifunctional biomaterial can be obtained by integrating anti-inflammatory and anti-oxidant Mixture B with anti-bacterial and anti-inflammatory tea tree oil and vitamin-carrying and oxygenreleasing nanoparticles, and thanks to the synergistic effect of this combination, effective results can be obtained in chronic wound treatments. The results of said in vitro experiments indicate that the invention is more effective in inhibiting bacterial growth when oxygen and essential oil are used together over a long period of time, the combined use of oxygen and essential oil does not cause toxic effects on skin cells (fibroblasts) involved in wound healing under hypoxic conditions, and the use of oxygen and EDTA -based hydrogel in hypoxic conditions leads to higher viability of skin cells (fibroblasts) involved in wound healing under hypoxic conditions.

[0070] The above embodiments are intended only to describe the technical concept and features of the present invention, and the purpose of the present invention is to ensure that those skilled in the art understand the content of the present invention and practice the present invention, and the scope of the present invention is not limited thereto. Equivalent changes or modifications made in accordance with the spirit of the invention are intended to be included in the scope of the invention.Industrial Applicability of the Invention

[0071] The invention relates to an anti-inflammatory and anti-bacterial wound dressing that simultaneously and continuously releases and distributes oxygen, essential oils, and vitamins within the same biomaterial, and to a production method of said wound dressing, and is industrially applicable

[0072] The invention is not limited to the example embodiments above, and the person skilled in the art can readily present other different embodiments of the invention. These should be considered within the protection scope of the invention claimed by the claims.

Claims

CLAIMS1. A wound dressing, characterized in that it comprises perfluorocarbon-based oxygen carrier periodic mesoporous organosilica (PMOF), alginate, laponite, vitamins, essential oil, and EDTA-functionalized gelatin methacrylate (GelMA).

2. The wound dressing according to claim 1, characterized in that it comprises perfluorocarbon-based oxygen-carrying periodic mesoporous organosilica (PMOF) in the range of 0.01-0.1 wt. %, alginate in the range of 3-8 wt. %, laponite in the range of 1-3 wt. %, vitamin in the range of 0.01-0.03 wt. %, essential oil in the range of 3-10 wt. %, and EDTA-functionalized GelMA in the range of 50-80 wt. %.

3. The wound dressing according to claim 2, characterized in that it comprises 0.01% by weight of perfluorocarbon-based oxygen-carrying periodic mesoporous organosilica (PMOF), 7% by weight of alginate, 3% by weight of laponite, 0.03% by weight of vitamin, 10% by weight of essential oil and 79.96% by weight of EDTA- functionalized GelMA.

4. The wound dressing according to any one of claims 1-3, characterized in that said vitamin is Vitamin A and / or Vitamin B and / or Vitamin C and / or Vitamin D and / or Vitamin E and / or Vitamin K.

5. The wound dressing according to any one of claims 1-3, characterized in that said essential oil is tea tree oil and / or lavender oil and / or thyme oil and / or peppermint oil and / or cinnamon oil and / or St. John's wort oil.

6. A production method of a wound dressing, characterized in that it comprises the process steps of:i. dissolving cetyltrimethyl ammonium bromide (CTAB) in a solution containing water, ethanol, and ammonia,ii. adding 1 ,2-bis(trimethoxysilyl)ethane (BTME) and 1H,1H,2H,2H- perfluorooctyltriethoxysilane (POTS) into the mixture and stirring, iii. stirring the mixture in an ethanol solution containing hydrochloric acid solution and obtaining periodic mesoporous organosilica (PMOF) and washing the obtained PMOF with ethanol and drying,iv. suspending PMOF in water and mixing with vitamin and centrifuging the mixture, washing with water, and drying,v. mixing gelatin methacrylate (GelMA)-water solution with 1 -ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC) - N-Hydroxysuccinimide (NHS) solution, then adding EDTA into the mixture and continuing mixing, vi. dialyzing and then lyophilizing the mixture,vii. mixing the lyophilized mixture with phosphate buffered saline (PBS) solution containing eosin Y, triethanolamine (TEA), and vinyl caprolactam (VC), viii. mixing the mixture with the dried mixture obtained in step (iv.) and subjecting it to sonication,ix. adding alginate and laponite into the sonicated mixture and mixing, x. cross-linking by using visible light and with calcium chloride (CaCl2), and then lyophilizing,xi. adding essential oil to the lyophilized mixture.

7. The production method according to claim 6, characterized in that in step (iv.), the PMOF is suspended in water and mixed with vitamin in the range of 0.01-0.03 wt. % at a temperature range of 20-24°Cfor 1 day.

8. The production method according to claim 6, characterized in that in step (iv.), said vitamin is Vitamin A and / or Vitamin B and / or Vitamin C and / or Vitamin D and / or Vitamin E and / or Vitamin K.

9. The production method according to claim 8, characterized in that in step (iv.) the mixture mixed with the vitamin is first centrifuged at 6000 rpm for 15 minutes and then washed twice with water.

10. The production method according to claim 9, characterized in that in step (iv.), after said washing process, the mixture is dried at room temperature in the range of 20- 24°Cfor 1 day.

11. The production method according to claim 6, characterized in that in process step (v.), a GelMA-water solution at a rate of 3% weight / volume (w / v) is mixed with a mixture of EDC-NHS at a concentration of 0.2 M for 1 hour, and then EDTA at aconcentration of 0.1 M is added to this mixture and mixed at room temperature in the range of 20-24°Cfor 24 hours.

12. The production method according to claim 6, characterized in that in process step (vi.), said mixture is dialyzed against deionized water for 3 days.

13. The production method according to claim 12, characterized in that in process step (vi.), after said dialysis process the mixture is subjected to lyophilization at -60°Cfor 1 day.

14. The production method according to claim 6, characterized in that in process step (vii.), the mixture is mixed in phosphate buffered saline (PBS) with eosin Y at a concentration of 0.1 M as photoinitiator, triethanolamine (TEA) at a rate of 1.3% w / v as co-initiator and vinyl caprolactam (VC) at a rate of 1.0% w / v as co-monomer.

15. The production method according to claim 14, characterized in that in process step (vii.) it comprises the process step of keeping the mixture at a temperature of 80°C for 10 minutes after mixing.

16. The production method according to claim 6, characterized in that in process step (viii.) said sonication duration is 20 minutes.

17. The production method according to claim 6, characterized in that in process step (ix.) said mixture is mixed by adding laponite at a rate of 3 wt. % and alginate at a rate of 7 wt. %.

18. The production method according to claim 17, characterized in that the process step (ix.) comprises the process step of transferring the mixture into a syringe and printing it onto a template on a 3D (3-D) printer.

19. The production method according to claim 6, characterized in that in process step (x.), the processes of cross-linking by using visible light at 450-550 nm with an intensity of 100 mW / cm2for 60-180 seconds range, followed with calcium chloride (CaCh) at a concentration of 0.1 M for 15 minutes are performed.

20. The production method according to claim 19, characterized in that in the process step (x.), after cross-linking, it is kept at -80°C for 24 hours and subjected to lyophilization for 24 hours.

21. The production method according to claim 6, characterized in that in process step (xi.), an essential oil is added to the mixture at a rate of 10 wt. %.

22. The production method according to claim 21, characterized in that in process step (xi.), said essential oil is tea tree oil and / or lavender oil and / or thyme oil and / or peppermint oil and / or cinnamon oil and / or St. John's wort oil.

23. The wound dressing produced by a method according to any one of claims 6-22.

24. The wound dressing in hydrogel form produced by a method according to any one of claims 6-22.

25. The wound dressing produced by a method according to any one of claims 6-22 for use in chronic wound treatments.

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