Flexible exosome-coated biopolymer wound dressing

Abstract

The present invention discloses a flexible, biocompatible wound dressing encapsulating granules of a natural biopolymer solution designed for enhanced wound healing. The solution comprises stem cell-derived exosomes (3–8% by weight), octenidine dihydrochloride (0.5–1%), chitosan (32–36%), hyaluronic acid (13–19%), allantoin (3–9%), and sodium calcium alginate (20–27%), with carboxymethyl cellulose (8–15%) and carbomer (3.5–5%) as secondary components. The dressing, manufactured by blending, granulating, and encapsulating the solution in a cotton substrate via ultrasonic sealing, ensures adaptability to wound contours, rapid antimicrobial action (within 30 minutes), and controlled exosome release for tissue regeneration. Sodium calcium alginate, derived from brown seaweed, manages exudate, while chitosan enhances healing. Alternative biopolymers like alginate or gelatin may substitute chitosan or alginate. The dressing is effective for chronic, surgical, and acute wounds, promoting a moist healing environment, infection control, and patient comfort.

Description

DescriptionTitle of Invention : Flexible exosome-coated biopolymer wound dressingTechnical Field

[0001] The present invention is in the field of medical equipment, nursing, pharmaceuticals, and especially in the field of wound dressings.Background Art

[0002] Over time, human efforts to promote wound healing have led to the use of both natural and synthetic materials, many of which possess antimicrobial and antiseptic properties. These materials have been used for centuries, and some continue to be commonly used today as antiseptics. The first step in wound irrigation is the selection of an appropriate irrigation solution. Solutions intended for topical use may include antibiotics, topical cleansers, antifungals, and anesthetics. Ideally, an irrigation fluid should be clear, sterilizable, non-hemolytic, non-toxic, inexpensive, and easy to apply. While various antibiotics and antiseptics have been used for wound irrigation, the ideal additive is still under investigation from multiple scientific perspectives. It is critical to consider the cytotoxicity of wound irrigation solutions, especially those containing antiseptic agents such as hydrogen peroxide, Betadine, and chlorhexidine, as these substances can be toxic to tissues and may negatively impact tissue repair.Wound cleaning solutions should not impede the healing process, as certain antiseptics have been shown in some studies to delay wound closure and hinder healing. The purpose of this invention is to provide a wound dressing that is suitable for all types of wounds, addressing these concerns and improving the healing process. Some patents address some solutions and methods for the problem, for example:

[0003] PCT patent application NO. W02015186101 pertains to a stimuli-responsive wound dressing made of lyophilized hyaluronic acid (HA) hydrogel with embedded devices. These devices, containing chitosan and hypromellose, can be biofilms or electrospun fiber mats. Upon contact with hydroxyl radicals from inflammation at the wound site, the HA hydrogel depolymerizes, releasing the embedded devices and maintaining a moist environment conducive tohealing.The hydrogel may also contain alginate, which absorbs water and exudates, and can act as a deodorizer. A crosslinking agent like adipic dihydrazide (ADH) may be added to enhance the hydrogel's properties.

[0004] Korean Application NO. KR1020070118730 entitle “WOUND DRESSING MATERIAL WITH EXCELLENT ABILITY TO MOISTURIZE SKIN, WHICH MAXIMIZES THE ANTIBACTERIAL EFFECTS OF CHITOSAN BY SECURING A BROAD SURFACE AREA OF CHITOSAN AND A MANUFACTURING METHOD FOR THE SAME” discloses a wound dressing with excellent skin moisturizing ability and a manufacturing method designed to prevent the loss of chitosan due to moisture are provided. The dressing contains chitosan as the main ingredient and features a chitosan nanofiber network with an average diameter of less than 1000 nm, within which hyaluronic acid is embedded in minute pores. The molecular weight of chitosan ranges from 3000 to 200,000, with a degree of acetylation greater than 70%. This chitosan nanofiber network is laminated on non-woven synthetic fibers that have an average diameter greater than 1000 nm.

[0005] US patent application NO. US20210085823 entitled “Methods of making chitosan / hyaluronic acid hydrogel compositions and compositions made therefrom “describes a hydrogel wound dressing therapy and methods for making it. The dressing is made by combining two biopolymers, chitosan and hyaluronic acid, which enhance wound closure. The composition consists of cross-linked chitosan / hyaluronic acid hydrogels with a specific cross-link density, resulting in a swelling ratio of 20 to 100. The said wound dressing includes a lyophilized hyaluronic acid (HA) hydrogel with embedded devices containing chitosan and hypromellose. The HA hydrogel depolymerizes upon contact with hydroxyl radicals from inflammation, releasing the devices into the wound site and maintaining a moist environment conducive to healing.

[0006] US patent application NO. US20210100925 relates to an adhesive wound dressing that incorporates an absorbent matrix adhering to the central portion of a polyurethane backing with an adhesive layer for the skin. The absorbent matrix consists of a breathable and porous polyethylene film in contact with the wound, an adjacent absorbent layer made of non-woven fabric (60-65% viscose, 25-30% polyester, and 5-15% polypropylene), a polyethylene layer, and a hydrophobicpolystyrene layer in contact with the polyurethane backing. The matrix is impregnated with a solution of polysaccharides or their salts.

[0007] PCT application NO. WO / 2014 / 161085 discloses a composition for wound dressing includes a flexible, pharmaceutically acceptable carrier material with a hydrogel composition coated onto it. The hydrogel comprises aldehydic hyaluronic acid (HA) modified with 1 -amino-3,3-diethoxy-propane (ADEP) and chitosan conjugated to the aldehydic HA using Schiff base linkage. The carrier can be made from natural or synthetic woven fibers, or it can be a polymeric sheet material. Additional components like buffer agents, softening agents, and antimicrobials may also be included. The exemplary embodiments detail a method for preparing this hydrogel, which retains the natural polysaccharide structure of HA without using crosslinking agents that break its backbone. This hydrogel does not contain growth factors, cytokines, or additional cells, making it injectable, bioactive, and biocompatible for improving wound healing.Summary of Invention

[0008]

[0009] The invention described details a sophisticated, flexible wound dressing designed to enhance wound healing through a combination of biocompatible, superabsorbent, and reparative components encapsulated in a malleable, cottonbased dressing. This advanced wound care product leverages natural and synthetic biopolymers, stem cell-derived exosomes, and antimicrobial agents to promote tissue regeneration, manage wound exudate, and prevent infection. The dressing is engineered for versatility, making it suitable for a wide range of wound types, including chronic wounds (e.g., diabetic ulcers), surgical wounds, burns, and acute superficial wounds. The following summary outlines the composition, manufacturing process, key features, and potential substitutes, while addressing technical and regulatory considerations. Composition and Core ComponentsThe wound dressing comprises a carefully selected blend of primary and secondary components, each chosen for their synergistic contributions to wound healing, infection control, and patient comfort. The primary components, listed in Table 1 of the invention, include:

[0010] Stem Cell-Derived Exosomes (3-8% by weight): These nanoscale vesicles, sourced from licensed, commercially available stem cell samples, are critical for their regenerative properties. Exosomes carry bioactive molecules such as growth factors and cytokines, which stimulate fibroblast proliferation, keratinocyte migration, angiogenesis, and extracellular matrix (ECM) remodeling. These processes accelerate tissue repair, reduce inflammation, and enhance healing, particularly for chronic wounds where traditional treatments often fail.

[0011] Octenidine Dihydrochloride (0.5-1 % by weight): This organic ammonium compound serves as a potent antimicrobial agent, effective against bacteria, fungi, and viruses. Its mechanism involves disrupting microbial cell walls, achieving rapid pathogen elimination (within 30 minutes) and preventing regrowth. Compared to alternatives like chlorhexidine or povidone-iodine, octenidine causes less tissue irritation, making it ideal for sensitive wounds.

[0012] Chitosan (32-36% by weight): A biopolymer derived from chitin, chitosan is a cornerstone of the dressing due to its biocompatibility, antimicrobial properties, and ability to form a complex with exosomes. It promotes fibroblast proliferation, collagen synthesis, and hemostasis, while maintaining an acidic wound environment that inhibits bacterial growth. Its water-retention capacity ensures a moist healing environment.

[0013] Hyaluronic Acid (13-19% by weight): A naturally occurring polysaccharide, hyaluronic acid (HA) enhances wound healing by promoting cell migration, angiogenesis, and tissue regeneration. Its exceptional water-retention capacity maintains a moist wound environment, reducing scab formation and improving patient comfort. HA’s biocompatibility minimizes adverse reactions.

[0014] Allantoin (3-9% by weight): This organic compound supports tissue repair by stimulating cell proliferation and acting as a humectant to maintain moisture. Its anti-inflammatory and keratinolytic properties soothe irritated skin and facilitate the removal of dead tissue, promoting smoother healing.

[0015] Sodium Calcium Alginate (20-27% by weight): Derived from brown seaweed, this biopolymer excels in exudate absorption, forming a gel-like barrier upon contact with wound fluid. This gel protects the wound, regulates moisture, andpromotes clot formation, making it effective for bleeding wounds. Its non-adherent nature ensures painless dressing changes.

[0016] The secondary components, comprise:

[0017] Carboxymethyl Cellulose (CMC) (8-15% by weight): A superabsorbent polysaccharide, CMC manages wound exudate by forming a protective, flexible layer that maintains a moist environment while preventing maceration. Its viscoelastic properties enhance dressing conformability, and it can serve as a delivery matrix for therapeutic agents.

[0018] Carbomer (3.5-5% by weight): A synthetic polymer derived from acrylic acid, carbomer acts as a thickening and stabilizing agent, forming a viscous gel that regulates moisture levels. Its pH-responsive properties allow it to adapt to the wound environment, and it supports the controlled release of active ingredients.

[0019] Manufacturing ProcessThe preparation of the wound dressing involves a multi-step process designed to ensure homogeneity, sterility, and functionality:

[0020] Primary Mixture Preparation: Octenidine dihydrochloride, hyaluronic acid, sodium calcium alginate, and allantoin are blended in a high-shear mixer for two hours at room temperature to achieve a uniform mixture. This step ensures the even distribution of active and reparative components.

[0021] Filler Preparation: CMC and carbomer are separately mixed to form a consistent powder, with flowability assessed to ensure suitability for granulation.

[0022] Biopolymer Complex Formation: Under aseptic conditions (e.g., in a Class 100 cleanroom), exosomes (3-8% by weight) are incorporated into chitosan to form a biopolymer complex. Sterility is maintained through validated sterilization techniques (e.g., heat or filtration) to prevent contamination.

[0023] Integration of Components: The biopolymer complex is blended with the primary mixture for one hour to ensure uniformity, verified through analytical methods such as Fourier-Transform Infrared Spectroscopy (FTIR).

[0024] Final Composite Preparation: The combined mixture is homogenized with the CMC-carbomer filler for three hours, with content uniformity and physical properties (e.g., pH 5.5-7.5, absorbency) tested to meet specifications.

[0025] Granulation: The composite is processed into granules (0.5-2 mm) using a fluid bed or high-shear granulator, with parameters optimized for consistent size and performance.

[0026] Dressing Assembly: A measured quantity of granules is applied to a flexible, medical-grade cotton substrate (or alternative materials like non-woven cellulose). Ultrasonic sealing (20-40 kHz) secures the granules, ensuring durability and flexibility. The dressing’s layered structure includes a breathable polyurethane film, a foam moisture control layer, non-woven spunbond fabric, a superabsorbent granule layer, and an exosome-coated hydrophilic antimicrobial layer.

[0027] Application: The final dressing is packaged in sterile, single-use pouches, ready for application to wounds. Its flexibility allows it to conform to irregular wound shapes, delivering antimicrobial, absorbent, and regenerative components effectively.

[0028] Key FeaturesThe dressing’s design incorporates several innovative features:

[0029] High Flexibility: The use of biocompatible polymers (e.g., chitosan, sodium calcium alginate) and a cotton-based substrate ensures adaptability to various wound shapes, enhancing patient comfort.

[0030] Controlled Exosome Release: A layer-by-layer coating technique encapsulates exosomes within biopolymer layers, allowing gradual release triggered by wound exudate. This ensures sustained delivery of regenerative agents.

[0031] Biodegradability: The dressing naturally degrades post-treatment, reducing the need for frequent replacements and minimizing environmental impact.

[0032] Antimicrobial Action: Octenidine dihydrochloride provides rapid pathogen elimination, reducing infection risk within 30 minutes.

[0033] Superabsorbency: CMC and sodium calcium alginate manage exudate, maintaining an optimal moisture balance to support healing.

[0034] Versatility: The dressing is effective for chronic wounds (e.g., diabetic ulcers), surgical wounds, burns, and acute wounds, with daily changes recommended for continuous healing.

[0035] Potential SubstitutesThe invention allows for alternative materials to maintain functionality:

[0036] Exosomes: Platelet-derived growth factors or synthetic peptides could replace exosomes, though regulatory approval would be required.

[0037] Octenidine Dihydrochloride: Benzalkonium chloride or silver nanoparticles may serve as alternative antimicrobials, subject to biocompatibility testing.

[0038] Chitosan / Sodium Calcium Alginate: Alginate, gelatin, or collagen could substitute, provided they offer similar structural and absorbent properties.

[0039] CMC / Carbomer: Hydroxyethyl cellulose, sodium polyacrylate, or xanthan gum may replace these fillers, ensuring equivalent absorbency and stability.

[0040] Cotton Substrate: Polyurethane or silicone-based materials could be used for enhanced flexibility or adhesion.

[0041] Layer-by-Layer Coating: Liposomal encapsulation or nanoparticle-based delivery systems may replace the exosome release mechanism.Technical Problem

[0042] Wounds resulting from various injuries go through multiple stages of healing, and wound dressings play a crucial and decisive role in this process by protecting the wound. An effective wound dressing should be designed to be suitable for all types of wounds, maintaining adequate moisture in the wound bed to support healing, ensuring sterility to prevent contamination and microbial entry, and being non-irritating, non-sensitizing, and non-toxic to the skin. It should also avoid adhering to the wound or leaving any residue when removed, require minimal replacements while still ensuring timely changes to prevent adherence to the skin, and absorb excess exudate while removing dead skin cells. Furthermore, it should allow for easy and comfortable removal from the wound bed, offer a variety of sizes and shapes to accommodate different body areas, and be affordable for all patients. The present invention addresses all these needs by providing a dressing suitable for all types of wounds. The goal of this invention is to develop a dressing that not only accelerates the healing process by coating the wound with exosomes but also offers flexibility and adaptability to different body shapes. This dressing is particularly beneficial for chronic wounds such asdiabetic ulcers, surgical wounds, and burn wounds, but can also be used effectively for acute and superficial wounds.Advantageous Effects of Invention

[0043] The flexible exosome-coated biopolymer dressing introduced in this patent combines advanced technologies with flexible biopolymers to significantly accelerate wound healing while preventing infection. Its innovative design ensures high flexibility, allowing it to conform to various body shapes, and incorporates a gradual release mechanism for exosomes, promoting sustained wound repair. Additionally, the dressing is biodegradable, eliminating the need for frequent replacements and reducing environmental impact. This combination of features not only enhances patient comfort and reduces treatment costs but also represents a groundbreaking advancement in wound care.Brief Description of Drawings

[0044] [Fig.1 shows the process for preparing natural polymer solution with prolonged drug release for wound dressings.

[0045] Fig.2 shows the layers of flexible exosome-coated biopolymer wound dressing. ]Description of Embodiments

[0046] As required, detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which can be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one of ordinary skill in the art to variously employ the present invention in virtually any appropriately detailed structure. Further, the terms and phrases used herein are not intended to be limiting; but rather, to provide an understandable description of the invention.

[0047] As used herein, the terms “about” or “approximately” apply to all numeric values, whether or not explicitly indicated. These terms generally refer to a range of numbers that one of skill in the art would consider equivalent to the recited values (i.e., having the same function or result).

[0048] The wound dressing discloses in the present invention, using a natural biopolymer solution, which is initially prepared in the form of granules. These granules are then encapsulated within a flexible and malleable dressing, preferably made of pure cotton (such as a tea bag-like structure). This configuration ensures optimal adaptability to the wound bed while maintaining comfort and ease of use.

[0049] The core components of the wound dressing, as described in the present invention, are as follows:

[0050] Exosomes derived from stem cells (3-8% by weight of the total composition):These small vesicles released from stem cells are known to play a significant role in wound healing and fibroblast stimulation, promoting tissue regeneration and repair.

[0051] Octenidine dihydrochloride (0.5-1 % by weight): An organic ammonium compound, this serves as an effective disinfectant for wounds, skin, and mucous membranes, helping to reduce bacterial load and prevent infection.

[0052] Chitosan (32-36% by weight): A biopolymer derived from chitin, chitosan acts as a complexing agent, providing both structural support and biocompatibility. It is also coated with exosomes to enhance its healing properties.

[0053] Hyaluronic acid (13-19% by weight): This natural polysaccharide, a component of the glycosaminoglycan family, is a key player in wound healing, promoting cell migration and tissue regeneration.

[0054] Allantoin (3-9% by weight): An organic compound, allantoin acts as a strong detoxifying and healing agent, aiding in tissue repair and providing soothing relief to damaged skin and wounds.

[0055] Sodium calcium alginate (20-27% by weight): Derived from brown seaweed, this polysaccharide biopolymer is highly effective in moisture absorption, helping to regulate wound exudate while maintaining an optimal moisture environment that accelerates healing.

[0056] In addition, secondary components are included to enhance the wound dressing's performance:

[0057] Carboxymethyl cellulose (CMC) (8-15% by weight): A polysaccharide biopolymer used as a filler and absorbent for wound exudates, CMC plays a critical role in maintaining a moist environment and aiding in the removal of excess fluids from the wound site.

[0058] Carbomer (3.5-5% by weight): A synthetic polymer derived from acrylic acid, carbomer acts as a stabilizing and thickening agent. It also helps regulate moisture levels in the wound, preventing both dehydration and excessive moisture accumulation, which is crucial for optimal healing.

[0059] The innovative formulation of this dressing is designed to provide immediate antimicrobial action. Upon contact with the wound, the antimicrobial component, particularly octenidine dihydrochloride, works swiftly to eliminate any infectious agents, typically within 30 minutes, while also preventing further microbial growth, thus reducing the risk of infection and promoting a clean healing environment. The dressing not only accelerates wound healing but also ensures the protection and regeneration of damaged tissue, making it highly effective for various wound types.

[0060] Furthermore, while the above components have been carefully selected for their unique and synergistic effects, alternative materials with similar properties could be considered without departing from the scope of the invention. For example, other biopolymers like alginate or gelatin may be used in place of chitosan or sodium calcium alginate, and other antimicrobial agents such as benzalkonium chloride or silver nanoparticles could potentially replace octenidine dihydrochloride without compromising the overall efficacy of the dressing.

[0061] The healing components of the dressing play a critical role across various stages of wound healing, including the inflammatory phase, granulation, and epithelialization, ultimately improving the overall wound healing process. The superabsorbent component of the dressing is designed to absorb wound exudates and secretions, effectively maintaining an optimal moisture balance at the wound site. The flexible nature of the dressing allows it to conform to deep or irregularly shaped wounds, ensuring that antimicrobial agents, moistureabsorbing compounds, and healing factors are delivered effectively to the affected area. The flexibility and malleability of the dressing, combined with thestem cell-derived exosomes, make it particularly innovative. Exosomes, which are small vesicles released from cells (including stem cells), play a vital role in tissue repair and regeneration. The exosomes used in this invention are sourced from licensed, commercially available stem cell samples to ensure their purity and efficacy.

[0062] This wound dressing is designed for a wide range of applications, including the treatment of deep and perforated wounds, as well as the healing of wounds that have progressed past the infectious stage. It is especially effective for chronic wounds such as diabetic ulcers, surgical wounds, and burn injuries. Additionally, it can be applied to acute and superficial wounds to enhance the healing process. The method of application involves using the dressing as a flexible bandage on deep and perforated wounds, with daily dressing changes recommended to ensure continuous healing.

[0063] Key features of this dressing, which contribute to its uniqueness and ensure the targeted, controlled release of therapeutic agents, include:

[0064] High Flexibility: The dressing’s ability to adapt to various body contours is due to the use of flexible biopolymers, which ensure comfort and secure application, even on challenging wound sites.

[0065] Gradual Release of Exosomes: The dressing utilizes advanced technologies, such as layer-by-layer coating, to facilitate the gradual release of exosomes. Exosomes are encapsulated within biopolymer layers made of materials like chitosan and sodium alginate. These layers are applied to a base matrix (e.g., hydrophilic fabric) and dissolve gradually in the presence of wound exudates. This controlled release system allows for precise regulation of exosome delivery, based on factors such as the number and thickness of the layers. Furthermore, the use of biocompatible materials ensures that the release process is both effective and safe for the body.

[0066] Biodegradability: Once the treatment period is completed, the dressing naturally biodegrades, eliminating the need for constant replacement. This ensures that the dressing is both environmentally friendly and convenient for the patient, reducing the need for frequent medical intervention.

[0067] While the above components and methods have been carefully selected for their specific roles in optimizing wound healing, alternative materials or technologies could be considered without departing from the scope of the invention. For instance, other flexible polymers such as polyurethane or silicone could be used as substitutes for the biopolymers in the dressing, and liposomal encapsulation or nanoparticle-based delivery systems could potentially replace the layer-by-layer exosome release mechanism. Such substitutions would still allow the dressing to fulfill its core therapeutic functions while maintaining its effectiveness in wound healing.

[0068] Table 1 shows the main ingredients of the flexible exosome-coated biopolymer wound dressing.biopolymer wound dressing.

[0070] Process for preparing a natural biopolymer solution with prolonged drug release for wound dressings as shoen in Fig.1

[0071] The components, including octenidine dihydrochloride, hyaluronic acid, sodium calcium alginate, and allantoin, are combined in the specified proportions. The mixture is thoroughly blended in a mixer for 2 hours at room temperature to ensure uniformity(11 ).

[0072] Separately, the filler materials, carboxymethyl cellulose (CMC) and carbomer, are mixed in a separate mixer and processed to form a consistent, uniform powder(12).

[0073] Under aseptic conditions, 3-8% by weight of exosomes, relative to the total composition, are added to chitosan to form a biopolymer complex(13). (Aseptic conditions refer to sterile procedures performed to prevent contamination by pathogens. These methods may include sterilization by heat, flame, or other sterilization techniques, all governed by medical and laboratory standards).

[0074] The biopolymer complex prepared in step 13 is then added to the mixture from step 11 (octenidine dihydrochloride, hyaluronic acid, sodium calcium alginate, and allantoin). The components are mixed thoroughly for one hour to achieve a uniform blend(14).

[0075] The resulting complex is then added to the powdered filler (carboxymethyl cellulose and carbomer) and mixed for an additional 3 hours to ensure homogeneity of the final formulation(15).

[0076] The completed mixture is processed into granules using a granulator, which shapes the final product for integration into the dressing^ 6).

[0077] A specified amount of granules is then placed inside a specially designed wound dressing made of pure cotton, which has high flexibility and malleability (similar to a tea bag). Ultrasonic stitching is performed to secure the granules inside the cotton dressing(17).

[0078] The wound dressing, now containing the super-absorbent and healing granules, is ready for use. It can be applied to the wound site, adjusting to the wound’s shape and form for effective healing and comfort.

[0079] This process ensures the creation of a flexible, super-absorbent wound dressing with prolonged drug release, optimized for accelerated healing and infection prevention.

[0080] Figure 2 shows the layers that make up the wound dressing. The layers that make up the wound dressing include:

[0081] 1. Highly breathable polyurethane film (outer protective layer),

[0082] 2. Moisture control layer (foam layer),

[0083] 3. Non-woven spunbond fabric layer,

[0084] 4. Superabsorbent granule layer ,

[0085] 5. Non-woven spunbond fabric layer,

[0086] 6. Exosome-coated hydrophilic fabric and antimicrobial layer.

[0087] Octenidine dihydrochloride is a highly effective chemical antiseptic widely used for disinfecting wounds, skin, and mucous membranes. It works by disrupting the cell walls of bacteria, fungi, and viruses, effectively eliminating pathogens and preventing their regrowth. Compared to other commonly used antiseptics, such as chlorhexidine and povidone-iodine, octenidine offers superior antimicrobial activity while causing significantly less irritation to body tissues, making it particularly suitable for patients with sensitive wounds or compromised immune systems. Its versatility has made it a popular choice in healthcare and medical products, with applications including wound and burn care, pre-surgical skin disinfection, hygiene products like hand sanitizers and wipes, mouthwashes to reduce bacterial growth during dental treatments, and gentle disinfection for damaged or sensitive skin. The inclusion of octenidine dihydrochloride in modern wound dressings enhances their antimicrobial properties, providing targeted infection control while minimizing tissue irritation, making it an essential component in advanced wound care formulations.

[0088] Hyaluronic acid (HA) is a naturally occurring polysaccharide found abundantly in the human body, particularly in connective tissues, skin, and synovial fluid, and its unique biological and physical properties make it a highly valuable component in advanced wound dressing formulations. HA possesses an exceptional ability to retain water, which helps maintain a moist wound environment, promoting optimalhealing conditions, reducing scab formation, and accelerating tissue repair. Being a natural and non-toxic substance, HA is highly biocompatible, minimizing the risk of adverse reactions or irritation when applied to wounds, making it suitable for a wide range of patients. It also plays a vital role in enhancing the wound healing process by stimulating the migration of fibroblasts and keratinocytes essential for tissue repair and epithelialization, encouraging angiogenesis to support the formation of new blood vessels and improve oxygen and nutrient supply to the wound site, and regulating the inflammatory response to reduce excessive inflammation while facilitating proper healing, especially in the early stages.Certain HA-based formulations can even provide antimicrobial properties, reducing the risk of infection and supporting a cleaner wound environment.Additionally, HA contributes to the flexibility and elasticity of wound dressings, ensuring they conform comfortably to various body shapes and movements, which enhances patient comfort and compliance. These combined properties make hyaluronic acid an essential ingredient in modern wound dressings, providing not only therapeutic benefits but also ensuring a high standard of safety and comfort for patients.

[0089] Allantoin, a naturally occurring compound found in various plants such as comfrey, is widely recognized for its restorative, soothing, and healing properties. It is frequently incorporated into skincare, cosmetic formulations, and advanced wound dressings due to its multifaceted benefits. Allantoin stimulates cell proliferation and tissue regeneration, aiding in the repair of damaged tissues. Its ability to accelerate the growth of new tissue makes it an excellent addition to wound care products, enhancing the overall healing process. As a potent humectant, allantoin attracts and retains moisture in the wound area, creating a moist environment essential for optimal healing. This not only facilitates tissue repair but also minimizes the formation of scabs, ensuring smoother healing outcomes. Allantoin possesses anti-inflammatory properties that help soothe irritated or inflamed skin. This makes it particularly effective for wounds that are painful, sensitive, or prone to discomfort. Allantoin's ability to soften and break down keratin helps remove dead skin cells from the wound site. This promotes wound cleaning and facilitates the regeneration of healthy tissue. Allantoin is biocompatible, non-toxic, and generally well-tolerated, even by individuals withsensitive skin. Its safe profile makes it a reliable choice for a wide range of wound care applications, including chronic and acute wounds. By combining these properties, allantoin significantly contributes to the efficacy of modern wound dressings, improving the healing process while ensuring patient comfort and minimizing the risk of adverse reactions.

[0090] Sodium calcium alginate, a biopolymer derived from brown seaweed, is a highly versatile material widely used in modern wound dressings due to its unique properties, making it an essential component in advanced wound care. With its exceptional absorbent capacity, sodium calcium alginate helps maintain a moist wound environment critical for optimal healing by absorbing excess exudate, preventing maceration, and reducing scab formation, which promotes faster tissue regeneration. As a naturally derived polymer, it is biocompatible and well- tolerated by the body, minimizing the risk of allergic reactions or irritation and making it suitable for various wound types, including those on sensitive or compromised skin. Upon contact with wound exudate, it forms a soft, gel-like barrier over the wound bed that protects the wound from external contaminants while creating a moist environment conducive to healing and reducing patient discomfort. Additionally, sodium calcium alginate aids in controlling bleeding by promoting clot formation, making it particularly effective for managing acute wounds, surgical incisions, and injuries with active bleeding. It also serves as an effective carrier for therapeutic agents such as antibiotics, growth factors, or antimicrobial compounds, allowing for the controlled and localized release of these substances directly at the wound site to enhance healing and reduce the risk of infection. Furthermore, its non-adherent nature ensures painless removal and minimizes disruption of newly formed tissue during dressing changes, significantly enhancing patient comfort and supporting the healing process.

[0091] Stem cell exosomes have emerged as a groundbreaking innovation in advanced wound dressings due to their extraordinary regenerative and therapeutic properties. These nanoscale vesicles, naturally released by stem cells, carry bioactive molecules that influence key biological processes essential for wound healing. Acting as mediators of cellular communication, exosomes transfer proteins, lipids, and RNA to recipient cells, influencing cellular behavior and promoting coordinated healing responses at the wound site. Rich in bioactivemolecules such as growth factors and cytokines, stem cell exosomes promote tissue regeneration and angiogenesis, which are crucial for restoring damaged tissue and enhancing oxygen and nutrient delivery to the wound. Their antiinflammatory components reduce excessive inflammation, creating an optimal environment for healing while minimizing tissue damage caused by prolonged inflammatory responses. Exosomes also stimulate the proliferation and migration of key cell types like fibroblasts, which produce collagen, and keratinocytes, essential for re-epithelialization, thereby accelerating the healing process.Furthermore, they play a pivotal role in synthesizing and remodeling the extracellular matrix (ECM), the structural framework that supports tissue repair and ensures the formation of functional, durable tissue. The regenerative capabilities of stem cell exosomes make them particularly effective for managing chronic wounds, such as diabetic ulcers or pressure sores, by addressing underlying cellular dysfunctions and initiating sustained healing in cases where traditional treatments often fall short.

[0092] Chitosan, a biopolymer derived from chitin — a natural substance found in the shells of crustaceans — has attracted significant attention in the field of wound care due to its exceptional properties. Its versatile and bioactive nature makes it a key component in advanced wound dressing formulations. Chitosan is highly biocompatible and biodegradable, making it safe and well-suited for medical applications, while its natural composition minimizes the risk of adverse reactions when in contact with human tissues. Chitosan exhibits potent antimicrobial activity against a broad spectrum of pathogens, including bacteria and fungi. This inherent property helps prevent infections in wounds, creating a protective environment conducive to healing. Additionally, chitosan's excellent waterretention capability maintains an optimal moist wound environment, critical for cell migration, tissue regeneration, and pain reduction during the healing process. Chitosan actively stimulates fibroblast proliferation and collagen synthesis — two essential processes for tissue repair and regeneration. By promoting these activities, it accelerates wound closure and improves healing outcomes. Furthermore, chitosan effectively facilitates blood clotting, making it highly useful for managing bleeding in acute wounds. Its hemostatic capability ensures quicker stabilization of wounds.Chitosan also helps maintain an acidicpH in the wound environment, which inhibits bacterial growth and supports the healing process. An acidic pH enhances the bioavailability of certain therapeutic agents within the dressing.

[0093] Carboxymethyl Cellulose (CMC), a cellulose derivative, is widely used in wound care due to its exceptional properties that enhance healing and patient comfort. Its versatile functionality makes it an essential component in modern wound dressings. CMC is highly biocompatible, meaning it can be safely applied to body tissues without causing adverse reactions, making it suitable for various wound care applications. Its strong hydrophilic nature enables CMC to absorb wound exudate effectively, maintaining a moist wound environment essential for optimal healing. Additionally, it aids in releasing excess moisture, preventing maceration of surrounding tissues. CMC can form flexible, protective layers over wounds, acting as a barrier against external contaminants while allowing gas exchange, thus promoting a safer and more conducive healing environment. The viscoelastic nature of CMC allows it to adapt and conform to the wound bed, improving both comfort and dressing efficacy. This property ensures a balance between viscosity (flow) and elasticity (shape retention), providing flexibility and durability during use. CMC can serve as a delivery matrix for therapeutic agents, such as antibiotics or growth factors, enabling the sustained and localized release of active ingredients directly to the wound site, enhancing treatment effectiveness. Furthermore, CMC contributes to maintaining an optimal pH level in the wound environment. By keeping the wound slightly acidic, it helps inhibit bacterial growth and supports faster healing.

[0094] Carbomer, a polymer derived from acrylic acid, is extensively utilized in pharmaceutical and cosmetic formulations due to its versatile properties. In the context of wound dressings, carbomer plays a significant role by enhancing performance and contributing to the overall effectiveness of the dressing.Carbomer serves as an effective thickening agent, stabilizing formulations and improving the viscosity of gels and ointments used in wound care. When neutralized, carbomer forms a clear, viscous gel that provides a moist environment essential for wound healing and tissue regeneration. Its hydrophilic nature allows carbomer to retain moisture effectively, keeping the wound hydrated and reducing the risk of scab formation. Carbomer can be formulated torespond to pH changes, making it ideal for creating adaptive dressings that adjust to the wound environment. It also serves as a matrix for the controlled release of therapeutic agents, such as antibiotics or anti-inflammatory drugs, ensuring a sustained and localized delivery directly to the wound site. Furthermore, carbomer is widely recognized as safe and biocompatible, making it suitable for direct contact with human tissues without causing adverse reactions.Industrial Applicability

[0095] This invention serves as a flexible wound dressing embedded with superabsorbent and healing granules, designed for use at the wound site.Enriched with chitosan, a natural and biodegradable biopolymer with antibacterial properties, it promotes effective wound healing. This advanced dressing is suitable for a wide range of applications, including the treatment of skin infections, deep and perforated wounds, and wounds that have progressed beyond the infectious stage. Its flexible design makes it ideal for managing chronic wounds such as diabetic ulcers, surgical incisions, and burns, as well as acute and superficial wounds. The dressing is applied directly to the wound site and is intended for daily use during dressing changes, offering a reliable and effective solution for various wound care needs;

Claims

Claims

1. flexible exosome-coated biopolymer wound dressing comprising:a) stem cell-derived exosomes in an amount of 3-8% by weight of the total composition,b) an antimicrobial agent in an amount of 0.5-1% by weight of the total composition,c) chitosan in an amount of 32-36% by weight of the total composition, d) hyaluronic acid in an amount of 13-19% by weight of the total composition,e) allantoin in an amount of 3-9% by weight of the total composition, f) sodium calcium alginate in an amount of 20-27% by weight of the total composition; which is configured as a multilayer wound dressing comprises:

2. i) a breathable polyurethane film as an outer protective layer;

3. ii) a foam layer for moisture control;

4. iii) at least one non-woven spunbond fabric layer;

5. iv) a superabsorbent granule layer containing the biopolymer composition;and

6. v) an exosome-coated hydrophilic fabric layer .

7. A method of manufacturing a wound dressing, comprising:a) preparing a biopolymer composition by blending:i) stem cell-derived exosomes in an amount of 3-8% by weight of the total composition;ii) an antimicrobial agent in an amount of 0.5-1% by weight of the total composition;iii) chitosan in an amount of 32-36% by weight of the total composition; iv) hyaluronic acid in an amount of 13-19% by weight of the total composition;v) allantoin in an amount of 3-9% by weight of the total composition; vi) sodium calcium alginate in an amount of 20-27% by weight of the total composition;b) mixing the biopolymer composition for at least two hours to achievehomogeneity;c) forming a biopolymer complex by aseptically combining the exosomes with the chitosan under sterile conditions;d) blending the biopolymer complex with the biopolymer composition to form a uniform mixture;e) processing the uniform mixture into granules;f) encapsulating the granules within a flexible and malleable substrate; andg) sealing the substrate to secure the granules.

8. The wound dressing according to claim 1 , further comprising:a) carboxymethyl cellulose (CMC) in an amount of 8-15% by weight of the total composition, andb) carbomer in an amount of 3.5-5% by weight of the total composition.

9. The wound dressing according to claim 1 , wherein the antimicrobial agent is octenidine dihydrochloride.

10. The wound dressing according to claim 1 , wherein the biopolymer composition further comprises at least one alternative biopolymer selected from the group consisting of alginate, gelatin, collagen, and pectin.

11. The wound dressing according to claim 1 , wherein the antimicrobial agent is selected from the group consisting of octenidine dihydrochloride, benzalkonium chloride, and silver nanoparticles.

12. The wound dressing according to claim 1 , wherein the exosomes are encapsulated within biopolymer layers comprising chitosan and sodium calcium alginate.

13. The method according to claim 2, further comprising blending carboxymethyl cellulose (CMC) in an amount of 8-15% by weight and carbomer in an amount of 3.5-5% by weight with the biopolymer composition prior to granulation, wherein the CMC and carbomer are premixed to form a uniform powder.

14. The method according to claim 2, wherein encapsulating the granules within the substrate comprises ultrasonic sealing at a frequency of 20-40 kHz.

15. The method according to claim 2, wherein the biopolymer complex is formed in a Class 100 cleanroom under aseptic conditions, using sterilization techniques selected from the group consisting of heat sterilization, filtration, and chemical sterilization.

16. The method according to claim 2, wherein the substrate is selected from the group consisting of pure cotton, non-woven cellulose, polyurethane, and silicone.i

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