Composite gel for promoting wound healing
By preparing a composite gel containing growth factors and therapeutic gases, the problem of providing personalized treatment in existing wound care methods has been solved, enabling synergistic treatment at different wound types and healing stages, significantly accelerating healing and reducing scar formation.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- WUXI XISHAN NJU INSTITUTE OF APPLIED BIOTECHNOLOGY
- Filing Date
- 2024-11-22
- Publication Date
- 2026-05-22
AI Technical Summary
Existing wound treatment methods struggle to provide personalized, synergistic growth factor and functional gas therapy across different types and healing stages, particularly in refractory wounds such as chronic wounds and diabetic ulcers, where healing efficiency is low.
By preparing a composite gel containing growth factors and therapeutic gases, and utilizing the synergistic effect of growth factors and therapeutic gases, the combination of gases and growth factors can be adjusted according to the wound type and healing stage to form a gel with microbubble structure, providing personalized treatment solutions.
It significantly accelerates the wound healing process, reduces scar formation, improves the local microenvironment, enhances healing efficiency, and adapts to the treatment needs of different wound types and healing stages.
Smart Images
Figure CN122070901A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a composite gel for promoting wound healing, particularly a composite gel containing growth factors and therapeutic gases. By selectively adjusting the combination of gases and growth factors, the synergistic effect between the two can be maximized to meet the treatment needs of different wound types and healing stages. This composite gel can be widely used in the clinical treatment of different types of wounds, especially refractory wounds such as chronic wounds and diabetic ulcers. Background Technology
[0002] Wound healing is a complex, multi-stage physiological process involving inflammatory responses, cell proliferation, and tissue remodeling, and is regulated by various cytokines, signaling molecules, and the microenvironment. Recent studies have found that functional gases such as oxygen, hydrogen, hydrogen sulfide, and nitric oxide significantly promote cell repair and regeneration. These gases possess anti-inflammatory, antioxidant, angiogenesis-promoting, and antibacterial properties, providing a suitable healing environment for the wound site, reducing the risk of infection, and improving local tissue microcirculation.
[0003] Furthermore, the role of growth factor-containing biomaterials in wound repair is receiving increasing attention. Growth factors play a crucial role in wound healing, regulating tissue repair and regeneration by promoting cell proliferation, migration, differentiation, and angiogenesis. Different types of growth factors, such as epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF), function at different healing stages (e.g., inflammation, proliferation, and remodeling), promoting epithelialization, angiogenesis, collagen synthesis, and wound closure. Therefore, combining growth factors with functional gases in wound healing may significantly improve healing efficiency.
[0004] Based on the above research findings, this invention proposes a composite gel in which growth factors and functional gases are co-loaded in a hydrogel. The combination of gases and growth factors is selectively adjusted according to different wound types and healing stages to maximize the synergistic effect between the two, providing an optimized microenvironment for the wound, significantly accelerating the healing process and reducing scar formation, thus meeting the treatment needs of different wound types and healing stages. Summary of the Invention
[0005] This invention provides a composite gel for promoting wound healing, aiming to address the shortcomings of existing wound treatment methods, particularly in the healing of refractory wounds such as chronic wounds and diabetic ulcers. The composite gel contains at least one growth factor and at least one therapeutic gas, and its synergistic effect can be maximized by precisely adjusting the combination of the gas and growth factor to meet the treatment needs of different types of wounds at different stages of the healing process.
[0006] I. Composition of the composite gel
[0007] 1. Growth factors
[0008] The growth factors in the composite gel include, but are not limited to, epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF-β), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), and keratinization factor (KGF). Growth factors can stimulate cell proliferation, migration, and differentiation, promoting tissue repair and angiogenesis. Specifically, EGF promotes epithelial cell proliferation and migration, FGF and VEGF contribute to angiogenesis, TGF-β regulates the synthesis and degradation of the extracellular matrix, and PDGF and IGF promote fibroblast proliferation and collagen synthesis during wound healing.
[0009] 2. Therapeutic gases
[0010] The therapeutic gases in the composite gel include oxygen (O2), hydrogen (H2), nitric oxide (NO), and hydrogen sulfide (H2S). These gases have unique physiological effects at different stages of wound healing. Oxygen mainly acts on the proliferation and remodeling stages of wound healing, improving tissue oxygen supply and enhancing wound healing speed by promoting cell metabolism, division, and new angiogenesis. Hydrogen and hydrogen sulfide, on the other hand, mainly reduce oxidative stress and inflammatory responses during the inflammatory stage of wound healing through their antioxidant and anti-inflammatory effects, promoting the activity of immune cells and cell proliferation.
[0011] 3. Matrix material.
[0012] The matrix of the composite gel uses highly biocompatible polymer materials, such as poloxamer, sodium hyaluronate, carbomer, and gelatin, which can form a hydrogel with appropriate viscosity to ensure the stable release of growth factors and therapeutic gases at the wound site. This matrix material provides mechanical support while maintaining a moist wound environment, promoting cell growth and healing.
[0013] II. Functions and advantages of composite gels.
[0014] The composite gel of the present invention has the following significant advantages:
[0015] 1. Synergistic effect promotes wound healing.
[0016] This invention combines growth factors with therapeutic gases to promote wound healing through their synergistic effect. Specifically, during the inflammatory phase of a wound, gases such as hydrogen, carbon monoxide, or hydrogen sulfide can reduce local oxidative stress and inhibit the inflammatory response through antioxidant and anti-inflammatory effects. Simultaneously, growth factors promote cell proliferation and migration, providing a favorable cellular basis for subsequent wound repair. During the proliferation and remodeling phase of the wound, gases such as oxygen and nitric oxide increase local oxygen supply, promote cell metabolism and division, and enhance the directional migration and proliferation of cells in the wound area. Growth factors further promote angiogenesis and collagen synthesis, thereby accelerating wound structural reconstruction and healing.
[0017] 2. Customizable treatment plans
[0018] The gas release and growth factor concentration of the composite gel can be adjusted according to the wound type and healing stage, providing personalized treatment options. For example, for chronic wounds or diabetic ulcers, the type of gas in the gel can be controlled according to the wound's oxygen demand and oxidative stress level, thereby achieving precision treatment.
[0019] 3. Improvement of the local microenvironment
[0020] The therapeutic gas in the composite gel is distributed in the form of microbubbles. These bubbles are slowly released, continuously improving the local microenvironment of the wound. The presence of microbubbles not only provides a continuous oxygen supply but also enhances blood circulation and gas exchange in the wound area through local pressure regulation, further promoting the healing process.
[0021] 4. Biocompatibility and safety
[0022] The matrix material used in the composite gel has excellent biocompatibility, can integrate well with human tissue, and does not produce an immune rejection reaction. At the same time, the concentration and release rate of the therapeutic gas in the gel are precisely controlled to ensure that it does not cause any adverse effects on the wound or surrounding tissues during treatment.
[0023] III. Preparation Method
[0024] The method for preparing the composite gel of the present invention includes the following steps:
[0025] 1. Preparation of growth factor hydrogels
[0026] Choose a suitable matrix material (such as poloxamer, sodium hyaluronate, etc.), dissolve it with growth factors in water, buffer solution or physiological saline to prepare growth factor hydrogel.
[0027] 2. Inject therapeutic gas
[0028] Therapeutic gases (such as oxygen, hydrogen, etc.) are injected into the growth factor hydrogel and thoroughly mixed so that the gas is distributed in the gel in the form of microbubbles.
[0029] 3. Formation of a composite gel
[0030] The thoroughly mixed bubble gel will form a therapeutic composite gel that provides long-term effective wound treatment by slowly releasing gas and growth factors.
[0031] Through the above steps, the prepared composite gel can continuously provide the required growth factors and therapeutic gases, accelerating wound healing while maintaining wound moisture and regulating the local microenvironment to meet the needs of different wound types and healing stages. Attached Figure Description
[0032] Figure 1 This refers to the cell proliferation promoted by growth factors and oxygen in Example 1.
[0033] Figure 2 Photograph of growth factors and oxygen promoting cell migration in Example 1.
[0034] Figure 3 This is a quantitative measure of the cell migration promoted by growth factors and oxygen in Example 1.
[0035] Figure 4 Photographs showing the effect of growth factor-oxygen composite hydrogel on promoting wound healing in mice in Example 2.
[0036] Figure 5 Figure 2 shows the results of the growth factor-oxygen composite hydrogel promoting wound healing in mice. Detailed Implementation
[0037] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.
[0038] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.
[0039] Example 1
[0040] A certain amount of growth factor was added to cell well plates, and its effects on cell proliferation and migration were measured under anaerobic / anaerobic conditions. Figure 1-3 As shown, growth factors can better promote cell proliferation and migration in the presence of oxygen.
[0041] Example 2
[0042] A certain amount of growth factor was dissolved in 100 g of pure water, and poloxamer 407 was added until completely dissolved to form a transparent solution. The resulting hydrogel was then mixed with oxygen by blowing air through it, allowing the oxygen to be evenly distributed throughout the gel structure, thus preparing an oxygen-containing growth factor composite gel.
[0043] To verify the therapeutic effect of the composite gel in a mouse wound model, mice were randomly divided into four groups: a blank control group, a growth factor gel group, an oxygen gel group, and a growth factor-oxygen composite gel group. A full-thickness skin wound approximately 1 cm in diameter was excised from the back of each mouse using a circular cutter, and the prepared gel was applied topically, changing the gel daily. The wound area was photographed every two days, and the shrinkage was statistically analyzed. The results showed that, compared with the single component, the growth factor-oxygen composite gel significantly promoted wound healing speed and shortened healing time in mice.
Claims
1. A composite gel for promoting wound healing, the composite gel comprising at least one growth factor and at least one therapeutic gas, the composite gel selectively adjusting the combination of the gas and the growth factor to maximize the synergistic effect between them, thereby meeting the treatment needs of different wound types and different stages of wound healing.
2. The composite gel as described in claim 1, characterized in that, The growth factors include one or more of epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF-β), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), or keratinization factor (KGF).
3. The composite gel as described in claim 1, characterized in that, The therapeutic gas is one or more of oxygen, hydrogen, nitric oxide, and hydrogen sulfide.
4. The composite gel as described in claim 1, characterized in that, The therapeutic gas is distributed in the gel in the form of microbubbles, allowing the gas to be slowly released at the wound site, thus improving the local microenvironment of the wound.
5. The composite gel as described in claim 1, characterized in that, The synergistic effect of the growth factors and therapeutic gases promotes wound healing through the following mechanisms: 1) During the inflammatory phase of a wound, the gas (such as hydrogen, carbon monoxide, or hydrogen sulfide) promotes the activity of immune cells, reduces local oxidative stress, and promotes cell proliferation and migration through growth factors. 2) During the proliferation and remodeling phase, the gases (such as oxygen and nitric oxide) promote cell metabolism and division, while growth factors further enhance the directed migration and proliferation of cells in the wound area, promote angiogenesis and collagen synthesis, and strengthen the structural reconstruction and repair of the wound area.
6. The composite gel as described in claim 1, characterized in that, The gel matrix is poloxamer, sodium hyaluronate, carbomer, gelatin, or other polymers suitable for biomedical applications.
7. The composite gel as described in claim 1, characterized in that, The concentration range of the growth factor is from 0.1 ng / mL to 1000 ng / mL.
8. The composite gel as described in claim 1, characterized in that, The preparation process includes the following steps: (1) Selecting a suitable matrix material and dissolving it with growth factors in water, buffer solution or physiological saline to prepare growth factor hydrogel; (2) Injecting therapeutic gas into the growth factor hydrogel and mixing it thoroughly to form a composite gel containing bubbles.
9. The composite gel as described in claim 1, characterized in that, The composite gel can maintain a moist wound environment and promote the healing process.