Exosome-glucan compound preparation and application thereof in tissue repair

Abstract

The exosome-glucan compound preparation provided by the invention comprises a stem cell exosome, the final concentration of the stem cell exosome in the exosome-glucan compound preparation is 1 * 10 < 8 > parts / mL to 1 * 10 < 12 > parts / mL based on particle concentration quantification or 1 mu g / mL to 500 mu g / mL based on exosome total protein quantification, and the final concentration of the stem cell exosome in the exosome-glucan compound preparation is 1 * 10 < 8 > parts / mL to 1 * 10 < 12 > parts / mL based on particle concentration quantification or 1 mu g / mL to 500 mu g / mL based on particle concentration quantification. The dextran is used as a matrix entrapment stem cell exosome, the weight-average molecular weight of the dextran is 10kDa to 5000kD, and the weight / volume percent of the dextran in the exosome-dextran compound preparation is 0.5% to 20%; glucan is used as a biocompatible matrix, and a lipid bilayer structure of the glucan wraps the stem cell exosome to form a physical protection barrier, so that the stem cell exosome is prevented from being degraded and inactivated in an in-vitro storage or in-vivo complex environment; and the degradation rate of the glucan matrix is matched with the wound healing period, so that long-acting slow release of the exosome is realized, and the bioavailability of a focus part is improved.

Description

Technical Field

[0001] This invention relates to the technical field of biological skin tissue repair agents, and in particular to an exosome-dextran compound preparation and its application in tissue repair. Background Technology

[0002] Repairing tissue damage, including trauma, burns, and chronic ulcers, has long been a major technical challenge in the fields of clinical medicine and skin care. Currently, commonly used clinical repair methods include debridement and suturing, skin grafting, topical antibacterial drugs, and growth factor preparations. However, in actual clinical applications, these methods have revealed shortcomings such as limited repair efficiency, easy immune response, and limited applicability, which obviously cannot meet the needs of wound repair for tissue damage.

[0003] In recent years, stem cell therapy has shown great potential in the field of tissue damage repair due to its strong multi-directional differentiation potential and tissue regeneration regulation capabilities, becoming a research hotspot in this field. However, stem cell therapy also faces many bottlenecks in practical translational applications: on the one hand, stem cell transplantation is prone to triggering immune rejection, thereby reducing the therapeutic effect; on the other hand, the proliferation and differentiation process of stem cells in vivo is difficult to precisely control, posing a potential risk of tumorigenesis; furthermore, the in vitro storage and transportation conditions of stem cells are demanding, resulting in high costs and further limiting large-scale clinical applications.

[0004] To overcome the aforementioned limitations, "cell-free therapy" is gradually becoming a new direction in the field of tissue repair. Among them, stem cell exosomes, as key active components of paracrine function of stem cells, especially mesenchymal stem cells (MSCs), are considered ideal candidates for the next generation of "cell-free therapy" due to their unique advantages. Exosomes are a type of lipid bilayer vesicle secreted by cells, rich in various bioactive molecules such as proteins, lipids, mRNA, and microRNA. Studies have shown that stem cell exosomes can exert multiple biological functions by targeting and delivering these bioactive substances, including regulating cell proliferation and migration, inhibiting inflammatory responses, promoting angiogenesis, and regulating extracellular matrix remodeling, demonstrating significant application prospects in tissue repair and skin anti-aging.

[0005] Despite the excellent therapeutic potential of stem cell exosomes, they are still subject to many technical constraints in the actual clinical translation process, mainly in the following three aspects: (1) Insufficient structural stability: the lipid bilayer structure of exosomes is prone to breakage in the in vitro storage environment and is easily degraded in the complex physiological microenvironment in vivo, such as wound exudate rich in proteases, which leads to rapid loss of their biological activity; (2) Low bioavailability: after exosomes are applied to the target site such as skin wounds, they are easily washed away by body fluids, resulting in a short residence time at the lesion site and difficulty in exerting a long-lasting and stable therapeutic effect; (3) Poor application convenience: most of the existing exosome preparations are liquid, which makes it difficult to effectively adhere to vertical wounds or irregular skin surfaces, further reducing the efficiency of local treatment.

[0006] Dextran is a neutral polysaccharide formed by glucan units linked by glycosidic bonds. It possesses excellent biocompatibility, biodegradability, and low immunogenicity, leading to its widespread application in the pharmaceutical and cosmetic fields. In the pharmaceutical field, dextran is commonly used as a plasma thickener, drug carrier, and surgical anti-adhesion agent; in the cosmetic field, it is frequently used as a humectant and thickener. Furthermore, research on constructing biomaterials such as hydrogels using dextran is relatively mature, and its good gelling properties, hydrophilicity, and biocompatibility give it the potential to serve as a carrier for bioactive substances.

[0007] Therefore, there is an urgent need to develop a novel compound formulation to effectively protect the bioactivity of stem cell exosomes, prolong their residence time at the site of injury and achieve a sustained-release effect, thereby maximizing the tissue repair and treatment capacity. Summary of the Invention

[0008] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide an exosome-dextran compound preparation and its application in tissue repair, which has the advantages of significantly improving the bioactivity stability of exosomes during storage and use, and the bioavailability of the compound preparation.

[0009] To achieve the above and other related objectives, in a first aspect, the present invention provides an exosome-dextran compound formulation comprising: Stem cell exosomes, wherein the final concentration of the stem cell exosomes in the exosome-dextran compound formulation is 1 × 10⁻⁶ based on particle concentration. 8 particles / mL to 1×10 12 particles / mL or 1 μg / mL to 500 μg / mL based on total exosome protein quantification; The dextran used as a matrix to encapsulate the stem cell exosomes has a weight-average molecular weight of 10 kDa to 5000 kDa and its weight / volume percentage in the exosome-dextran compound formulation is 0.5% to 20%.

[0010] To achieve the above technical solution, dextran, as a biocompatible matrix, encapsulates stem cell exosomes in its lipid bilayer structure, forming a physical protective barrier to prevent degradation and inactivation of stem cell exosomes during in vitro storage or in complex in vivo environments. Simultaneously, the dextran molecular chains, with a weight-average molecular weight ranging from 10 kDa to 5000 kDa, form a loose and porous network structure that neither destroys exosome activity nor isolates them from external interference, thus significantly prolonging the retention time of stem cell exosome activity. Furthermore, a dextran weight / volume percentage of 0.5%-20% allows for formulation adaptability to wound surfaces, enhancing the adhesion of the formulation to vertical or irregular wounds and preventing rapid flushing away of exosomes by body fluids. Moreover, the degradation rate of the dextran matrix matches the wound healing cycle, achieving "long-acting sustained release" of exosomes and thereby improving bioavailability at the lesion site.

[0011] Preferably, the weight-average molecular weight of the dextran is 40 kDa to 500 kDa.

[0012] Preferably, it also contains hyaluronic acid.

[0013] To achieve the above technical solution, the molecular chains of hyaluronic acid can be interwoven into the dextran network, making the gel pore size and exosome particle size more well matched, thereby improving the exosome loading rate and avoiding excessive pore size that could lead to exosome burst release, thus further optimizing the sustained release curve. On the other hand, the high moisturizing properties of hyaluronic acid can supplement dextran, achieving the effect of optimizing the wound healing microenvironment.

[0014] Preferably, the exosome-dextran compound preparation is in the form of a hydrogel, solution, or lyophilized powder.

[0015] Preferably, the stem cell exosomes are derived from mesenchymal stem cells cultured in vitro, obtained by collecting the culture supernatant of the mesenchymal stem cells and purifying it through centrifugation, membrane filtration, and ultracentrifugation.

[0016] To achieve the above technical solution, the in vitro culture of mesenchymal stem cells can ensure batch consistency and activity of exosomes. The three-step purification process provides a dual guarantee of high purity and high activity, providing a quality assurance of core raw materials for the application of exosome-dextran compound preparations in tissue repair.

[0017] Preferably, the mesenchymal stem cells are one of human umbilical cord mesenchymal stem cells, human adipose mesenchymal stem cells, human bone marrow mesenchymal stem cells, and combinations thereof.

[0018] On the other hand, the present invention also provides the application of an exosome-dextran compound preparation as described in any of the above claims in tissue repair.

[0019] As described above, the exosome-dextran compound preparation provided by the present invention and its application in tissue repair have at least the following beneficial effects: 1. As a biocompatible matrix, dextran encapsulates stem cell exosomes in its lipid bilayer structure, forming a physical protective barrier to prevent the degradation and inactivation of stem cell exosomes during in vitro storage or in complex in vivo environments. The dextran molecular chains, with a weight-average molecular weight ranging from 10 kDa to 5000 kDa, form a loose and porous network structure that can both preserve the activity of exosomes and isolate them from external interference, thereby significantly prolonging the activity retention time of stem cell exosomes. 2. Using a weight / volume percentage of 0.5%-20% for dextran can form a formulation suitable for the wound surface, enhancing the adhesion of the formulation to vertical or irregular wound surfaces and preventing exosomes from being rapidly washed away by body fluids. 3. The degradation rate of the dextran matrix matches the wound healing cycle, thereby achieving "long-lasting sustained release" of exosomes and improving the bioavailability of the lesion site. Attached Figure Description

[0020] Figure 1 This is a diagram of a typical "cup-shaped" vesicle structure observed under a transmission electron microscope for stem cell exosomes; Figure 2 This is a nanoparticle tracking analysis diagram of stem cell exosomes; Figure 3 This is a comparison graph of cell viability between the exosome-glucan compound preparation and Comparative Example 1 at different storage times; Figure 4 This is a comparison chart of cell scratch healing rates; Figure 5 This is a comparison chart of wound healing rates in rats. Detailed Implementation

[0021] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0022] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0023] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0024] Unless otherwise specified, the instruments, reagents, and materials used in the following embodiments are all conventional instruments, reagents, and materials already available in the prior art and can be obtained through legitimate commercial channels. Unless otherwise specified, the experimental methods and detection methods used in the following embodiments are all conventional experimental methods and detection methods already available in the prior art.

[0025] Example: This invention provides an exosome-dextran compound formulation comprising: stem cell exosomes and a dextran matrix for encapsulating the stem cell exosomes. The preparation steps of the stem cell exosomes include: Cell preparation: P3-P5 generation mesenchymal stem cells were selected. The mesenchymal stem cells were derived from one of the following: human umbilical cord mesenchymal stem cells, human adipose mesenchymal stem cells, human bone marrow mesenchymal stem cells, or combinations thereof. Trypan blue staining was used to detect the mesenchymal stem cells to verify that the cell viability was ≥90%.

[0026] Cell resuscitation: Remove the cryovials from the -80℃ freezer and immediately place them in a 37℃ constant temperature water bath for rapid thawing. After thawing, quickly transfer them to 15ml centrifuge tubes, add 5 times the volume of complete culture medium at 37℃, gently pipette to mix, centrifuge at 4℃ and 300×g for 5 minutes, and discard the supernatant.

[0027] Inoculation and culture: at 5×10 3 cells / cm 2The cells were seeded at a density of 12 mL in each T75 / T175 cell culture flask. The complete culture medium was formulated as follows: DMEM / F-12 medium + 10% exosome-free fetal bovine serum + 1% penicillin-streptomycin antibiotics + 2 ng / mL basic fibroblast growth factor. The culture conditions were 37°C, 5% CO2, and saturated humidity incubator. The complete culture medium was changed every 48 hours, and cell morphology was observed under a microscope daily.

[0028] Pretreatment and washing: When the cell confluence reaches 80%-90%, discard the old complete culture medium and wash the cells three times with sterile PBS buffer (pH 7.4) at 37°C.

[0029] Serum-free induction of secretion: Replace with serum-free DMEM / F-12 medium, adding 10 mL of serum-free medium to each T75 flask; continue culturing for 48 hours in a saturated humidity incubator at 37℃ and 5% CO2; if it is necessary to increase exosome production, replace with fresh serum-free medium after 24 hours of culture, continue culturing for another 24 hours, and then combine the two supernatants.

[0030] Supernatant collection: The cell culture supernatant was gently collected using a sterile pipette at 4°C and transferred to a sterile centrifuge tube.

[0031] The entire process of gradient centrifugation for impurity removal was conducted at 4°C. Sterile, enzyme-free polypropylene centrifuge tubes were used, and the tubes were balanced with an electronic balance before each centrifugation to prevent vibration and potential tube breakage. After centrifugation, the centrifuge door was opened only after the centrifuge speed had completely decreased to 0 to avoid disturbing the supernatant due to pressure differences. Specifically, the gradient centrifugation impurity removal steps included: Step 1: Centrifuge at 300×g for 10 minutes to remove intact cells and cell clumps. Carefully aspirate the supernatant and transfer it to a new centrifuge tube. Step 2: Centrifuge at 2000×g for 10 minutes to remove dead cells and large cell debris, and transfer the supernatant to a new centrifuge tube; Step 3: Centrifuge at 10000×g for 30 minutes to remove large vesicles and residual cell debris. Aspirate the supernatant and filter it through a 0.22μm polyethersulfone (PES) membrane. Collect the filtered supernatant. Further filter the supernatant through the membrane to remove tiny impurities and protein aggregates, and avoid contaminating the ultracentrifuge tube and exosomes.

[0032] Ultracentrifugation: Slowly transfer the filtered supernatant to a sterile, 4°C polycarbonate ultracentrifuge tube. If the volume is insufficient, add to the volume with sterile PBS buffer pre-cooled to 4°C. Perform a first ultracentrifugation at 100,000×g for 90 minutes. After centrifugation, gently aspirate the supernatant with a sterile pipette in a clean bench, retaining the white flocculent precipitate at the bottom of the tube. Add 1 mL of sterile PBS buffer pre-cooled to 4°C, gently pipette the precipitate, and let it stand at room temperature for 10 minutes to allow the precipitate to dissolve completely. Transfer the resuspended solution to a new pre-cooled ultracentrifuge tube, add to the volume with pre-cooled PBS, and centrifuge again at 100,000×g for 90 minutes. Aspirate the supernatant, retain the precipitate, and gently resuspend it in 200 μL of pre-cooled PBS to obtain the exosome concentrate.

[0033] The obtained exosome concentrate was identified as follows: ① Transmission electron microscopy (TEM) observation: Take 10 μL of exosome concentrate and add it dropwise onto a Formvar carbon membrane-coated copper grid. Let it stand at room temperature for 5 minutes, then blot away excess liquid with filter paper. Add 2% phosphotungstic acid solution (pH 6.8) and negatively stain for 5 minutes. Blot away the stain with filter paper and allow the copper grid to air dry at room temperature for 30 minutes. (See also...) Figure 1 Typical "cup-shaped" vesicle structures with diameters of 40-150 nm were observed using transmission electron microscopy.

[0034] ②Nanoparticle tracking analysis (NTA): Take 5 μL of exosome concentrate, dilute to 1 mL with pre-cooled sterile PBS, and repeat the test 3 times at room temperature (25°C), with each test lasting 60 seconds. (See reference...) Figure 2 The peak particle size recorded was approximately 110 nm.

[0035] ③ Protein quantification: Using the BCA protein quantification kit, with bovine serum albumin (BSA) as the standard, standard curves were established for 0, 25, 50, 100, 200, and 400 μg / mL. After diluting the exosome concentrate at a ratio of 1:10, three replicate wells were set for each sample. The absorbance was measured at a wavelength of 562 nm using an ELISA reader, and the total protein concentration was calculated.

[0036] Repackaging and storage: In a clean bench, dispense 50-100 μL of the exosome concentrate into sterile, enzyme-free EP tubes, add 10% glycerol as a cryoprotectant, and label each tube with the preparation date, cell source, and concentration. Store in a sealed container at -80°C. Before use, the exosome concentrate should be slowly thawed at 4°C, and then gently mixed by pipetting.

[0037] The exosome concentrate is prepared using an in vitro culture method for mesenchymal stem cells, which ensures batch consistency and activity of the exosomes. The three-step purification process provides dual assurance for high purity and high activity.

[0038] Using the prepared stem cell exosome concentrate, dextran, and hyaluronic acid as raw materials, an exosome-dextran compound formulation was prepared. The resulting exosome-dextran compound formulation was prepared in one of the following forms: hydrogel, solution, or lyophilized powder. The final concentration of stem cell exosomes in the exosome-dextran compound formulation was 1 × 10⁻⁶ based on particle concentration. 8 particles / mL to 1×10 12 The particles / mL or quantified based on total exosome protein from 1 μg / mL to 500 μg / mL; the weight / volume percentage of dextran in the exosome-dextran compound is 0.5% to 20%, and the weight-average molecular weight of the dextran used is 10 kDa to 5000 kDa, more preferably 40 kDa to 500 kDa.

[0039] Experimental example: The preparation steps of the exosome-dextran compound formulation include: Raw material preparation: (a) Exosome concentrate pre-cooled at 4°C for 30 minutes; (b) PBS buffer; (c) 1% (w / v) dextran solution: 1g of dextran powder and 0.5g of hyaluronic acid were accurately weighed using an electronic balance in a laminar flow hood. The weight average molecular weight of the dextran was 70kDa. The powder was slowly added to 99mL of sterile PBS buffer pre-cooled to 4°C. A sterile magnetic stir bar was placed in the solution, and the mixture was stirred at 37°C and 50rpm for 75 minutes until completely dissolved. After cooling to room temperature, the solution was sterilized by vacuum filtration through a 0.22μm polyethersulfone (PES) filter membrane. Calculation of proportions: To achieve a final total protein concentration of 100 μg / mL from the target exosomes, the required volume of exosome concentrate is calculated as follows: (100 μg / mL × 100 mL) ÷ 1000 μg / mL (concentrate concentration) = 10.0 mL. Gentle mixing: Place 100 mL of 1% dextran solution in a 4℃ clean bench, start the magnetic stirrer at 30 rpm, and slowly add 10.0 mL of pre-cooled 4℃ exosome concentrate along the beaker wall; Homogenization: Stir continuously for 30 minutes, and gently blow the bottom of the solution with a sterile pipette every 5 minutes to ensure no sedimentation; Gel formation triggering and verification: Transfer the mixture to a sterile container and let it stand at 4°C for 2 hours; and verify by the "inverted test tube method". If the gel does not flow after the test tube is inverted, it is a qualified composite hydrogel.

[0040] Comparative Example 1: Take 10.0 mL of exosome concentrate and add it to 100 mL of sterile PBS buffer and stir until completely dissolved to obtain an exosome solution with a final total protein concentration of 100 μg / mL.

[0041] Comparative Example 2: PBS buffer.

[0042] Comparative Example 3: 1% (w / v) dextran solution.

[0043] Bioactivity comparison experiment of formulation: Human immortalized epidermal cells (Hacat) were used to test the activity of experimental cases and control groups with different storage times. Specifically, human immortalized epidermal cells were seeded into 96-well plates and starved for 12 hours; the 96-well plates were divided into two groups, with 6 replicate wells in each group.

[0044] 10.0 mL of exosome-dextran compound preparation and 10.0 mL of exosome solution were stored at 25°C. Samples were taken on days 0, 3, and 7. The samples were added to the corresponding wells of the Hacat plate. After culturing for 48 hours, 10 μL of CCK-8 reagent was added to each well. The plates were incubated at 37°C in the dark for 2 hours. The absorbance (OD value) of each well was measured at 450 nm using a microplate reader, and the data were recorded.

[0045] See Figure 3 On day 0, the experimental case and Comparative Example 1 had comparable abilities to promote Hacat proliferation; on days 3 and 7, the proliferation-promoting activity of Comparative Example 1 decreased significantly, while the activity of the experimental case decreased significantly less than that of Comparative Example 1.

[0046] Cell scratch comparison experiment: Immortalized human epidermal cells (Hacat) were seeded into 6-well plates and cultured until confluence. A uniform scratch was made in the center of the cell layer using a 200 μL pipette tip. After washing with sterile PBS buffer, the following culture media were added: Blank control group (PBS buffer); Dextran group (Comparative Example 3); Exosome group (Comparative Example 1); Formulation group (experimental example).

[0047] Images were taken under a microscope at 0 and 24 hours, and the scratch healing rate was calculated using ImageJ software. (See attached image.) Figure 4 The healing rate is calculated as follows: (0-hour scratch area - 24-hour scratch area) / 0-hour scratch area × 100%.

[0048] Comparative experiment of rat full-thickness skin defect model: Twenty male SD rats were anesthetized, and their backs were prepared and disinfected. Two full-thickness circular skin defects were created using an 8mm diameter skin punch. The 20 male SD rats were divided into four groups (E, F, G, and H), with three rats and six wounds in each group. Group E received sterile PBS buffer solution as a blank control, Group F received Comparative Example 3 as a dextran group, Group G received Comparative Example 1 as an exosome group, and Group H received experimental samples as a formulation group. The drugs were administered once every three days thereafter. Photos were taken on days 0, 3, 7, 10, and 14. The wound area was calculated using ImageJ software, and the wound healing rate was calculated.

[0049] See Figure 5 On days 7 and 10, the wound healing rate of group H was significantly higher than that of groups G, F and E; on day 14, the wounds of group H were basically healed, but there were still visible wounds in group G.

[0050] The exosome-dextran compound formulation provided in this application utilizes dextran as a biocompatible matrix. Its lipid bilayer structure encapsulates stem cell exosomes, forming a physical protective barrier. Bioactivity comparison experiments confirm that the compound formulation exhibits significantly improved room temperature stability. A dextran weight / volume percentage of 0.5%-20% creates a formulation suitable for wound surfaces, enhancing adhesion to vertical or irregular wounds. Combined with the characteristic that the degradation rate of the dextran matrix matches the wound healing cycle, the formulation is slowly and continuously released at the wound site. Cell scratch assays demonstrate that the compound formulation provided in this application is significantly more effective than exosomes or dextran alone in promoting fibroblast migration. Comparative experiments using a rat full-thickness skin defect model also confirm the synergistic effect of the compound formulation in accelerating animal wound healing.

[0051] The results of cell scratch comparison experiments and rat full-thickness skin defect model comparison experiments confirmed that the exosome-glucan compound preparation with dextran as matrix provided in this application has excellent effects in promoting cell proliferation and migration and accelerating animal wound healing, reflecting its extremely high clinical and market value in tissue repair.

[0052] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. An exosome-dextran compound preparation, characterized in that, Include: Stem cell exosomes, wherein the final concentration of the stem cell exosomes in the exosome-dextran compound formulation is 1 × 10⁻⁶ based on particle concentration. 8 particles / mL to 1×10 12 particles / mL or 1 μg / mL to 500 μg / mL based on total exosome protein quantification; The dextran used as a matrix to encapsulate the stem cell exosomes has a weight-average molecular weight of 10 kDa to 5000 kDa and its weight / volume percentage in the exosome-dextran compound formulation is 0.5% to 20%.

2. The exosome-dextran compound preparation according to claim 1, characterized in that, The weight-average molecular weight of the dextran is 40 kDa to 500 kDa.

3. The exosome-dextran compound preparation according to claim 1, characterized in that, It also contains hyaluronic acid.

4. The exosome-dextran compound preparation according to claim 1, characterized in that, The exosome-dextran compound preparation is in the form of hydrogel, solution, or lyophilized powder.

5. The exosome-dextran compound preparation according to claim 1, characterized in that, The stem cell exosomes are derived from mesenchymal stem cells cultured in vitro. They are obtained by collecting the culture supernatant of the mesenchymal stem cells and purifying it through centrifugation, membrane filtration, and ultracentrifugation.

6. The exosome-dextran compound preparation according to claim 1, characterized in that, The mesenchymal stem cells mentioned are one of the following: human umbilical cord mesenchymal stem cells, human adipose mesenchymal stem cells, human bone marrow mesenchymal stem cells, and combinations thereof.

7. The application of an exosome-dextran compound preparation as described in any one of claims 1-6 in tissue repair.

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