Piezoelectric responsive composite stent based on body surface micro-motion driving and application of piezoelectric responsive composite stent

Abstract

The invention provides a piezoelectric responsive composite stent based on body surface micro-motion driving and application thereof, and belongs to the technical field of biomedical materials. Comprising a piezoelectric material matrix selected from a polylactic acid-polyvinylidene fluoride composite fiber membrane with improved wet stability; the surface bioactive modification layer comprises collagen, hyaluronic acid and / or polypeptide containing an RGD sequence and is used for enhancing cell adhesion and proliferation; and the growth factor slow-release unit is composed of degradable polymer microspheres entrapped with vascular endothelial growth factors and / or basic fibroblast growth factors, and is embedded in the piezoelectric material matrix. An electric field adaptive to skin repair is generated by responding to natural micro-motion of a body surface and is used for regeneration and repair of chronic wounds, burns and full-thickness skin defects.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a piezoelectric responsive composite scaffold driven by micro-motion on the body surface and its application. Background Technology

[0002] As the largest organ in the human body, the repair of skin damage (especially chronic wounds, large-area burns, and scar control) remains a major clinical challenge. Traditional repair materials are mostly passive fillers, lacking the ability to dynamically regulate the microenvironment. For example, collagen sponges and silicone dressings only serve a passive filling function and cannot dynamically regulate the wound microenvironment. Furthermore, chronic wounds (such as diabetic ulcers) have impaired cellular electrical response function and lack effective activation methods.

[0003] Existing piezoelectric materials (such as PLLA and BaTiO3) have mature applications in bone regeneration, but they have not been optimized for the characteristics of skin that are moist, dynamic, and structurally complex. There is no intelligent material system that can drive the piezoelectric scaffold to generate an electric field through natural micro-movements on the body surface (breathing, muscle traction) and actively regulate skin regeneration in conjunction with biochemical factors. Summary of the Invention

[0004] This invention provides a piezoelectric responsive composite scaffold driven by micro-motions on the body surface and its application. It generates an electric field adapted to skin repair by responding to natural micro-motions on the body surface, and is used for the regenerative repair of chronic wounds, burns and full-thickness skin defects.

[0005] To address the aforementioned technical problems, this invention provides a piezoelectrically responsive composite scaffold driven by micro-motions on the body surface, comprising:

[0006] The piezoelectric material matrix is ​​selected from polylactic acid-polyvinylidene fluoride (PLLA / PVDF) composite fiber membrane with improved wet stability or bioceramic porous structure containing barium titanate (BaTiO3) and zinc oxide (ZnO);

[0007] A surface bioactive modification layer, including collagen, hyaluronic acid and / or peptides containing RGD sequences, is used to enhance cell adhesion and proliferation;

[0008] The growth factor sustained-release unit is composed of biodegradable polymer microspheres encapsulating vascular endothelial growth factor (VEGF) and / or basic fibroblast growth factor (bFGF), embedded in the piezoelectric material matrix;

[0009] The composite scaffold can generate a micro-electric field of 10-200mV / mm under the action of micro-movements on the body surface (breathing, muscle traction, etc.), which is used to regulate the migration, proliferation and angiogenesis of wound cells to promote skin regeneration and repair.

[0010] The piezoelectric material matrix has a multi-level porous structure with a pore size range of 50 to 200 μm and a porosity of not less than 90%.

[0011] The matrix is ​​a oriented nanofiber structure with gradient-distributed pores to optimize stress transmission and electric field uniformity.

[0012] The growth factor sustained-release unit has a release period of 48 to 96 hours, and the cumulative release rate in the first 72 hours is 60% to 85%.

[0013] Its outer surface integrates a flexible strain sensor and a stress loading feedback module to form a closed-loop control system, enabling on-demand energy supply.

[0014] The above-mentioned composite scaffold is used in the preparation of medical dressings for the repair of chronic wounds, diabetic ulcers, burns and full-thickness skin defects.

[0015] This invention utilizes natural micro-movements of the body surface to power a piezoelectric scaffold, requiring no external power source, resulting in high safety and compliance. It generates a micro-electric field (10-200mV / mm) in situ adapted to skin repair, activating cellular electrical responses and restoring the electrical response function of fibroblasts in diabetic wounds. It reveals the regulatory effect of piezoelectric micro-fields on dysfunctional fibroblasts in diabetic wounds, restoring / enhancing their migration / proliferation capabilities. For the first time, it integrates piezoelectric responsiveness, hierarchical porous structure, and biochemical sustained-release function, breaking through the performance boundaries of single materials. The dual stimulation of electrical signals and biochemical factors significantly improves angiogenesis and orderly collagen deposition, reducing scarring. Its flexibility and wet stability match the skin's curvature and physiological environment, enhancing clinical adaptability. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of a multi-level composite stent structure;

[0017] Wherein, 1 represents the piezoelectric material matrix, 2 represents the surface bioactive modification layer, 3 represents the growth factor sustained-release unit, and 4 represents the skin. Detailed Implementation

[0018] Exemplary embodiments of the present disclosure will now be described in more detail with reference to the accompanying drawings. While exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

[0019] In the following description, certain specific details are set forth for the purpose of illustrating various disclosed embodiments in order to provide a thorough understanding of the various disclosed embodiments. However, those skilled in the art will recognize that embodiments may be practiced without one or more of these specific details. In other instances, well-known apparatuses, structures, and techniques associated with this application may not have been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments.

[0020] Throughout this specification, references to "an embodiment" or "an embodiment" indicate that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Therefore, the appearance of "in an embodiment" or "an embodiment" in various places throughout the specification does not necessarily refer to the same embodiment. Furthermore, a particular feature, structure, or characteristic may be combined in any manner in one or more embodiments.

[0021] In the following description, in order to clearly demonstrate the structure and working method of the present invention, a number of directional terms will be used. However, terms such as "front", "back", "left", "right", "outside", "inside", "outward", "inward", "up", and "down" should be understood as convenient terms and not as limiting terms.

[0022] Example 1: Fabrication and structural characterization of composite scaffolds

[0023] 1.1 Preparation of piezoelectric material matrix:

[0024] Raw material selection: poly-L-lactic acid (PLLA, molecular weight 150,000) and polyvinylidene fluoride (PVDF, β phase content ≥70%), mass ratio 70:30.

[0025] Solution preparation: Dissolve PLLA and PVDF in a 3:1 mixture of dichloromethane and dimethylformamide to a final concentration of 12 wt%. Stir magnetically for 4 hours until a homogeneous and transparent solution is formed.

[0026] Electrospinning conditions: jet voltage 15 kV, needle-to-collector distance 18 cm, flow rate 0.5 mL / h, ambient humidity 40%±5%, temperature 25±2℃. The collector was a rotating drum (800 rpm) to obtain partially oriented nanofiber membranes.

[0027] 1.2 Surface activation and bioactivity modification:

[0028] The fiber membrane was placed in an oxygen plasma reactor (power 50 W, time 90 s) for surface activation treatment.

[0029] RGD peptide (0.1 mg / mL) was covalently grafted onto the fiber surface using an EDC / NHS coupling reaction at 4°C for 12 hours.

[0030] Rinse three times with deionized water and vacuum dry for later use.

[0031] 1.3 Embedding of growth factor sustained-release units:

[0032] Gelatin microspheres containing VEGF (concentration 100 μg / mL) were prepared using a water-in-oil-in-water (W / O / W) double emulsion method. The target microspheres had a diameter of 20 ± 5 μm and an encapsulation efficiency of ≥ 85%.

[0033] Gelatin microspheres were uniformly dispersed in a PLGA solution (concentration 5 wt%), lightly vacuum dried, and then uniformly spread onto the prepared fiber membrane.

[0034] Microspheres were fixed in the fiber membrane structure by low-temperature pressing (30℃, 0.1 MPa, 5 min).

[0035] 1.4 Structural and performance characterization:

[0036] Scanning electron microscopy (SEM): confirmed a hierarchical porous structure with a pore size range of 50–200 μm and a porosity of 93%.

[0037] Piezoelectric performance testing: using d 33 The piezoelectric constant was measured using a measuring instrument in static mode, and the result was 22 pC / N.

[0038] Mechanical properties: tensile modulus 1.2 MPa, matching the mechanical range of human dermal tissue (0.5–2 MPa).

[0039] Sustained-release curve determination: After soaking in PBS (pH 7.4, 37°C), the cumulative release rate was 81% after 72 hours, and the release period lasted for 96 hours.

[0040] Example 2: Animal Experiment Verification

[0041] 2.1 Animal Models and Grouping

[0042] Model: Male Sprague-Dawley rats (8 weeks old, weighing 200–250 g) were used to establish a diabetic model (blood glucose ≥16.7 mmol / L) by intraperitoneal injection of streptozotocin (STZ).

[0043] A full-thickness skin defect with a diameter of 1.5 cm was prepared on the back (including full-thickness dermal excision).

[0044] Grouping (n=8 per group):

[0045] Experimental Group A: The piezoelectric responsive composite scaffold of this invention + daily mechanical stimulation (simulating respiratory rate 1Hz, 10% strain, 15min / d).

[0046] Experimental Group B: The piezoelectric responsive composite scaffold of the present invention (without mechanical stimulation);

[0047] Control group 1: Commercial collagen sponge;

[0048] Control group 2: No treatment, natural healing.

[0049] 2.2 Observation and Evaluation Indicators

[0050] Wound closure rate: The wound area was photographed and measured on days 0, 7, 14, and 21, and the closure percentage was calculated.

[0051] Histological analysis: Wound tissue was taken for H&E staining (epidermal regeneration thickness) and Masson staining (collagen arrangement order).

[0052] Immunohistochemical detection: CD31 staining was used to count the density of new blood vessels (unit: cells / mm²); Ki-67 staining was used to analyze the cell proliferation index.

[0053] Collagen type ratio: Western blot analysis of the Collagen I / III ratio.

[0054] 2.3 Experimental Results (14 days)

[0055] Wound closure rate: Group A 95±3%, Group B 87±4%, Collagen sponge group 70±5%, Natural healing group 52±6%.

[0056] Neovascularization density (CD31) + Group A: 35±4 pieces / mm², Group B: 28±3 pieces / mm², Collagen Sponge Group: 15±3 pieces / mm², Natural Healing Group: 9±2 pieces / mm².

[0057] Collagen I / III ratio: Group A 2.8±0.3, Group B 2.3±0.2, Collagen sponge group 1.2±0.4, Natural healing group 0.9±0.3.

[0058] 2.4 Statistical Methods

[0059] Data are expressed as mean ± standard deviation. One-way ANOVA was used for comparisons between groups, and P < 0.05 was considered statistically significant.

[0060] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A piezoelectrically responsive composite scaffold driven by micro-motions on the body surface, characterized in that, include: The piezoelectric material matrix is ​​selected from polylactic acid-polyvinylidene fluoride composite fiber membrane with improved wet stability or bioceramic porous structure containing barium titanate and zinc oxide. A surface bioactive modification layer, including collagen, hyaluronic acid and / or peptides containing RGD sequences, is used to enhance cell adhesion and proliferation; The growth factor sustained-release unit is composed of biodegradable polymer microspheres encapsulating vascular endothelial growth factor and / or basic fibroblast growth factor, embedded in the piezoelectric material matrix; The composite scaffold can generate a micro-electric field of 10-200mV / mm under the action of micro-movement on the body surface, which is used to regulate the migration, proliferation and angiogenesis of wound cells to promote skin regeneration and repair.

2. The composite support according to claim 1, wherein the piezoelectric material matrix has a multi-level pore structure with a pore size range of 50 to 200 μm and a porosity of not less than 90%.

3. The composite scaffold according to claim 1 or 2, wherein the matrix is ​​an oriented nanofiber structure with gradient-distributed pores to optimize stress transmission and electric field uniformity.

4. The composite scaffold according to claim 1, wherein the release period of the growth factor sustained-release unit is 48 to 96 hours, and the cumulative release rate in the first 72 hours is 60% to 85%.

5. The composite support according to any one of claims 1 to 4, wherein a flexible strain sensor and a stress loading feedback module are integrated on its outer surface to form a closed-loop control system for on-demand power supply.

6. The use of the composite scaffold according to any one of claims 1 to 5 in the preparation of medical dressings for the repair of chronic wounds, diabetic ulcers, burns and full-thickness skin defects.

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