Medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia, preparation and application

Abstract

The application discloses a medical implantable magnetic response dynamic anti-adhesion biomimetic cilium, and a preparation and application thereof. The biomimetic cilium comprises a flexible polymer substrate, a biomimetic cilium array and a surface lubricating layer. The preparation method is as follows: by controlling the viscosity (500-800 mPa·s) of a polymer / magnetic particle mixed solution, a cluster structure is self-assembled under a magnetic field by using the synergistic effect of rheology and the magnetic field, and a physical template is not needed. The structure combines the air cushion stability and the lubricity of the surface, and provides excellent passive anti-adhesion capacity; meanwhile, under the driving of an external magnetic field, the cilium cluster can swing with a large amplitude, and actively removes proteins, bacteria and stone crystals. The application solves the problems of easy failure of an existing static coating and insufficient protection of a uniform cilium structure, and is suitable for medical devices such as catheters and stents.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to the field of surface modification technology for medical implantable devices, and particularly to the preparation and application of implantable magnetically responsive dynamic anti-adhesion biomimetic cilia. Background Technology

[0002] Biomedical materials (such as urinary catheters, ureteral stents, and vascular stents) face severe biofouling problems after implantation. For example, the surface of urinary system implants is highly susceptible to protein adsorption, bacterial colonization forming biofilms, and urinary salt crystal deposition (stones), which can lead to infection, tubing blockage, and even implantation failure. Existing anti-adhesion strategies mainly include superhydrophobic surfaces and liquid-injectable porous surfaces. Superhydrophobic surfaces rely on micro / nanostructures to trap air cushions, but these air cushions are prone to collapse and failure under complex fluid and pressure conditions within the body. While porous surfaces offer good lubrication, the lubricant is easily lost and lacks long-term effectiveness. In addition, magnetically responsive surfaces based on magnetic particle doping (such as magnetic micropillars / cilia) have been used for droplet manipulation or microfluidic delivery. However, existing technologies typically employ template or spraying methods for fabrication and often aim for uniformly distributed array structures. Uniformly distributed cilia have weak stability in trapping air layers underwater, and existing designs are not optimized for "anti-stone" and "anti-biofilm" strong adhesion contaminants such as solid / semi-solid substances, lacking an effective mechanism for actively removing already attached contaminants. Summary of the Invention

[0003] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia, its preparation, and application structure. These biomimetic cilia exhibit a non-uniform clustered distribution, significantly improving the stability of the lubrication layer and air cushion, and possessing a magnetically driven active cleaning function. Another objective of this invention is to provide a method for preparing the above structure, which eliminates the need for a template and achieves self-assembly of the clustered structure through rheological control and magnetic field induction.

[0004] To achieve the above objectives, the present invention adopts the following technical solution: Medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia include: a flexible polymer substrate, a biomimetic cilia array, and a surface lubrication layer; the biomimetic cilia array is integrally formed with the flexible polymer substrate, and the biomimetic cilia array is formed by solidifying a polymer matrix and magnetic particles uniformly dispersed in the polymer matrix, and the magnetic particles are completely encapsulated by the polymer matrix; the surface lubrication layer wets and covers the surface and gaps of the biomimetic cilia array; wherein, the biomimetic cilia array presents a non-uniform clustered distribution structure on the surface of the flexible polymer substrate, and the non-uniform clustered distribution structure is formed by the local aggregation of multiple cilia units to form cilia clusters, and relatively sparse regions are formed between the cilia clusters.

[0005] Furthermore, the materials of the flexible polymer substrate and the polymer matrix are selected from polydimethylsiloxane, medical-grade silicone rubber, or polyurethane; the magnetic particles are selected from carbonyl iron powder, iron oxide nanoparticles, or neodymium iron boron microparticles; and the surface lubricating layer is biocompatible silicone oil or perfluoropolyether oil.

[0006] Furthermore, the diameter of a single ciliary in the biomimetic ciliary array is 30-50 μm, and the height is 300-700 μm; the diameter of the ciliary cluster is 50-200 μm, the height is 300-700 μm, and the spacing is 200-500 μm; the average particle size of the magnetic particles is 1-10 μm. This setting is based on a ciliary diameter of 30-50 μm, ensuring that the magnetic particles in a single ciliary are uniformly distributed radially, avoiding the imbalance of ciliary mechanical properties caused by particle agglomeration. When using 1 μm magnetic particles, this ratio setting can more significantly improve the uniformity of the composite material.

[0007] Furthermore, under the action of a 0.1T alternating magnetic field, the tip of the ciliary tuft swings with an amplitude greater than ±80μm.

[0008] A method for preparing a medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in any of the above claims includes the following steps: S1 Preparation of Mixture and Degassing: Mix the polymer prepolymer, curing agent and magnetic particles, adjust the dynamic viscosity of the mixture at 25°C to 500-800 mPa·s, and perform degassing treatment; S2 coating: The mixture is coated onto the surface of the substrate; S3 Magnetic Field Induced Molding: The coating layer obtained in step S2 is placed in a vertical magnetic field above a neodymium iron boron magnet with a magnetic induction intensity of 0.1-1T. Utilizing the shear-thinning rheological properties of the mixture in the dynamic viscosity range of 500-800mPa·s at 25℃, the primary magnetic chains formed by the magnetic particles become unstable and oscillate due to the attraction of transverse magnetic dipoles, and then spontaneously converge into non-uniformly distributed cluster precursors. Under the dynamic balance between magnetic pull and fluid viscous resistance, the polymer matrix is ​​pulled upward to grow, forming highly non-uniform fibrillary precursors. S4 thermosetting: Under the condition of maintaining the magnetic field, the cilia precursor is heated and cured to obtain a cured cilia array; S5 Lubrication Treatment: The cured fiber array is immersed in lubricating liquid, and after removal, excess lubricating liquid is removed to obtain the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia.

[0009] Furthermore, in step S1, the polymer prepolymer is a polydimethylsiloxane prepolymer, and the mass ratio of the polymer prepolymer to the curing agent is 10:1; the mass ratio of the polymer prepolymer to the magnetic particles is 3:1 to 1:3.

[0010] Furthermore, in step S3, the magnetic field strength is 0.3-0.8T; in step S4, the heating and curing temperature is 60-80℃, and the curing time is 2-4 hours.

[0011] Furthermore, in step S5, the lubricant is dimethyl silicone oil with a viscosity of 50-100 cSt.

[0012] A medical implantable device, wherein at least a portion of the outer surface of the medical implantable device is covered with medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in any of the above claims; the medical implantable device includes one of a urinary catheter, a ureteral stent, a vascular stent, an anti-adhesion patch, or an artificial joint.

[0013] The application of any of the above-mentioned medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia in the preparation of medical devices with active sludge removal function, wherein the active sludge removal function is characterized by being able to remove more than 80% of protein, bacterial biofilm or urinary salt crystals on the surface of the device within 1 minute under a 0.1T alternating magnetic field, and the medical device includes a urinary catheter or a ureteral stent.

[0014] The non-uniform clustered distribution structure and surface lubrication layer prevent the initial adhesion of biological contaminants to the instrument surface; and when cleaning is required, an alternating magnetic field or a rotating magnetic field is applied in vitro to drive the biomimetic ciliary array to generate mechanical oscillation, using shear force to peel off attached proteins, bacterial biofilms or mineral crystals. When driven by a rotating magnetic field, the magnetic field strength is 0.2-0.5T and the rotation frequency is 3-8Hz, the oscillation amplitude of the ciliary cluster tip can reach ±90μm, and the removal rate of bacterial biofilm within 1 minute is not less than 75%.

[0015] The "non-uniform clustered distribution structure" of the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia of this invention does not rely on physical templates or array magnets. The core is achieved by controlling the synergistic effect of the rheological properties of the polydimethylsiloxane / carbonyl iron powder mixture and the magnetic field. After the polydimethylsiloxane prepolymer is mixed with the curing agent, carbonyl iron powder of a specific particle size is added and the viscosity of the mixture is controlled within the range of 500-800 mPa·s (this viscosity range can ensure the uniform dispersion of carbonyl iron powder particles and form a local agglomeration driving force under the action of the magnetic field). When a vertical magnetic field is applied, the carbonyl iron powder particles are pulled towards the magnetic pole by the magnetic field lines. The specific viscosity of the mixture causes "local aggregation resistance" to be generated during the movement of the particles. The magnetic attraction of adjacent particles and the fluid viscosity resistance interact, so that the particles are not arranged as individual entities along the magnetic field lines, but rather drag the surrounding polymer solution protrusions with "micro-agglomerates" as the core, and finally form medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia. This forming mechanism requires no additional template and can be achieved simply by matching rheological parameters with a magnetic field, which is different from the formation method of uniform cilia in existing technologies.

[0016] The formation of the "non-uniform clustered distribution structure" in this invention is primarily due to the nonlinear coupling control of the magnetic dipole interaction of magnetic particles (carbonyl iron powder) under a vertical magnetic field and the shear-thinning rheological properties of the polymer solution (polydimethylsiloxane).

[0017] Its dynamic process can be divided into the following three stages.

[0018] Chain precursor formation stage: When a vertical magnetic field acts on the coating layer, the uniformly dispersed magnetic particles are instantaneously magnetized. The magnetic dipole attraction generated between the particles overcomes the thermal motion and rapidly arranges them into a primary chain structure along the direction of the magnetic field lines.

[0019] Unsteady Cluster Evolution Stage: Due to the precise control of the viscosity of the prepolymer mixture within the range of 500-800 mPa·s, this specific viscosity environment endows the fluid with significant damping characteristics. Under the continuous action of the magnetic field force, adjacent primary magnetic chains undergo unstable oscillation due to the attraction of transverse magnetic dipoles. At this time, the viscous resistance of the fluid is not uniformly distributed, but rather undergoes a shear thinning effect as the magnetic chains locally aggregate, leading to a sharp drop in resistance in local areas. This, in turn, induces the surrounding magnetic chains to undergo coordinated unstable merging towards the core region, forming a coarse "cluster precursor".

[0020] Rheological locking and morphological solidification stage: As the volume of the cluster structure increases, the magnetic pull on it also increases, causing the polymer matrix to protrude upwards. When the expansion stress generated by the magnetic flux clusters reaches a dynamic equilibrium with the surface tension and viscous resistance of the polymer solution, a cluster array with non-uniform height and density is formed. Subsequently, through a thermosetting process, this transient non-uniform cluster distribution caused by rheological instability is permanently locked onto the surface of the flexible substrate.

[0021] Magnetic particle content control: The proportion of carbonyl iron powder directly affects the magnetization and mechanical modulus of the composite material. With a low proportion of carbonyl iron powder, the biomimetic cilia of the medical implantable magnetically responsive dynamic anti-adhesion device exhibit good flexibility and significant passive micro-movement under environmental disturbances, which is beneficial for interfering with the initial adhesion of pollutants. With a high proportion of carbonyl iron powder, the biomimetic cilia of the medical implantable magnetically responsive dynamic anti-adhesion device exhibit strong magnetic responsiveness, large active oscillation amplitude under a magnetic field, and strong cleaning power.

[0022] Magnetic field modulation: The magnetic field strength mainly regulates the final height of the medical implantable magnetic response dynamic anti-adhesion bionic cilia.

[0023] The functional principle and passive anti-crystal adhesion mechanism: The medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia structure and its surface silicone oil layer work together to form a discontinuous "solid-liquid-gas" or "solid-liquid-liquid" composite interface on the device surface. This greatly reduces the direct contact area and adhesion points between urinary salt crystals and the solid flexible polymer substrate. At the same time, the flexibility of the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia causes them to oscillate slightly during urine flow, further interfering with the directional growth and tight adhesion of the crystals.

[0024] Active magnetic response cleaning mechanism: When cleaning is detected or preventatively required, a low-frequency alternating or rotating magnetic field is applied to the external site of the implanted device. The carbonyl iron powder within the biomimetic cilia of the medical implantable magnetically responsive anti-adhesion device responds to the magnetic field, driving the entire cilia array to produce synchronized wave-like or oscillating movements. This movement generates continuous shear stress and microfluidic disturbance on the coating surface, effectively: preventing further deposition of new crystals on the surface; "sweeping away" loosely attached microcrystal clusters from the flexible polymer substrate; and even causing fatigue damage to initially formed thinner stone shells, causing them to peel off. The cleaning effect is achieved by the natural flow of urine carrying away the shed material.

[0025] The beneficial effects of this invention lie in its strong structural stability: the non-uniform cluster structure, combined with the lubricating layer, forms a stable "solid-liquid-liquid" or "solid-liquid-gas" composite interface. Experiments show that after 4 hours of fluid flushing, the contact angle of the surface of this invention can still be maintained above 150°, which is significantly better than that of ordinary uniform structures.

[0026] Dual anti-fouling mechanism: Normally, it relies on a lubricating layer and air cushion for passive anti-adhesion; when initial scaling occurs, a magnetic field drives the ciliary tufts to oscillate significantly (amplitude > ±80μm), actively "sweeping away" stone crystals or biofilms using shear force, achieving intelligent cleaning. Simple manufacturing process: It abandons expensive and complex physical templates, utilizing rheological principles and magnetic field self-assembly in one step, suitable for large-scale fabrication on curved instruments such as catheters. Good biocompatibility: The magnetic particles are completely encapsulated by a cross-linked polymer matrix, exhibiting no cytotoxicity and meeting implantation requirements. Attached Figure Description

[0027] Figure 1 This is a cross-sectional micrograph of the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia of the present invention, wherein the labels include: 100-glass substrate; 101-flexible polymer substrate; 102-magnetic particles; 103-cilia tuft; 104-surface lubrication layer.

[0028] Figure 2 This is a top-view micrograph of the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia of the present invention, showing several "island-like" cilia clusters distributed on a flexible polymer substrate with a dark background, with gaps between the clusters.

[0029] Figure 3 This is a process flow diagram of the preparation method of the present invention, showing five steps: S1 preparation of mixture and degassing; S2 coating; S3 magnetic field induced molding; S4 thermosetting; and S5 lubrication treatment.

[0030] Figure 4 This is a micrograph of the structure of the present invention in a passive anti-adhesion state, showing that biological contaminants fall on the surface of the lubricating layer. Due to the cluster structure locking in the lubricating oil and air cushion, the contaminants are in a "suspended" state and easily slide off.

[0031] Figure 5 This is a micrograph of the structure of the present invention in an active cleaning state, showing that under the action of an external magnetic field, the cilia tufts swing dramatically, generating shear force.

[0032] Figure 6 and Figure 7 The images are side and top views of the scanning electron microscope (SEM) of the sample prepared in Example 1, showing obvious non-uniform cluster distribution characteristics.

[0033] Figure 8 and Figure 9 These are, respectively, a side view and a top view of the scanning electron microscope (SEM) of the sample prepared in Example 2.

[0034] Figure 10 and Figure 11 These are, respectively, a side view and a top view of the scanning electron microscope (SEM) of the sample prepared in Example 3.

[0035] Figure 12 and Figure 13 These are, respectively, a side view and a top view of the scanning electron microscope (SEM) of the sample prepared in Example 4.

[0036] Figure 14 The effects of different mass ratios of polydimethylsiloxane (PDMS) to carbonyl iron powder (Fe) on the height of the obtained cilia are shown in Examples 1-4.

[0037] Figure 15 The effects of different mass ratios of polydimethylsiloxane (PDMS) to carbonyl iron powder (Fe) on the top-view diameter of the obtained cilia are shown in Examples 1-4.

[0038] Figure 16 This is a bar chart comparing the antibacterial rates against Escherichia coli in embodiments and comparative examples of the present invention.

[0039] Figure 17 This is a bar chart comparing the antibacterial rates against Staphylococcus aureus in embodiments and comparative examples of the present invention.

[0040] Figure 18 These are microscopic images comparing the antibacterial effects of typical biological pollutants, showing the actual antibacterial effects against Escherichia coli and Staphylococcus aureus under different surface conditions (smooth surface, ciliated surface, ciliated silicone oil composite surface, and ciliated silicone oil dynamic response surface). Among them, a(1)-a(8) correspond to the microscopic morphology of different test groups.

[0041] Figure 19 Side and top SEM images of the Example 1 sample after immersion in artificial urine for 7 days (Fig. a1, Fig. b1), 14 days (Fig. a2, Fig. b2), and 21 days (Fig. a3, Fig. b3) are shown to evaluate the chemical stability and resistance to urinary salt deposition of the structure. Detailed Implementation

[0042] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments.

[0043] Example 1: Preparation and Degassing of the Mixture (S1): Polydimethylsiloxane prepolymer and curing agent were mixed at a mass ratio of 10:1. Carbonyl iron powder with an average particle size of 10 μm was added, resulting in a polydimethylsiloxane to carbonyl iron powder mass ratio of 2.5:1. The viscosity of the mixture was adjusted to 800 mPa·s by mechanical stirring, followed by vacuum degassing.

[0044] S2 Coating: Spin-coating the mixture onto the cleaned glass substrate 100 (as a support for the molding of the flexible polymer substrate 101).

[0045] S3 Magnetic Field Induced Molding: The coated sample is placed above a 50×30×15mm (length×width×height) N52 neodymium iron boron magnet, and a vertical magnetic field with a magnetic induction intensity of 0.8T is applied for 20-30 minutes. The magnetic field lines are perpendicular to the liquid surface. Under the combined action of magnetic force and rheological resistance, the mixture self-assembles to form clusters of protrusions, forming a flexible polymer substrate 101, cilia clusters 103 (protrusions growing upward from the flexible polymer substrate 101, presenting a clustered shape), and magnetic particles 102 (black dots dispersed in the cilia clusters 103 and the flexible polymer substrate 101).

[0046] S4 thermosetting: Maintain a magnetic field and heat in a 60℃ oven for 2.5 hours to cure.

[0047] S5 Lubrication Treatment: After cooling, the sample is immersed in dimethyl silicone oil (with a viscosity of 100 cSt at 25°C) for 24 hours, then removed and drained to form a surface lubrication layer 104 (a fluid layer covering the surface of the cilia tufts 103 and filling the gaps). This step significantly improves the instantaneous slippage and long-term lubrication retention of the surface.

[0048] Example 2: The difference from Example 1 is that the mass ratio of polydimethylsiloxane to carbonyl iron powder is 2:1.

[0049] Example 3: S1 Preparation of the mixture and degassing: Polydimethylsiloxane prepolymer and curing agent were mixed at a mass ratio of 10:1, and carbonyl iron powder with an average particle size of 1 μm was added. The mass ratio of polydimethylsiloxane to carbonyl iron powder was 1.5:1. The viscosity of the mixture was adjusted to 500 mPa·s by mechanical stirring, and then degassed under vacuum.

[0050] S2 Coating: Spin-coating the mixture onto the cleaned glass substrate 100 (as a molding support for the flexible polymer substrate 101).

[0051] S3 Magnetic Field Induced Molding: The coated sample is placed above a 50×30×10mm (length×width×height) N52 neodymium iron boron magnet, and a vertical magnetic field with a magnetic induction intensity of 0.3T is applied for 20-30 minutes. The magnetic field lines are perpendicular to the liquid surface. Under the combined action of magnetic force and rheological resistance, the mixture self-assembles to form clusters of protrusions, forming a flexible polymer substrate 101, cilia clusters 103 (protrusions growing upward from the flexible polymer substrate 101, presenting a clustered shape), and magnetic particles 102 (black dots dispersed in the cilia clusters 103 and the flexible polymer substrate 101).

[0052] S4 thermosetting: Maintain a magnetic field and heat in an 80℃ oven for 4 hours to cure.

[0053] S5 Lubrication Treatment: After cooling, the sample is immersed in dimethyl silicone oil (with a viscosity of 50 cSt at 25°C) for 24 hours, then removed and drained to form a surface lubrication layer 104 (a fluid layer covering the surface of the cilia tufts 103 and filling the gaps). This step significantly improves the surface's immediate slippage and long-term lubrication retention.

[0054] Example 4: The difference from Example 3 is that the mass ratio of polydimethylsiloxane to carbonyl iron powder is 1:1.

[0055] Reference Figure 1 and Figure 2The medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia provided by this invention have a structure consisting of, from bottom to top, a glass substrate 100 (for experimental preparation support), a flexible polymer substrate 101, and an integrally formed cilia cluster 103. For example... Figures 6 to 13 The microstructures of the samples prepared in Examples 1 to 4 are shown respectively. The core feature of this invention is that the biomimetic cilia are not uniformly distributed on the substrate surface, but present a unique "non-uniform cluster distribution structure".

[0056] Combination Figures 6 to 13 The microscopic characterization shows that each ciliary cluster 103 is encapsulated with high-density magnetic particles 102, which are completely encapsulated by a polymer matrix, ensuring biocompatibility in medical implant environments. This cluster structure not only increases the layering of surface roughness, but more importantly, it creates relatively wide gaps between the ciliary clusters, which, together with the surface lubrication layer 104, constitute a stable liquid-injectable porous surface.

[0057] The preparation process of this invention is as follows: Figure 3 As shown in Figures S1-S5. During the preparation process, the mass ratio of the polymer matrix to the magnetic particles has a crucial influence on the final morphology. (Refer to...) Figure 14 and Figure 15 The data curves show a clear linear or nonlinear correlation between the height of the cilia and the top-view diameter as the magnetic particle content changes. By controlling the viscosity of the mixture in the range of 500-800 mPa·s, and utilizing the synergistic effect of rheology and magnetic field, the cluster structure described above can be self-assembled without a physical template.

[0058] like Figure 16-17 Experimental background and group settings.

[0059] Through the study of Escherichia coli ( Figure 16 ) and Staphylococcus aureus ( Figure 17 The antibacterial adhesion efficiency on different surfaces was quantitatively evaluated using the plate count method. The experiment consisted of four groups: Smooth group (comparative example): unstructured, flat polydimethylsiloxane surface.

[0060] Cilia group: Surfaces that only have biomimetic cilia arrays but are not lubricated or magnetically driven.

[0061] Cilia-Silicone Oil group: Injected with silicone oil lubricant but in a static (non-magnetic field driven) state on the cilia surface.

[0062] Cilia-Silicone Oil (Dynamic) group (Example 1 of the present invention): a cilia surface that is injected with silicone oil lubricant and driven by an alternating magnetic field of 0.1T and 5Hz to generate oscillation.

[0063] Figure 16-17 Data analysis and performance comparison.

[0064] Passive anti-adhesion effect (static group): From Figure 16 and Figure 17 It can be seen that the antibacterial rates of the Smooth and Cilia groups were both low (around 50%), indicating that the microstructure alone has limited inhibitory effect on bacterial colonization. The antibacterial rate of the Cilia-Silicone Oil group increased to about 80%, which is attributed to the good locking effect of the non-uniform cluster structure on the lubricating layer, and the resulting liquid interface reduced the initial attachment points of bacteria.

[0065] Active sludge removal effect (dynamic group): In the embodiments of the present invention, after applying a dynamic magnetic field (Dynamic group), the antibacterial rate against both bacteria was significantly increased to over 95%, approaching 100%. This proves that under the drive of an alternating magnetic field, the violent oscillation (amplitude up to ±100μm) generated by the ciliary tufts produces a continuous shear force on the surface liquid layer.

[0066] In-depth explanation of the antibacterial mechanism.

[0067] Synergistic effect of physical barrier and shear stripping: In the passive state, the micro-nano gaps formed by the non-uniform cluster distribution lock in the lubricating oil, keeping the bacteria in a "suspended" state. In the active state, the magnetically responsive cilia clusters directly shatter the early biofilm structure that the bacteria are trying to build through mechanical oscillation, and use strong fluid shearing to peel the bacteria off the surface, achieving a dual protection mechanism of "passive anti-adhesion + active cleaning".

[0068] Broad-spectrum antibacterial properties: comparison Figure 16 and Figure 17 It is evident that the present invention exhibits extremely high clearance efficiency against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus), demonstrating that this dynamic surface has broad-spectrum application value in addressing infections caused by a variety of common clinical pathogens.

[0069] This invention possesses both passive protection and active cleaning functions. (Refer to...) Figure 4 In a passive state, the ciliary clusters 103 use the micro-nano gaps generated by their non-uniform distribution to lock in lubricating oil and air, keeping biological pollutants in a "suspended" state, making it difficult for them to form initial adhesion.

[0070] When a certain amount of contaminants accumulates on a surface, active cleaning can be achieved by using an external magnetic field. For example... Figure 5 As shown, under the action of an alternating magnetic field, due to the large aspect ratio and magnetic response sensitivity of the cilia tuft, the tips of the cilia can produce large-amplitude oscillations. Figure 18 This visually demonstrates the effect of the technology: comparison Figure 18As can be seen on the smooth surface of a(1) and the dynamic response surface of a(8), bacteria and biofilm are effectively peeled off under the strong shear force generated by dynamic oscillation, and its antibacterial rate and anti-adhesion performance are significantly better than those of the smooth surface of a(1) and a(8). Figure 18 Other static control groups.

[0071] Considering the complexity of the medical implantation environment, Figure 19 The morphological evolution of the present invention after immersion in artificial urine for 21 days is shown. SEM images show that even after long-term acid and alkali erosion and fluid scouring, the physical structure of the ciliary tufts 103 remains intact, with no obvious urinary salt deposition or polymer degradation on the surface, demonstrating the reliability of this structure in long-term clinical implantation applications.

[0072] Choosing a lubricant with a viscosity of 50-100 cSt can form a stable liquid film within the gap, preventing it from being lost due to gravity and allowing it to form a dynamic lubricating layer as the cilia oscillate and move with the array.

[0073] Implementation examples, effect verification, and application prospects.

[0074] This invention achieves precise control of the mixture viscosity within the range of 500-800 mPa·s by accurately adjusting the mass ratio of polymer prepolymer to magnetic particles, without the need for additional viscosity modifiers. Experiments show that when the mass ratio is high (low proportion of magnetic particles), the viscosity tends to be 500 mPa·s; when the mass ratio is low (high proportion of magnetic particles), the viscosity is close to 800 mPa·s.

[0075] 1. Structural characterization and stability verification.

[0076] Morphological observation: such as Figure 6 As shown, the obtained medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia exhibit obvious non-uniform cluster distribution characteristics.

[0077] Passive anti-adhesion stability: In a flushing test simulating urine (flow rate 10 cm / s), the sample of Example 1 exhibited excellent stability. After 4 hours of flushing, its surface water contact angle remained above 150°, while the contact angle of the comparative planar structure without magnetic particles and a lubricating layer dropped to below 110°. This fully demonstrates that the non-uniform cluster structure can more effectively lock the lubricating layer and the air cushion.

[0078] 2. Dynamic cleaning efficiency and mechanical performance.

[0079] Magnetic response oscillation performance: Under an alternating magnetic field of 0.1T, the oscillation amplitude of the ciliary tip of the sample in Example 1 is greater than ±80μm, and can reach up to ±100μm (about 30° deflection angle).

[0080] Active sludge removal mechanism: Cleaning experiments on simulated stone layers (formed by drying of calcium crystal simulated liquid) showed that after applying an alternating magnetic field of 0.1T and 5Hz, the ciliary clusters 103 vibrated violently, and the attached crystals broke off within 1 minute.

[0081] Diverse motion modes: The cilia can be driven to swing left and right by an alternating magnetic field (0.1T, 5Hz), while the rotating magnetic field (0.2-0.5T, 3-8Hz) can induce wave-like motion. Both modes can achieve efficient active dredging.

[0082] 3. Biosafety and lubrication optimization.

[0083] Cytotoxicity evaluation: According to GB / T 16886.5-2017 standard, the cell viability of samples in Examples 1-4 was tested by the MTT assay, and the cell viability was all above 95%. This indicates that the carbonyl iron powder was tightly coated by the polymer matrix, with no toxic precipitation, and fully meets the standards for medical implantation.

[0084] Lubricant viscosity matching: Experiments have shown that the ideal viscosity of lubricating oil at 25°C is between 50-100 cSt. Viscosities below 10 cSt are prone to leakage, while viscosities above 1000 cSt will hinder the dynamic response efficiency of cilia.

[0085] 4. Expand application areas.

[0086] Besides urological instruments, this magnetically responsive biomimetic structure also shows broad promise in other medical fields: Vascular stents: By passively inhibiting thrombus adhesion and actively removing deposits from the inner wall, the risk of in-stent restenosis is reduced.

[0087] Anti-adhesion patch: Used in abdominal surgery to reduce tissue adhesion and remove surface fibrin deposits through magnetic field.

[0088] Artificial joints: Optimize the lubrication of contact surfaces and reduce the generation of wear particles, thereby reducing the incidence of aseptic loosening.

[0089] The above-described embodiments are merely preferred embodiments of the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia, characterized in that, include: The invention comprises a flexible polymer substrate, a biomimetic cilia array, and a surface lubrication layer. The biomimetic cilia array is integrally formed with the flexible polymer substrate. The biomimetic cilia array is solidified from a polymer matrix and magnetic particles uniformly dispersed within the polymer matrix, with the magnetic particles completely encapsulated by the polymer matrix. The average particle size of the magnetic particles is 1-10 μm. The surface lubrication layer impregnates and covers the surface and gaps of the biomimetic cilia array. The biomimetic cilia array exhibits a non-uniform clustered distribution structure on the surface of the flexible polymer substrate. This non-uniform clustered distribution structure is formed by the local aggregation of multiple cilia units to form cilia clusters, with relatively sparse regions between the cilia clusters. The diameter of a single cilia in the biomimetic cilia array is 30-50 μm, and its height is 300-700 μm. The diameter of each cilia cluster is 50-200 μm, its height is 300-700 μm, and the spacing between them is 200-500 μm.

2. The medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in claim 1, characterized in that, The flexible polymer substrate and the polymer matrix are selected from polydimethylsiloxane, medical-grade silicone rubber, or polyurethane; the magnetic particles are selected from carbonyl iron powder, iron tetroxide nanoparticles, or neodymium iron boron microparticles; and the surface lubricating layer is biocompatible silicone oil or perfluoropolyether oil.

3. A method for preparing a medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in any one of claims 1-2, characterized in that, Includes the following steps: S1 Preparation of the mixture and degassing: The polymer prepolymer, curing agent and magnetic particles are mixed, and the dynamic viscosity of the mixture at 25°C is adjusted to 500-800 mPa·s, and degassing is performed; S2 Coating: The mixture is coated on the surface of the substrate; S3 Magnetic field-induced molding: The coating layer obtained in step S2 is placed in a vertical magnetic field above a neodymium iron boron magnet with a magnetic induction intensity of 0.1-1T, which pulls the polymer matrix to grow upward to form a highly non-uniform cilia precursor; S4 Thermal curing: Under the condition of maintaining the magnetic field, the cilia precursor is heated and cured to obtain a cured cilia array; S5 Lubrication treatment: The cured cilia array is immersed in a lubricating liquid, and after removal, excess lubricating liquid is removed to obtain the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia.

4. The method for preparing the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in claim 3, characterized in that, In step S1, the polymer prepolymer is a polydimethylsiloxane prepolymer, and the mass ratio of the polymer prepolymer to the curing agent is 10:1; the mass ratio of the polymer prepolymer to the magnetic particles is 3:1 to 1:

3.

5. The method for preparing the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in claim 3, characterized in that, In step S3, the magnetic field strength is 0.3-0.8T; in step S4, the heating and curing temperature is 60-80℃, and the curing time is 2-4 hours.

6. The method for preparing the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in claim 3, characterized in that, In step S5, the lubricant is dimethyl silicone oil with a viscosity of 50-100 cSt at 25°C.

7. A medical implantable device, characterized in that, At least a portion of the outer surface of the medical implantable device is covered with medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia as described in any one of claims 1-2; the medical implantable device includes one of a urinary catheter, a ureteral stent, a vascular stent, an anti-adhesion patch, or an artificial joint.

8. The application of the medical implantable magnetically responsive dynamic anti-adhesion biomimetic cilia according to any one of claims 1-2 in the preparation of a medical device with active sludge removal function.

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