Micro-robot for preventing formation of microbial-induced crystalline deposits

Abstract

The present application belongs to the technical field of medical devices. The present application discloses a micro robot for preventing microorganism-induced crystalline sediment formation, comprising a degradable main body; at least one driving arm for reversible phase change to generate movement in response to physiological temperature fluctuation is arranged on the degradable main body, and an anchoring arm body for resisting fluid scouring effect to make the degradable main body stably stay in the target physiological cavity is arranged on the other side of the degradable main body away from the driving arm. The present application has the advantages of being capable of effectively inhibiting crystal formation and biofilm construction, and being capable of maintaining good anti-fouling ability for a long time in vivo to avoid becoming a new stone core.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and more specifically, to a microrobot for preventing the formation of microbial-induced crystal deposits. Background Technology

[0002] In clinical practice, infectious stones are a serious complication of urinary tract infections with a high recurrence rate and significant pathogenicity. The main components of infectious stones are struvite (magnesium ammonium phosphate) and carbonate apatite. Their formation is closely related to a special type of urease-producing bacteria, among which *Proteus mirabilis* is the most prevalent and potent pathogen. The formation mechanism of infectious stones is unique and persistent, with the core being the construction of a "crystalline biofilm." Specifically, the formation mechanism involves urease-producing bacteria colonizing a surface, simultaneously hydrolyzing urea in biological fluids (such as urine) and producing large amounts of ammonia. This causes a rapid increase in local pH to a highly alkaline level (e.g., pH > 7.5), promoting rapid supersaturation of phosphates and magnesium ions, leading to precipitation and the formation of insoluble crystals. At the same time, bacteria also secrete a sticky biofilm matrix composed of polysaccharides, proteins, and extracellular DNA, forming a complex and robust structured biofilm. These biofilms can effectively protect bacteria, making them highly resistant to antibiotics and immune system attacks, and accelerate the growth and fusion of crystals, ultimately forming infectious stones.

[0003] Currently, antibiotics are commonly used in clinical practice to prevent and treat infectious stones caused by urease-producing bacteria. However, current treatment methods and preventative measures have significant limitations: on the one hand, antibiotic treatment struggles to effectively penetrate biofilms and is ineffective against already formed biofilms. On the other hand, although surgery can remove most stones, recurrence is common due to the persistent presence of biofilms. Furthermore, existing prevention strategies often rely on chemicals or drugs, which may lead to bacterial resistance and cannot fundamentally prevent biofilm formation.

[0004] How to solve the above-mentioned technical difficulties has become an urgent technical problem to be solved. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a microrobot that can effectively inhibit crystal formation and biofilm construction, and can maintain good antifouling ability in vivo for a long time to avoid becoming the core of new stones, for preventing the formation of microbial-induced crystal deposits.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] The present invention provides a microrobot for preventing the formation of microbially induced crystal deposits, comprising a biodegradable body; at least one drive arm is provided on the biodegradable body for undergoing a reversible phase transition in response to physiological temperature fluctuations to generate motion; and an anchoring arm is provided on the other side of the biodegradable body away from the drive arm for resisting fluid scouring to keep the biodegradable body stably stationary in a target physiological cavity.

[0008] It also includes the following control method steps:

[0009] S1. According to the preset standards, the biodegradable body, along with the drive arm and the anchoring arm, is placed into the target physiological chamber through an external endoscope.

[0010] S2. By using the resistance of the anchoring arm to fluid erosion, the biodegradable body and the drive arm are placed in a predetermined position within the target physiological cavity.

[0011] S3. Based on physiological temperature fluctuations, the driving arm, together with the biodegradable body and the anchoring arm, autonomously generates continuous and slight reciprocating motion to destroy the foundation of biofilm construction and repel protein adsorption and bacterial approach, thereby inhibiting biofilm formation from physical and chemical sources to prevent crystal nucleation and growth.

[0012] S4. At a preset time point, an external ultrasound device is used to apply ultrasound of a predetermined intensity to the area where the biodegradable body, the driving arm, and the anchoring arm are located to generate local active oxygen to kill surface bacteria and remove organic matrix, thereby enabling the biodegradable body, the driving arm, and the anchoring arm to have good anti-fouling ability for a long time to integrate sonodynamic treatment and effectively avoid becoming a new stone core.

[0013] Preferably, the drive arm is a NiTi nickel-titanium shape memory alloy wire, and the outer walls of the drive arm, the biodegradable body, and the anchor arm are all pre-coated with a two-layer structure. The inner layer is an anti-biofilm coating with a porous surface morphology for synovial fluid infusion, and the outer layer is a coating composed of a sound-sensitive agent. The anti-biofilm coating is an amphoteric polymer coating composed of polymethacryloyloxyethyl phosphorylcholine and polysulfobetaine methacrylate in a preset mass ratio. The drive arm utilizes the diurnal rhythmic fluctuations of the human body's core temperature as its sole energy source to propel the biodegradable main body and anchor arm into continuous micro-motion. This motion aims to physically interfere with the initial adhesion of bacteria to the instrument surface and the early formation of biofilms, thereby preventing stone formation at its source. Furthermore, to prevent the drive arm, biodegradable main body, and anchor arm themselves from becoming stone cores, their surfaces are pre-coated with anti-biofilm and acoustic sensitizer coatings. For example, the anti-biofilm coating is an amphoteric polymer coating used to form a stable hydration layer to repel bacterial adhesion. The acoustic sensitizer is integrated into the anti-biofilm coating, thus incorporating sonodynamic therapy functionality. This design allows for the activation of the acoustic sensitizer with low-intensity ultrasound during routine ultrasound follow-ups, generating reactive oxygen species to remove any potentially formed micro-biofilms or crystal deposits in situ, non-invasively, achieving periodic maintenance. By combining the "passive chemical defense" of the anti-biofilm coating with the "active physical interference" of the drive arm along with the biodegradable body and anchor arm, and the "on-demand therapeutic maintenance" of the sonic sensitizer, a new, long-lasting, and maintainable prevention strategy is provided for medical staff to target highly recurrent infectious stones.

[0014] Preferably, the movement of the drive arm is used to generate microfluidic shear forces in the biofluid, thereby interfering with the initial attachment of microorganisms to its surface or the formation of a biofilm.

[0015] Preferably, the NiTi nickel-titanium shape memory alloy wire can undergo austenite-R phase reversible transformation in the temperature range of 36°C to 38°C.

[0016] Preferably, the sound-sensitive agent is composed of any one of organic or inorganic sound-sensitive agents.

[0017] Preferably, the organic sound-sensitive agent is composed of any one of porphyrin or phthalocyanine; the inorganic sound-sensitive agent is composed of any one of titanium dioxide nanoparticles or manganese dioxide nanoparticles.

[0018] Preferably, the biodegradable matrix is ​​composed of any one of polylactic acid-glycolic acid copolymer, polycaprolactone, or polylactic acid.

[0019] Preferably, the biodegradable matrix is ​​composed of polylactic acid-glycolic acid copolymer, polycaprolactone, and polylactic acid in a preset mass ratio.

[0020] Preferably, the anchoring arm is at least one flexible arm extending outward from the other side of the biodegradable body away from the drive arm and having a predetermined curved shape, or a curled tail.

[0021] Preferably, in step S4, the external ultrasonic device applies ultrasound to the biodegradable body and the area where the drive arm and anchor arm are located with a predetermined intensity of less than 3 W / cm² and a frequency of 1 MHz to 3 MHz.

[0022] Preferably, in step S4, the preset time for the external ultrasonic device to apply ultrasound to the biodegradable body and the area where the drive arm and anchor arm are located is 5-15 minutes.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] In this invention, the biodegradable body, along with the driving arm and anchoring arm, is placed in the target physiological chamber via an external endoscope according to preset standards. This directly targets the core of infectious stone formation, namely, interfering with the construction process of crystalline biofilm, rather than simply inhibiting crystal aggregation. The strategy is more fundamental, highly targeted, and directly addresses the root cause. The anchoring arm's resistance to fluid erosion keeps the biodegradable body and driving arm in a predetermined position within the target physiological chamber. Based on physiological temperature fluctuations, the driving arm, along with the biodegradable body and anchoring arm, autonomously generates continuous, slight reciprocating motion to disrupt the foundation of biofilm construction and repel protein adsorption and bacterial approach. This, in turn, inhibits biofilm formation from both physical and chemical sources, preventing crystal nucleation and growth. Long-lasting; driven by body temperature, requiring no external energy, the biodegradable body can eventually be safely absorbed by the human body without the need for secondary surgery, improving the patient's quality of life; at preset time points, external ultrasound equipment applies ultrasound of predetermined intensity to the areas where the biodegradable body, drive arm, and anchor arm are located to generate local reactive oxygen species to kill surface bacteria and remove organic matrix, thereby giving the biodegradable body, drive arm, and anchor arm good anti-fouling ability for a long time to integrate sonodynamic therapy, effectively preventing it from becoming the core of new stones; by transforming the implant from an irreversible consumable with a life cycle into a "regenerative medical device" that can be functionally maintained and regenerated through conventional, non-invasive means, its effective working life is greatly extended, ensuring long-term preventive effects. Therefore, by using a drive arm pre-designed with an anti-biofilm coating and a sonicating agent, along with a biodegradable body and anchoring arm, the anti-biofilm coating provides "passive chemical defense," which, combined with the "active physical interference" provided by the drive arm, biodegradable body, and anchoring arm, effectively inhibits crystal formation and biofilm construction. The sonicating agent provides "on-demand therapeutic maintenance," efficiently removing residual bacteria on the surface and destroying newly formed biofilm matrix or microcrystals. This maintains good antifouling ability in vivo for a long time to prevent it from becoming the core of new stones. Thus, this triple defense mode, consisting of "passive chemical defense," "active physical interference," and "on-demand therapeutic maintenance," provides healthcare professionals with a novel, long-lasting, and maintainable prevention strategy for highly recurrent infectious stones. Therefore, this invention has the advantages of effectively inhibiting crystal formation and biofilm construction, and maintaining good antifouling ability in vivo for a long time to prevent it from becoming the core of new stones. Attached Figure Description

[0025] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0026] Figure 1 This is a schematic diagram of the structure of the microrobot for preventing the formation of microbially induced crystallized deposits as described in this invention;

[0027] Figure 2This is a cross-sectional schematic diagram of the drive arm of the microrobot used to prevent the formation of microbially induced crystallized deposits according to the present invention.

[0028] Figure 3 This is a schematic diagram of the reversible phase transition and mechanical movement of the microrobot used to prevent the formation of microbially induced crystallized deposits according to the present invention.

[0029] Figure 4 This is a flowchart of the control method for a microrobot used to prevent the formation of microbial-induced crystallized deposits, as described in this invention.

[0030] Explanation of reference numerals in the attached drawings: 1. Biodegradable main body, 2. Drive arm, 3. Anchor arm body. Detailed Implementation

[0031] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0032] See Figures 1 to 4 As shown, this embodiment provides a microrobot for preventing the formation of microbially induced crystallized deposits, including a biodegradable body 1; at least one drive arm 2 is provided on the biodegradable body 1 for undergoing a reversible phase transition in response to physiological temperature fluctuations to generate motion; and an anchoring arm 3 is provided on the other side of the biodegradable body 1 away from the drive arm 2 for resisting fluid scouring to keep the biodegradable body 1 stably stationary in the target physiological cavity.

[0033] It also includes the following control method steps:

[0034] S1. According to the preset standards, the biodegradable main body 1, together with the driving arm 2 and the anchoring arm 3, is placed in the target physiological chamber through an external endoscope. It can directly target the core of infectious stone formation, that is, interfere with the construction process of crystalline biofilm, rather than simply inhibiting crystal aggregation. The strategy is more fundamental, highly targeted, and directly addresses the root cause of the disease.

[0035] S2. Using the resistance of the anchor arm 3 to the fluid scouring action, the biodegradable body 1 and the drive arm 2 are placed in a predetermined position within the target physiological cavity.

[0036] S3. Based on physiological temperature fluctuations, the driving arm 2, together with the biodegradable body 1 and the anchoring arm 3, autonomously generates continuous and slight reciprocating motion to disrupt the foundation of biofilm construction and repel protein adsorption and bacterial approach, thereby inhibiting biofilm formation from a physical and chemical source to prevent crystal nucleation and growth; driven by body temperature, no external energy is required, and the biodegradable body can eventually be safely absorbed by the human body without the need for secondary surgery to remove it, thus improving the patient's quality of life;

[0037] S4. At a preset time point, an external ultrasound device is used to apply ultrasound of a predetermined intensity to the area where the biodegradable main body 1, the driving arm 2, and the anchoring arm 3 are located to generate local active oxygen to kill surface bacteria and remove organic matrix, thereby enabling the biodegradable main body 1, the driving arm 2, and the anchoring arm 3 to have good anti-fouling ability for a long time to integrate sonodynamic treatment and effectively avoid becoming a new stone core.

[0038] In this embodiment, the drive arm 2 is a NiTi nickel-titanium shape memory alloy wire, and the outer walls of the drive arm 2, the biodegradable body 1, and the anchor arm 3 are all pre-loaded with a two-layer coating structure, wherein the inner layer is an anti-biofilm coating with a porous surface morphology for synovial fluid injection, and the outer layer is a coating composed of a sound-sensitive agent.

[0039] In this embodiment, the drive arm 2 utilizes the diurnal rhythmic fluctuations of the human body's core temperature as its sole energy source to drive the biodegradable body 1 and the anchor arm 3 to generate continuous microscopic movement. This movement aims to physically interfere with the initial attachment of bacteria to the instrument surface and the early formation of biofilms, thereby preventing stone formation at its source. Furthermore, to prevent the drive arm 2, biodegradable body 1, and anchor arm 3 from becoming stone cores themselves, all three employ a pre-designed structure with an anti-biofilm coating and a sonosensitive agent coating. For example, the anti-biofilm coating is an amphoteric polymer coating used to form a stable hydration layer to repel bacterial attachment. The sonosensitive agent is integrated into the anti-biofilm coating, thus incorporating sonodynamic therapy functionality. This design allows for the activation of the sonosensitive agent using low-intensity ultrasound during routine ultrasound follow-ups, generating reactive oxygen species to remove any potentially formed micro-biofilms or crystal deposits in situ and non-invasively, achieving periodic maintenance of the drive arm 2, biodegradable body 1, and anchor arm 3. By combining the "passive chemical defense" of the anti-biofilm coating with the "active physical interference" of the drive arm 2 along with the biodegradable body 1 and the anchoring arm 3, and the "on-demand therapeutic maintenance" of the acoustic sensitizer, a new, long-lasting, and maintainable prevention strategy is provided for medical staff to target highly recurrent infectious stones.

[0040] In this embodiment, the movement of the drive arm 2 is used to generate microfluidic shear force in the biofluid, thereby interfering with the initial attachment of microorganisms to its surface or the formation of biofilm.

[0041] In this embodiment, the NiTi nickel-titanium shape memory alloy wire can undergo austenite-R phase reversible transformation in a temperature range of 36°C to 38°C.

[0042] In this embodiment, the anti-biofilm coating is an amphoteric polymer coating composed of polymethacryloyloxyethyl phosphorylcholine and polysulfobetaine methacrylate in a preset mass ratio.

[0043] In this embodiment, the sound-sensing agent is either an organic sound-sensing agent or an inorganic sound-sensing agent.

[0044] In this embodiment, the organic acoustic sensitizer is composed of either porphyrin or phthalocyanine; the inorganic acoustic sensitizer is composed of either titanium dioxide nanoparticles or manganese dioxide nanoparticles.

[0045] In this embodiment, the biodegradable body 1 is composed of any one of polylactic acid-glycolic acid copolymer, polycaprolactone, or polylactic acid.

[0046] In this embodiment, the biodegradable body 1 is composed of polylactic acid-glycolic acid copolymer, polycaprolactone, and polylactic acid combined according to a preset mass ratio standard.

[0047] In this embodiment, the anchoring arm 3 is at least one flexible arm extending outward from the other side of the biodegradable body 1 away from the driving arm 2 and having a preset curved shape, or a curled tail.

[0048] In this embodiment, in step S4, the external ultrasonic device applies a predetermined ultrasonic intensity of less than 3 W / cm² and a frequency of 1 MHz to 3 MHz to the area where the biodegradable body 1, the drive arm 2, and the anchor arm 3 are located.

[0049] In this embodiment, in step S4, the preset time for the external ultrasonic device to apply ultrasound to the area where the biodegradable body 1, the drive arm 2, and the anchor arm 3 are located is 5-15 minutes.

[0050] In this embodiment, firstly, according to preset standards, the biodegradable body 1, along with the driving arm 2 and the anchoring arm 3, is placed in the target physiological chamber through an external endoscope. This directly targets the core of infectious stone formation, namely, interfering with the construction process of the crystalline biofilm, rather than simply inhibiting crystal aggregation. This strategy is more fundamental, highly targeted, and directly addresses the root cause of the disease. Secondly, the anchoring arm 3's resistance to fluid erosion keeps the biodegradable body 1 and the driving arm 2 in a predetermined position within the target physiological chamber. Based on physiological temperature fluctuations, the driving arm 2, along with the biodegradable body 1 and the anchoring arm 3, automatically... The biodegradable body generates continuous, slight reciprocating motions to disrupt the foundation of biofilm construction and repel protein adsorption and bacterial approach, thereby inhibiting biofilm formation from a physical and chemical source to prevent crystal nucleation and growth. Driven by body temperature, requiring no external energy, the biodegradable body 1 can ultimately be safely absorbed by the human body without the need for secondary surgery, improving the patient's quality of life. Then, at preset time points, an external ultrasound device applies ultrasound of a predetermined intensity for a predetermined time to the areas where the biodegradable body 1, the driving arm 2, and the anchoring arm 3 are located, causing the acoustic sensor on its surface to generate localized reactive oxygen species to kill surface bacteria and clean the surface. In addition to the organic matrix, the biodegradable main body 1, as well as the drive arm 2 and anchor arm 3, possess excellent long-term anti-fouling capabilities for integrated sonodynamic therapy, effectively preventing them from becoming the core of new stones. By transforming the implant from an irreversible consumable into a "regenerative medical device" that can be functionally maintained and regenerated through conventional, non-invasive methods, its effective working life is greatly extended, ensuring long-term preventive effects. Finally, the drive arm 2, pre-designed with an anti-biofilm coating and acoustic sensitizer structure, along with the biodegradable main body 1 and anchor arm 3, utilize the anti-biofilm coating to provide "passive chemical defense." The "active physical interference" provided by the drive arm 2, together with the biodegradable body 1 and the anchoring arm 3, can effectively inhibit crystal formation and biofilm construction. The "on-demand therapeutic maintenance" provided by the sonosensitive agent can efficiently remove residual bacteria on the surface and destroy newly formed biofilm matrix or microcrystals in situ, thereby maintaining good antifouling ability in the body for a long time to avoid becoming the core of new stones. Therefore, the triple defense mode composed of "passive chemical defense" combined with "active physical interference" and "on-demand therapeutic maintenance" can provide medical staff with a new, long-lasting, and maintainable prevention strategy for highly recurrent infectious stones.

[0051] In this embodiment, the present invention, by employing functional language, is not limited to applications at specific anatomical sites and can be applied to any physiological environment where infectious stones are easily formed.

[0052] In this embodiment, the application principle of the multi-layered defense system is as follows:

[0053] The first layer of defense (active physical interference): disrupting the foundation of biofilm formation. The driving arm 1 is constructed of special NiTi shape memory alloy wire, whose phase transition temperature is precisely controlled, allowing it to be driven by the diurnal rhythmic fluctuations of the organism's core body temperature, generating continuous, slight reciprocating motion. This motion generates persistent fluid shear forces in the microenvironment. Biofilm formation begins with the fragile "primary attachment" and "microcolony development" stages of bacteria. This embodiment, through the generated gentle physical force, is sufficient to continuously interfere with and prevent bacteria from completing these two crucial initial steps, preventing them from establishing a stable foothold on the surfaces of the driving arm 2, the degradable body 1, and the anchoring arm 3, thereby inhibiting biofilm formation at its physical source.

[0054] The second layer of defense (passive chemical barrier): constructing a "bacteriostatic" surface. To fundamentally solve the biofouling problem faced by any implant, the entire outer surface of the drive arm 2, as well as the biodegradable body 1 and anchor arm 3, is covered with an advanced anti-biofilm coating, preferably an amphoteric polymer coating, such as polymethacryloyloxyethyl phosphorylcholine (pMPC) or polysulfobetaine methacrylate (pSBMA). These coatings, through the simultaneous presence of positive and negative charge centers on their molecules, use strong electrostatic forces to tightly bind water molecules to the surface, forming a dense and stable "hydration shell." This hydration layer constitutes a powerful barrier both energy-wise and physically, effectively repelling protein adsorption and bacterial approach, thereby achieving a bacterial attachment reduction rate of over 99%, achieving a "bacteriostatic" effect. This passive barrier, combined with the aforementioned active physical interference, constitutes an extremely robust "dual-effect synergistic anti-biofilm system."

[0055] The third layer of defense (on-demand therapeutic maintenance): Integrated sonodynamic therapy (SDT) functionality. To achieve long-term functional maintenance and remove any micro-deposits that might breach the first two layers of defense, a non-toxic "sound sensitizer" is integrated into the anti-biofilm coating. Sonodynamic therapy is a technique that uses low-intensity, non-destructive ultrasound (such as the level used in routine diagnostics) to activate the sound sensitizer. During a routine ultrasound examination, the physician can briefly irradiate the area containing the drive arm 2, the biodegradable body 1, and the anchor arm 3. After absorbing the acoustic energy, the sound sensitizer transfers the energy to surrounding oxygen molecules, generating highly reactive but extremely limited reactive oxygen species (ROS). These ROS can efficiently remove any residual bacteria, destroy newly formed biofilm matrix, or microcrystals on the surface of the drive arm 2, the biodegradable body 1, and the anchor arm 3 in situ, effectively performing a non-invasive "in-situ cleaning" and "functional reset" of the drive arm 2, the biodegradable body 1, and the anchor arm 3.

[0056] Specific implementation examples are as follows:

[0057] like Figure 1 As shown, a microrobot for preventing the formation of microbially induced crystallized deposits, consisting of a drive arm 2, a biodegradable body 1, and an anchoring arm 3, has an overall size in the millimeter range (e.g., a total diameter in the range of 5-15 mm). It can be inserted into a target physiological cavity via minimally invasive surgery (e.g., through an endoscopic working channel). Specifically, it includes a biodegradable body 1, at least one (preferably multiple, e.g., 4-8) flexible drive arms 2 distributed radially or otherwise pre-defined from the biodegradable body 1, and a flexible anchoring arm 3 with a pre-defined shape. Figure 1 The “pig tail-like” curled tail shown in the figure, the outer walls of the drive arm 2, the biodegradable body 1, and the anchor arm 3 are all covered with an advanced anti-biofilm coating, in which a non-toxic “sound-sensing agent” is integrated.

[0058] 1) Degradable main body 1

[0059] The biodegradable main body 1 is made of a biocompatible and biodegradable polymer material. This design ensures that after fulfilling its preventative function, the invention can be safely broken down into non-toxic metabolites over time and ultimately absorbed by the body, thus avoiding the need for a secondary surgery to remove it, and greatly reducing patient suffering and medical burden.

[0060] (1) Material Selection: In a preferred embodiment, the biodegradable substrate 1 is made of polylactic acid-glycolic acid copolymer (PLGA). PLGA is a medical polymer material approved by the U.S. Food and Drug Administration (FDA) and has excellent biocompatibility, a designable degradation time, and good processability. In vivo, it decomposes into lactic acid and glycolic acid through hydrolysis. These two small molecules are ultimately metabolized into carbon dioxide and water through the tricarboxylic acid cycle and are non-toxic to the human body.

[0061] (2) Controllable Degradation Characteristics: An important feature of this invention is that the degradation rate of the degradable substrate 1 can be precisely controlled according to clinical needs. This can be achieved by changing the monomer ratio of lactic acid (LA) to glycolic acid (GA) in PLGA. For example, increasing the proportion of the more hydrophilic GA will accelerate the hydrolysis and degradation rate of the polymer. In addition, the degradation cycle can also be controlled by controlling the molecular weight and crystallinity of the polymer. For example, for applications requiring short-term (e.g., within one month) prevention, amorphous PLGA with a higher GA ratio can be selected; while for applications requiring long-term (e.g., several months to one year) prevention, high molecular weight or semi-crystalline PLGA or other polymers with slower degradation can be selected.

[0062] (3) Manufacturing technology: The biodegradable body 1 can be manufactured using a variety of microfabrication techniques known in the art. For mass production, micro-molding is an efficient and repeatable method capable of producing tiny parts with precise dimensions and complex geometries. For personalized medicine or rapid prototyping, 3D printing (additive manufacturing) technologies, such as stereolithography (SLA) or fused deposition modeling (FDM), offer a flexible alternative that allows for the customization of the shape and size of the robotic body to the specific anatomy of a particular patient.

[0063] 2) Autonomous driving mechanism

[0064] like Figures 2 to 3 One of the core innovations of this invention lies in its completely autonomous driving mechanism, which cleverly utilizes the minute energy fluctuations naturally present within the host body as its sole power source. Specifically, it utilizes a shape memory alloy: the core of each driving arm 2 is a specially engineered nickel-titanium (NiTi) shape memory alloy wire. NiTi shape memory alloy wire is a well-known shape memory alloy, widely used in medical devices due to its excellent biocompatibility (the TiOx layer formed on the surface effectively prevents the release of nickel ions) and powerful shape memory effect (SME). The driving mechanism of this invention utilizes the reversible solid-state phase transition that occurs in the NiTi shape memory alloy wire at a specific temperature.

[0065] Utilizing physiological temperature fluctuations: A key ingenious step of this invention lies in the fact that it does not rely on external energy sources (such as electricity, magnetism, or light) or significant temperature changes to trigger a phase transition. Instead, it utilizes the minute but regular diurnal fluctuations in the core body temperature of mammals (including humans) over a 24-hour period. Normal human core body temperature typically fluctuates between approximately 36.1°C and 37.2°C, with peaks usually occurring in the evening and troughs in the early morning. This approximately 1°C temperature window constitutes the entire energy source driving the movement of this invention.

[0066] Precise thermomechanical control: To enable NiTi shape memory alloy wires to respond to such minute temperature changes, their phase transformation temperature must be controlled with extreme precision. This invention precisely sets the temperature window for the austenite-R phase (AR) reversible phase transformation within the aforementioned physiological body temperature fluctuation range through precise compositional blending and thermomechanical treatment. The AR phase transformation has a key advantage over the more common austenite-martensite (AM) phase transformation: extremely narrow temperature hysteresis. This means that the temperature change required to drive the phase transformation is very small, making it ideal for capturing and utilizing minute fluctuations in core body temperature. Methods for achieving this precise control include:

[0067] (1) Composition control: fine-tuning the atomic ratio of nickel and titanium during alloy manufacturing.

[0068] (2) Heat treatment: The formed NiTi shape memory alloy wire is subjected to specific aging treatment, such as holding it at a temperature of 300-500°C for a specific time (e.g., 30-60 minutes), which can effectively adjust the phase transformation temperature.

[0069] (3) Additive manufacturing parameter control: If NiTi parts are manufactured using additive manufacturing technologies such as selective laser melting (SLM), the phase transformation temperature of the final product can be controlled by precisely controlling the laser energy density (determined by laser power, scanning speed, and scanning spacing). Studies have shown that using a low energy density of less than 75 J / mm³, the austenite endpoint transformation temperature can be controlled below 37°C, which is precisely the operating range required by this invention.

[0070] like Figure 3 When the core body temperature rises during the day and exceeds a certain threshold (e.g., the As temperature), the NiTi shape memory alloy wire transforms from the R phase to the austenitic phase, restoring its preset "memory" shape (e.g., straightened state). When the core body temperature drops at night and falls below another threshold (e.g., the Rs temperature), the alloy wire transforms back to the R phase, exhibiting another morphology (e.g., bent state). This slow and continuous reciprocating motion, day after day, drives the entire drive arm 2 to produce slight but powerful oscillations or deformations.

[0071] 3) Anchoring arm body 3

[0072] The anchoring arm 3 is designed to ensure that the invention remains stably within the target physiological cavity (such as the renal pelvis or bladder) after implantation, resisting the flushing effect of biological fluids (such as urine) without displacement or expulsion. This structure is made of flexible, biocompatible materials, and its design can be adjusted according to the specific application site. In a preferred embodiment, such as... Figure 1 As shown, the anchoring arm 3 is designed as a "pigtail-like" coiled structure similar to the end of a double-J ureteral stent. This structure, through its own elasticity and predetermined shape, forms a gentle interaction with the inner wall structure of the cavity (such as the renal pelvis wall or the trigone of the bladder), thereby achieving stable mechanical fixation. In other embodiments, the anchoring arm 3 may be one or more flexible arms extending from the main body with predetermined curved shapes.

[0073] 4) Collaborative multi-layered defense

[0074] This invention prevents biofilm formation through an innovative, three-tiered synergistic defense system. These three tiers are: active physical interference, passive chemical barriers, and on-demand sonodynamic maintenance.

[0075] (1) Active physical interference with biofilm formation

[0076] This is the first and most proactive line of defense in this invention. As previously described, the drive arm 2 generates continuous, slow micro-motion driven by the diurnal fluctuations in core body temperature. This motion generates a persistent, low-intensity fluid shear force field in the surrounding microenvironment.

[0077] The formation of biofilms begins with the fragile "primary attachment" stage, where bacteria attach to the surface through weak, reversible physical forces such as van der Waals forces. Subsequently, bacteria progress to the "irreversible attachment" and "microcolony development" stages and begin secreting EPS matrix. The gentle yet persistent physical force generated by the drive arm 2 of this invention is insufficient to damage human tissue, but sufficient to continuously interfere with and disrupt the bacteria's completion of these crucial initial steps.

[0078] Fluid shear force can physically "sweep away" any few bacteria that might attempt to attach, preventing them from establishing a stable foothold on the surfaces of the drive arm 2, the biodegradable body 1, and the anchoring arm 3, thereby inhibiting biofilm formation from a physical and dynamic perspective. This proactive physical defense mechanism fundamentally solves the problem of traditional static implants serving as a "breeding ground" for bacterial attachment.

[0079] (2) Passive chemical barrier against biofouling

[0080] To fundamentally address the biofouling problem faced by any implant, the entire outer surface of the drive arm 2, the biodegradable body 1, and the anchor arm 3 undergoes special functional modification to construct a passive chemical barrier. Preferred embodiment: Anti-biofilm coating and acoustic sensitizer. For example, a functional coating, a zwitterionic polymer anti-biofilm coating, is applied to the surface of the drive arm 2, the biodegradable body 1, and the anchor arm 3. The zwitterionic polymer, polymethacryloyloxyethyl phosphorylcholine (pMPC) or polysulfobetaine methacrylate (pSBMA), is of great interest due to its excellent anti-biofouling properties. An acoustic sensitizer coating is applied to the anti-biofilm coating.

[0081] Mechanism of Action: Each repeating monomer unit of this type of polymer contains an equal number of positive and negative charge centers. This unique chemical structure allows it to tightly bind water molecules around the polymer chain through strong electrostatic forces, forming a dense, stable "hydration shell" similar to the structure of bulk water. This hydration layer constitutes a strong barrier both energy-wise and physically. When biomolecules such as proteins or bacteria attempt to approach the surface, they must first overcome the high energy barrier required to disrupt this stable hydration layer, which is thermodynamically extremely disadvantageous. Therefore, the surface can effectively repel non-specific protein adsorption and bacterial approach, thus achieving extremely high antifouling performance. Experimental data show that this type of coating can reduce the adsorption of proteins from 100% blood plasma to below 10 ng / cm², and the bacterial adhesion reduction rate can be as high as 99% or more.

[0082] Coating Preparation: To form a firmly bonded coating on the substrate material (such as PCL or NiTi) of this invention, a multi-step chemical grafting method can be employed. For example, firstly, utilizing the strong adhesion of polydopamine (pDA), a "primer" layer is deposited on the substrate surface; then, through surface-initiated free radical polymerization (such as SI-ATRP techniques), zwitterionic monomers (such as SBMA) are grafted onto the pDA layer to form a well-structured, high-density polymer layer. This method ensures the long-term stability and durability of the coating.

[0083] (3) On-demand sonodynamic therapeutic maintenance

[0084] To achieve long-term functional maintenance of the device and remove any micro-deposits that might breach the first two lines of defense, this invention innovatively integrates a third layer of defense: sonodynamic therapy (SDT). This design transforms the implant from a passive consumable into an actively managed, regenerable system. Integration of sonosensitizers: Referring to Figure 2, during the preparation of the anti-biofilm coating, one or more non-toxic sonosensitizers are stably integrated into the polymer network through physical embedding or chemical bonding. The highly hydrated porous structure of the zwitterionic polymer coating provides an ideal matrix for carrying these functional molecules.

[0085] Selection of sound-sensing agents: An ideal sound-sensing agent should possess high sound sensitivity, good biocompatibility, and be non-toxic when not excited by ultrasound. This invention can employ a variety of sound-sensing agents, including:

[0086] Organic sound sensitizers include porphyrins and their derivatives (such as protoporphyrin IX, PpIX), phthalocyanines, and chlorophyllin e6 (Ce6). These molecules have good biocompatibility and are the most widely studied sound sensitizers.

[0087] Inorganic sound-sensing agents: such as titanium dioxide (TiO2) nanoparticles, manganese dioxide (MnO2) nanoparticles, etc. These materials have the advantage of high chemical stability.

[0088] Mechanism of action and clinical application

[0089] Following implantation, this invention provides continuous self-protection through its dual-effect anti-biofilm system. During routine follow-up periods (e.g., 1, 3, and 6 months post-operation), clinicians can use a standard diagnostic-grade ultrasound probe to deliver short-duration (e.g., 5-15 minutes) low-intensity, non-focused ultrasound to the area containing the invention.

[0090] Ultrasound parameters: The ultrasound used is low-intensity therapeutic ultrasound, typically with a frequency of 1-3 MHz and an intensity below 3 W / cm². Ultrasound with these parameters can non-invasively penetrate human tissue to reach the location of this invention without producing significant thermal effects, making it safe for surrounding tissues.

[0091] Generation of Reactive Oxygen Species (ROS): After absorbing sound energy, the sound-sensing agent molecule is excited to a high-energy state. Subsequently, it transfers energy to surrounding oxygen molecules, producing highly reactive but extremely limited reactive oxygen species (ROS), such as singlet oxygen (ROS). 1 O2) and hydroxyl radicals (•OH).

[0092] In-situ cleaning effect: These ROS have strong local oxidation capabilities, which can rapidly kill any residual bacteria attached to the surface of this invention, destroy the newly formed EPS biofilm matrix, and even decompose tiny crystal deposits. Due to the extremely short lifespan and extremely small diffusion distance of ROS (typically at the nanoscale), their killing effect is strictly limited to the surface of this invention and will not cause damage to the surrounding normal host tissue.

[0093] This process is equivalent to a non-invasive, in-situ "chemical cleaning" and "functional reset" of the invention. This periodic maintenance ensures that the anti-biofilm function of the invention remains optimal throughout its implantation cycle. This innovative application of SDT (Self-Drug Therapy) for implant "functional maintenance" rather than "disease treatment" is a key aspect of the invention, fundamentally changing the paradigm of implantable medical device design and use.

[0094] (4) Usage and clinical application

[0095] 1.1 Methods for preventing infection-induced biomineralization

[0096] The microrobot for preventing microbial-induced crystallization deposits, as described in any of the foregoing embodiments, is placed in a target physiological cavity via minimally invasive surgery. For example, after urological surgery, the microrobot can be placed in the renal pelvis or bladder to prevent recurrence of struvite stones associated with urinary tract infections. After implantation, the microrobot will operate autonomously, continuously combating biofilm formation through its multi-layered defense system.

[0097] 1.2 In Vivo Function Maintenance Methods

[0098] Methods for maintaining the functionality of implantable medical devices in vivo

[0099] 1.2.1 Provides a microrobot implanted in the host to prevent the formation of microbially induced crystal deposits;

[0100] 1.2.2 At predetermined time points (e.g., during routine imaging follow-ups), low-intensity ultrasound energy is periodically applied to the anatomical area where the microrobot used to prevent the formation of microbial-induced crystal deposits is located using an external ultrasound device for a duration sufficient to activate the acoustic sensor to generate reactive oxygen species. This effectively and non-invasively restores or enhances the anti-biofouling properties of the device surface, ensuring its long-term preventive effect. This represents a paradigm shift in the management of implantable medical devices.

[0101] In summary, the system described above has the advantages of effectively inhibiting crystal formation and biofilm construction, and maintaining good antifouling ability in vivo for a long time to avoid becoming a new stone core.

[0102] The above specific embodiments are merely several preferred embodiments of the present invention. Based on the technical solutions of the present invention and the relevant teachings of the above embodiments, those skilled in the art can make various alternative improvements and combinations to the above specific embodiments.

Claims

1. A microrobot for preventing the formation of microbially induced crystallized deposits, comprising a biodegradable body (1); characterized in that: At least one drive arm (2) is provided on the biodegradable body (1) for undergoing a reversible phase transition in response to physiological temperature fluctuations to generate motion. An anchoring arm (3) is also provided on the other side of the biodegradable body (1) away from the drive arm (2) to resist fluid scouring and keep the biodegradable body (1) stably in the target physiological cavity. It also includes the following control method steps: S1. According to the preset standards, the biodegradable body (1), together with the drive arm (2) and the anchoring arm (3), is placed in the target physiological chamber through an external endoscope. S2. Using the resistance of the anchor arm (3) to the fluid scouring action, the biodegradable body (1) and the drive arm (2) are placed in the predetermined position in the target physiological cavity. S3. Based on physiological temperature fluctuations, the driving arm (2), together with the degradable body (1) and the anchoring arm (3), autonomously generate continuous and slight reciprocating motion to destroy the foundation of biofilm construction and repel the adsorption of proteins and the approach of bacteria, thereby inhibiting the formation of biofilm from the physical and chemical source to prevent crystal nucleation and growth. S4. At a preset time point, an external ultrasound device is used to apply ultrasound of a predetermined intensity to the area where the biodegradable body (1), the driving arm (2), and the anchoring arm (3) are located to generate local active oxygen to kill surface bacteria and remove organic matrix, thereby enabling the biodegradable body (1), the driving arm (2), and the anchoring arm (3) to have good anti-fouling ability for a long time to integrate sonodynamic therapy and effectively avoid becoming a new stone core.

2. The microrobot for preventing the formation of microbially induced crystallized deposits according to claim 1, characterized in that: The drive arm (2) is a NiTi nickel-titanium shape memory alloy wire, and the outer walls of the drive arm (2), the biodegradable body (1), and the anchor arm (3) are all pre-loaded with a two-layer coating structure, wherein the inner layer is an anti-biofilm coating with a porous surface morphology for synovial fluid injection, and the outer layer is a coating composed of a sound-sensitive agent.

3. The microrobot for preventing the formation of microbially induced crystallized deposits according to claim 2, characterized in that: The anti-biofilm coating is an amphoteric polymer coating composed of polymethacryloyloxyethyl phosphorylcholine and polysulfobetaine methacrylate in a preset mass ratio.

4. The microrobot for preventing the formation of microbially induced crystallized deposits according to claim 2, characterized in that: The sound-sensing agent is composed of any one of organic or inorganic sound-sensing agents.

5. The microrobot for preventing the formation of microbially induced crystallized deposits according to claim 4, characterized in that: The organic acoustic sensitizer is composed of any one of porphyrin or phthalocyanine; the inorganic acoustic sensitizer is composed of any one of titanium dioxide nanoparticles or manganese dioxide nanoparticles.

6. The microrobot for preventing the formation of microbially induced crystallized deposits according to any one of claims 1 to 5, characterized in that: The biodegradable body (1) is composed of any one of polylactic acid-hydroxyacetic acid copolymer, polycaprolactone, or polylactic acid.

7. The microrobot for preventing the formation of microbially induced crystallized deposits according to any one of claims 1 to 5, characterized in that: The biodegradable body (1) is composed of polylactic acid-hydroxyacetic acid copolymer, polycaprolactone and polylactic acid in a preset mass ratio standard.

8. The microrobot for preventing the formation of microbially induced crystallized deposits according to any one of claims 1 to 5, characterized in that: The anchoring arm (3) is at least one flexible arm extending outward from the other side of the biodegradable body (1) away from the drive arm (2) and having a preset curved shape, or a curled tail.

9. The microrobot for preventing the formation of microbially induced crystallized deposits according to any one of claims 1 to 5, characterized in that: In step S4, an external ultrasonic device applies ultrasound to the area containing the biodegradable body (1), the drive arm (2), and the anchor arm (3) with a predetermined intensity of less than 3 W / cm² and a frequency of 1 MHz to 3 MHz.

10. The microrobot for preventing the formation of microbially induced crystallized deposits according to any one of claims 1 to 5, characterized in that: In step S4, the preset time for the external ultrasonic device to apply ultrasound to the biodegradable body (1) and the areas where the drive arm (2) and anchor arm (3) are located is 5-15 minutes.

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