A small-scale robot for biofilm eradication

Small-scale robotics with H2O2 and iron oxide nanoparticles, combined with enzymes, address the challenge of biofilm eradication by degrading the matrix and removing debris, effectively preventing reinfection on diverse surfaces.

JP7601766B2Active Publication Date: 2024-12-17THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

Patent Information

Application Number
JP2021530103
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2018-11-28
Filing Date
2019-11-25
Publication Date
2024-12-17
Estimated Expiration
2039-11-25

AI Technical Summary

Technical Problem

Existing techniques fail to effectively eradicate bacteria within biofilm matrices, degrade the biofilm matrix, and remove biofilm debris, leading to reinfection due to the complex structural and biological properties of biofilms.

Method used

Utilizing small-scale robotics with H2O2 and iron oxide nanoparticles, combined with enzymes like mutanase and dextranase, to actuate biohybrid robots that degrade the biofilm matrix and remove debris by magnetically controlled movement.

Benefits of technology

The method effectively eradicates bacteria, degrades the biofilm matrix, and removes debris, preventing reinfection on various surfaces, including biological and non-living surfaces, by using magnetically actuated iron oxide nanoparticles and enzymes.

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Abstract

Disclosed herein are systems and methods for eradicating biofilms by killing bacteria within the biofilm, degrading the matrix, and removing biofilm debris. The disclosed subject matter provides techniques for administering a suspension of H2O2 and iron oxide nanoparticles to substantially eradicate bacteria within the biofilm matrix, degrading the biofilm matrix, actuating the iron oxide nanoparticles to assemble into a biohybrid robot suitable for removing biofilm debris, and powering the biohybrid robot to remove biofilm debris from accessible or enclosed surfaces. In some embodiments, the disclosed subject matter includes embedding iron oxide nanoparticles in a hydrogel to form a soft robotic structure, administering the soft robotic structure to a biofilm-covered site, and magnetizing the soft robotic structure to substantially eradicate bacteria within the biofilm matrix, degrading the biofilm matrix, and removing biofilm debris from enclosed surfaces.
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Description

[Technical field]

[0001] Statement regarding federally sponsored research This invention was made with Government support under Grant No. R01DE025848 awarded by the National Institutes of Health (NIH). The Government has certain rights in this invention.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority from U.S. Provisional Patent No. 62 / 772,306, filed November 28, 2018, which is incorporated herein by reference. [Background technology]

[0003] background A biofilm is a structured community of bacterial cells surrounded by a matrix of extracellular polymeric substances attached to a surface. Biofilms can form on biotic surfaces, such as teeth and mucosal surfaces, and on abiotic surfaces, such as implanted medical devices and catheters, thereby causing infections and medical complications in patients. Biofilms can also be present in natural and industrial environments. For example, biofilms can contaminate man-made aquatic systems, such as cooling towers, pools, and spas. In industrial environments, biofilms can develop inside pipes, causing clogging and corrosion. The extracellular matrix of such biofilms can contain polymeric substances such as exopolysaccharides (EPS), which are complex and mechanically stable scaffolds that provide cohesion / adhesion, act as a barrier against antimicrobial agents, and protect the bacteria within them.

[0004] Certain techniques to combat biofilms are largely ineffective, as they fail to both eradicate and remove the biofilm, leading to reinfection. Antimicrobial approaches such as antibiotics and immune responses may not be able to address the complex structural and biological properties of biofilms, and biofilms retain the ability to rapidly re-establish if biofilm debris and bacteria are not removed. Summary of the Invention [Problem to be solved by the invention]

[0005] Thus, a need exists for techniques that effectively substantially eradicate bacteria within a biofilm matrix, degrade the biofilm matrix, and remove the resulting biofilm debris. [Means for solving the problem]

[0006] overview Disclosed herein are systems and methods that use small-scale robotics to eradicate bacteria within a biofilm matrix.

[0007] The disclosed subject matter provides a technique for administering a suspension of H2O2 and iron oxide nanoparticles to substantially eradicate bacteria within a biofilm matrix, degrade the biofilm matrix, actuate the iron oxide nanoparticles to assemble into a biohybrid robot suitable for removing biofilm debris caused by biofilm decomposition, and actuate the biohybrid robot to remove biofilm debris from a surface. In some embodiments, the suspension can be formulated with 500 micrograms to 5000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol. In some embodiments, the suspension can be formulated with enzymes including mutanase, dextranase, DNase, protease, lipase, amyloglucosidase, glucose oxidase, or combinations thereof to degrade the biofilm matrix. For example, the suspension can be formulated with 1% H2O2 and 1.75U / 8.75U of mutanase / dextranase to substantially eradicate bacteria and degrade the biofilm matrix.

[0008] In some embodiments, an array of permanent magnets or electromagnets can apply a magnetic field from the permanent magnets to the biofilm to actuate the iron oxide nanoparticles and assemble them into a biohybrid robot. In some embodiments, the magnetic field can move the biohybrid robot to remove biofilm debris from a surface (e.g., biofilm removal from biotic and abiotic surfaces, including dental, dentures, implants, windows or other glass, plastic surfaces on which biofilms may form).

[0009] In some embodiments, the disclosed subject matter can include embedding iron oxide nanoparticles into a hydrogel to form a soft robotic structure to perform a specific task to remove biofilm from an enclosed surface. In some embodiments, the hydrogel can be a stimuli-responsive polymer. The soft robotic structure can be 3% agar by volume and 10% iron oxide nanoparticles by volume. For example, the soft robotic structure can be magnetized along its short axis, which can realign with the direction of a magnetic field.

[0010] In some embodiments of the disclosed subject matter, the soft robotic structures can be vane shaped to scrape biofilm from the walls of closed surfaces and move biofilm debris, in some embodiments, the soft robotic structures can be double helix shaped to drill through biofilm blockages and dislodge biofilm from walls.

[0011] The disclosed technology can be applied to eradicate bacteria within a biofilm matrix, degrade the matrix, and remove biofilm debris on biotic surfaces, such as teeth and mucosal surfaces, as well as abiotic surfaces, such as implanted medical devices and catheters, or surgical instruments, including endoscopes, cannulas / cannulas, thereby preventing infections and medical complications in patients. Additionally, the disclosed technology can be applied to eradicate bacteria within a biofilm matrix, degrade the matrix, and remove biofilm debris in natural and industrial environments, such as man-made water systems (e.g., cooling towers, pools, aquariums, spas), glass / plastic surfaces such as windows and food packaging, and inside pipes, water lines, and other enclosed surfaces. [Brief description of the drawings]

[0012] The accompanying drawings, which are incorporated herein and constitute a part of this disclosure, illustrate preferred embodiments of the invention and serve to explain the principles of the invention.

[0013] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] FIG. 1 illustrates the dual catalytic and magnetic functions of iron oxide nanoparticles. [Diagram 2] FIG. 2 shows the application of a suspension of iron oxide nanoparticles onto a biofilm. [Diagram 3] FIG. 3 shows the dose-dependent eradication activity of iron oxide nanoparticles. [Figure 4] FIG. 4 shows the dose-dependent degradation of extracellular matrix by the enzymes mutanase and dextranase. [Diagram 5] FIG. 5 shows two platforms for iron oxide nanoparticles. [Figure 6] 6A-6E show bacterial regrowth with and without removal of biofilm debris. [Figure 7] FIG. 7 shows iron oxide nanoparticles being manipulated by a magnetic element. [Figure 8]FIG. 8 illustrates the removal of large areas of biofilm debris by magnetically controlled movement of iron oxide nanoparticles. [Figure 9] Figure 9 shows the controlled movement of iron oxide nanoparticles on well-defined paths with micrometer-scale geometric precision. [Figure 10] FIG. 10 shows model representations of a vane-shaped soft robotic structure and a double helix-shaped soft robotic structure. [Figure 11] FIG. 11 illustrates a vane-shaped soft robotic structure cleaning biofilm on the wall of a cylindrical tube. [Figure 12] FIG. 12 illustrates a double helix soft robotic structure penetrating a biofilm clog in a cylindrical tube. [Figure 13] 13A-C show examples of the use of iron oxide nanoparticles for endodontic disinfection and treating biofilms within dental canals.

[0014] Throughout the drawings, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the present invention will be described in detail with reference to the drawings, it is done so in connection with the illustrative embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Detailed Description A technique is presented for eradicating biofilms using iron oxide nanoparticles, substantially eradicating bacteria within the biofilm matrix, degrading the biofilm matrix, and removing biofilm debris caused by biofilm eradication. Iron oxide nanoparticles are administered to a biofilm-covered surface, either in suspension or as a soft robotic structure. Once administered, the catalytic function of the iron oxide nanoparticles substantially eradicates the bacteria and degrades the biofilm matrix. The magnetic function of the iron oxide nanoparticles is activated to actuate the iron oxide nanoparticles for assembly suitable for removal of biofilm debris.

[0016] FIG. 1 illustrates the dual catalytic magnetic function of iron oxide nanoparticles according to an embodiment of the disclosed subject matter. Iron oxide nanoparticles 101 can catalyze hydrogen peroxide (H2O2) to substantially eradicate bacteria 102 and degrade biofilm matrix 103. Biofilm matrix degradation is key to disrupt structural scaffolding while facilitating penetration and bacterial eradication. The bacterial eradication effect is greatly enhanced when the biofilm matrix is ​​degraded. The biofilm matrix is ​​degraded when it is degraded enough to eradicate bacteria. When the bacteria within the biofilm matrix are killed, the bacteria are substantially eradicated. The iron oxide nanoparticles can be magnetically activated 104 to actuate the iron oxide nanoparticles and assemble them into a biohybrid robot, which can then move the biohybrid robot to remove biofilm debris from a surface.

[0017] FIG. 2 illustrates the application of a suspension of iron oxide nanoparticles on a biofilm according to an embodiment of the disclosed subject matter. The iron oxide nanoparticles catalyze hydrogen peroxide (H2O2) to generate free radicals. These free radicals can substantially eradicate bacteria embedded within the extracellular matrix of the biofilm. The free radicals can also degrade the extracellular matrix of the biofilm. This degradation occurs more slowly than the free radicals can substantially eradicate bacteria.

[0018] 3 shows the dose-dependent eradication activity of iron oxide nanoparticles according to embodiments of the disclosed subject matter. A concentration of 500 micrograms to 5000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol achieves maximum efficacy in eradicating bacteria.

[0019] Figure 4 shows the dose-dependent extracellular matrix degradation of the enzymes mutanase and dextranase according to an embodiment of the disclosed subject matter. The catalytic function of iron oxide nanoparticles degrades the biofilm matrix more slowly than it substantially eradicates the bacteria, but the rate of degradation can be increased with enzymes such as mutanase and dextranase. The combination of 1.75 U mutanase and 8.75 U dextranase achieves the greatest effect on extracellular matrix degradation.

[0020] FIG. 5 illustrates two exemplary platforms of iron oxide nanoparticles according to embodiments of the disclosed subject matter. These platforms allow iron oxide nanoparticles to remove biofilm debris. In the first platform, iron oxide nanoparticles 501 are suspended and administered to a surface covered with biofilm. Once the iron oxide nanoparticles perform their catalytic function, they are actuated to assemble into a biohybrid robot 502 using magnetic elements. In some embodiments, the magnetic elements can be permanent magnets or an array of electromagnets that apply a magnetic field. In the second platform, iron oxide nanoparticles are embedded in a hydrogel to form a soft robotic structure 503. In some embodiments, these structures can be vane shaped 504 or double helix shaped 505. The shape of the structures can allow for removal and eradication of biofilm from limited and inaccessible locations.

[0021] 6A-6E show bacterial regrowth with and without removal of biofilm debris according to embodiments of the disclosed subject matter. In FIG. 6A, the biofilm-covered surface was not treated with iron oxide nanoparticles. In FIG. 6B, the biofilm-covered surface was treated with iron oxide nanoparticles, but biofilm debris was not removed from the surface. Both FIGS. 6A and 6B show biofilm regrowth, indicating that biofilm retains the ability to rapidly re-establish itself if biofilm debris is not removed. In FIG. 6C, the biofilm-covered surface was treated with iron oxide nanoparticles, and biofilm debris was removed from the surface by magnetic actuation. In FIG. 6C, biofilm regrowth was not observed. FIGS. 6D and 6E show the amount of biomass and viable cells on the surfaces of FIGS. 6A-6C, respectively. Both surfaces of FIGS. 6A and 6B show high levels of biomass and viable cells, while FIG. 6C shows no detected biomass or viable cells.

[0022] 7 shows iron oxide nanoparticles being manipulated by a magnetic element according to an embodiment of the disclosed subject matter. Once the iron oxide nanoparticles 701 have substantially eradicated the bacteria and degraded the biofilm matrix, the magnetic element is activated 702. The magnetic element actuates the iron oxide nanoparticles to assemble into a biohybrid robot 703 and controls the movement of the biohybrid robot 703. In some embodiments, the biohybrid robot can form rod-like structures 704 that can penetrate the biofilm debris and remove the biofilm debris by incorporating the biohybrid robot into the biohybrid robot.

[0023] FIG. 8 illustrates the removal of large areas of biofilm debris by magnetically controlled movement of a biohybrid robot, according to embodiments of the disclosed subject matter. The biohybrid robot can navigate large areas of a biofilm-covered surface. In some embodiments, the biohybrid robot can follow a defined trajectory that starts at the center of the biofilm-covered surface and moves gradually outward in a concentric manner. Following this trajectory, the biohybrid robot can remove biofilm debris from the contaminated surface. This trajectory can also continuously draw individual iron oxide nanoparticles into the superstructure, thereby increasing their size and density.

[0024] FIG. 9 illustrates the controlled movement of a bio-hybrid robot on a well-defined path with micrometer-scale geometric precision according to embodiments of the disclosed subject matter. A bio-hybrid robot 901 can move on a well-defined path 902 with micrometer-scale geometric precision 903. For example, biofilms can be removed without damaging nearby host tissues, or biofilms can be sampled at specific pathological sites. In some embodiments, a suspension of iron oxide nanoparticles can be concentrated near a biofilm-covered surface to enable localized biofilm eradication.

[0025] FIG. 10 shows model representations of vane-shaped and double helix-shaped soft robotic structures according to embodiments of the disclosed subject matter. Iron oxide nanoparticles are embedded in hydrogels to form soft robotic structures. These structures can be shaped to perform specific tasks, such as eradicating biofilms from limited and inaccessible locations. The hydrogel can be permeable to H2O2, so the iron oxide nanoparticles can perform catalytic functions as described above. In some embodiments, the hydrogel can be a stimuli-responsive polymer. For example, the hydrogel can be a thermo-reversible gelling agar polymer, or another stimuli-responsive polymer, including pH and temperature responsive polymers. In some embodiments, the soft robotic structure can be 3% weight per volume of agar and 10% weight per volume of iron oxide nanoparticles. In some embodiments, both structures can be magnetized along their short axes to realign with the magnetic field direction.

[0026] FIG. 11 illustrates a vane-shaped soft robotic structure cleaning biofilm on a cylindrical tube wall, according to an embodiment of the disclosed subject matter. The vane shape can have a central core with a fin-like structure. The vane-shaped structure 1101 can rotate with applied magnetic torque from a magnetic element and can be moved forward at a speed by applying a force using the magnetic element. This rotation can generate localized fluid shear stress and scrape the curved surface of the tube 1102. As the vane-shaped structure moves forward, it sweeps over the curved surface, thereby scraping and displacing the biofilm debris. The displaced (displaced) biofilm debris forms a pile 1103 that can be removed from the tube by washing it off with water.

[0027] FIG. 12 illustrates a double helix shaped soft robotic structure penetrating a biofilm clog in a cylindrical tube, according to an embodiment of the disclosed subject matter. In a double helix shape, two helices can be wrapped around a central axis. The chiral shape of the double helix shaped structure 1201 allows it to be moved forward with a magnetic torque applied from a magnetic element, thereby propelling the structure like a corkscrew 1202. This movement causes the double helix shaped structure to drill through the biofilm blockage 1203 and dislodge the biofilm from the wall. As the structure moves forward, it forms a pile that can be removed from the tube by washing it off with water.

[0028] 13A-C show an example of the use of a biohybrid robot to treat biofilms in a dental canal, according to an embodiment of the disclosed subject matter. In particular, FIGS. 13A and 13B show cross-sectional views of a dental canal. In FIG. 13A, iron oxide nanoparticles can be administered into the isthmus, a narrow corridor between two root canals with a width of about 200 to 600 micrometers, and then moved from one end to the other and actuated for assembly into a biohybrid robot that can traverse the entire extent of the isthmus. As shown in FIG. 13B, a double-helix-shaped soft robotic structure made of iron oxide nanoparticles can also be magnetically controlled over the extent of the dental canal (FIG. 13B). FIG. 13A shows a longitudinal cross-section of a dental canal. At t=0 s, the biohybrid robot is in one of the root canals. At t=11.5 s, the biohybrid robot passes the isthmus. At t=14.5 s, the biohybrid robot reaches the other root canal. FIG. 13B shows a latitudinal cross-section of a dental canal. At t=0 s, the double helix shaped soft robot is at the top of the root canal. The biohybrid robot then moves down the root canal until it reaches the bottom of the root canal at t=17.7 s. Figure 13C shows the eradication of biofilm in the isthmus by the biohybrid robot, shown before and after the treatment. The biofilm was fluorescently labeled for visualization.

[0029] More generally, the disclosed technology can be applied to eradicate bacteria within a biofilm matrix, degrade the matrix, and remove biofilm debris on biotic surfaces, such as teeth and mucosal surfaces, as well as abiotic surfaces, such as implanted medical devices and catheters, or surgical instruments, including endoscopes, cannulas / cannulas, thereby preventing infections and medical complications in patients. Additionally, the disclosed technology can be applied to eradicate bacteria within a biofilm matrix, degrade the matrix, and remove biofilm debris in natural and industrial environments, such as man-made water systems (e.g., cooling towers, pools, aquariums, spas), glass / plastic surfaces such as windows and food packaging, and the interior of pipes, water lines, and other enclosed surfaces.

[0030] The foregoing merely illustrates the principles of the disclosed subject matter. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. It will thus be appreciated that those skilled in the art will be able to devise numerous techniques, not explicitly described herein, which embody the principles of the disclosed subject matter and are therefore within its spirit and scope. In relation to the present invention, the following is further disclosed: [1] 1. A method for eradicating bacteria within a biofilm matrix, disintegrating the matrix, and removing the biofilm, comprising: H 2 O 2 and administering a suspension of iron oxide nanoparticles to a biofilm having bacteria therein, wherein the suspension is adapted to substantially eradicate the bacteria and degrade the biofilm matrix; Actuating iron oxide nanoparticles to assemble into a biohybrid robot suitable for bacterial eradication and removal of biofilm debris caused by matrix degradation; and Moving the biohybrid robot to remove biofilm debris from a surface. [2] The method of claim 1, wherein the suspension comprises 500 micrograms to 5,000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol. [3] The method of claim 2, wherein the suspension comprises at least one enzyme adapted to degrade the biofilm matrix. [4] The method of claim 3, wherein the at least one enzyme comprises mutanase, dextranase, DNase, protease, lipase, amyloglucosidase, glucose oxidase, or a combination thereof. [5] The suspension is 1% H 2 O 2 and 1.75U / 8.75U of mutanase / dextranase. [6] The method of any one of claims 1 to 7, wherein said actuating comprises applying a magnetic field to actuate iron oxide nanoparticles and assembling them into a biohybrid robot. [7] The method of claim 6, wherein the moving comprises applying a magnetic field to move the bio-hybrid robot. [8] 1. A system for eradicating bacteria within a biofilm matrix, for matrix disruption, and for biofilm elimination, the system comprising: H adapted to substantially eradicate bacteria and degrade the biofilm matrix 2 O 2 and a suspension of iron oxide nanoparticles; and Magnetic elements adapted to actuate iron oxide nanoparticles for assembly into a biohybrid robot suitable for bacterial eradication and removal of biofilm debris caused by matrix degradation. [9] The system described in [8], wherein the suspension contains 2000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol.

[10] The system described in [9], wherein the suspension comprises at least one enzyme adapted to degrade the biofilm matrix.

[11] The system described in

[10] , wherein the at least one enzyme comprises mutanase and dextranase.

[12] The suspension is 1% H 2 O 2 and 1.75U / 8.75U mutanase / dextranase.

[13] The system described in [8], wherein the magnetic element includes at least one of an array of permanent magnets or electromagnets adapted to apply a magnetic field to the biofilm to actuate the iron oxide nanoparticles and assemble them into a biohybrid robot.

[14] The system described in

[13] , in which a permanent magnet powers a biohybrid robot adapted to remove biofilm debris from a biofilm matrix.

[15] 1. A method for eradicating bacteria within a biofilm matrix, disintegrating the matrix, and removing the biofilm, comprising: embedding iron oxide nanoparticles in hydrogels adapted to form soft robotic structures; administering the soft robotic structure to a biofilm-covered surface; and Magnetizing a soft robotic structure, where the soft robotic structure is adapted to substantially eradicate the bacteria, degrade the biofilm matrix, and remove biofilm debris caused by the biofilm eradication.

[16] The method according to

[15] , wherein the hydrogel is a stimuli-responsive polymer.

[17] The method described in

[16] , in which the soft robotic structure is 3 vol.% agar and 10 vol.% iron oxide nanoparticles.

[18] The method described in

[15] , in which a soft robotic structure adapted to realign with the magnetic field direction is magnetized along its short axis.

[19] The method described in

[18] , in which the soft robotic structure is vane-shaped and adapted to scrape and move biofilm debris from the walls of the enclosed surface.

[20] The method described in

[18] , in which the soft robotic structure is double helix shaped and adapted to drill through the biofilm blockage and remove the biofilm from the wall.

[21] H 2 O 2 and the method described in [1], in which a suspension of iron oxide nanoparticles is administered into the root canal for endodontic disinfection or biofilm removal.

[22] The method according to

[21] , wherein the bio-hybrid robot is adapted to move through the isthmus to disrupt the biofilm and remove biofilm debris.

[23] H 2 O 2 and a system described in

[14] , in which a suspension of iron oxide nanoparticles is administered into the root canal for endodontic disinfection or biofilm removal.

[24] The system described in

[21] , wherein the bio-hybrid robot is adapted to move through the isthmus to disrupt the biofilm and remove biofilm debris.

[25] The method of

[20] , further comprising moving a soft robotic structure across the dental canal for endodontic disinfection or biofilm removal.

Claims

1. 1. A system for eradicating bacteria within a biofilm matrix, for matrix disruption, and for biofilm elimination, the system comprising: H adapted to substantially eradicate bacteria and degrade the biofilm matrix 2 O 2 and a suspension of iron oxide nanoparticles; and a magnetic element adapted to actuate the iron oxide nanoparticles by a magnetic field in order to assemble them into a biohybrid robot suitable for eradicating bacteria and removing biofilm debris caused by matrix degradation; Moreover, the iron oxide nanoparticles are embedded in a hydrogel and adapted to form a soft robotic structure, the soft robotic structure configured to enable removal and eradication of biofilms from limited and inaccessible locations of a vessel or tube; Moreover, the soft robotic structure is vane-shaped or double helix-shaped and is adapted to scrape and move biofilm from the wall of the enclosed surface of the tube by adhering to the wall, and to drill through the biofilm blockages and clogs and remove the biofilm from the wall by rotating itself, and the soft robotic structure is magnetized and attracted to a magnetic field; Moreover, the soft robotic structure follows a defined trajectory of a rotating magnetic field, starting from the center of the biofilm-covered surface and gradually moving concentrically outwards. The aforementioned system.

2. 10. The system of claim 1, wherein the suspension comprises 2000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol.

3. The system of claim 2 , wherein the suspension comprises at least one enzyme adapted to degrade the biofilm matrix.

4. The system of claim 3 , wherein the at least one enzyme comprises mutanase and dextranase.

5. The suspension is 1% H 2 O 2 and 1.75 U / 8.75 U of mutanase / dextranase.

6. 2. The system of claim 1, wherein the magnetic element comprises, at a minimum, one of an array of permanent magnets or electromagnets adapted to apply a magnetic field to the biofilm to actuate iron oxide nanoparticles to assemble into a biohybrid robot.

7. The system of claim 6 , wherein the permanent magnet is configured to move the bio-hybrid robot and adapted to remove biofilm debris from the biofilm matrix.

8. H 2 O 2 and a suspension of iron oxide nanoparticles is administered into a root canal for endodontic disinfection or biofilm removal.

9. The system of claim 1 , wherein the bio-hybrid robot is adapted to move through an isthmus to disrupt biofilm and remove biofilm debris.

10. The system of claim 1, wherein the vane shape is configured with a central core having a fin-like structure and adapted to rotate with applied magnetic torque from the magnetic element to remove biofilm from walls of an enclosed surface.

11. The system of claim 1 , wherein the double helix shaped structure is configured to wrap two helices around a central axis to drill through biofilm blockages / clogs and remove biofilm from walls.

12. 10. The system of claim 1, wherein the suspension comprises 500 to 5000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol.

13. The system of claim 1 , wherein the hydrogel is a stimuli-responsive polymer.

14. 10. The system of claim 1, wherein the soft robotic structure is 3% agar and 10% iron oxide nanoparticles by volume.

Citation Information

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