Medical device for targeted application of therapeutic agents to the round window of the cochlea - Patents.com

Abstract

A medical device (1) for delivering a therapeutic agent by bioprinting is provided, the medical device (1) comprising: a rod body (2); a bioprinting cartridge (4) disposed near a distal end of the rod body (2), the bioprinting cartridge (4) comprising a top layer (43) comprising a solution (435) containing the therapeutic agent and an absorbing compound (421) disposed to convert light energy from laser radiation (31) into thermal energy and heat the solution (435) containing the therapeutic agent to generate a jet of the solution; and an optical fiber (3) extending longitudinally within a lumen of the rod body (2) and delivering a laser current to the absorbing compound (421).

Description

[Technical field]

[0001] The present invention relates to a medical device for the targeted application of therapeutic agents. In particular, the present invention relates to a medical device for the targeted application of therapeutic agents to small and difficult to access areas such as the round window of the cochlea. The present invention is particularly advantageous in the treatment of disorders of the neurosensory epithelium of the inner ear. [Background technology]

[0002] The cochlea is the coiled portion of the inner ear that contains the auditory nerve endings and is the site of many ear disorders.

[0003] Many therapeutic drugs in development or already available, such as gene therapy drugs, are aimed at treating various disorders of the human inner ear that cause hearing loss, tinnitus or vertigo. The round window is the preferred entry route for injecting drugs to treat these conditions. The diameter of the round window in adults is about 2 mm. It is composed of a 40-60 μm thick membrane made up of three cell layers. This membrane vibrates against the acoustic vibrations that enter the inner ear. This membrane acts as a pressure valve, allowing waves to travel in the fluid of the cochlea. This membrane provides privileged access to the fluid within the cochlea, which is surrounded by bone.

[0004] A known method for injecting such agents into the inner ear is direct intracochlear injection through the round window using a microcatheter, which penetrates and passes through the round window to inject the therapeutic agent. Summary of the Invention [Problem to be solved by the invention]

[0005] One drawback is the high risk of neurosensory impairment and subsequent hearing loss due to microperforation of the round window membrane (mechanical trauma to the cochlear structures). For these reasons, this method cannot be applied to humans in current clinical practice.

[0006] Local transtympanic injection is also known. The therapeutic agent is injected into the middle ear in large quantities (in liquid or gel form). This method relies on the mechanism of diffusion through natural membranes. As a result, the amount of drug that comes into contact with the round window diffuses and migrates into the cochlea.

[0007] One of the disadvantages of this method is the inability to control the penetration of the therapeutic agent into the inner ear and therefore the amount administered. Another disadvantage is the amount of product in the middle ear, which may contaminate the surrounding tissue. In fact, it is very difficult to deposit such a substance very accurately in the round window. For example, the humidity of the middle ear makes such accuracy difficult. Furthermore, the middle ear canal is connected to the nasal cavity. Therefore, with such a method, there is a significant risk that the subject will inhale the therapeutic agent.

[0008] As a result, there is a need to inject these substances into the inner ear while simultaneously allowing good control of the dosage, lack of contamination of the surrounding tissue, and being atraumatic to the sensory structures of the inner ear.

[0009] The present invention proposes to solve this problem by overcoming the above mentioned drawbacks. [Means for solving the problem]

[0010] According to one aspect, the present invention relates to a medical device for delivery of a therapeutic agent by bioprinting comprising a rod body including a bioprinting cartridge disposed near a distal end of the rod body, the cartridge including a top layer including a solution including a therapeutic agent and an absorbing compound capable of converting light energy from laser radiation into thermal energy and disposed to heat the solution including the therapeutic agent to cause ejection of the solution, the medical device further including an optical fiber extending longitudinally within the lumen of the rod body for directing a laser stream onto the absorbing compound.

[0011] The advantage of using bioprinting is that small droplets of a few picoliters in size containing the therapeutic agent can be generated on the round window in a fast and highly targeted manner. Indeed, the thermal energy converted by the absorbing compound is transferred to the top layer of the solution, causing local evaporation of said solution until a vapor bubble is formed, the explosion of which releases a microdroplet containing the therapeutic agent. A further advantage is that the therapeutic agent is applied without direct contact with the circular membrane. The therapeutic agent thus applied diffuses into the fluid of the inner ear. In this way, the therapeutic agent can be precisely impacted on the surface of the round window membrane in a non-traumatic manner, without the risk of damage, and the dosage of the therapeutic agent is controlled.

[0012] In one embodiment, the cartridge further comprises an absorbent layer including a lower surface and an upper surface disposed opposite the top layer, said absorbent layer comprising said absorbing compound.

[0013] One advantage is that the absorbing compound is concentrated in contact with the top layer, facilitating the transfer of thermal energy to the solution containing the therapeutic agent.

[0014] In another embodiment, the absorbing compound is diluted in the top layer.

[0015] One advantage is that it facilitates the manufacture of the cartridge and reduces the volume of said cartridge, another advantage is that the light energy of the beam is converted into thermal energy directly in the center of the solution containing the therapeutic agent, thereby facilitating the creation of vapor bubbles and the ejection of droplets containing the therapeutic agent.

[0016] In one embodiment, the bioprinting cartridge further comprises a transparent support plate positioned to support the top layer.

[0017] One advantage is that it provides physical support for the top layer, which may be liquid or viscous, while allowing the light beam to pass through with minimal energy loss.

[0018] In one embodiment, the absorbent layer is a metal coating on the top surface of the support plate.

[0019] In one embodiment, the support plate is a glass plate. Glass is advantageously transparent to ultraviolet and infrared wavelengths.

[0020] In one embodiment, the absorbing compound comprises a metal such as gold, titanium or silver. These compounds are particularly advantageous for generating thermal energy from a light beam.

[0021] In one embodiment, the thickness of the absorbing layer is from 10 nm to 150 nm.

[0022] In one embodiment, the therapeutic agent comprises a therapeutic agent for intracochlear therapy.

[0023] In one embodiment, the therapeutic agent is in liquid form.

[0024] In one embodiment, the solution containing the therapeutic agent comprises a liquid, viscous or gel-like solution in which the therapeutic agent is diluted.

[0025] In one embodiment, the medical device further comprises a focusing lens disposed between the cartridge and the distal end of the optical fiber to focus the laser beam exiting the optical fiber onto the absorbing compound.

[0026] In one embodiment, the medical device further comprises a rod body guide means.

[0027] In one embodiment, the cartridge is disposed within a receptacle in the rod body, optionally near the distal end of the rod body.

[0028] In one embodiment, the cartridge is removably disposed within the receptacle. One advantage is that the rod can be reused by replacing the cartridge.

[0029] In one embodiment, the medical device further comprises a connection means at the proximal end of the optical fiber for connecting the optical fiber to a laser source.

[0030] In one embodiment, the shaft body is a catheter body.

[0031] In one embodiment, the medical device comprises multiple coaxial optical fibers extending longitudinally within the lumen of the rod body to deliver laser currents to the absorbing compound at different locations.

[0032] According to a second aspect, the invention relates to a medical system comprising a medical device according to the invention and a laser source connected to the proximal end of an optical fiber.

[0033] In one embodiment, the laser source is designed to emit a pulsed laser beam. In one embodiment, the medical system further comprises means for directing the laser beam from the laser source into at least one of the plurality of coaxial optical fibers of the medical device.

[0034] In one embodiment, the means for directing the laser beam is configured to feed the coaxial optical fibers one after the other, preferably sequentially. One advantage is that the microdrops can be dispensed one at a time at different locations on the cartridge in order to accelerate the deposition rate on the target and to better distribute the therapeutic agent on the target surface.

[0035] Further features and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying drawings. [Brief description of the drawings]

[0036] [Figure 1] FIG. 1 is a schematic diagram of a medical device of the present invention and a system including the medical device and a means for generating a laser stream on a bioprinting cartridge at a distal end of a catheter according to one embodiment of the present invention. [Figure 2A]FIG. 1 is a schematic cross-sectional view of a bioprinting cartridge subjected to a laser stream generating a jet of droplets containing a therapeutic agent according to one embodiment of the present invention, in which the cartridge includes an absorbent layer. [Figure 2B] FIG. 1 is a schematic cross-sectional view of a bioprinting cartridge subjected to a laser stream generating a jet of droplets containing a therapeutic agent according to one embodiment of the present invention, in which an absorbing compound is diluted in the top layer. [Diagram 3] 1 is a schematic diagram of the end of an optical fiber according to one embodiment of the present invention, and the passage of a laser stream through a focusing lens onto a bioprinting cartridge, and the distal end of a catheter including a receptacle to receive the cartridge. [Figure 4] FIG. 2 is a schematic diagram of the distal end of a catheter with a cartridge disposed in the sidewall of the catheter body. [Diagram 5] 1 is a schematic diagram of a distal end of a catheter including a distal wall that forms a central passage for the passage of a therapeutic agent projected, the distal wall being designed to be positioned against a target, thereby controlling the distance between the cartridge and the target. [Figure 6] FIG. 1 is a schematic diagram of a cross-section of a medical device abutting the cochlea to deliver a therapeutic agent onto the round window membrane of the cochlea. [Figure 7] 1 is a schematic diagram of a medical device according to an embodiment of the present invention, and a system including the medical device and a means for generating a laser stream onto a bioprinting cartridge at a distal end of a catheter according to an embodiment of the present invention, the catheter including a plurality of coaxial optical fibers, a control element arranged to divert the laser stream into one of the coaxial fibers according to instructions provided by a computer. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] The present invention comprises a medical device that includes a shaft, such as a catheter, that allows for the delivery of a bioink containing a therapeutic agent onto a membrane target (eg, a round window).

[0038] The bioink is placed on a cartridge containing an absorbing compound capable of converting the optical energy of the laser beam into thermal energy. The heat generated by the absorbing compound in the bioink locally evaporates the bioink, generating a vapor bubble in the depth of the bioink, which expands and collapses, forming the bioinkjet.

[0039] Surprisingly, the inventors have discovered that such a jet of bioink on the round window membrane allows very precise targeting of the round window membrane and improves membrane penetration of the therapeutic agent while ensuring good control of the dosage of the therapeutic agent without damaging the round window membrane or contaminating the surrounding tissue or space.

[0040] rod The medical device 1 according to the invention comprises a rod.

[0041] A rod should be understood as an elongate body, the distal part of which is designed to be inserted into a canal or orifice.

[0042] The shaft body is preferably a catheter body 2 .

[0043] In the remainder of this description, the term "catheter body" will be used to refer to such a shaft body.

[0044] The catheter body 2 extends longitudinally from a proximal end intended for handling by an operator to a distal end 21 .

[0045] The distal end 21 of the catheter body is preferably designed to be inserted into the subject's middle ear via a minimally invasive approach known in otologic surgery. In a preferred example, the catheter body is designed to be inserted through an incision in the wall near the tympanic membrane.

[0046] The cross section of the catheter body is preferably circular, oval, elliptical, or any shape without straight edges. One advantage is that it reduces the risk of tissue damage when inserting the catheter body into a canal or orifice.

[0047] The catheter body is preferably rigid, allowing for better control of the position and orientation of the catheter body during the bioprinting procedure.

[0048] The catheter may include a means for guiding the distal portion of the catheter body. The guiding means is configured to orient the distal end 21 in a predetermined direction, in particular relative to the longitudinal axis of the proximal portion of the catheter body. One advantage is that it is easier to aim the catheter tip at the round window once it is inserted into the middle ear.

[0049] The catheter body 2 may include one or more lumens extending therethrough and along the longitudinal axis of the catheter body.

[0050] In particular, the distal end 21 of the catheter body 2 is designed to be introduced into the middle ear of a subject, for example through the tympanic membrane or through a hole in the bony wall of the subject's skull.

[0051] The distal end 21 of the catheter body 2 is preferably as large as the round window of a subject, for example, the dimensions of the catheter body according to a cross section perpendicular to the longitudinal axis of the catheter body 2 are between 0.1 mm and 5 mm, preferably between 1 mm and 3 mm.

[0052] Fiber Optics The medical device includes one or more optical fibers 3. The optical fibers 3 are designed to carry a laser stream from the proximal end of the catheter body to the distal portion of the catheter body 2.

[0053] The optical fiber 3 is disposed within the lumen of the catheter body 2 .

[0054] Preferably, the medical device 1 includes a connector for connecting the optical fiber 3 to the laser source 5 so as to direct the laser stream from the laser source 5 to the distal end 32 of the optical fiber.

[0055] 3, the optical fiber 3 extends to face the bioprinting cartridge 4. The distal end 32 of the optical fiber 3 and the bioprinting cartridge 4 are positioned such that the laser beam 31 is directed towards the bioprinting cartridge 4.

[0056] In one embodiment, the distal end 32 of the optical fiber 3 is positioned at a distance of 5 cm or less from the bioprinting cartridge 4. In a particular embodiment, the distal end 32 of the optical fiber 3 is positioned in contact with the cartridge 4. To this end, the optical fiber may include a means for generating a focused light beam at its distal end. In another embodiment, the distal end 32 of the optical fiber is positioned at a distance between 1000 and 3000 μm from the bioprinting cartridge 4.

[0057] In one embodiment, the bioprinting cartridge 4 is positioned along the longitudinal axis of the optical fiber.

[0058] The medical device 1 may also include optical means for directing the laser beam 31 towards the bioprinting cartridge 4. In the embodiment shown in Figure 4, the medical device 1 includes at least one mirror 47 positioned and oriented to deflect the laser beam 31 towards the bioprinting cartridge 4.

[0059] In one embodiment, the bioprinting cartridge 4 is positioned to fire a jet of bioink through the side window 22 of the catheter body 2. A mirror 47 then deflects the laser beam 31 towards the underside of the bioprinting cartridge 4.

[0060] In one embodiment, the distal end of the laser fiber is movable relative to the cartridge so that the cartridge can be illuminated at different successive points, in another embodiment, optical means such as optical lenses and / or mirrors are designed to illuminate the cartridge at different successive points, for example to scan the cartridge with a laser beam.

[0061] This allows a shot to be created from several points on the top layer, and therefore a scan of the target to be fired.

[0062] Multiple optical fibers Several optical fibers can be arranged coaxially to increase the number of impact points on the absorbent layer or cartridge 4. The optical fibers can be arranged in the same lumen of the catheter body or in respective coaxial lumens.

[0063] In the embodiment shown in Figures 7 and 8, the medical device 1 includes a plurality of coaxial optical fibers.

[0064] The plurality of coaxial optical fibers are for carrying laser streams to one or more lumens of the catheter body. The plurality of coaxial optical fibers are disposed from the proximal end of the catheter body to the distal portion of the catheter body 2.

[0065] Each optical fiber is positioned such that the laser beam from the distal part of the optical fiber reaches the cartridge 4 at a different point. One advantage of multiple coaxial laser fibers is that the cartridge can be scanned without mechanically moving the cartridge, the fiber, the catheter body, or the lens located between the distal part of the optical fiber and the cartridge. Indeed, it is possible to illuminate different zones of the cartridge depending on which optical fiber is fed by the laser stream.

[0066] Preferably, the device includes at least nine coaxial optical fibers for illuminating at least nine zones of the cartridge.

[0067] In the embodiment shown in Figure 8, at least one of the laser fibers is designed to illuminate the target with light in the visible range, preferably laser light. One advantage of this is that it allows the operator to illuminate the target and facilitate guidance of the distal portion of the catheter. To this end, the medical device further includes a second laser connected to provide power to the optical fiber to illuminate the target.

[0068] The fiber can be configured to illuminate the target through the cartridge. In one particular mode, the cartridge can include a through hole that allows the light beam emitted by the fiber to pass through. In another mode, the cartridge is sufficiently transparent to ensure illumination of the target by the light beam passing through the thickness of the cartridge.

[0069] cartridge The bioprinting cartridge 4 (also referred to herein as "cartridge") includes at least one absorbent compound and a top layer that includes a therapeutic agent.

[0070] By "upper side" it is meant the direction towards the target or opposite the direction of origin of the laser beam on the cartridge 4. By "lower side" it is meant the direction in which the laser beam 31 lands on the cartridge 4.

[0071] "Bioprinting" refers to the deposition of a material (referred to herein as a "bioink") containing a therapeutic agent onto living tissue by firing jets of the material.

[0072] Top layer Top layer 43 includes a therapeutic agent. Preferably, the therapeutic agent includes an inner ear therapeutic agent and / or a gene therapy agent. Preferably, top layer 43 includes a therapeutic agent dispersed or diluted in a liquid phase or a viscous or gel phase, such as a phase including a hydrogel.

[0073] In a particular embodiment, the therapeutic agent is diluted in a phase designed to be in gel form at least at body temperature (about 36° C.). One advantage is that the gel-like deposit ensures the mechanical stability of the droplets released on the membrane, improving the absorption of the therapeutic agent through the round window. In a first example, the phase is designed to be liquid at room temperature (about 23° C.) to improve cartridge manufacturing. In a second example, the therapeutic agent is diluted in a phase designed to be gel-like at body temperature and room temperature. The fact that the top layer is gelled advantageously allows the cartridge to be handled without the risk of losing the top layer and also allows larger cartridge sizes to be manufactured.

[0074] The liquid phase preferably comprises an aqueous liquid. The liquid phase may comprise serum, such as fetal bovine serum. This liquid phase containing the therapeutic agent is hereinafter referred to as a "bio-ink."

[0075] The therapeutic agent may be in liquid or solid form, for example in the form of a medicated powder.

[0076] In one embodiment, the therapeutic agent comprises fluorescent latex beads, cells, liposomes (adeno-associated viruses containing plasmids) and / or pharmacological agents.

[0077] The therapeutic agent can include a marking agent.

[0078] The top layer 43 extends in a plane of a predetermined thickness. The thickness of the top layer 43 is 100 μm to 10 mm, and more preferably 100 μm to 5 mm.

[0079] The diameter of the cartridge can range from 100 μm to 3 mm.

[0080] The volume of the top layer is preferably 15 μL to 100 μL.

[0081] The top layer may include a fluorescent agent, such as fluorescein, as a marking agent. In an alternative or cumulative embodiment, the top layer includes a corticoid substance, such as dexamethasone.

[0082] The top layer 43 is positioned opposite an outlet of the catheter body 2, for example its distal end 21 or side window 22, to enable droplets containing the therapeutic agent to be sprayed.

[0083] The top layer 43 of the cartridge 4 can be positioned such that its plane is oriented substantially perpendicular to the longitudinal axis of the catheter body. This arrangement advantageously allows droplets 433 containing the therapeutic agent to be expelled in a direction substantially parallel to the longitudinal axis of the catheter body. In this case, the target, e.g., the round window, is advantageously easier for the operator to aim.

[0084] Absorbing Compound The cartridge includes an absorbing compound, the absorbing compound including at least one compound capable of converting light energy from a laser beam into thermal energy.

[0085] In a first embodiment shown in Figure 2A, the cartridge 4 comprises an absorbing layer 42. The absorbing layer 42 is a thin layer comprising at least one compound 421 capable of converting light energy from a laser beam into thermal energy. Preferably, the absorbing layer 42 is a metal layer.

[0086] When the absorbent layer 42 is heated, it transfers at least a portion of this thermal energy to the top layer 43. Heating the liquid contained in this top layer 43 creates gas bubbles 431 in contact with the absorbent layer 42. Essentially, the bio-ink liquid in contact with the absorbent layer 42 is heated until it contacts the absorbent layer 42 causing localized evaporation. Heating causes the gas bubbles 431 in contact with the absorbent layer 42 to grow.

[0087] The expansion of the gas bubbles 431 and their collapse, after they reach a critical size, triggers the formation of a bio-inkjet 433 containing the therapeutic agent. As a result, a microdrop 433 of the bio-ink is transported from the top layer in a direction substantially perpendicular to the plane of the top layer.

[0088] Laser beam 31 provides the energy necessary to generate and eject picoliter-sized droplets at high speed, which are then projected onto a target substrate.

[0089] Preferably, the absorbing layer 42 comprises a metal compound such as gold, platinum or silver, which have the advantage that they are good thermal conductors and efficiently convert light energy into thermal energy.

[0090] The absorbing layer 42 may include a metal layer such as gold, platinum, or silver.

[0091] Alternatively, the absorbent layer 42 may include a polymer layer formulated to enhance absorbency.

[0092] The thickness of the absorbing layer 42 is preferably between 10 nm and 150 nm. The advantage of such a thickness is that it reduces the distance between its lower surface receiving the laser beam and its upper surface in contact with the upper layer. Thus, such an absorbing layer 42 transfers heat to the upper layer more efficiently.

[0093] Preferably, the absorbent layer 42 is a coating layer.

[0094] In a second embodiment, shown in FIG. 2B, the same purpose can be achieved by diluting the solution 435 of the top layer 43 with the absorbing compound 421. Metal particles, such as gold, platinum or silver particles, can be dispersed in the top layer. Metal particles dispersed in the solution 435 of the top layer advantageously reduce the volume of the cartridge and facilitate its manufacture. In this case, the cartridge 4 only comprises the support layer 41 and the top layer 43 superimposed on the support layer 41. Another advantage is that it is easier to generate a "droplet" emission, since the heat is generated directly in the volume of the top layer and not on its surface.

[0095] In this embodiment, the absorbing compound 421 and therapeutic agent are diluted in a liquid or gel matrix that is preferably transparent to the laser radiation emitted by the distal end of the optical fiber.

[0096] Preferably, the concentration and thickness of the absorbing compound 421 in the top layer is set so that 50 to 100% of the laser light energy is absorbed by the absorbing compound 421 in the top layer 43 .

[0097] support plate In one embodiment, the cartridge 4 further comprises a support plate 41. The support plate 41 preferably comprises a rigid material that supports the absorbent layer 42 and / or the top layer 43.

[0098] In one embodiment, the absorbing layer 42 is disposed between the backing plate 41 and a top layer 43 containing a therapeutic agent. The absorbing layer 42 is preferably a coating deposited on the top surface of the backing plate 41 in contact with the top layer 43. In this case, the backing plate 41 must be transparent to the laser beam 31 so that the laser beam 31 can reach the absorbing layer 42.

[0099] The backing plate 41 is preferably in contact with the absorbent layer 42 such that the absorbent layer 42 is sandwiched between the backing plate 41 and the top layer containing the therapeutic agent.

[0100] In another embodiment shown in FIG. 2B, a support plate 41 is placed in contact with the top layer 43 .

[0101] Generally, the support layer is positioned to support the top layer.

[0102] The thickness of the support plate 41 is preferably 200 μm to 5 mm.

[0103] The bioprinting cartridge 4 is positioned such that the laser beam 31 emitted from the distal end 32 of the optical fiber 3 reaches the underside of the absorbing layer 42 or absorbing compound 421, optionally via a support plate 41.

[0104] The support layer 41 is preferably a glass plate. Glass is particularly advantageous for its transparency properties so that the laser beam, especially at infrared or ultraviolet wavelengths, can pass through the support plate and reach the absorbing compound.

[0105] Laser Beam Focusing 2A to 4, the catheter 1 further comprises one or more focusing lenses 44 (also known as converging lenses), which allow the laser beam 31 emitted from the distal end 32 of the optical fiber to be focused onto the absorbing layer 42 or the absorbing compound 421 diluted in the solution 435 containing the therapeutic agent, advantageously allowing the light energy to be concentrated in the solution 435, thus generating the gas bubbles 431 and the bio-ink droplet jet in the upper layer more quickly.

[0106] The focusing lens 44 is preferably positioned at a distance from the lower surface of the absorbing layer 42 equal to or substantially equal to its focal length. In another mode, the focusing lens 44 is positioned at a distance from the top layer 43 equal to or substantially equal to its focal length.

[0107] The focal length is the distance between the geometric center of the lens and the point (focal point) where a set of parallel light rays converge after passing through the focusing lens 44 .

[0108] Thus, an absorbing compound 421 (optionally the underside of an absorbing layer) is placed at the focal position of the focusing lens 44, and all the parallel light rays reaching the lens are focused to the same point on the absorbing compound 421. At this point, the thermal energy generated is increased by the conversion of light energy to thermal energy. This facilitates the generation of the bio-ink droplet jet.

[0109] In one embodiment, the focusing lens 44 is disposed in direct contact with the distal end of the optical fiber. For example, the focusing lens may be formed by the distal end of the optical fiber.

[0110] Robot Support In one embodiment, the medical device 1 includes means for controlling the translational and / or rotational movement of the catheter body.

[0111] The control means may include robotic means. One advantage is that the round window can be more easily aimed and the catheter can be stabilized during the procedure.

[0112] The guiding means may be connected to optical means, such as a camera or a laser sight. Advantageously, the optical means make it possible to maintain the orientation of the distal end 21 of the catheter relative to the subject. For example, the camera or laser sight is configured to detect the subject's movements and to automatically generate commands to the control means to correct the orientation and / or position of the distal end in response to the user's movements.

[0113] Receptacle In one embodiment, the bio-ink cartridge 4 is removable from the catheter, which advantageously allows the cartridge 4 to be replaced after use and the remaining medical device 1 and catheter body 2 to be reused.

[0114] Thus, the catheter body 2 includes a receptacle 46, shown in Figure 3, designed to receive the bio-ink cartridge 4. In one embodiment, the receptacle 46 is located at or near the distal end 21 of the catheter. The receptacle 46 is designed to receive the bio-ink cartridge 4 from its side, allowing free passage of the laser beam 31 through the absorbing compound and free firing of the bio-ink in a direction substantially perpendicular to the surface of the top layer.

[0115] In one embodiment, shown in FIG. 3, the receptacle may be held in the center of the catheter body by an arm 45 .

[0116] The receptacle 46 may include reversible connection means complementary to the cartridge connection means to allow for removable attachment between the cartridge 4 and the receptacle 46 .

[0117] Stop Support In a first embodiment, shown in FIG. 3, the cartridge is disposed at the distal end of the catheter.

[0118] 5, the catheter body includes a stop wall 25. The stop wall 25 extends longitudinally distally of the catheter body to a distal opening 24. The stop wall 25 forms a launch zone 24 between the cartridge and the distal end, allowing bio-ink droplets 433 to pass from the cartridge to the distal opening 24.

[0119] The stopping wall is designed to abut the target, the abutment of the distal end 26 of this wall 25 against the target advantageously ensuring that a predetermined distance is maintained between the cartridge 4 and the target.

[0120] The stop walls 25 are side walls that surround the launch region 23. As shown in Figure 5, the side walls can be round, circular, or form a hollow ovoid around the passage region 23. The medical device can include a single tubular abutment wall 25 as shown in Figure 5. The medical device can include multiple stop walls 25 of the same length around the launch region 23.

[0121] 6, the abutment wall 25 is placed against the cochlear bone 51 surrounding the round window membrane 50. The first advantage is to maintain the distance d between the cartridge 4 and the membrane 50. The second advantage is to provide support to stabilize the catheter head against the target, in this case the round window membrane 50.

[0122] Preferably, the stopping wall 25 is designed to define a distance d between the cartridge and the distal opening 26 of between 500 μm and 10,000 μm, very preferably between 1,000 μm and 5,000 μm.

[0123] In one embodiment, the medical device includes means for monitoring the distance d between the cartridge and the distal end 26 of the stop wall 25 .

[0124] For this purpose, the stopping wall 25 is translatable relative to the cartridge 4. For example, the stopping wall 25 can be attached to the catheter body on a screw thread in order to adjust the distance d between the cartridge 4 and the distal opening 26. In another example, the cartridge can be translated in order to adjust the distance d between the cartridge 4 and the distal opening 26. In the latter example, the cartridge 4 is integral with an optical fiber and / or with optical means (focusing lenses, mirrors) ensuring the focusing of the laser beam on the absorbing compound 421.

[0125] Preferably, the distal end of the abutment wall 25 includes a sensor for detecting when the abutment wall is in direct contact with the cochlea 51. The sensor may include a pressure sensor or an impedance sensor for detecting direct contact with the cochlea.

[0126] In yet another embodiment, the catheter body includes at least two target optical fibers designed to emit laser beams in the visible range and positioned to emit intersecting laser beams at a predetermined distance from the cartridge.

[0127] One advantage is that as the user approaches the target with the catheter body, they visualize two points of the two aiming laser beams. When the target is at a distance equal to a predetermined distance from the cartridge, the two points merge and the user visualizes a single point.

[0128] Preferably, the target optical fibers are positioned so that their beams intersect at a distance d between 500 μm and 10,000 μm from the cartridge.

[0129] Healthcare System The invention also relates to a medical system 100 comprising the above-mentioned medical device 1 and a laser source 5. The laser source 5 is designed to generate a laser beam.

[0130] Preferably, the laser source 5 is designed to generate a laser beam having a wavelength between 400 nm and 2 μm. The wavelength is advantageously selected at a wavelength at which the absorbing compound 421 is able to convert light energy into thermal energy. The laser source 5 is connected to the medical device 1 such that the laser current generated by the laser source passes through the optical fiber 3 of the medical device 1.

[0131] Any type of laser can be used. The laser source is preferably designed to emit a laser beam whose wavelength does not damage living tissue.

[0132] Preferably, the laser source is designed to emit an infrared laser beam, preferably a laser source emitting a laser beam having a wavelength between 1000 nm and 1100 nm.

[0133] The advantage of infrared light is that it reduces the risk of damaging living tissue.

[0134] In one embodiment, the laser source is a semiconductor material. In particular, laser sources including Nd-YAG (neodymium doped yttrium aluminum garnet) lasers can be used.

[0135] In other embodiments, ultraviolet light may be used.

[0136] Preferably, the laser source is designed to emit a pulsed laser beam. One advantage of pulsed light is that it allows bubble generation and microdroplet ejection without a layer of absorbing compound.

[0137] In an embodiment in which the medical device 1 includes multiple coaxial optical fibers as described above, the medical system 100 can include multiple laser sources 5, with a proximal portion of each fiber connected to the laser source 5. In another embodiment shown in Figure 7, the medical system 100 includes a laser source 5 and a means 101 for directing a laser beam from the laser source 5 to a selected laser fiber. The means 101 for directing the laser beam 31 can include a mirror and / or at least one controllable optical lens for deflecting the laser beam towards a selected optical fiber.

[0138] In one embodiment, the controllable elements are subordinate to a controller, such as a processor or CALC computer.

[0139] In another embodiment, the medical system 100 includes a first laser source 5 for moving the microdrops to the target and a second light source for illuminating the target via an optical fiber as described above.

[0140] In one embodiment, the system includes means for acquiring an image of a region of the longitudinal extension of the catheter body. Preferably, at least one of the coaxial optical fibers is connected to an image acquisition device. The system is then configured to acquire and, optionally, display in real time, a video channel showing the target in front of the distal end of the catheter body during the approach.

[0141] Illumination Sequence When the microdroplets are ejected from the top layer, a disturbance of the surface state is observed. After ejection, the top layer relaxes until it returns to a substantially flat surface. The time between ejection of the microdroplets and return to this state is called the "relaxation time" and depends on the therapeutic agent and the phase in which it is diluted in the top layer.

[0142] If the droplets are ejected when the top layer has a disturbed surface condition, the direction of the jet will be more random and less precise.

[0143] In one embodiment, the medical system is configured to deflect light through the coaxial optical fiber described above in a predetermined sequence.

[0144] Preferably, the system is configured to make the time between two shots from the same optical fiber greater than or equal to a predetermined time, which is preferably greater than the relaxation time of the top layer.

[0145] In one example, the predetermined sequence includes illumination of the cartridge by multiple optical fibers in a sequence such that two successive illuminations are never emitted by two adjacent optical fibers.

[0146] A first optical fiber is "adjacent" to a second optical fiber means that the second optical fiber has the shortest distance to the first optical fiber among the multiple coaxial optical fibers, or is one of the three shortest distances to the first optical fiber.

[0147] This improves the accuracy of solution injection by such sequences.

[0148] The invention relates to a computer program product arranged for a medical system to carry out said sequence. The invention also relates to a computer readable medium, such as a MEM memory (preferably non-transitory) containing said computer program.

Claims

1. A medical device (1) for delivering a therapeutic agent by bioprinting, comprising: A rod body (2) is provided, The rod body (2) is a bioprinting cartridge (4) disposed near a distal end of the rod body (2), the bioprinting cartridge (4) including a top layer (43) containing a solution (435) containing the therapeutic agent; and an absorbing compound (421) disposed to convert light energy from a laser beam (31) into thermal energy and heat the solution (435) containing the therapeutic agent to generate a jet of the solution; an optical fiber (3) extending longitudinally within the lumen of said rod body (2) and delivering a laser beam to said absorbing compound (421); Including, Medical device (1).

2. the cartridge further comprises an absorbent layer (42) containing the absorbent compound (421); The absorbent layer (42) includes a lower surface and an upper surface disposed opposite the top layer (43). A medical device (1) according to claim 1.

3. The absorbing compound (421) is diluted in the top layer (43). A medical device (1) according to claim 1.

4. The bioprinting cartridge (4) further comprises a transparent support plate (41) arranged to support the top layer (43). A medical device (1) according to claim 1.

5. The absorbing compound (421) comprises a metal such as gold, titanium, or silver; A medical device (1) according to claim 1.

6. the therapeutic agent comprises a therapeutic agent for intracochlear therapy; A medical device (1) according to claim 1.

7. the solution (435) containing the therapeutic agent comprises a liquid solution, a viscous solution, or a gel solution in which the therapeutic agent is diluted; A medical device (1) according to claim 1.

8. and a focusing lens (44) disposed between the cartridge (4) and the distal end of the optical fiber (32) for focusing the laser beam (31) emitted from the optical fiber onto the absorbing compound (421). A medical device (1) according to claim 1.

9. The cartridge (4) is removably disposed in a receptacle (46) of the rod body (2). A medical device (1) according to claim 1.

10. a plurality of coaxial optical fibers each extending longitudinally within the lumen of the rod body (2) and directing a laser beam to the absorbing compound (421) at different positions; A medical device (1) according to claim 1.

11. A medical device according to any one of claims 1 to 10, comprising a laser source (5) connected to the proximal end of the optical fiber. A medical system (100).

12. The medical device of claim 10, a laser source; means for sequentially supplying the laser beam (31) to the plurality of coaxial optical fibers; Including, A medical system (100).

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