Shearing type stem cell membrane dissociation and injection integrated device

Abstract

The invention discloses a shear type stem cell membrane dissociation and injection integrated device, which belongs to the field of biomedical engineering and comprises a negative pressure adsorption module, a mechanical crushing module and a multi-point injection module. The negative pressure adsorption module is used for absorbing stem cell membranes from the culture carrier; the mechanical crushing module is connected with the negative-pressure adsorption module, and is used for monitoring and adjusting shearing force in real time through a rotary blade and a pressure sensor, so that the diaphragm is dissociated into cell micelles in a low-damage manner; the multi-point injection module is connected with the mechanical smashing module and comprises 5-10 spacing-adjustable needle heads, uniform flow division is achieved through a flow division structure and an elastic membrane, a needle head vibrator is integrated to prevent blockage, and an external injection pushing structure is arranged to enhance injection pushing force. The device achieves integrated operation from adsorption, dissociation to injection, has the advantages of being easy and convenient to operate, small in cell damage, high in injection uniformity and the like, and is suitable for deep tissue or large-area treatment application in regenerative medicine.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical engineering, in particular to a shearing type stem cell membrane sheet dissociation and injection integrated device. BACKGROUND

[0002] At present, in the field of regenerative medicine and tissue engineering, stem cell membrane sheet technology has become an effective means for treating ischemic diseases, myocardial repair and tissue regeneration due to its ability to maintain cell-cell connections and extracellular matrix integrity. Traditional stem cell membrane sheet transplantation methods usually use direct attachment technology, such as attaching the cultured cell membrane sheet to the surface of the target tissue through surgical methods. However, this method has many defects, such as: traditional membrane sheet transplantation requires open surgery or large incisions, increasing the risk of trauma and infection for patients, especially for deep tissue applications; existing technologies usually rely on temperature-responsive materials or enzyme digestion to detach the membrane sheet, which not only takes time, but also may affect cell survival rate and function due to temperature fluctuations or enzyme activity; traditional methods cannot achieve multi-point, precise injection, resulting in uneven cell distribution and affecting treatment effect.

[0003] In recent years, some studies have attempted to convert stem cell membrane sheets into injectable formulations, such as dispersing the membrane sheet into a single cell suspension by mechanical whipping or enzyme digestion. However, these methods have the following problems: repeated whipping or enzyme treatment can damage cell-cell connections and extracellular matrix, reducing cell activity and paracrine function; manual operation is difficult to standardize, and single needle injection cannot meet the treatment needs of large area tissues.

[0004] Therefore, there is an urgent need to develop an integrated, low-damage, and high-efficiency stem cell membrane sheet delivery device. The present application is based on solving the above technical problems, by integrating mechanical crushing, low shear force control and multi-channel injection technology, to provide an innovative solution for the clinical translation of stem cell membrane sheets. SUMMARY

[0005] The purpose of the present application is to provide an integrated stem cell membrane sheet processing device that integrates negative pressure adsorption, low-damage dissociation and multi-point injection functions to solve the problems of large trauma, low cell activity and uneven distribution of traditional transplantation methods. Through integrated design and multi-needle synchronous injection, efficient preparation and uniform delivery of cell microclusters are achieved.

[0006] To solve the above technical problems, the present application specifically provides the following technical solutions: The shearing stem cell membrane sheet dissociation injection integrated device comprises a negative pressure adsorption module for sucking stem cell membrane sheets from a culture carrier, a mechanical crushing module connected to the negative pressure adsorption module for dissociating the membrane sheets into cell microclusters, and a multi-point injection module connected to the mechanical crushing module and comprising 5-10 needle heads for injecting cell suspensions into target tissues. The device integrates the functions of negative pressure adsorption, mechanical crushing and multi-point injection, and realizes the whole process operation from sucking, dissociating to injecting the stem cell membrane sheets. Through synchronous injection by the multi-needle heads, uniform distribution of the cell microclusters in the target tissues can be achieved, and the treatment effect is improved, which is especially suitable for deep tissue or large-area regenerative medicine applications.

[0007] The multi-point injection module comprises a slidable needle seat assembly comprising 5-10 needle seats provided with guide rails at the bottom, an adjusting knob, a transmission mechanism for driving the needle seats to move radially synchronously to adjust the distance between the needle heads, and locking bolts for fixing the positions of the adjusted needle seats. Through the design of the slidable needle seat assembly and the adjusting knob, the distance between the needle heads can be adjusted and controlled synchronously, so that the device can adapt to the injection requirements of different tissue regions.

[0008] The multi-point injection module is provided with a flow distribution structure to divide the cavity into 5-10 flow channels, and the end of each flow channel is provided with an elastic diaphragm. The flow distribution structure reasonably divides the cavity into multiple independent flow channels, and each flow channel corresponds to a needle head, which structurally ensures the basic uniformity of fluid distribution. The elastic diaphragm is located at the end of each flow channel, and its core function is to dynamically respond to the pressure fluctuations in the flow channel by using its flexibility and deformation ability. When the pressure of a certain channel instantaneously increases, the elastic diaphragm is forced to deform outward, locally increasing the volume of the flow channel and temporarily storing fluid and buffering pressure; on the contrary, when the pressure decreases, the diaphragm rebounds and pushes the fluid out, thereby compensating for the insufficient flow of that channel. This mechanical adjustment mechanism based on self-feedback of fluid pressure can realize real-time adaptive balance of the outlet flow of each needle head without external intervention, effectively eliminating the problem of uneven distribution caused by flow resistance differences.

[0009] The multi-point injection module is integrated with a needle head vibrator, which comprises a driving unit, a transmission rod connected to the driving unit, and a slidable needle seat assembly connected to the transmission rod. The integrated needle head vibrator can apply micro-vibration before injection, effectively preventing the cell microclusters from being blocked in the needle head and improving the injection smoothness.

[0010] The multi-point injection module is provided with a push structure on the outside, which can move axially to provide auxiliary injection power. The push structure provides axial auxiliary power to enhance the injection thrust and ensure that the cell suspension can be smoothly injected into tissues with high density.

[0011] The mechanical crushing module comprises a rotating unit and a pressure sensor, the rotating unit is provided with a rotating blade and a controller, the pressure sensor is used for detecting the shear force change in the dissociation process of the membrane sheet in real time, and the controller receives the signal of the pressure sensor and dynamically adjusts the rotating speed of the rotating blade. By monitoring the shear force in real time through the pressure sensor and dynamically adjusting the rotating speed of the rotating blade combined with the controller, low-damage control of the dissociation process is realized. This mechanism maximally protects the cell activity and functional integrity, and avoids the damage of excessive mechanical force to the cells.

[0012] The negative pressure adsorption module comprises an adsorption head connected with a cavity of the negative pressure adsorption module, and the cavity is an elastic air bag. The elastic air bag as the core component of the negative pressure adsorption module can realize negative pressure suction through manual extrusion, and can effectively suck the stem cell membrane sheet without damaging the structure.

[0013] The adsorption head is of a replaceable structure, and the adsorption end face of the adsorption head is provided with an annular sealing edge. The replaceable design of the adsorption head is convenient for cleaning and sterilization, and the annular sealing edge can further improve the adsorption efficiency.

[0014] Specifically, a hand-held part is arranged in the middle part of the device.

[0015] Specifically, a touch screen is arranged, which is used for setting the crushing time, rotating speed, injection flow rate parameters, and displaying the pressure feedback data in real time. The touch screen integrates the parameter setting and real-time data display functions, so that the operation process is visualized and controllable, and the accuracy and repeatability of the operation are improved.

[0016] The shear type stem cell membrane sheet dissociation and injection integrated device provided by the application realizes the whole-process integration of stem cell membrane sheet processing and delivery. The device gently and non-destructively sucks the cell membrane sheet through the negative pressure adsorption module, and realizes low-damage mechanical dissociation by means of the real-time shear force sensing and control system, so that the cell activity and functional integrity are maximally maintained. The multi-point injection module has an adjustable needle distance and a self-adaptive uniform flow structure, and can realize the uniform distribution of cell micro-aggregates in tissues, and significantly improve the treatment effect. The overall operation is integrated and customizable, which effectively reduces the open surgery trauma and operation time, and is suitable for various clinical scenes such as deep tissue repair and regenerative medicine. BRIEF DESCRIPTION OF DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the application or the technical solutions in the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only exemplary, and those skilled in the art can also obtain other implementation drawings according to the provided drawings without creating any inventive labor.

[0018] Figure 1An exploded view (visual representation) of the integrated shearing-type stem cell membrane dissociation and injection device described in Example 1. Figure 1 ).

[0019] Figure 2 An exploded view (visual representation) of the integrated shearing-type stem cell membrane dissociation and injection device described in Example 1. Figure 2 ).

[0020] Figure 3 This is a schematic diagram of the multi-point injection module described in Embodiment 1.

[0021] Figure 4 This is a schematic diagram of the mechanical crushing module described in Embodiment 1.

[0022] Figure 5 This is a schematic diagram of the external appearance of the integrated device for dissociating and injecting stem cell membranes according to the present invention.

[0023] Explanation of reference numerals in the attached diagram: 1-Negative pressure adsorption module; 11-Adsorption head; 2-Mechanical crushing module; 21-Rotating unit; 22-Pressure sensor; 3-Multi-point injection module; 31-Needle; 32-Sliding needle seat assembly; 33-Needle seat; 4-Injection structure; 5-Diverting structure; 6-Needle vibrator; 7-Touch screen; 8-Handheld part. Detailed Implementation

[0024] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] The concepts involved in this application will first be described with reference to the accompanying drawings. It should be noted that the following descriptions of various concepts are only for the purpose of making the content of this application easier to understand and do not constitute a limitation on the scope of protection of this application; furthermore, the embodiments and features in the embodiments of this application can be combined with each other unless otherwise specified. This application will now be described in detail with reference to the accompanying drawings and embodiments.

[0026] Example 1 like Figures 1-2 As shown, the integrated device for dissociating and injecting stem cell membranes includes: a negative pressure adsorption module 1 for aspirating stem cell membranes from a culture carrier; a mechanical pulverizing module 2 connected to the negative pressure adsorption module 1 for dissociating the membranes into cell clusters; and a multi-point injection module 3 connected to the mechanical pulverizing module 2, containing 5-10 needles 31 for injecting the cell suspension into the target tissue.

[0027] The application provides an integrated device integrating negative pressure adsorption, mechanical crushing and multi-point injection functions, and realizes full-process operation from stem cell membrane sheet suction, dissociation to injection. Through synchronous injection of multiple needles, uniform distribution of cell micro-aggregates in target tissues can be realized, and treatment effect is improved, which is especially suitable for deep tissue or large-area regenerative medicine applications.

[0028] As Figure 3 , the multi-point injection module 3 includes a slidable needle seat assembly 32 containing 5-10 needle seats 33, the bottom of the needle seat 33 is provided with a guide rail, the slidable needle seat assembly 32 is provided with an adjusting knob, the needle seat 33 is driven to move radially synchronously to adjust the distance between the needle heads 31 through a transmission mechanism, and the slidable needle seat assembly 32 is also provided with a locking bolt for fixing the position of the adjusted needle seat 33. Through the design of the slidable needle seat assembly 32 and the adjusting knob, the adjustability and synchronous control of the distance between the needle heads are realized, so that the device can adapt to the injection requirements of different tissue regions.

[0029] The multi-point injection module 3 is provided with a flow splitting structure 5 to divide the cavity into 5-10 flow channels, and the end of each flow channel is provided with an elastic diaphragm. The flow splitting structure 5 reasonably divides the cavity into multiple independent flow channels, and each flow channel corresponds to a needle head 31, which structurally guarantees the basic uniformity of fluid distribution. The elastic diaphragm is located at the end of each flow channel, and its core function is to dynamically respond to the pressure fluctuation in the flow channel by using its flexibility and deformation ability. When the pressure of a certain path instantaneously increases, the elastic diaphragm is forced to deform outward, locally increasing the volume of the flow channel, which has the effect of temporarily storing fluid and buffering pressure; on the contrary, when the pressure decreases, the diaphragm rebounds and pushes the fluid out, thereby compensating for the insufficient flow of that path. This mechanical adjustment mechanism based on fluid pressure self-feedback can realize real-time self-adaptive balance of the outlet flow of each needle head without external intervention, effectively eliminating the problem of uneven distribution caused by flow resistance difference.

[0030] The multi-point injection module 3 integrates a needle head vibrator 6, the needle head vibrator 6 includes a driving unit, the driving unit is connected to a transmission rod, and the transmission rod is connected to the slidable needle seat assembly 32. The integrated needle head vibrator 6 can apply micro-vibration before injection, effectively preventing cell micro-aggregates from being blocked in the needle head, and improving the smoothness of injection.

[0031] As Figure 4The mechanical crushing module 2 comprises a rotating unit 21 and a pressure sensor 22. The rotating unit is provided with a rotating blade and a controller. The pressure sensor 22 is used to detect the change of shear force in the film dissociation process in real time. The controller receives the signal of the pressure sensor 22 and dynamically adjusts the rotating speed of the rotating blade. Preferably, the pressure sensor 22 is a micro sensor array, which is embedded in the inner wall of the cavity of the mechanical crushing module 2 at an interval of 60°-120°, for real-time and multi-point monitoring of the three-dimensional stress distribution change in the cavity during the film dissociation process. By real-time monitoring of the shear force by the pressure sensor 22 and dynamic adjustment of the rotating speed of the rotating blade by the controller, low-damage control of the dissociation process is realized. This mechanism maximizes the protection of cell activity and functional integrity, avoiding excessive mechanical force damage to cells.

[0032] As Figure 5 The multi-point injection module 3 is provided with a push injection structure 4 on the outside, which can move axially to provide auxiliary injection power. The push injection structure 4 provides axial auxiliary power to enhance the injection thrust and ensure that the cell suspension can be smoothly injected into high-density tissues.

[0033] The negative pressure adsorption module 1 comprises an adsorption head 11 connected to the cavity of the negative pressure adsorption module 1, which is an elastic air bag. The elastic air bag, as the core component of the negative pressure adsorption module 1, can effectively adsorb stem cell films without damaging their structure by manual compression to achieve negative pressure suction. The adsorption head 11 is a replaceable structure, and the adsorption end face of the adsorption head 11 is provided with an annular sealing edge. The replaceable design of the adsorption head 11 facilitates cleaning and sterilization, and the annular sealing edge can further improve the adsorption efficiency.

[0034] Specifically, a hand-held part 8 is arranged in the middle of the device.

[0035] Specifically, a touch screen 7 is provided for setting the crushing time, rotating speed, injection flow rate parameters, and displaying real-time pressure feedback data. The touch screen 7 integrates parameter setting and real-time data display functions, making the operation process visual and controllable, and improving the accuracy and repeatability of the operation.

[0036] Example two On the basis of example one, the multi-point injection module 3 is improved to realize precise and adjustable control of injection depth, and the specific scheme is as follows: The multi-point injection module 3 further comprises depth limiting rings corresponding to the number of the needle heads 31, which are sleeved outside the needle heads 31 and are connected with the inner thread on the needle seat 33 through the outer thread on the outer wall of the depth limiting rings. The depth limiting rings can move along the axial direction of the needle heads 31 relative to the needle seat 33. By rotating the needle seat 33, the mechanical properties of the thread are converted into the linear motion of the depth limiting rings, so as to limit and set the depth of the needle heads 31.

[0037] The injection operation process is as follows: According to the preoperative planning, rotate each depth limiting ring and adjust the depth limiting ring to the preset depth; Make the whole device perpendicular to the skin surface, so that the end faces of all the depth limiting rings smoothly contact the skin. Since the depth limiting rings are blocked by the skin surface, the downward movement of the needle seat is also stopped, thereby realizing the control of the depth of the needle heads 31; The needle heads 31 accurately penetrate the tissue to a certain depth and perform injection. After the injection is completed, the device is withdrawn.

[0038] When the operator pushes the device, the hand can clearly feel the tactile feedback of the sudden increase in resistance when all the depth limiting rings simultaneously contact the tissue. This provides a clear operation node to remind the operator to start injection. The simultaneous contact of multiple depth limiting rings with the tissue surface ensures that the injection reference surface of all the needle heads 31 is in close contact with the skin surface. Even if the surface is uneven, the consistency of the injection depth of each point can be ensured through pre-setting adjustment.

[0039] Example Three: Operation steps of the shearing type stem cell membrane sheet dissociation and injection integrated device according to Example One.

[0040] S1. Preparation: Ensure that the device has been sterilized, the adsorption head 11 has been installed and the sealing is checked; Turn on the touch screen 7 and set the dissociation parameters (such as rotation speed and time) and injection parameters; Adjust the distance between the needle heads 31 of the slidable needle seat assembly 32.

[0041] S2. Adsorb stem cell membrane sheet: Align the adsorption head 11 with the stem cell membrane sheet on the culture carrier; Gently press the elastic air bag to generate negative pressure and adsorb the membrane sheet into the adsorption head 11; S3. Dissociate the membrane sheet into cell microclusters: Add an appropriate amount of sterile normal saline or cell culture solution in the cavity of the mechanical crushing module 2 for forming cell suspension during the dissociation process; Start the mechanical crushing module 2 and rotate the blade to work; The pressure sensor 22 monitors the shear force in real time, and the controller automatically adjusts the rotation speed to maintain low damage dissociation; After dissociation is completed, a uniform cell micro-cluster suspension is formed.

[0042] S4. Preparation before injection: The device is perpendicular to the target tissue surface; If the suspension is too dense, a proper amount of sterile normal saline can be supplemented through the injection module inlet to dilute it to a suitable injection concentration; Start the needle vibrator 6 to prevent the needle from being blocked.

[0043] S5. Injection operation: The bolus structure 4 provides auxiliary thrust to uniformly inject the cell suspension into the tissue through the needles 31 of the multi-point injection module 3.

[0044] S6. Completion and cleaning: After injection is completed, the device is withdrawn; The suction head 11 and the needle 31 are disassembled for cleaning and sterilization.

[0045] It should be noted that the terms used in the present application are only for the purpose of describing specific embodiments, and are not intended to limit the scope of the present application. As shown in the specification of the present application, unless the context clearly indicates otherwise, the terms "one", "a", "an", and / or "the" do not specifically refer to the singular, but also include the plural. The terms "include", "contain" or any other variants thereof are intended to cover non-exclusive inclusion, so that the process, method or device including a series of elements not only includes those elements, but also includes other elements not explicitly listed, or further includes elements inherent to such process, method or device. Without more limitations, the element defined by the statement "including a" does not exclude the presence of additional identical elements in the process, method or device including the element.

[0046] It should also be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application. Unless otherwise specified and limited, the terms "mount", "connect", "connect" and the like should be broadly understood, for example, it can be a fixed connection, or a detachable connection, or an integral connection; it can be a mechanical connection, or an electrical connection; it can be directly connected, or indirectly connected through an intermediate medium, or it can be the communication between two elements inside. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0047] The embodiments and / or implementation methods described above are merely preferred embodiments and / or implementation methods for implementing the technology of the present invention, and are not intended to limit the implementation methods of the technology of the present invention in any way. Any person skilled in the art may make some modifications to other equivalent embodiments without departing from the scope of the technical means disclosed in the content of the present invention, but these should still be regarded as the technology or embodiments that are substantially the same as the present invention. This document uses specific examples to illustrate the principles and implementation methods of this application. The descriptions of the above embodiments are only for the purpose of helping to understand the methods and core ideas of this application. The above descriptions are only preferred embodiments of this application. It should be noted that due to the limitations of written expression, while there are objectively infinite specific structures, those skilled in the art can make several improvements, modifications, or changes without departing from the principles of this application, and can also combine the above technical features in an appropriate manner. These improvements, modifications, changes, or combinations, or the direct application of the inventive concept and technical solution to other situations without modification, should all be considered within the scope of protection of this application.

Claims

1. A shearing-type stem cell membrane dissociation and injection integrated device, characterized in that, include: The negative pressure adsorption module (1) is used to aspirate stem cell membranes from the culture carrier; the mechanical crushing module (2) is connected to the negative pressure adsorption module (1) and is used to dissociate the membranes into cell clusters; the multi-point injection module (3) is connected to the mechanical crushing module (2) and contains 5 to 10 needles (31) for injecting cell suspension into the target tissue.

2. The integrated device for dissociation and injection of stem cell membranes according to claim 1, characterized in that, The multi-point injection module (3) is provided with a chamber, and a sliding needle seat assembly (32) is provided in the chamber. The sliding needle seat assembly (32) includes 5 to 10 needle seats (33). The bottom of the needle seat (33) is provided with a guide rail. The sliding needle seat assembly (32) is provided with an adjustment knob. The needle seats (33) are driven to move radially synchronously through a transmission mechanism to adjust the needle spacing (31). The sliding needle seat assembly (32) is also provided with a locking bolt for fixing the position of the needle seat (33) after adjustment.

3. The integrated device for dissociation and injection of stem cell membranes according to claim 2, characterized in that, The multi-point injection module (3) has a flow diversion structure (5) that divides the chamber into 5 to 10 flow channels, and an elastic diaphragm is provided at the end of the flow channel.

4. The integrated device for dissociation and injection of stem cell membranes according to claim 2, characterized in that, The multi-point injection module (3) integrates a needle vibrator (6), which includes a drive unit connected to a transmission rod connected to the slidable needle seat assembly (32).

5. The integrated device for dissociation and injection of stem cell membranes according to claim 1, characterized in that, The multi-point injection module (3) is fitted with a push-in structure (4) on its outer side. The push-in structure (4) can move along the axial direction to provide auxiliary injection power.

6. The integrated device for dissociation and injection of stem cell membranes according to claim 1, characterized in that, The mechanical crushing module (2) includes a rotating unit (21) and a pressure sensor (22). The rotating unit is equipped with a rotating blade and a controller. The pressure sensor (22) is used to detect the shear force change during the membrane dissociation process in real time. The controller receives the signal from the pressure sensor (22) and dynamically adjusts the rotation speed of the rotating blade.

7. The integrated device for dissociation and injection of stem cell membranes according to claim 1, characterized in that, The negative pressure adsorption module (1) includes an adsorption head (11), which is connected to the cavity of the negative pressure adsorption module (1), and the cavity is an elastic airbag.

8. The integrated device for dissociation and injection of stem cell membranes according to claim 7, characterized in that, The adsorption head (11) is a replaceable structure, and the adsorption end face of the adsorption head (11) is provided with an annular sealing edge.

9. The integrated device for dissociation and injection of stem cell membranes according to claim 1, characterized in that, It also includes a handheld part (8), which is located in the middle of the device.

10. The integrated device for dissociation and injection of stem cell membranes according to claim 1, characterized in that, It is equipped with a touch screen (7) for setting crushing time, rotation speed, injection flow rate parameters, and displaying pressure feedback data in real time.

Images