A bioprinted intervertebral disc tissue engineering scaffold based on organoids

Abstract

The present invention provides a bio-printed intervertebral disc tissue engineering scaffold based on organoids, which belongs to the technical field of intervertebral disc tissue engineering scaffolds. It includes a shell, the shell is filled with intervertebral disc organoid microspheres, and the upper end of the shell is connected to a mounting block, an artificial bionic fiber ring, the artificial bionic fiber ring is arranged on the outside of the shell, and the artificial bionic fiber ring contains left-handed polylactic acid, hyaluronic acid HA, vascular endothelial growth factor, type I collagen, polycaprolactone PCL, collagen and nano-hydroxyapatite, wherein the vascular endothelial growth factor is encapsulated in biodegradable nanoparticles and uniformly dispersed in the fiber ring material. The present application increases the internal surface area of ​​the microchannel through a multi-level grid structure of microchannels with different diameters and directions, provides more contact points for the exchange of nutrients, oxygen and metabolic waste, and monitors the microchannel through an intelligent response system to reduce the possibility of blockage.

Description

Technical Field

[0001] The present invention relates to the technical field of intervertebral disc tissue engineering scaffolds, and more specifically, to an organoid-based bioprinted intervertebral disc tissue engineering scaffold. Background Art

[0002] Degenerative disc disease is a common and frequently occurring disease in modern society. Among them, herniated disc is the most common and is a common cause of low back and leg pain, seriously affecting the quality of life of patients. When the intervertebral disc degenerates, its height will decrease and its normal mechanical conduction function will be impaired.

[0003] With the continuous advancement of medical technology, tissue engineering scaffolds using organoids for bioprinting have also become a hot topic. They are mainly based on the structure and function of natural intervertebral discs. Through bioprinting technology, a similar three-dimensional scaffold structure is constructed to provide cells with a growth environment similar to that in the body, inducing cells to grow and differentiate according to normal physiological patterns, thereby achieving the regeneration of intervertebral disc tissue. In addition, bioprinting technology can precisely control the distribution of cells and materials, and construct tissue engineering scaffolds with complex structures and functions, providing a new strategy for the treatment of intervertebral disc diseases.

[0004] However, when constructing organoids, there are significant differences between individual organoids in the same batch, as well as between organoid samples in different batches, and the controllability of organoid formation is poor. Based on the above technical problems, the existing technology has also provided some solutions. For example, the Chinese patent with authorization announcement number CN115154674B discloses a 3D bioprinted bone tissue engineering scaffold based on bone organoids. By setting microchannels, end 3 and filling cavities, the graft can be vascularized, and endothelial cells can migrate and proliferate on the scaffold, thereby stably transmitting oxygen, nutrients and growth factors to promote bone tissue growth.

[0005] However, in actual use, the microchannel may be just a simple tubular structure that does not take into account the complex environment in the body. After implantation into the human body, fragments produced by cell metabolism, deposition of extracellular matrix components, and possible inflammatory response products are easily accumulated in the microchannel, and nutrients and signal molecules cannot be evenly delivered to various areas in the filling cavity. For example, organoids close to the microchannel can obtain sufficient nutrients and stimulation, and grow and differentiate faster, while organoids far away from the microchannel will grow slowly due to lack of sufficient support, and may even undergo necrosis, ultimately leading to uneven organoid growth. Summary of the Invention

[0006] In response to the problem in the prior art that the microchannels of tissue scaffolds cannot evenly transport nutrients, resulting in slow organoid production or even necrosis, the purpose of the present invention is to provide a bio-printed intervertebral disc tissue engineering scaffold based on organoids.

[0007] In order to solve the above problems, the present invention adopts the following technical solutions:

[0008] An organoid-based bioprinted intervertebral disc tissue engineering scaffold comprising;

[0009] a shell, wherein the shell is filled with intervertebral disc organoid microspheres, and the upper end of the shell is connected to a mounting block;

[0010] An artificial biomimetic fiber ring, which is arranged on the outside of the shell and contains poly (L-lactic acid), hyaluronic acid (HA), vascular endothelial growth factor, type I collagen, polycaprolactone (PCL), collagen, and nanohydroxyapatite. The vascular endothelial growth factor is encapsulated in biodegradable nanoparticles and uniformly dispersed in the fiber ring material. The artificial biomimetic fiber ring also contains elastin-derived peptides to give it better elasticity and flexibility.

[0011] The ends are located at both ends of the shell, and the opposite ends of the two ends are connected to an intervertebral disc organoid filling cavity, the intervertebral disc organoid filling cavity is filled with in vitro cultured intervertebral organoid microspheres with a diameter of 500 to 1000 microns, and the inner wall of the intervertebral disc organoid filling cavity is coated with a cell adhesion peptide or specific growth factor fixation layer;

[0012] A microchannel unit connected between two intervertebral disc organoid-filled cavities, wherein the microchannel unit comprises a multi-level grid structure formed by a plurality of microchannels, and the inner wall of the microchannel unit has a self-cleaning coating to prevent microchannel clogging;

[0013] It also includes an intelligent response system based on sensor feedback data. The sensor is a micro biosensor installed inside the shell, and the micro biosensor is used to detect physical and chemical parameter data inside the shell.

[0014] Optionally, the microchannels of the multi-level grid structure have different diameters and directions, and the design of the microchannels includes but is not limited to spiral, grid or radial shapes to promote uniform distribution and interaction of the intervertebral disc organ microspheres in the entire shell.

[0015] Optionally, the self-cleaning coating comprises a biocompatible polymer having anti-fouling and lubricating properties.

[0016] Optionally, the intelligent response system includes:

[0017] A data receiving module, which is used to receive detection data from the micro biosensor;

[0018] a data analysis module configured to process and analyze the data received by the data receiving module to determine whether the parameters deviate from a preset normal range;

[0019] A trigger module, which can initiate corresponding response actions when the data analysis module determines that the key parameters deviate from the normal range;

[0020] The response execution module includes but is not limited to a sustained-release unit activation unit, which is used to trigger the sustained-release unit pre-buried in the shell to release the corresponding bioactive substance to improve the material exchange efficiency.

[0021] Optionally, the sustained-release unit comprises a plurality of sustained-release modules containing different bioactive substances, and distributed in different areas within the shell, wherein at least one sustained-release module contains a pro-angiogenic factor, at least one sustained-release module contains a nutritional supplement, and at least one sustained-release module contains an anti-inflammatory factor.

[0022] Optionally, the inner surface of the shell is further provided with a micro-nano structure capable of promoting cell adhesion and proliferation.

[0023] Optionally, the intervertebral disc organoid microspheres are pretreated before filling to improve their survival rate, proliferation ability and differentiation potential.

[0024] Optionally, a degradable metal wire reinforcement skeleton is provided inside the mounting block to enhance the mechanical strength of the mounting block. A fiber structure is also provided inside the shell, and the fiber structure is annularly wound around the outside of the multiple microchannel units.

[0025] Optionally, the shell is integrally printed by a multi-nozzle bioprinter, and the spatial gradient distribution of different materials is precisely controlled during the printing process.

[0026] Optionally, the manufacturing process of the shell further includes post-processing the printed shell, such as heat treatment, chemical treatment or bioactivation treatment, to further improve its biocompatibility and mechanical properties.

[0027] Compared with the prior art, the technical solution provided by the present invention has at least the following beneficial effects:

[0028] In the above scheme, the internal surface area of ​​the microchannel is increased by using a multi-level grid structure of microchannels with different diameters and directions, providing more contact points for the exchange of nutrients, oxygen and metabolic waste, and forming more diffusion paths, which helps to evenly distribute and quickly exchange substances in the microchannel, so that the intervertebral disc organoid microspheres can more effectively obtain the required nutrients and oxygen. At the same time, the self-cleaning coating inside the microchannel can reduce the possibility of microchannel blockage, ensure the continuous and effective transmission of nutrients and signal molecules, and facilitate the excretion of metabolic waste.

[0029] Through the intelligent response system, when abnormal parameter changes related to the appearance of microchannels are monitored, the data analysis module in the intelligent response system quickly processes and analyzes these data. Once it is determined that the microchannel is blocked, the trigger module of the intelligent response system is immediately activated, instructing the sustained-release units near or at specific positions of the microchannel to release bioactive substances. The assimilated and released bioactive substances can stimulate local angiogenesis or cell activity, promote the remodeling or repair of tissues around the microchannel, provide better growth conditions for intervertebral disc organoid microspheres and surrounding tissue cells, and reduce the occurrence of local inflammation caused by microchannel blockage.

[0030] Tonghua encapsulates vascular endothelial growth factor in biodegradable nanoparticles and evenly disperses them in the annulus fibrosus material, which can achieve precise and sustained release of vascular endothelial growth factor at different stages of intervertebral disc repair, effectively promote angiogenesis, provide more adequate nutrition supply for intervertebral disc organoids, promote their growth and tissue regeneration. At the same time, by adding elastin-derived peptides to the artificial bionic annulus fibrosus, it can provide the artificial bionic annulus fibrosus with better elasticity and flexibility, making its mechanical properties closer to those of the natural intervertebral disc annulus fibrosus and enhancing its adaptability to the complex mechanical environment in the body. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The accompanying drawings, which are incorporated herein and constitute a part of the specification, illustrate embodiments of the invention and, together with the description, further serve to explain the principles of the invention and to enable one skilled in the art to make and use the invention.

[0032] Figure 1 It is a schematic diagram of the three-dimensional structure of the present invention;

[0033] Figure 2 For the present invention Figure 1 Schematic diagram of the cross-section structure Figure 1 ;

[0034] Figure 3 Schematic diagram of the connection structure between the intervertebral disc organoid filling cavity and the microchannel unit in the present invention;

[0035] Figure 4 For the present invention Figure 3 Schematic diagram of the cross-section structure in ;

[0036] Figure 5 A schematic diagram of the internal structure of the housing provided by the present invention;

[0037] Figure 6 For the present invention Figure 1 Schematic diagram of the cross-section structure Figure 2 ;

[0038] Figure 7A schematic diagram of the structure of the housing provided by the present invention when installed between two vertebral bodies;

[0039] Figure 8 The system framework provided by the present invention Figure 1 ;

[0040] Figure 9 The system frame provided by the present invention Figure 2 .

[0041] [reference numerals]

[0042] 1. Shell; 11. Mounting block; 101. Degradable metal wire reinforced skeleton; 12. Micro-nano structure; 13. Fiber structure;

[0043] 2. Artificial bionic fiber ring;

[0044] 3. End; 31. Intervertebral disc organoids fill the cavity;

[0045] 4. Microchannel unit; 41. Self-cleaning coating;

[0046] 5. Intelligent response system; 51. Micro biosensor; 52. Data receiving module; 53. Data analysis module; 54. Trigger module; 55. Response execution module;

[0047] 6. Sustained-release unit.

[0048] As shown in the figure, in order to clearly implement the structure of the embodiment of the present invention, specific structures and devices are marked in the figure, but this is only for illustrative purposes and is not intended to limit the present invention to the specific structure, device and environment. According to specific needs, ordinary technicians in this field can adjust or modify these devices and environments. DETAILED DESCRIPTION

[0049] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments. It is also noted that, to provide a more detailed description, the following embodiments are best and preferred embodiments, and those skilled in the art may employ alternative methods for implementing certain known technologies. Furthermore, the accompanying drawings are intended only to provide a more detailed description of the embodiments and are not intended to limit the present invention.

[0050] It should be noted that references in the specification to "one embodiment," "an embodiment," "an exemplary embodiment," "some embodiments," etc. indicate that the described embodiments may include specific features, structures, or characteristics, but not every embodiment necessarily includes such specific features, structures, or characteristics. In addition, when specific features, structures, or characteristics are described in conjunction with an embodiment, it is within the knowledge of persons skilled in the relevant art to implement such features, structures, or characteristics in conjunction with other embodiments (whether or not explicitly described).

[0051] In general, terms can be understood, at least in part, from their use in context. For example, depending at least in part on the context, the term "one or more" as used herein can be used to describe any feature, structure, or characteristic in the singular sense, or can be used to describe a combination of features, structures, or characteristics in the plural sense. Additionally, the term "based on" can be understood as not necessarily intended to convey an exclusive set of factors, but can instead, depending at least in part on the context, allow for the presence of other factors that are not necessarily explicitly described.

[0052] It will be understood that the meanings of “on,” “over,” and “above” in the present invention should be interpreted in the broadest manner, so that “on” means not only “directly on” something but also includes the meaning of being “on” something with intervening features or layers, and “on” or “above” means not only “on” or “above” something but also includes the meaning of being “on” or “above” something with no intervening features or layers.

[0053] Additionally, spatially relative terms such as "below," "beneath," "lower," "above," and "upper" may be used herein for descriptive convenience to describe the relationship of one element or feature to another element or features, as illustrated in the accompanying drawings. Spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the accompanying drawings. The device may be oriented in other ways, and the spatially relative descriptors used herein should be similarly interpreted accordingly.

[0054] like Figures 1 to 9As shown, an embodiment of the present invention provides an organoid-based bioprinted intervertebral disc tissue engineering scaffold, comprising a shell 1, wherein the shell 1 is filled with intervertebral disc organoid microspheres, and the upper end of the shell 1 is connected to a mounting block 11, and an artificial biomimetic fiber ring 2 is further provided on the outside of the shell 1, wherein the artificial biomimetic fiber ring 2 comprises poly (L-lactic acid), hyaluronic acid HA, vascular endothelial growth factor, type I collagen, polycaprolactone PCL, collagen and nanohydroxyapatite, wherein the vascular endothelial growth factor is encapsulated in biodegradable nanoparticles and uniformly dispersed in the fiber ring material, and the artificial biomimetic fiber ring 2 also comprises elastin-derived peptides to give it better The shell 1 has elasticity and flexibility, and ends 3 are provided at both ends of the shell 1. The opposite ends of the two ends 3 are connected to an intervertebral disc organoid filling cavity 31. The intervertebral disc organoid filling cavity 31 is filled with in vitro cultured intervertebral disc organoids and has a diameter of 500 to 1000 microns. The inner wall of the intervertebral disc organoid filling cavity is coated with a cell adhesion peptide or a specific growth factor fixation layer. A microchannel unit 4 is provided between two adjacent intervertebral disc organoid filling cavities 31. The microchannel unit 4 has a multi-level grid structure composed of multiple microchannels, and the inner wall of the microchannel unit 4 has a self-cleaning coating 41 to prevent microchannel clogging.

[0055] like Figure 2 As shown, the embodiment of the present invention further includes an intelligent response system 5 based on sensor feedback data. The sensor is a micro biosensor 51 installed inside the housing 1 . The micro biosensor 51 is used to detect physical and chemical parameter data inside the housing 1 .

[0056] Vascular endothelial growth factor (VEGF) is a highly specific vascular endothelial cell growth factor that promotes increased vascular permeability, extracellular matrix degeneration, and endothelial cell migration, thereby promoting the formation of surrounding tissue. The addition of elastin-derived peptides to the artificial biomimetic annulus fibrosus 2 can mimic the mechanical properties of the natural annulus fibrosus, improving the elasticity and flexibility of the scaffold and making it more adaptable to the physiological environment of the intervertebral disc. The multi-layered grid structure of the microchannel units 4 increases the internal surface area of ​​the microchannels, creating more diffusion pathways and providing more contact points for the exchange of nutrients, oxygen, and metabolic waste, further facilitating the uniform distribution and rapid exchange of substances within the microchannels. The complex microchannels increase the redundancy of the substance exchange pathways. Even if some microchannels are blocked, nutrients and signal molecules can still be transported through other pathways. Furthermore, the self-cleaning coating 41 within the microchannels reduces the possibility of microchannel blockage. Furthermore, the micro-biosensor 51 monitors abnormal parameters related to microchannel blockage, such as the oxygen concentration or nutrient concentration gradient within the housing 1, so that timely response can be taken when a potential blockage occurs.

[0057] like Figure 4 As shown, the self-cleaning coating 41 comprises a biocompatible polymer having anti-fouling and lubricating properties.

[0058] Biocompatible polymers can not only prevent dirt and bacteria from adhering to the joint surface, reducing the risk of infection, but also ensure that no harm is caused to the human body during long-term contact with human tissues and body fluids.

[0059] like Figure 6 and Figure 7 As shown, the intelligent response system 5 includes:

[0060] a data receiving module 52 for receiving detection data from the micro-biosensor 51;

[0061] a data analysis module 53 configured to process and analyze the data receiving module 52 to determine whether the parameters deviate from a preset normal range;

[0062] A trigger module 54 is capable of initiating corresponding response actions when the data analysis module 53 determines that the key parameters deviate from the normal range;

[0063] The response execution module 55 includes but is not limited to a slow-release unit 6 activation unit, which is used to trigger the slow-release unit 6 pre-embedded in the shell 1 to release the corresponding bioactive substance to improve the material exchange efficiency.

[0064] The sustained-release unit 6 includes a plurality of sustained-release modules containing different bioactive substances, and is distributed in different areas of the shell 1, wherein at least one sustained-release module contains a pro-angiogenic factor, at least one sustained-release module contains a nutritional supplement, and at least one sustained-release module contains an anti-inflammatory factor.

[0065] By adopting the above technical solution, when the micro biosensor 51 detects abnormalities in parameters such as pressure, pH value, oxygen concentration, and cytokine concentration in the housing 1, the data analysis module 53 in the intelligent response system 5 will analyze the data collected by the sensor and compare it with the preset normal range. When it is found that certain parameters deviate from the normal range and meet the characteristic pattern of microchannel blockage, the system will determine that the microchannel may be blocked. At this time, the trigger module 54 will initiate the corresponding response action. The sustained-release unit 6 is composed of a plurality of tiny sustained-release capsules. These capsules are evenly distributed around the intervertebral disc organoid filling cavity 31 and in key areas near the microchannel, for example, near the wall of the intervertebral disc organoid filling cavity 31. A sustained-release capsule is set at a certain distance. When the trigger module 54 issues an instruction, certain parts of the capsule shell, such as electrical signals or chemical signals, open specific nanochannels. The moisture in the external environment will enter the sustained-release capsule due to the action of osmotic pressure. As the volume of the liquid in the sustained-release capsule increases, the internal pressure increases, thereby squeezing the bioactive substance through the semipermeable sustained-release capsule to achieve release. The released pro-angiogenic factors, anti-inflammatory factors and nutritional supplements can reduce the inflammatory response caused by microchannel blockage, and the intelligent response system 5 can send data to external user terminals and other receiving devices through wireless transmission technology. Doctors or researchers can understand the changes in tissue microenvironment during the intervertebral disc repair process based on this.

[0066] like Figure 2 As shown, the inner surface of the shell 1 is further provided with a micro-nano structure 12 that can promote cell adhesion and proliferation.

[0067] A degradable metal wire reinforcement skeleton 101 is provided inside the mounting block 11 to enhance the mechanical strength of the mounting block 11 . A fiber structure 13 is also provided inside the shell 1 , and the fiber structure 13 is annularly wound around the outside of the multiple microchannel units 4 .

[0068] like Figure 6 and Figure 7As shown, the micro-nano structure 12 can be nanofibers, nanopores or micro-concave-convex structures to improve the integration ability of the stent and the host tissue, promote the adhesion and proliferation of cells on the surface of the stent, and thus accelerate the regeneration and repair of tissues. In the initial stage after the shell 1 is implanted into the human body, the mounting block 11 needs to withstand various mechanical loads from spinal activities, such as pressure, shear force, etc. The degradable metal wire reinforced skeleton 101 can significantly enhance the mechanical strength of the mounting block 11, making it stronger. As time goes by and the intervertebral disc repair process proceeds, the requirements for the mechanical properties of the mounting block 11 will change, and the degradable metal wire will gradually degrade, so that the mechanical properties of the mounting block 11 can dynamically match the repair process. In the process of gradual regeneration of the intervertebral disc tissue and gradual stabilization of the stent's own structure, the mechanical strength of the mounting block 11 is appropriately reduced to avoid the mounting block 11 being too strong and causing damage to the intervertebral disc. The surrounding newborn tissue produces an adverse stress shielding effect, which is beneficial for the newborn tissue to better adapt to the physiological mechanical environment and promote the natural repair of the intervertebral disc. When 3D bioprinting the mounting block 11, the degradable metal wire can be pre-placed in the path of the printing nozzle so that it is wrapped inside the mounting block 11 material during the printing process to form an integral structure. This can ensure that its position in the mounting block 11 is accurate and evenly distributed, and it has good bonding force with the mounting block 11 material, thereby effectively playing its role in enhancing mechanical properties. The fiber structure 13 can be made of collagen fibers, nanofibers, etc., which can enhance the strength of the scaffold and provide more sites for cell attachment. These fibers can be arranged in a ring shape, which helps to better withstand torsional and tensile stresses, just like in the annulus fibrosus of a natural intervertebral disc, the collagen fibers are arranged in an orderly manner to maintain its mechanical stability.

[0069] The intervertebral disc organoid microspheres are pretreated before filling to improve their survival rate, proliferation ability and differentiation potential.

[0070] The shell 1 is integrally printed by a multi-nozzle bioprinter, and the spatial gradient distribution of different materials is precisely controlled during the printing process.

[0071] The manufacturing process of the shell 1 also includes post-processing the printed shell 1, such as heat treatment, chemical treatment or bioactivation treatment, to further improve its biocompatibility and mechanical properties.

[0072] By adopting the above-mentioned technical solution, unreacted chemicals or impurities that may remain on the surface of the stent can be removed during the pretreatment of the intervertebral disc organoid microspheres and the post-treatment of the shell 1, which helps to reduce the immune response or rejection reaction that may be triggered after the microsphere implantation, improve the success rate of the operation and the comfort of the patient, and by precisely controlling the spatial gradient distribution of different materials, such as gradually increasing the proportion of materials with higher bioactive components in the area close to the intervertebral disc organoid filling cavity 31, a more favorable local microenvironment can be provided for the microspheres, and the proportion of materials with higher mechanical strength in the artificial bionic fiber ring 2 that bears a larger mechanical load is appropriately increased, so that it can better withstand the mechanical effects of pressure, tension, shear force, etc. during spinal movement, thereby achieving precise adaptation of materials in different functional areas of the shell 1, so that the entire shell 1 can meet the biological needs of the growth of intervertebral disc organoid microspheres and adapt to the requirements of the spinal mechanical environment.

[0073] The workflow of the technical solution of the present invention is as follows:

[0074] First, patient data is collected, and various biomaterials for printing the shell 1 are prepared according to the formula, and formulated into bio-ink with suitable rheological properties to ensure that it can pass through the print nozzle smoothly. After the tissue scaffold is printed, it is subjected to heat treatment, chemical treatment or bioactivation treatment.

[0075] Then, according to the degenerative position of the patient's intervertebral disc, the bioprinted intervertebral disc tissue engineering scaffold is carefully placed in the cleaned intervertebral space, ensuring that the mounting blocks 11 at both ends of the scaffold are in close contact with the adjacent vertebral bones.

[0076] After the implantation is completed, the micro biosensor 51 embedded in the housing 1 starts to work and monitors the parameters in the housing 1 in real time.

[0077] The present invention encompasses any alternatives, modifications, equivalents, and solutions that fall within the spirit and scope of the present invention. To provide a thorough understanding of the present invention, specific details are described in detail below in connection with the preferred embodiments of the present invention, but those skilled in the art will be able to fully understand the present invention without these detailed descriptions. Furthermore, to avoid unnecessary confusion regarding the essence of the present invention, well-known methods, processes, procedures, components, and circuits have not been described in detail.

[0078] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A bioprinted intervertebral disc tissue engineering scaffold based on organoids, characterized in that: include; a shell, wherein the shell is filled with intervertebral disc organoid microspheres, and the upper end of the shell is connected to a mounting block; An artificial biomimetic fiber ring, which is arranged on the outside of the shell and contains poly (L-lactic acid), hyaluronic acid (HA), vascular endothelial growth factor, type I collagen, polycaprolactone (PCL), collagen, and nanohydroxyapatite. The vascular endothelial growth factor is encapsulated in biodegradable nanoparticles and uniformly dispersed in the fiber ring material. The artificial biomimetic fiber ring also contains elastin-derived peptides to give it better elasticity and flexibility. Ends, the ends being located at both ends of the shell, and the opposite ends of the two ends are connected to an intervertebral disc organoid filling cavity, the intervertebral disc organoid filling cavity is filled with in vitro cultured intervertebral organoid microspheres, and the inner wall of the intervertebral disc organoid filling cavity is coated with a cell adhesion peptide or a specific growth factor fixation layer; A microchannel unit connected between two intervertebral disc organoid-filled cavities, wherein the microchannel unit comprises a multi-level grid structure formed by a plurality of microchannels, and the inner wall of the microchannel unit has a self-cleaning coating to prevent microchannel clogging; Also included is an intelligent response system based on sensor feedback data, wherein the sensor is a micro biosensor installed inside the housing, and the micro biosensor is used to detect physical and chemical parameter data inside the housing; The intelligent response system includes: A data receiving module, which is used to receive detection data from the micro biosensor; a data analysis module configured to process and analyze the data received by the data receiving module to determine whether the parameters deviate from a preset normal range; A trigger module, which can initiate corresponding response actions when the data analysis module determines that the key parameters deviate from the normal range; The response execution module includes but is not limited to a sustained-release unit activation unit, which is used to trigger the sustained-release unit pre-buried in the shell to release the corresponding bioactive substance to improve the efficiency of material exchange. The sustained-release unit includes a plurality of sustained-release modules containing different bioactive substances and distributed in different areas of the shell, wherein at least one sustained-release module contains a pro-angiogenic factor, at least one sustained-release module contains a nutritional supplement, and at least one sustained-release module contains an anti-inflammatory factor.

2. The organoid-based bioprinted intervertebral disc tissue engineering scaffold according to claim 1, characterized in that: The microchannels of the multi-level grid structure have different diameters and directions. The design of the microchannels includes but is not limited to spiral, grid or radial shapes to promote uniform distribution and interaction of the intervertebral disc organ microspheres in the entire shell.

3. The organoid-based bioprinted intervertebral disc tissue engineering scaffold according to claim 1, characterized in that: The self-cleaning coating comprises a biocompatible polymer with anti-fouling and lubricating properties.

4. The organoid-based bioprinted intervertebral disc tissue engineering scaffold according to claim 1, characterized in that: The inner surface of the shell is also provided with a micro-nano structure capable of promoting cell adhesion and proliferation.

5. The organoid-based bioprinted intervertebral disc tissue engineering scaffold according to claim 1, characterized in that: The intervertebral disc organoid microspheres are pretreated before filling to improve their survival rate, proliferation ability and differentiation potential.

6. The organoid-based bioprinted intervertebral disc tissue engineering scaffold according to claim 1, characterized in that: A degradable metal wire reinforcement skeleton is provided inside the installation block to enhance the mechanical strength of the installation block. A fiber structure is also provided inside the shell, and the fiber structure is annularly wound around the outside of multiple microchannel units.

7. The organoid-based bioprinted intervertebral disc tissue engineering scaffold according to claim 1, characterized in that: The shell is integrally printed by a multi-nozzle bioprinter, and the spatial gradient distribution of different materials is precisely controlled during the printing process.

8. The organoid-based bioprinted intervertebral disc tissue engineering scaffold according to any one of claims 1 to 7, characterized in that: The manufacturing process of the shell also includes post-processing the printed shell, such as heat treatment, chemical treatment or bioactivation treatment, to further improve its biocompatibility and mechanical properties.

Images