CN214388359U - Composite cell scaffold - Google Patents

Abstract

The present application discloses composite cell scaffolds. The composite cell scaffold comprises a plurality of cell units, wherein each cell unit comprises: the cell implantation device comprises a bracket, a first electrode and a second electrode, wherein a cell accommodating cavity is formed in the bracket and is used for loading target implantation cells; the prevascularization module is internally provided with a prevascularization cavity; the prevascularization cavity is communicated with the cell accommodating cavity through the semipermeable membrane. The composite cell scaffold according to the embodiment of the application has at least the following beneficial effects: through the setting of prevascularization module, the stent loaded with target implanted cells is connected with the prevascularization module, so that the target implanted cells in the stent can exchange oxygen and nutrients through a capillary network in the prevascularization module, and the target implanted cells in the stent can be ensured to play a role in a long time, thereby meeting the effectiveness and the long-acting property of stent implantation.

Description

Composite cell scaffold

Technical Field

The application relates to the technical field of cell therapy, in particular to a composite cell scaffold.

Background

With the intensive research in the fields of regenerative medicine and tissue engineering, cell therapy has been used as an effective supplement and substitute for drug therapy, and is gradually becoming a great development direction of medical treatment. Cell therapy is generally to implant autologous or allogeneic cells into a specific site of a patient to replace the missing or damaged cells to improve their physiological functions, particularly bioactive substance secretion. When the bioactive substance secretion cell scaffold is used for treatment, the distance between cells and capillaries is required to be within 300-400 mu m so as to ensure that the cells loaded in the scaffold survive and fully exert functions. However, there are no sites in the body that fully satisfy this condition, and there are no other possible sites suitable for implantation that achieve the desired results. Therefore, the implanted stent can only be partially attached to the surface of the capillary vessel of the human body, and the other part which is not attached to the capillary vessel can not be exchanged in time due to the lower concentration of oxygen, nutrient substances and the like, so that the loaded cells can not play the normal function, the survival rate is reduced, even the death is caused, and the lasting effect of the product is lower.

SUMMERY OF THE UTILITY MODEL

The present application is directed to solving at least one of the problems in the prior art. To this end, the present application proposes a composite cell scaffold capable of long-term functioning.

In a first aspect of the present application, there is provided a composite cell scaffold comprising a plurality of cell units, the cell units comprising:

the cell implantation device comprises a bracket, a first electrode and a second electrode, wherein a cell accommodating cavity is formed in the bracket and is used for loading target implantation cells;

the prevascularization module is internally provided with a prevascularization cavity;

the prevascularization cavity is communicated with the cell accommodating cavity through the semipermeable membrane.

The composite cell scaffold according to the embodiment of the application has at least the following beneficial effects:

through the setting of the prevascularization module, the stent loaded with cells is connected with the prevascularization module, so that the cells in the stent can exchange oxygen and nutrients through a capillary network in the prevascularization module, the target implanted cells in the stent can be ensured to be supplied with oxygen and nutrients in vivo immediately after being implanted, the cell death caused by acute hypoxia/culture is avoided, the buffer time is provided for the induction and growth of the capillary vessels of the human body, and the effectiveness and the long-acting property of stent implantation are met.

According to some embodiments of the present application, the target implant cells loaded in the scaffold have a function of producing bioactive substances, including but not limited to hormones, enzymes, trophic factors, neurotransmitters or other active substances having an effect of participating in a stimulus response to internal and external environments, maintaining environmental stability in the body, and the like.

According to some embodiments of the present application, to ensure that the substance exchange is normally maintained in the patient after implantation of the target implant cells, the semi-permeable membrane should allow molecules below 150kd (kilodaltons) to pass through, but not allow molecules above 150kd to pass through.

According to some embodiments of the application, the prevascularization chamber comprises:

the main channel cavity is used for supplying prevascularization culture solution;

and the branch cavity is communicated with the main channel cavity.

In the process of prevascularization of the module, prevascularization culture solution is supplied to the cavity through the main channel cavity, so that a proper growth environment is provided for endothelial cells in the cavity, and the vascular structure is promoted to be constructed.

According to some embodiments of the present application, the inner wall of the branch lumen has a pre-vascular layer formed by endothelial cell adherence, or the branch lumen has a three-dimensional microvascular network formed by endothelial cells. Generally, the method for inducing angiogenesis by tissue engineering comprises a method for constructing a blood vessel, a natural or artificial blood vessel stent for promoting vascularization by using endothelial cells and growth factors and cytokines, and the like. The first type is prevascularization of a prefabricated pipeline/cavity, which means that a prevascularization cavity is formed on the inner wall of a branch cavity through adherent growth of endothelial cells, and specifically, endothelial cells and a culture solution are injected into the inner wall of the branch cavity to enable the endothelial cells to grow in an adherent manner in the branch cavity through a bioreactor dynamic culture method, so that the branch cavity is endothelialized to form a prevascularization layer. The second type is a tissue engineering three-dimensional capillary network, which is a dynamic perfusion system with endothelial cells integrated with static pressure control in a branch cavity through a chip to provide a dynamic micro-fluidic three-dimensional culture environment and form a three-dimensional capillary network which grows on a non-adherent wall and is finally the same as or similar to a human capillary network structure.

Among them, endothelial cells include but are not limited to vascular endothelial cells, endothelial cells derived from differentiation of pluripotent stem cells, vascular endothelial progenitor cells, and other cell types that can be used for prevascularization.

According to some embodiments of the application, the main channel lumen has an opening for surgical vessel anastomosis. The main channel cavity is used as a total artificial blood vessel, the small blood vessels in the branch cavities are converged in the total artificial blood vessel of the main channel cavity, and the anastomosis of the host operation blood vessel is completed through the opening of the main channel cavity, so that the operation is more convenient and faster.

According to some embodiments of the application, the area of the direct covering and communicating contact between the prevascularization cavity and the semipermeable membrane is a first area, the area of the contact between the prevascularization module and the semipermeable membrane is a second area, and the ratio of the first area to the second area is not less than 50%. The function of the cells loaded in the stent body is related to the vascular network coverage rate of the pre-vascularization module on the semi-permeable membrane, and the higher the ratio of the communication contact area of the pre-vascularization cavity and the pre-vascularization module on the semi-permeable membrane is, the higher the vascular coverage rate on the semi-permeable membrane is. The higher the vessel coverage, the more cells in the stent can survive and function through the vessel. Preferably, the area ratio is not less than 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%. Wherein, the area of the direct covering, communicating and contacting of the prevascularization cavity and the semipermeable membrane refers to the area of the part of the prevascularization cavity, which is in contact with the semipermeable membrane and enables the substance to selectively pass through.

According to some embodiments of the present application, the composite cell scaffold further comprises a shell encasing the scaffold and the prevascularization module. Through the setting of casing, for compound cell support provides overall structure's supporting role and protecting function against shock.

According to some embodiments of the application, the housing is provided with a fixing member, and the stent and the prevascularization module are fixed with the housing by the fixing member. Through the setting of mounting, make the relative position of support, prevascularization module and casing more stable, simultaneously, can make the equipment between casing and support, the prevascularization module more simple and convenient.

According to some embodiments of the present application, the cell unit is a plurality of cell units, and the plurality of cell units are stacked layer by layer to form a composite cell scaffold. The scaffold formed by a single cell unit has limited cell loading capacity, and a plurality of cell units can be stacked layer by layer to form a combination of a plurality of scaffolds loaded with cells so as to effectively improve the cell loading capacity of the whole composite cell scaffold.

According to some embodiments of the application, the cell unit further comprises a substrate, the different cell units being separated by the substrate.

According to some embodiments of the present application, a fixing member is disposed on the substrate, and the cell unit is fixedly connected to the substrate through the fixing member.

According to some embodiments of the application, the prevascularized cavities of different cell units are in communication with each other through an artificial blood vessel.

According to some embodiments of the present application, the cell-containing chamber on the scaffold may be selected from an integral integrated chamber or a plurality of independent chambers as desired.

Additional aspects and advantages of the present application will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the present application.

Drawings

The present application is further described with reference to the following figures and examples:

fig. 1 is a front view of a composite cell scaffold structure of an embodiment of the present application.

Fig. 2 is a schematic structural view of a pre-vascularized cavity of a composite cell scaffold of an embodiment of the present application.

Fig. 3 is a schematic view of the projected area of the prevascularization cavity and prevascularization module of the embodiment of the present application shown in fig. 2.

Fig. 4 is a schematic structural view of a pre-vascularized lumen of a composite cell scaffold of an embodiment of the present application.

Fig. 5 is a schematic view of the projected area of the prevascularization lumen and prevascularization module of the embodiment of the present application shown in fig. 4.

Fig. 6 is an electron micrograph of a prevascularized structure with an endothelial cell layer attached to the inner wall of the prevascularized cavity according to an embodiment of the present application, wherein a is a schematic view of the prevascularized structure and B is an electron micrograph of the prevascularized structure.

Fig. 7 is a capillary network of a prevascularized cavity of an embodiment of the present application, a is a three-dimensional capillary photograph within a rhomboid branched cell, B is an electron micrograph of the branched cell after 6 days of culture, and C is a three-dimensional capillary photograph within a rounded rectangular branched cell.

Fig. 8 is a schematic of a stack-up of a composite cell scaffold of an embodiment of the present application.

Fig. 9 is a schematic structural diagram of a substrate according to an embodiment of the present application.

Reference numerals: the device comprises a prevascularization module 110, a prevascularization cavity 111, a semipermeable membrane 120, a stent 130, a cell accommodating cavity 131, target implanted cells 132, a main channel cavity 210, a first opening 211, a second opening 212, a branch cavity 220, a branch chamber 221, endothelial cells 610, a cell unit 810, an artificial blood vessel 820, a substrate 910, a pore 911 and a limiting column 912.

Detailed Description

The conception and the resulting technical effects of the present application will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, and not all embodiments, and other embodiments obtained by those skilled in the art without inventive efforts based on the embodiments of the present application belong to the protection scope of the present application.

The following detailed description of embodiments of the present application is provided for the purpose of illustration only and is not intended to be construed as a limitation of the application.

In the description of the present application, the meaning of a plurality is one or more, the meaning of a plurality is two or more, and the above, below, exceeding, etc. are understood as excluding the present number, and the above, below, within, etc. are understood as including the present number. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.

In the description of the present application, unless otherwise expressly limited, terms such as set, mounted, connected and the like should be construed broadly, and those skilled in the art can reasonably determine the specific meaning of the terms in the present application by combining the detailed contents of the technical solutions.

In the description of the present application, reference to the description of the terms "one embodiment," "some embodiments," "an illustrative embodiment," "an example," "a specific example," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

Referring to fig. 1, a front view of a composite cell scaffold structure of an embodiment of the present application is shown. The composite cell scaffold includes a scaffold 130, a semi-permeable membrane 120, and a prevascularization module 110. The support 130 has a plurality of cell accommodating chambers 131 which are communicated or independent, and the target implanted cells 132 are loaded in the cell accommodating chambers 131. The prevascularization module 110 is internally provided with a prevascularization cavity 111, the prevascularization cavity 111 is internally provided with a certain number of capillaries, and the prevascularization cavity 111 is communicated with the cell accommodating cavity 131 in the stent 130 through the semipermeable membrane 120, so that target implanted cells 132 loaded in the cell accommodating cavity 131 exchange oxygen and other nutrient substances through the capillaries in the prevascularization cavity 111, and the target implanted cells 132 in the stent 130 can be ensured to play a role in a long time, thereby meeting the effectiveness and the long-acting property of stent implantation.

Referring to fig. 2 and 4, in some embodiments of the present disclosure, the prevascularization chamber 111 includes a main channel chamber 210 and a branch chamber 220, and the branch chamber 220 includes a plurality of branch cells 221 arranged in an array. The adjacent branch cells 221 communicate with each other, and the branch cells 221 adjacent to the main passage chamber 210 communicate with the main passage chamber 210, thereby communicating the main passage chamber 210 with the branch chamber 220. The structure of the prevascularization chamber 111 on the prevascularization module 110 can be processed by using a photolithography technique, for example. In order to achieve good precision, the processing can be specifically completed by a photoetching machine with the precision of more than 1 micron. The matrix of the prevascularization module 110 may be a microfluidic chip made of Polydimethylsiloxane (PDMS)/polymethyl methacrylate (PMMA).

Referring to fig. 1, 2 and 4, in some embodiments of the present application, the main channel cavity 210 has openings at two ends, namely a first opening 211 and a second opening 212, and the first opening 211 and the second opening 212 can inject and discharge nutrient solution required for the prevascularization of endothelial cells into the prevascularization cavity 111 during the prevascularization of the prevascularization cavity 111. After the prevascularization cavity 111 is completed, the main channel cavity 210 can be used as a total artificial blood vessel of a composite cytoskeleton for collecting microvessels inside the prevascularization cavity 111, and when the main channel cavity 210 is implanted into a host body, the main channel cavity 210 is matched with blood vessels of an implanted part in the host body through the first opening 211 and the second opening 212, so that the implantation operation is more convenient and faster.

In some embodiments of the present application, the area of the pre-vascularized cavity 111 in direct covering and communicating contact with the semi-permeable membrane 120 is a first area, the area of the pre-vascularized module 110 in contact with the semi-permeable membrane 120 is a second area, and the ratio of the first area to the second area is not less than 50%. Referring to fig. 3 and 5, the first area is a hatched portion in fig. 3 and 5, and the second area is a box in fig. 3 and 5, in a ratio of not less than 50%. This also means that at least 50% of the target implant cells 132 loaded in the scaffold 130 are able to exchange oxygen and other nutrients through the prevascularization module 110 in time after implantation to ensure proper survival and function. As can be seen by comparing fig. 3 and 5, when the branch cell 221 is diamond-shaped or nearly elliptical, the ratio of the areas is significantly smaller than when the branch cell 221 is rectangular with rounded corners. When the area ratio is larger, the amount of the target implanted cells 132 that can be kept alive and function is larger, and the effect and the durability of the composite cell scaffold are better. The area ratio may be not less than 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%. Of course, the shape of the branched cell 221 is not particularly limited to the shapes of rhombus, rectangle, ellipse, and rounded rectangle described in the above schematic diagram, and other shapes include circles, and various extended regular or irregular polygonal shapes such as triangle, trapezoid, quadrangle, pentagon, hexagon, heptagon, octagon, nonagon, decagon, undecenon, and dodecagon. The branch cells 221 are not limited to the parallel array arrangement described above, and may be arranged in a cross-branch shape, a leaf vein shape, or other arrangements known in the art. In addition, the number of different branch cells 221 and the flow channels between the branch cells 221 in the prevascularization chamber 111 may be tens, hundreds, thousands, tens of thousands, hundreds of thousands to hundreds of thousands of communication flow channel systems, and the width and flow direction thereof may be properly adjusted to avoid blockage and excessive or insufficient local flow rate. Moreover, in the case of a blockage damage occurring in a part of the branch cells 221, the damaged or blocked branch cells 221 do not affect the normal operation of the other part.

In some embodiments of the present application, the prevascularization method of the prevascularization cavity 111 can adopt the common method of inducing angiogenesis by tissue engineering, including the methods of constructing blood vessels, growth factors and cytokines to promote vascularization, natural or artificial blood vessel stents, and the like.

In some embodiments of the present application, the prevascularization method of the prevascularization cavity 111 is to construct a capillary network mainly by endothelial cells, so that the composite cell scaffold is not required to grow host blood vessels at the implantation site into the composite cell scaffold during use. The prevascularization method by endothelial cells specifically comprises the steps of attaching endothelial cells to the inner wall of the prevascularization cavity 111 to form a prevascularization layer to obtain a composite prevascularization structure, or forming a three-dimensional microvascular network which mainly comprises endothelial cells and has the same or similar structure with a human capillary network in the prevascularization cavity 111.

The composite prevascularization structure is obtained by adhering endothelial cells to the inner wall of the prevascularization cavity 111 to form a prevascularization layer, wherein the endothelial cells and corresponding culture solution are injected into the prevascularization cavity 111 to make the endothelial cells grow adherent to form the prevascularization layer, and the prevascularization layer and the prevascularization cavity 111 form the composite prevascularization structure. As shown in fig. 6, a in fig. 6 is a schematic diagram of the pre-vascular layer structure, and B is an electron micrograph of the pre-vascular layer structure, and the pre-vascular layer is formed by adherent growth of endothelial cells 610 on the inner wall of the pre-vascularized cavity 111.

The method for forming the three-dimensional microvascular network mainly composed of endothelial cells in the prevascularization cavity 111 comprises the steps of injecting hydrogel mixed with the endothelial cells into the prevascularization cavity 111, and then respectively connecting the first opening 211, the second opening 212 or more openings with two/more pipeline ports of a dynamic perfusion system to form a reciprocating liquid circulation loop between the prevascularization cavity 111 and the dynamic perfusion system, and controlling culture solution in the dynamic perfusion system to flow in a reciprocating mode in the prevascularization cavity 111 and the dynamic perfusion system at a certain flow rate and flow direction through static pressure or other modes to simulate an in-vivo induced growth environment of the endothelial cells, so that the endothelial cells generate the three-dimensional microvascular network with the same or similar functions as a human capillary network structure in the prevascularization cavity 111. Referring to fig. 7, a is a photograph of a capillary vessel in the branch chamber 221 of fig. 3 having a diamond shape of the prevascularized chamber 111 prepared by the above-mentioned prevascularization method, B is a photograph of the branch chamber 221 after 6 days of culture, and C is a photograph of a capillary vessel in the branch chamber 221 of fig. 5 having a rectangular shape with rounded corners of the prevascularized chamber 111 prepared by the above-mentioned prevascularization method. As can be seen, a plurality of capillaries (one of which is shown by the arrow in the direction of B) can be formed in the branch chamber 221 by the above method to form a good three-dimensional microvascular network for substance delivery.

In some embodiments of the present application, the semi-permeable membrane 120 has a thickness of 5 to 100 μm. The thickness of the semi-permeable membrane 120 has a certain influence on the speed of material transfer between the pre-vascularization module 110 and the scaffold 130 and the overall thickness of the composite cell scaffold, and when the thickness is 5 to 100 μm, a plurality of aspects can be considered.

In some embodiments of the present application, the semi-permeable membrane 120 is a double-layer asymmetric composite semi-permeable membrane. The double-layer composite semipermeable membrane is compounded by using a functional film (such as a composite membrane formed by compounding a PTFE nanofiltration layer and a micron pore PTFE support membrane and a PP/PE non-woven membrane) made of a non-degradable material. The functional film itself may be subjected to hydrophilic modification and anti-fiberization modification treatments to obtain the corresponding effects. The hydrophilic nanometer membrane barrier in the membrane material plays a role in regulating and controlling the pore structure and permeability of the membrane, small molecules are filtered and screened, meanwhile, macromolecular immune protein is blocked, the anti-rejection physical barrier effect is realized, and anti-rejection medicines are not required to be taken additionally during implantation. On the other hand, the micro-pores and hydrophilic property of the outer layer are favorable for the surface adhesion of vascular cells and the induction of new blood vessels in a host body.

In some embodiments of the present application, the semi-permeable membrane 120 is a hydrogel-tuned membrane pore type scaffold semi-permeable membrane. The semipermeable membrane can specifically take a PTFE membrane with larger pores as a skeleton structure, and non-degradable natural polymer cellulose, betaine, alginic acid and modified derivatives thereof are added into the skeleton structure to fill the pores of the skeleton structure. The composite semipermeable membrane with a proper network pore structure is obtained by adjusting the pores of the framework structure and the crosslinking degree of the hydrogel filled in the framework structure, so that the function of physically shielding immune component attack is realized. The hydrogel component in the semipermeable membrane can be further subjected to anti-fibrosis modification, so that the adhesive capacity of the composite cell scaffold to immune cells is reduced, the fibrosis effect caused by inflammatory signals is prevented, and the in-vivo long-term stability is improved.

In some embodiments of the present application, the semi-permeable membrane 120 is a nanoneedle erosion process stent semi-permeable membrane. Specifically, a nano-film pore structure can be realized in the substrate through a zinc oxide nano-needle corrosion process, and a micro-pore support film is compounded on the surface layer to form a double-layer film structure. The substrate of the semi-permeable membrane 120 may be selected from Polyurethane (PU)/polyethylene terephthalate (PET) or other biocompatible synthetic macromolecular materials. The nano-pore physical barrier membrane on the inner layer of the semipermeable membrane can effectively intercept high molecular weight immune components, shield immune factors such as antibodies from attacking bioactive substance secreting cells and does not influence normal nutrient substance/waste metabolism of the cells. The micron pore membrane on the surface of the semipermeable membrane can further reduce the fibrosis characteristic and immune cell adhesion of the stent through surface hydrophilic graft modification and anti-fibrosis modification, and improve the in vivo stability of the stent material and the surface vascularization capability of endothelial cells.

In some embodiments of the present application, the semipermeable membrane 120 is an electrospun (electrostatic direct write), non-woven process stent semipermeable membrane. By adopting a non-degradable or slowly degradable biocompatible electrostatic spinning, electrostatic direct writing and non-woven barrier membrane (such as PTFE, PVDF, PAN, PP, PE, PEGDA or PEGMA and the like), the barrier membrane can independently realize filtration and screening of small molecular substances, block macromolecular immune protein and realize the effect of resisting immunological rejection. The barrier membrane can further improve the overall anti-rejection function, the vascularization promotion function and the anti-fibrosis function by combining the hydrogel filling and adjusting the pore and surface modification function.

In some embodiments of the present application, the composite cell scaffold further comprises a shell encasing the scaffold 130 and the prevascularization module 110. Through the arrangement of the shell, the support function of the whole structure is provided for the composite cell scaffold. The housing may be selected from materials such as polyetheretherketone (peek), polyethylene terephthalate (PET) or other polymer materials with similar properties.

Referring to fig. 8, in some embodiments of the present application, the scaffold 130, the prevascularization module 110, and the semi-permeable membrane 120 form a cell unit 810, and a plurality of the cell units 810 are stacked one on another to form a composite cell scaffold. The scaffold of a single cell unit has a limited cell loading capacity, and in order to load more cells, a plurality of cell units can be stacked layer by layer to form a combination of scaffolds with a plurality of loaded cells, thereby effectively improving the cell loading capacity of the whole composite cell scaffold. Furthermore, the scaffolds 130 of different cell units 810 are isolated from each other and not communicated with each other; the prevascularization cavities 111 of different cell units 810 are mutually communicated or are also kept in a mutually non-communicated state through artificial blood vessels 820, the artificial blood vessels 820 can be in millimeter level, and the preparation method can be specifically used for culturing endothelial cell layers on the inner wall of the cavity in an adherent manner by adopting the cell perfusion culture method to form artificial blood vessels or other preparation methods of artificial blood vessels well known in the art. Alternatively, the vascular prosthesis 820 may also serve as a junction for a different prevascularization module 110. Different prevascularization lumens 111 may be anastomosed to the host vessel via corresponding main channel lumens 210, respectively, or may otherwise form an overall junction.

Referring to fig. 8 and 9, in some embodiments of the present application, a substrate 910 is disposed between different cell units 810, the size, thickness and material of the substrate 910 are adapted to the cell units 810, and at the same time, the substrate 910 needs to have certain mechanical properties to ensure that the substrate 910 can independently support the cell units 810 between different layers and separate the different cell units 810 from each other. Further, an aperture 911 may be formed on the substrate 910 to maintain communication between the upper and lower cell units 810. The size of the aperture 911 may be set to the micrometer level in order to allow the different cells 810 to perform separate and integrated functions, respectively. In addition, a protruding fixing member may be provided on the substrate 910, and the cell unit 810 may be fixedly connected to the substrate 910 by the fixing member. For example, the fixing member is a cylindrical limiting post 912 disposed on the substrate 910, and limiting through holes matched with the limiting post 912 are disposed on the stent 130 and the prevascularization module 110, so that the fixing member can be fixed with the substrate 910 through the limiting post 912. The restraint posts 912 or other fasteners known in the art must not functionally affect the substrate 910 and the cell units 810 (including the scaffold 130 and the prevascularization module 110) secured thereto. Furthermore, the substrates 910 may be assembled with each other by fasteners or by a housing.

In some embodiments of the present application, the target implant cells 132 loaded in the scaffold have a function of generating bioactive substances, including but not limited to hormones, enzymes, trophic factors, neurotransmitters, or other active substances having an effect of participating in the stimulation response of the internal and external environments, maintaining the stability of the internal environment of the body, and the like. For example, islet cells, islet precursor cells, pluripotent stem cell-derived islet-like cells, various genetically engineered insulin-secreting cells, liver precursor cells, pluripotent stem cell-derived liver cells, various genetically engineered liver protein-secreting cells, or thyroid cells, pluripotent stem cell-derived thyroid cells, various genetically engineered thyroid protein-secreting cells, factor VIII-secreting cells, pluripotent stem cell-derived factor VIII-secreting cells, and various genetically engineered factor VIII-secreting cells.

The present application has been described in detail with reference to the embodiments, but the present application is not limited to the embodiments described above, and various changes can be made within the knowledge of those skilled in the art without departing from the gist of the present application. Furthermore, the embodiments and features of the embodiments of the present application may be combined with each other without conflict.

Claims (10)

1. Composite cell scaffold, characterized in that it comprises a plurality of cell units, said cell units comprising:

the scaffold is provided with a cell accommodating cavity which is used for loading target implanted cells;

a prevascularization module having a prevascularization cavity therein;

the semipermeable membrane, the prevascularization cavity with the cell holding chamber passes through the semipermeable membrane intercommunication.

2. The composite cytoskeleton of claim 1, wherein the prevascularization cavity comprises:

a main channel cavity for supplying a prevascularization culture solution;

and the branch cavity is communicated with the main channel cavity.

3. The composite cell scaffold according to claim 2, wherein the inner wall of said branch cavities has a pre-vascular layer formed by endothelial cell attachment.

4. The composite cytoskeleton of claim 2 wherein the branched lumen has a three-dimensional microvascular network of endothelial cells within the branched lumen.

5. The composite cell scaffold according to claim 2, wherein said primary channel lumen has openings for surgical vascular anastomosis.

6. The composite cytoskeleton according to any one of claims 1 to 5, wherein the area of the prevascularization chamber in direct covering communication contact with the semipermeable membrane is a first area, the area of the prevascularization module in direct covering contact with the semipermeable membrane is a second area, and the ratio of the first area to the second area is not less than 50%.

7. The composite cytoskeleton of any one of claims 1-5, further comprising a shell encasing the scaffold and the prevascularization module.

8. The composite cytoskeleton according to any one of claims 1 to 5, wherein the cell unit further comprises a substrate, a fixing member is arranged on the substrate, and the scaffold and the prevascularization module are fixedly connected with the substrate through the fixing member.

9. The composite cell scaffold according to any one of claims 1 to 5, wherein said cell units are in plurality, and a plurality of said cell units are stacked one on another to form said composite cell scaffold.

10. The composite cytoskeleton according to claim 9, wherein the prevascularization modules of different cell units are in communication with each other through an artificial blood vessel.

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