CN110478089A - A kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation - Google Patents

Abstract

A kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation disclosed by the invention, it includes main part, the main part has been arranged concentrically first passage in the axial direction, the main part is additionally provided with second channel in the axial direction, and the second channel is uniformly arranged centered on the axis of first passage；The main part has been disposed radially third channel, the third channel connection first passage and second channel, so that first passage and the nutrient solution of second channel conveying are spread in tissue via third channel.A kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation provided by the invention, large segmental bone defect is treated suitable for ectopic osteogenesis, its is structurally reasonable, by active scaffold landfill in internal muscle, pass through the double-deck effect of blood vessel and nerve, promote the effect of ectopic osteogenesis, to treat and repair large segmental bone defect.

Description

A vascularized and neuralized osteoactive scaffold suitable for large segmental bone defect repair

technical field

The invention relates to the technical field of medical devices, in particular to a vascularized and neuralized osteoactive scaffold suitable for repairing large segmental bone defects.

Background technique

In recent years, with the rapid development of bone tissue engineering, the application of bone tissue engineering technology to treat bone defects is the current development trend. Compared with in situ osteogenesis, the ectopic osteogenesis model can reduce the variables that affect osteogenesis in the experiment, and can evaluate the bone formation. Effects of cells, osteogenic inductive materials. Heterotopic ossification (HO) refers to ectopic deformity ossification that occurs in normal soft tissues other than bone tissue, and is a dynamic process; heterotopic ossification is a type of ectopic ossification.

Patent CN105013016A discloses a tissue engineered bone for bone defect regeneration and repair and its construction method and application. The tissue engineered bone is a composite layered structure composed of three layers of bone marrow mesenchymal stem cell aggregates and two layers of bone matrix particles; the composite layered The structure is a complex composed of bone marrow mesenchymal stem cell aggregates-bone matrix particles-bone marrow mesenchymal stem cell aggregates-bone matrix particles-bone marrow mesenchymal stem cell aggregates; bone marrow mesenchymal stem cell aggregates include bone marrow mesenchymal stem cell aggregates Mesenchymal stem cells and extracellular matrix secreted by and distributed around bone marrow mesenchymal stem cells. The method is suitable for the regeneration and repair of bone defects, realizes the physiological regeneration of bones and improves the repair and treatment effect of bone defects.

Patent CN104096266A discloses a tissue-engineered bone based on the endochondral osteogenesis system, in which mesenchymal stem cells are planted on porous bone scaffold materials to construct a tissue-engineered complex, and then cultured for chondrogenic differentiation in vitro for 2 weeks. Then, hypertrophic chondrocytes were induced and cultured for 2 weeks to obtain them. The tissue engineered bone based on the endochondral osteogenesis system constructed by the method of the invention can form ectopic bone in vivo and successfully repair bone defects, avoiding the problems of uniform vascularization of large tissue engineered bones and ensuring sufficient nutritional supply.

Patent CN108478876A discloses a method for preparing a vascularized bone tissue engineering scaffold, which includes the following steps: using a chemical precipitation method, an aqueous solution containing a water-soluble calcium salt, a water-soluble copper salt, a water-soluble zinc salt and a surfactant and a phosphate react with an aqueous solution to prepare a calcium-deficient apatite slurry, and dry to obtain a powder; wherein, the molar ratio of the water-soluble calcium salt, water-soluble copper salt, and water-soluble zinc salt is 15 to 168:1:1 ; The obtained powder is mixed with the liquid phase solution to form a slurry, then injected into a mold, dried and molded, and sintered at a high temperature to obtain a porous calcium phosphate ceramic support; the microspheres loaded with GDF-5 are loaded on the surface of the obtained porous calcium phosphate ceramic support , and obtain the bone tissue engineering scaffold for promoting vascularization after vacuum drying. The tissue engineering scaffold obtained by the invention has excellent osteoconductivity, osteoinductivity, biodegradability and vascularization-promoting performance, solves the problem of rapid repair of bone defects, and has good practical application prospects.

At present, there is a lack of research on the application of ectopic osteogenesis in bone defect repair. The use of ectopic osteogenesis for bone defect repair has special advantages in the treatment of bone infection bone defects, because in the treatment of bone infection bone defects, the infection must be controlled in the first stage, and bone formation cannot be performed at the bone defect site at this time. Using this time for ectopic bone formation, and transplanting the whole piece to the bone defect after the bone infection is controlled, has a faster and better recovery effect than directly placing the tissue engineering scaffold in the defect.

Therefore, it is urgent to design a vascularized and neuralized osteogenic scaffold suitable for repairing large bone defects, which can effectively improve the quality and speed of ectopic osteogenesis in vivo.

Contents of the invention

The object of the present invention is to solve the above-mentioned technical problems. The present invention provides a vascularized and neuralized osteoactive scaffold suitable for the repair of large segmental bone defects, which is suitable for ectopic osteogenesis in the treatment of large segmental bone defects. The active stent is embedded in the muscle in the body, and through the double-layer effect of blood vessels and nerves, it can promote the effect of ectopic bone formation to treat and repair large bone defects.

In order to solve the above-mentioned technical problems, the present invention provides a vascularized and neuralized osteoactive scaffold suitable for repairing large segmental bone defects, comprising a main body, the main body is provided with a first channel concentrically along the axial direction, and the main body A second channel is also provided along the axial direction, and the second channel is uniformly arranged with the axis of the first channel as the center; the main body part is provided with a third channel along the radial direction, and the third channel communicates with the first channel and The second channel enables the nutrient solution transported by the first channel and the second channel to diffuse in the human tissue through the third channel.

In some embodiments, the diameter of the first channel is larger than the diameter of the second channel.

In some embodiments, the diameter of the second channel is 1/8-1/4 of the diameter of the first channel.

In some embodiments, the diameter of the third channel is not greater than the diameter of the second channel.

In some embodiments, the third passage is arranged horizontally on the main body, and the axis of the third passage is perpendicular to the axis of the main body.

In some embodiments, the second channels are evenly distributed around the axis of the first channel, and the second channels are arranged along the radial direction of the main body.

In some embodiments, the third passage is obliquely arranged on the main body, and an included angle exists between the axis of the third passage and the axis of the main body.

In some embodiments, the included angle between the axis of the third channel and the main body is ±60°.

In some embodiments, the first channel is provided with a hydrogel containing endothelial progenitor cells to promote blood vessel formation within the active scaffold.

In some embodiments, the second channel is provided with a hydrogel containing neural stem cells to facilitate the formation of nerves within the active scaffold.

Beneficial effects of the present invention:

The present invention provides a vascularized and neuralized osteoactive scaffold suitable for repairing large segmental bone defects, which is suitable for ectopic osteogenesis to treat large segmental bone defects, and has a reasonable structure. The double-layer effect of blood vessels and nerves can promote the effect of ectopic osteogenesis to treat and repair large bone defects; at the same time, the generated blood vessels can carry the osteoprogenitor cells, oxygen, nutrients and growth-promoting factors required for osteogenesis (such as Hormones, etc.) to the bone surface, the nervous system in bone tissue can regulate the function of bone cells by secreting neuropeptides, and actively participate in the bone formation of osteoblasts; moreover, under physiological conditions, the nervous system enters the bone together with blood vessels, The two promote each other and promote ectopic osteogenesis.

Description of drawings

The above-mentioned advantages of the present invention will become clearer and easier to understand through the detailed description in conjunction with the following drawings, which are only schematic and do not limit the present invention, wherein:

Fig. 1 is a schematic structural view of a vascularized and neuralized osteoactive scaffold suitable for repairing large segmental bone defects according to the present invention;

Fig. 2 is a longitudinal sectional view corresponding to the active stent in Fig. 1;

Fig. 3 is a transverse cross-sectional view corresponding to the active stent in Fig. 1;

Fig. 4 is a schematic diagram of the electron microscope results of the bone repair part;

Fig. 5a and Fig. 5b are display diagrams of CT reconstruction results.

In the picture:

10. Main body; 11. First channel; 12. Second channel; 13. Third channel.

Detailed ways

A vascularized and neuralized osteogenic active scaffold suitable for repairing large segmental bone defects described in this application will be described in detail below with reference to specific embodiments and accompanying drawings.

The examples described here are specific specific implementations of the present invention, and are used to illustrate the concept of the present invention. They are all explanatory and exemplary, and should not be construed as limiting the implementation of the present invention and the scope of the present invention. In addition to the embodiments described here, those skilled in the art can also adopt other obvious technical solutions based on the claims of the application and the contents disclosed in the description, and these technical solutions include adopting any obvious changes made to the embodiments described here. Replacement and modified technical solutions.

The accompanying drawings in this specification are schematic diagrams, which assist in explaining the concept of the present invention, and schematically represent the shapes of various parts and their interrelationships. Note that the same reference numerals are used to designate the same parts in order to clearly show the structure of each component of the embodiment of the present invention.

A schematic structural view of a vascularized and neuralized osteoactive scaffold suitable for repairing large segmental bone defects according to the present invention, as shown in Figures 1 to 3, which includes a main body 10, which is concentrically arranged along the axial direction There is a first passage 11, and the main body 10 is also provided with a second passage 12 along the axial direction, and the second passage 12 is uniformly arranged around the axis of the first passage 11; the main body 10 is arranged radially There is a third channel 13 , and the third channel 13 communicates with the first channel 11 and the second channel 12 , so that the nutrient solution delivered by the first channel 11 and the second channel 12 diffuses in the human tissue through the third channel 13 .

The first channel 11 is provided with hydrogel, which contains endothelial progenitor cells, to promote the formation of blood vessels in the active scaffold; the second channel 12 is provided with hydrogel, which contains neural stem cells, to promote the formation of blood vessels in the active scaffold. Nerves form within the scaffold. During clinical treatment, the active stent of the present invention is embedded in the muscles in the body, through the double-layer effect of blood vessels and nerves, the effect of ectopic osteogenesis is promoted to treat and repair large bone defects, and the generated blood vessels can Carry the osteoprogenitor cells, oxygen, nutrients and growth-promoting factors (such as hormones) required for osteogenesis to the bone surface, and the nervous system in the bone tissue can regulate the function of bone cells by secreting neuropeptides, and actively participate in the formation of osteoblasts. Bone formation, so that the nervous system and blood vessels enter the bone together, and the two promote each other to promote ectopic bone formation.

As an embodiment of the present invention, the diameter of the first channel 11 is larger than the diameter of the second channel 12 . The setting of the second channel 12 can make the nutrient solution passing through the first channel 11 diffuse relatively uniformly on the outer peripheral side of the main body 10; specifically, the nutrient solution can diffuse to the main body through the third channel 13 and the second channel 12 On the peripheral side of 10, the endothelial progenitor cells in the nutrient solution promote the formation of blood vessels in the active scaffold, and the neural stem cells in the nutrient solution promote the formation of nerves in the active scaffold, and promote ectopic osteogenesis through the double-layer action of blood vessels and nerves.

As an embodiment of the present invention, the diameter of the second channel 12 is 1/8-1/4 of the diameter of the first channel 11 . Preferably, the diameter of the second channel 12 is 3/16 of the diameter of the first channel 11 , and the nutrient solution can diffuse to the outer peripheral side of the main body 10 through the third channel 13 and the second channel 12 .

In some embodiments, the diameter of the third channel 13 is not greater than the diameter of the second channel 12, the third channel 13 is arranged vertically, and it communicates with the first channel 11 and the second channel 12, and the nutrient solution can pass through the third channel 13 And the diffusion of the second channel 12 to the peripheral side of the main body 10, the endothelial progenitor cells in the nutrient solution promote the formation of blood vessels in the active stent, the neural stem cells in the nutrient solution promote the formation of nerves in the active stent, and the third channel 13 makes the Endothelial progenitor cells, osteoprogenitor cells, and growth-promoting factors in the first channel 11 contact and exchange with neuropeptides in the third channel 13 to promote ectopic osteogenesis.

As an embodiment of the present invention, the third passage 13 is horizontally arranged on the main body 10 , and the axis of the third passage 13 is perpendicular to the axis of the main body 10 , as shown in FIG. 2 . As a variation of this embodiment, the third passage 13 is obliquely disposed on the main body 10 , and an included angle exists between the axis of the third passage 13 and the axis of the main body 10 . In some embodiments, the included angle between the axis of the third channel 13 and the main body 10 is ±60°. Preferably, the included angle between the axis of the third channel 13 and the main body 10 is ±45°, that is, the third channel 13 can be inclined upwards, or it can be inclined downwards, as long as the third channel 13 and the first channel It is only necessary that the first channel 11 and the second channel 12 communicate with each other.

In some embodiments, the cross-sectional area of the third channel 13 is the same, and it can also be set in the form of a gradual change in the cross-sectional area. Specifically, the cross-sectional area of the third channel 13 can gradually increase from the inside to the outside, so as to gently transport the nutrient solution in the third channel 13 and improve the absorption effect of the active stent on the nutrient solution.

As an embodiment of the present invention, the second channels 12 are evenly distributed around the axis of the first channel 11, and the second channels 12 are arranged along the radial direction of the main body 10, as shown in FIG. 3 , The second channel 12 is arranged in one turn along the radial direction of the main body part 10; as a variation of this embodiment, the second channel 12 is arranged in multiple turns along the radial direction of the main body part 10, such as two second channels 12 or three circles of the second channel 12 promote the effect of ectopic bone formation through the double-layer action of blood vessels and nerves.

The following is a brief description of the steps and process of using a vascularized and neuralized osteoactive scaffold suitable for large-segment bone defect repair according to the present invention to treat large-segment bone defects:

For bone infection and bone defect, it needs to be treated in stages, the first stage is to control the infection at the bone defect site, and the second stage is bone grafting and bone repair at the bone defect site. However, if the second part of the bone graft is implanted with autologous bone, the bone harvesting area will be damaged, and the amount of autologous bone is limited. If it is directly placed into a tissue engineering scaffold, the effect is not good enough. Therefore, we employ active scaffolds for a new phased treatment approach.

Phase 1, in addition to controlling bone infection, the prepared active scaffold is embedded in the muscle or subcutaneously. After that, the vascular endothelial cells loaded in the scaffold will facilitate the vascularization of the scaffold, and the loaded neural stem cells will facilitate the neuralization of the scaffold. Vascularization and neuralization contribute to ectopic osteogenesis of the scaffold. The specific steps are: carry out in the operation room dedicated to experimental animals that has been irradiated by ultraviolet rays. After the anesthesia takes effect, use a special shaver for animals to prepare the skin of the operation area; Iodine is used to disinfect the skin in the area, and the towel is routinely spread to expose the back of the experimental animal;

Then, two incisions about 2 cm in length were made on both sides of the back spine. After the skin was lifted, the subcutaneous tissue and superficial fascia were separated with vascular forceps and tissue scissors, reaching deep into the deep fat layer until the superficial muscle fascia was exposed;

Next, use a blunt separator to separate the pocket-shaped muscle bag, infiltrate the active scaffold of the present invention with physiological saline and put it flat into the muscle bag, then suture the wound layer by layer and mark it.

Table 1 is a comparison table of blood test results, and electron microscope results of the bone repair part, as shown in Figure 4.

Table 1 blood test results show

The results in Table 1 show that the active scaffold has no cytotoxicity in the process of ectopic osteogenesis.

Stage 2, the active scaffold obtained in the previous stage is used to treat bone defects, which has better results. The specific steps are: the active scaffold is first ectopically formed into bone for 2 weeks and then implanted into the bone defect; the control test is: directly The tissue engineering scaffold was implanted into the bone defect site, and Table 2 is a comparison table of mechanical experiment results.

Table 2 Comparison table of mechanical experiment results

It can be seen from Table 2 that implanting the active scaffold into the bone defect after 2 weeks of ectopic osteogenesis has a better osteogenesis effect at 20 weeks than directly implanting the tissue engineering scaffold into the bone defect.

Figure 5a and Figure 5b show the results of CT reconstruction. The ectopic osteogenic active scaffold has a good bone formation effect in vivo. In the rabbit radius defect model, the active scaffold was implanted into the bone defect after 2 weeks of ectopic osteogenesis, as shown in Fig. As shown in Figure 5a, the tissue engineering scaffold was directly implanted into the bone defect site, and Figure 5b shows that it has a better osteogenic effect at 20 weeks.

The present invention provides a vascularized and neuralized osteoactive scaffold suitable for repairing large segmental bone defects, which is suitable for ectopic osteogenesis to treat large segmental bone defects, and has a reasonable structure. The double-layer effect of blood vessels and nerves can promote the effect of ectopic bone formation, and it has good promotion value for the treatment and repair of large bone defects.

The present invention is not limited to the above-mentioned embodiment, and anyone can draw other various forms of products under the enlightenment of the present invention, but no matter make any changes in its shape or structure, all those with the same or similar features as the present application The technical solutions all fall within the protection scope of the present invention.

Claims (10)

1. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation, including main part, the main body Portion has been arranged concentrically first passage in the axial direction, and the main part is additionally provided with second channel in the axial direction, and described second Channel is uniformly arranged centered on the axis of first passage；The main part has been disposed radially third channel, and the third is logical Road is connected to first passage and second channel, so that first passage and the nutrient solution of second channel conveying are via third channel in human body Diffusion in tissue.

2. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 1, It is characterized in that, the diameter of the first passage is greater than the diameter of second channel.

3. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 2, It is characterized in that, the diameter of the second channel is the 1/8-1/4 of the diameter of first passage.

4. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 1, It is characterized in that, the diameter of the third channel is not more than the diameter of second channel.

5. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 1, It is characterized in that, the third channel is horizontally set on main part, the axis of third channel is vertical with the axis of the main part.

6. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 1, It is characterized in that, the second channel is uniformly distributed centered on the axis of first passage, also, the second channel is along main part Radial direction setting.

7. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 1, It is characterized in that, the third channel is inclined at main part, the axis presence of the axis of third channel and the main part One angle.

8. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 7, It is characterized in that, the angle of the axis of the third channel and the main part is ± 60 °.

9. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 1, It is characterized in that, hydrogel is provided in the first passage, containing endothelial progenitor cells, to promote to be formed in active scaffold Blood vessel.

10. a kind of vascularization neuralization osteogenic activity bracket suitable for large segmental bone defect reparation according to claim 1, It is characterized in that, hydrogel is provided in the second channel, containing neural stem cell, to promote to be formed in active scaffold Nerve.