A hierarchical bionic pore-porous composite scaffold

Abstract

The present invention discloses a layered bionic pore-porous composite scaffold, comprising an outer layer and an inner layer; the outer layer is a dense porous structure imitating compact bone, and the inner layer is a loose porous structure imitating cancellous bone and loaded with bone morphogenetic protein-2 (BMP-2); the layered bionic pore-porous composite scaffold has a number of pores running through the outer layer and the inner layer, which are used to induce rapid vascular growth. The present invention has obvious advantages in terms of layered structure, pore design, and BMP-2 loading mode. The relatively dense structure of the outer layer simulates cortical bone to meet the mechanical properties of the scaffold, and the loose porous structure of the inner layer ensures the growth of tissue blood vessels. At the same time, the pore structure can induce rapid vascular growth, and the BMP-2 loaded in the inner porous area can induce osteogenic differentiation of cells growing along the pores, avoiding excessive osteogenesis caused by the diffusion of BMP-2, and comprehensively realizing the overall rapid vascularization bone regeneration of the scaffold.

Description

Technical Field

[0001] The invention relates to the field of bionic stents, and in particular to a layered bionic pore-porous composite stent. Background Art

[0002] Inflammation, tumors, trauma, congenital malformations, etc. often cause defects and loss of jaw bones, with a high incidence rate. It not only affects the appearance, but also leads to abnormalities in chewing, swallowing and speech, seriously affecting the patient's quality of life. Large-scale defects are even life-threatening. There are currently two main methods used in the clinic for the treatment of jaw defects: 1. Autologous bone transplantation is the gold standard for clinical treatment, but it has the disadvantages of limited autologous bone sources and trauma repairing trauma; 2. Bone replacement scaffold implantation, such as the use of hydroxyapatite scaffolds. The jaw bone is composed of a relatively dense outer layer of compact bone and a relatively loose inner layer of cancellous bone. The existing scaffolds use a porous structure to ensure tissue and blood vessel growth, and most of them can only construct one of the structures, and cannot simulate the natural layered structure of bones. In addition, the bone induction ability of traditional bone replacement materials is limited. In order to improve the osteoinduction performance, they are often loaded with osteoinduction factors such as bone morphogenetic protein-2 to enhance the osteogenic effect. However, the bone morphogenetic protein-2 loaded on the surface of the scaffold diffuses into the surrounding tissues and easily causes excessive osteogenesis.

[0003] Patent CN210077950U discloses a 3D printed bionic bone scaffold. This patent combines 3D printing technology to design a loose scaffold core layer and at least three layers of annular scaffold shell layers that are tightly nested from the inside to the outside and have decreasing porosity to simulate the natural bone structure. However, the scaffold produced by this method is not satisfactory in terms of treatment effect, especially the regenerative treatment of large jaw defects, which is still a major clinical problem. The reason is that the rapid vascularization of the scaffold is the key to the regeneration of large jaws. The mechanical properties of the scaffold and the vascular ingrowth cannot be achieved at the same time; at the same time, the speed at which blood vessels grow along the pores of the scaffold is also limited, which greatly slows down the rate of bone regeneration. Summary of the invention

[0004] The purpose of the present invention is to provide a hierarchical bionic pore-porous composite scaffold, which achieves good mechanical strength through a hierarchical structure, and also designs pores to induce blood vessels to grow in, thereby achieving rapid vascularization of the scaffold. In addition, by loading bone morphogenetic protein-2 in the internal porous area, only cells growing along the pores are induced to undergo osteogenic differentiation, thereby avoiding excessive osteogenesis.

[0005] In order to achieve the above-mentioned purpose, the present invention provides a layered bionic pore-porous composite scaffold, which includes an outer layer and an inner layer; the outer layer is a dense porous structure imitating compact bone, with a porosity of 50%-60%, and the inner layer is a loose porous structure imitating cancellous bone, with a porosity of 80%-90%, and the inner porous area is loaded with bone morphogenetic protein-2; the layered bionic pore-porous composite scaffold has a plurality of pores penetrating the outer layer and the inner layer for inducing the growth of blood vessels.

[0006] Preferably, the pore size of the outer layer is 50-100 μm.

[0007] Preferably, the pore size of the inner layer is 500-750 μm.

[0008] Preferably, the diameter of the pores is 250-500 μm.

[0009] Preferably, the holes are evenly arranged.

[0010] The present invention has obvious advantages in terms of layered structure, pore design, and bone morphogenetic protein-2 loading method. The relatively dense structure of the outer layer simulates compact bone to meet the mechanical properties of the scaffold, and the loose porous structure of the inner layer ensures the growth of tissue blood vessels. At the same time, the pore structure can induce rapid growth of blood vessels, and the bone morphogenetic protein-2 loaded in the inner porous area can induce osteogenic differentiation of cells growing along the pores, avoiding excessive osteogenesis caused by the diffusion of bone morphogenetic protein-2, and comprehensively realizing the overall rapid vascularization of the scaffold.

[0011] (1) The relatively dense structure of the outer layer simulates compact bone to match the strength of the jawbone; the loose porous structure of the inner layer simulates cancellous bone. The layered structure design meets the load-bearing requirements of the bone repair scaffold and comprehensively achieves good mechanical strength of the scaffold.

[0012] (2) The laterally penetrating channel structure can induce rapid vascular ingrowth, simplifying the vascularization problem of segmental mandibular defect regeneration to be solved into bidirectional vascular ingrowth regulation within the thickness of the mandibular bone, thereby achieving the purpose of rapid vascularization of the stent.

[0013] (3) The inner layer of the scaffold is loaded with bone morphogenetic protein-2, which can induce host cells to differentiate into osteoblasts, enhance the osteogenic induction effect of the scaffold, avoid excessive osteogenesis caused by the overall loading of bone morphogenetic protein-2 on the traditional scaffold, and achieve the effect of accurately controlling the range of bone regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Schematic diagram of the appearance structure of the layered bionic pore-porous composite scaffold.

[0015] Figure 2Schematic diagram of the cross-sectional structure of the layered bionic pore-porous composite scaffold.

[0016] In the figure, 1-outer layer, 2-inner layer, 3-pores, 4-blood vessels. DETAILED DESCRIPTION

[0017] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0018] like Figure 1 As shown, the present invention provides a layered bionic pore-porous composite scaffold. The layered bionic pore-porous composite scaffold includes an outer layer 1, an inner layer 2, and a plurality of pores 3 that penetrate the outer layer 1 and the inner layer 2. The outer layer 1 is a dense porous structure that imitates compact bone. Compact bone, also known as "compact bone, cortical bone", is a dense bone tissue located in the outer layer of the bone and the long bone shaft, and is composed of closely arranged bone plates. The porosity of the outer layer 1 is 50%-60%, and the pore size is 50-100μm. The inner layer 2 is a loose porous structure that imitates cancellous bone. Cancellous bone is distributed at the two ends of long bones, short bones, flat bones and the inside of irregular bones. It is composed of many needle-shaped or sheet-shaped trabeculae interwoven with each other, and is spongy. The bone density is lower than that of compact bone and it is elastic. The porosity of the inner layer 2 is 80%-90%, and the pore size is 500-750μm. The pores 3 are used to induce rapid vascular in-growth, and the diameter of the pores 3 is 250-500 μm. In some embodiments, the pores 3 are evenly arranged. The loose porous structure of the inner layer 2 is loaded with bone morphogenetic protein-2 (BMP-2), which is used to induce host cells growing along the pores 3 to differentiate into osteoblasts, enhance the osteoinductive effect of the scaffold, avoid excessive osteogenesis caused by the diffusion of BMP-2 loaded on the surface of the scaffold, and achieve the effect of accurately controlling the range of bone regeneration.

[0019] like Figure 2 As shown, after the layered bionic pore-porous composite stent disclosed in the present invention is placed into a human body, the pores 3 can induce the rapid growth of blood vessels 4, thereby achieving rapid vascularization of the entire stent.

[0020] The layered bionic pore-porous composite scaffold disclosed in the present invention can be prepared by 3D printing technology, and can be printed with the same material; it can also be combined with multi-channel 3D printing technology, select different slurries, and prepare by partitioning and layering. Specifically, one or more synthetic polymer materials such as calcium phosphate-based and calcium silicate-based bioceramics, poly(lactic acid) (PLGA), polylactic acid (PLA), polyglycolic acid (PGA) and the like can be selected as slurries for printing the inner and outer layer scaffolds. When printing each layer, the scaffold structure is printed first, and the inner layer scaffold simulates cancellous bone when printing, which is a reticular porous structure with a pore size of 500-750μm. When printing the outer layer scaffold, the compact bone structure is simulated, which is a relatively dense structure, wherein the slurry is mixed with polymer material microspheres with a diameter of 50-100μm as a porogen; after the scaffold structure is printed, the pore structure is printed using polymer slurry, with a tube diameter of 250-500μm; after completion, the next layer is printed, and the printing of the overall structure is completed by stacking layer by layer. Finally, during sintering, the polymer material melts at high temperature to form pores in the channels and outer scaffolds, while the bioceramics harden and finally form a layered bionic pore-porous composite scaffold. After the scaffold is sintered, the BMP-2 solution is dripped into the inner porous area, and the scaffold is freeze-dried to ensure that the factor is evenly loaded in the porous area.

[0021] The layered bionic pore-porous composite scaffold prepared by the present invention can be used for the repair of mandibular segmental defects to replace the commonly used autologous bone transplantation in clinical practice. When used specifically, autologous mesenchymal stem cells can be loaded to enhance the bone inductivity of the scaffold to improve the healing effect. In particular, the porous structure of the scaffold increases the surface area of ​​the scaffold, which can increase the loading rate of stem cells to a certain extent. At the same time, the porous structure is conducive to the growth of blood vessels, which can provide nutrition for the loaded stem cells, increase their survival rate, and jointly promote bone regeneration. The dense outer layer structure in the layered structure enables the overall strength of the scaffold to meet the needs of load-bearing, while the loose and porous internal structure gives the scaffold a certain mechanical conduction effect, which comprehensively realizes the complex requirements for the mechanical properties of the scaffold during the mandibular chewing movement. The internal porous area loaded with BMP-2 can induce the osteogenic differentiation of cells growing along the pores, avoiding the excessive osteogenesis caused by the diffusion of BMP-2 due to the load on the surface of the scaffold, and achieving the effect of accurately controlling the range of bone regeneration. The stent material can be used in conjunction with titanium plates for fixation; extension parts can also be designed at both ends of the stent, with retention holes on them, which are connected to the bone ends through absorbable retention nails to play a retention role.

[0022] Although the content of the present invention has been described in detail through the above preferred embodiments, it should be appreciated that the above description should not be considered as a limitation of the present invention. After reading the above content, it will be apparent to those skilled in the art that various modifications and substitutions of the present invention will occur. Therefore, the protection scope of the present invention should be limited by the appended claims.

Claims

1. A layered bionic pore-porous composite scaffold, characterized in that: The layered bionic pore-porous composite scaffold comprises an outer layer and an inner layer; the outer layer is a dense porous structure imitating compact bone, with a porosity of 50%-60%, and the inner layer is a loose porous structure imitating cancellous bone, with a porosity of 80%-90%, and the inner porous area is loaded with bone morphogenetic protein-2 for inducing osteogenic differentiation of cells growing along the pores; the layered bionic pore-porous composite scaffold has a plurality of pores penetrating the outer layer and the inner layer for inducing the growth of blood vessels.

2. The layered bionic pore-porous composite scaffold according to claim 1, characterized in that: The pore size of the outer layer is 50-100 μm.

3. The layered bionic pore-porous composite scaffold according to claim 1, characterized in that: The pore size of the inner layer is 500-750 μm.

4. The layered bionic pore-porous composite scaffold according to claim 1, characterized in that: The diameter of the pores is 250-500 μm.

5. The layered bionic pore-porous composite scaffold according to claim 1, characterized in that: The holes are evenly arranged.

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