阅读说明：本技术 一种仿生学三相组织工程支架 (Bionic three-phase tissue engineering bracket ) 是由 陈灿 史强 于 2019-08-15 设计创作，主要内容包括：本申请公开了一种仿生学三相组织工程支架,包括多个支架层,支架层沿纵向叠加,所述支架层包括沿横向依次分布的骨支架、软骨支架和肌腱支架,相邻层的骨支架至少部分相互抵接,相邻层的软骨支架至少部分相互抵接,相邻层的肌腱支架至少部分相互抵接,其中至少两层支架层中的骨支架、软骨支架和肌腱支架的所占区域的位置和/或比例不同。上述方案通过控制各个支架层中的骨支架、软骨支架和肌腱支架所占区域的位置和/或比例,使得由各个支架层叠加得到的工程支架具有仿生特性,可以根据实际组织中骨支架、软骨支架以及肌腱支架的位置和/或比例进行构建,使其具有较为正常的组织型态,而非简单地平齐结构,更加符合人体生理结构。(The application discloses bionics three-phase tissue engineering support, including a plurality of support layers, the support layer is along vertical stack, the support layer includes bone support, cartilage support and the tendon support that distributes in proper order along transversely, and the mutual butt of bone support part at least of adjacent layer, the mutual butt of cartilage support part at least of adjacent layer, the mutual butt of tendon support part at least of adjacent layer, wherein the position and/or the proportion in the shared region of bone support, cartilage support and tendon support in at least two-layer support layer are different. Above-mentioned scheme is through the position and/or the proportion of the shared region of bone scaffold, cartilage support and tendon support in the control each support layer for the engineering support who obtains by each support layer stack has bionical characteristic, can construct according to the position and/or the proportion of bone scaffold, cartilage support and tendon support in the actual tissue, makes it have comparatively normal tissue form, and not simply parallel and level structure, accords with human physiology structure more.)

1. The utility model provides a bionics three-phase tissue engineering support, its characterized in that includes a plurality of support layers, and the support layer is along vertical stack, the support layer includes along horizontal bone scaffold, cartilage support and the tendon support that distributes in proper order, the mutual butt of bone scaffold part at least of adjacent layer, the mutual butt of cartilage support part at least of adjacent layer, the mutual butt of tendon support part at least of adjacent layer, wherein the shared region position and/or the proportion of bone scaffold, cartilage support and tendon support in at least two-layer support layer are different.

2. A biomimetic three-phase tissue engineering scaffold according to claim 1, wherein the bone scaffold, cartilage scaffold and tendon scaffold of each layer are of a unitary structure.

3. A biomimetic three-phase tissue engineering scaffold according to claim 2, wherein the cartilage scaffold and tendon scaffold of each layer are longitudinally layered, or the bone scaffold and cartilage scaffold of each layer are longitudinally layered.

4. A biomimetic three-phase tissue engineering scaffold according to claim 3, wherein the cartilage scaffold and tendon scaffold of each layer are in a longitudinally layered structure, and part of the bone scaffold of each layer is longitudinally layered; or

The bone scaffold and the cartilage scaffold of each layer are in a longitudinal layered structure, and part of the tendon scaffold of each layer is layered in the longitudinal direction.

5. A biomimetic three-phase tissue engineering scaffold according to claim 1, wherein the upper and lower surfaces of each layer of bone scaffold, cartilage scaffold and tendon scaffold are provided with growth factor coatings.

6. The biomimetic three-phase tissue engineering scaffold according to claim 1, wherein the scaffold layers have the same length and width; preferably, the tissue engineering scaffold is a cuboid structure.

7. A biomimetic three-phase tissue engineering scaffold according to claim 1, wherein the bone scaffold, cartilage scaffold and tendon scaffold in each scaffold layer have different area ratios.

8. The biomimetic three-phase tissue engineering scaffold according to claim 1, wherein the abutting area of the bone scaffold of the adjacent layer is greater than or equal to 30%, preferably 50%, of the cross-sectional area of the smaller cross-sectional area of the adjacent layer; the abutting area of the cartilage support abutted by the adjacent layer is more than or equal to 30%, preferably 50% of the cross-sectional area of the smaller cross-sectional area of the adjacent layer; the abutting area of the tendon support of the adjacent layer is equal to or larger than 30%, preferably 50% of the cross-sectional area of the smaller cross-sectional area of the adjacent layer.

9. The biomimetic three-phase tissue engineering scaffold according to claim 1, wherein the bone scaffold in at least one scaffold layer is partially or fully abutted with the cartilage scaffold in the adjacent layer; and/or

The tendon scaffold in at least one scaffold layer is partially or completely abutted with the cartilage scaffold in the adjacent layer.

10. The biomimetic three-phase tissue engineering scaffold according to claim 1, wherein the proportion of the bone scaffold in the scaffold layer increases in the longitudinal direction, and the proportion of the tendon scaffold in the scaffold layer decreases in the longitudinal direction; or

The proportion of the positions of the bone scaffolds in the scaffold layer is reduced along the longitudinal direction, and the proportion of the tendon scaffolds in the scaffold layer is increased along the longitudinal direction.

Technical Field

The invention mainly relates to a bone tendon connection point defect repair technology, in particular to a bionic three-phase tissue engineering scaffold and a construction method thereof.

Background

The following is merely an admission that the inventors are knowledgeable in the relevant art and does not necessarily constitute prior art.

The advent and explosion of tissue engineering technology has motivated clinicians and researchers to attempt to address this problem through tissue engineering strategies. The traditional tissue engineering bone tendon interface regeneration strategy has the following problems: 1) the existing bracket is biomimetically designed only from one or two aspects of morphological structure, gradient mineralization and mechanical property, and is lack of multiple biomimetic characteristics; 2) the existing scaffold is mostly prepared from artificial synthetic materials, and different areas of bones, fibrocartilage and tendons of the scaffold lack the characteristic of directional induced differentiation of stem cells; 3) the introduction of exogenous seed cells has the risk of tumorigenesis, and the seed cells are loaded on the stent in vitro, so the operation process of constructing the tissue engineering graft is complicated and the storage is difficult. The concept of 'region-induced active scaffold' provides a new thinking mode for the research of tissue engineering bone tendon interface regeneration strategy. The mode emphasizes that different areas of the stent respectively have the induction effects of osteogenesis, chondrogenesis and tenogenesis, and a suitable microenvironment is provided for in-vivo in-situ regeneration. The design is favorable for directly inducing endogenous stem cells from an in vivo environment to migrate into the scaffold and directionally differentiate, thereby avoiding the introduction of seed cells and being favorable for repairing a characteristic bone-fibrocartilage-tendon structure in situ. However, the existing tissue engineering scaffold does not consider how to simulate a normal bone tendon interface bone-cartilage-tendon three-phase structure, so that the existing scaffold lacks dual bionic characteristics of normal tissue morphology and traction-resistant mechanical property.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides the three-phase tissue engineering scaffold which can effectively simulate a normal bone tendon interface and has bionic characteristics and the embodiment of the construction method thereof.

In one aspect, the embodiment provides a bionics three-phase tissue engineering support, including a plurality of scaffold layers, the scaffold layers are along vertically stacking, the scaffold layers include bone scaffold, cartilage scaffold and tendon scaffold along transversely distributing in proper order, the bone scaffold of adjacent layer is at least partly to butt each other, the cartilage scaffold of adjacent layer is at least partly to butt each other, the tendon scaffold of adjacent layer is at least partly to butt each other, wherein the position and/or the proportion of the shared region of bone scaffold, cartilage scaffold and tendon scaffold in at least two layers of scaffold layers are different.

In one embodiment, the bone scaffold, cartilage scaffold and tendon scaffold of each layer are of a unitary structure.

In one embodiment, the cartilage scaffold and the tendon scaffold of each layer are in a longitudinally layered structure, or the bone scaffold and the cartilage scaffold of each layer are in a longitudinally layered structure.

In one embodiment, the cartilage scaffold and the tendon scaffold of each layer are in a longitudinally layered structure, and part of the bone scaffold of each layer is longitudinally layered; or the bone scaffold and the cartilage scaffold of each layer are in a longitudinal layered structure, and part of the tendon scaffold of each layer is layered in the longitudinal direction.

In one embodiment, the upper and lower surfaces of each of the bone scaffold, cartilage scaffold and tendon scaffold are provided with a growth factor coating.

In one embodiment, the lengths and widths of the support layers are the same.

In one embodiment, the tissue engineering scaffold is a cuboid structure.

In one embodiment, the bone scaffold, cartilage scaffold and tendon scaffold in each scaffold layer have different area ratios.

In one embodiment, the abutting area of the bone scaffold of the adjacent layer is greater than or equal to 30%, preferably 50%, of the cross-sectional area of the smaller cross-sectional area of the adjacent layer, the abutting area of the cartilage scaffold of the adjacent layer is greater than or equal to 30%, preferably 50%, of the cross-sectional area of the smaller cross-sectional area of the adjacent layer, and the abutting area of the tendon scaffold of the adjacent layer is greater than or equal to 30%, preferably 50%, of the cross-sectional area of the smaller cross-sectional area of the adjacent layer.

In one embodiment, the bone scaffold in at least one scaffold layer is partially or fully abutted with the cartilage scaffold in an adjacent layer.

In one embodiment, the tendon scaffold in at least one scaffold layer is partially or fully abutted with the cartilage scaffold in the adjacent layer.

In one embodiment, the proportion of the bone scaffold in the scaffold layer increases in the longitudinal direction, and the proportion of the tendon scaffold in the scaffold layer decreases in the longitudinal direction.

In one embodiment, the proportion of the bone scaffold in the scaffold layer decreases in the longitudinal direction, and the proportion of the tendon scaffold in the scaffold layer increases in the longitudinal direction.

Compared with the prior art, the scheme has the advantages that:

the positions and/or the proportions of the areas occupied by the bone scaffold, the cartilage scaffold and the tendon scaffold in each scaffold layer are controlled, so that the engineering scaffold obtained by superposing each scaffold layer has bionic characteristics, can be constructed according to the positions and/or the proportions of the bone scaffold, the cartilage scaffold and the tendon scaffold in actual tissues, has a relatively normal tissue form, is not simply a parallel and level structure, and better accords with a human physiological structure.

Drawings

Fig. 1 is a schematic structural diagram of a three-phase tissue engineering scaffold in example 1.

Fig. 2 is a schematic structural diagram of the three-phase tissue engineering scaffold in example 1 during installation.

Fig. 3 is a schematic view of the combination of tendon and muscle and bone.

FIG. 4 is a CT image of a control group, a simple stent group and a biomimetic stent group

FIG. 5 is a comparison of bone density for the control group, the scaffold alone group and the biomimetic scaffold group.

Fig. 6 is a comparison graph of trabecular bone thickness for the control group, the pure scaffold group and the biomimetic scaffold group.

Fig. 7 shows histological H & E staining experiments of the control group, the scaffold-only group, and the biomimetic scaffold group.

Fig. 8 is a schematic structural view (closed) of one of the scaffold layers in example 2.

Fig. 9 is a schematic structural view (expanded) of one of the scaffold layers in example 2.

Fig. 10 is a schematic structural view (closed) of another stent layer in example 2.

Fig. 11 is a schematic structural view (expanded) of another stent layer in example 2.

The labels in the figure are: 1. a bone scaffold; 2. a cartilage scaffold; 3. a tendon scaffold; 4. a tendon; 5. a bone; 6. muscles.

Detailed Description

To further illustrate the technical means and effects of the present invention adopted to achieve the predetermined objects, the following detailed description of the embodiments, structures, features and effects according to the present invention with reference to the accompanying drawings and preferred embodiments is as follows:

in the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "provided" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements.

The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art. In addition, the technical features involved in the different embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.

The terms "plurality" and "a plurality" in the present disclosure and appended claims refer to two or more than two unless otherwise specified.