阅读说明：本技术 一种plla/zif-8复合骨支架及其制备方法 (PLLA/ZIF-8 composite bone scaffold and preparation method thereof ) 是由 杨友文 帅词俊 彭淑平 昝君 于 2019-09-20 设计创作，主要内容包括：本发明提供了一种PLLA/ZIF-8复合骨支架及其制备方法,所述复合骨支架按质量百分比计组成如下：PLLA 97～99.5wt％,ZIF-8 0.5～3wt％。所述复合骨支架的制备方法为：将左旋聚乳酸和ZIF-8粉末液相混合,经搅拌和超声、分离、干燥后得到复合粉末。随后利用选择性激光烧结工艺,复合粉末在层层烧结后,最终得到PLLA/ZIF-8复合骨支架。本发明利用ZIF-8与PLLA基体之间存在良好的结合,从而提高PLLA与ZIF-8的界面结合,进而提高其力学强度。此外,利用ZIF-8在酸性环境降解的特性,提高PLLA的降解速率和细胞增殖。(The invention provides a PLLA/ZIF-8 composite bone scaffold and a preparation method thereof, wherein the composite bone scaffold comprises the following components in percentage by mass: 97-99.5 wt% of PLLA and 80.5-3 wt% of ZIF. The preparation method of the composite bone scaffold comprises the following steps: and mixing the levorotatory polylactic acid and the ZIF-8 powder, and stirring, performing ultrasonic treatment, separating and drying to obtain the composite powder. And then sintering the composite powder layer by using a selective laser sintering process to finally obtain the PLLA/ZIF-8 composite bone scaffold. The invention utilizes the good combination between the ZIF-8 and the PLLA matrix, thereby improving the interface combination of the PLLA and the ZIF-8 and further improving the mechanical strength of the PLLA and the PLLA. In addition, the degradation rate and cell proliferation of PLLA are improved by utilizing the characteristic that ZIF-8 is degraded in an acidic environment.)

1. A PLLA/ZIF-8 composite bone scaffold, which is characterized in that: the composite bone scaffold comprises, by mass, PLLA 97-99.5 wt% and ZIF-80.5-3 wt%.

2. The PLLA/ZIF-8 composite bone scaffold of claim 1, wherein: the composite bone scaffold comprises, by mass, PLLA 97-99 wt% and ZIF-81-3 wt%.

3. A method of preparing a PLLA/ZIF-8 composite bone scaffold according to claim 1 or 2, comprising the steps of: dropwise adding the ethanol solution A dispersed with the PLLA powder into the ethanol solution B dispersed with the ZIF-8 powder or dropwise adding the ethanol solution B dispersed with the ZIF-8 powder into the ethanol solution A dispersed with the PLLA powder, stirring under ultrasound to form PLLA/ZIF-8 mixed suspension, carrying out solid-liquid separation, drying and grinding the obtained solid phase to obtain composite powder, and selectively carrying out laser sintering on the composite powder to obtain the PLLA/ZIF-8 composite bone scaffold.

4. The method of preparing a PLLA/ZIF-8 composite bone scaffold according to claim 3, wherein: the particle size of the PLLA powder is 100-150 mu m, and the melting point is 175-180 ℃.

5. The method of preparing a PLLA/ZIF-8 composite bone scaffold according to claim 3, wherein: the particle size of the ZIF-8 powder is 0.5-4 mu m, and the purity is more than or equal to 98%.

6. The method of preparing a PLLA/ZIF-8 composite bone scaffold according to claim 3, wherein: in the ethanol solution A dispersed with PLLA powder, the solid-liquid mass volume ratio of the PLLA powder to ethanol is 0.3-0.5 g: 1 ml.

In the ethanol solution B dispersed with the ZIF-8 powder, the solid-liquid mass-volume ratio of the ZIF-8 powder to ethanol is 0.005-0.02 g: 1 ml.

7. The method of preparing a PLLA/ZIF-8 composite bone scaffold according to claim 3, wherein: the stirring time under ultrasonic is 60-120 min, the rotating speed is 800-1200 r/min, and the temperature is 30-60 ℃.

8. The method of preparing a PLLA/ZIF-8 composite bone scaffold according to claim 3, wherein: the parameters of the selective laser sintering process are as follows: the laser power is 1.5-4W, the scanning speed is 100-200 mm/s, the scanning interval is 0.5-1.5 mm, the spot diameter is 0.3-0.5 mm, the thickness of the powder layer is 0.1-0.2 mm, and the preheating temperature of the powder bed is 130-160 ℃.

Technical Field

The invention belongs to the technical field of biological materials, and particularly relates to a PLLA/ZIF-8 bone scaffold and a preparation method thereof.

Background

Levorotatory polylactic acid (PLLA) is taken as a typical biodegradable high molecular material, and has the advantages of wide source, no toxicity of degradation products, good biocompatibility and the like. In addition, PLLA is also a few degradable implant materials approved by the U.S. Food and Drug Administration (FDA). However, PLLA has relatively insufficient mechanical strength and relatively slow degradation rate, and its application in the field of bone repair is limited due to low bioactivity.

Aiming at insufficient mechanical strength of PLLA, some scholars propose to add inorganic nano nucleating agent to enhance the mechanical strength, and the method utilizes heterogeneous nucleation effect of the nano nucleating agent to induce macromolecules to nucleate on the inorganic nano nucleating agent, so as to accelerate crystallization rate of polymers and refine crystal grains, thereby improving the mechanical strength of the polymers. However, the inorganic filler and the polymer matrix have larger difference in physicochemical properties, so that poor interface bonding between the inorganic filler and the polymer is easily caused, and the mechanical reinforcing effect is weakened. Furthermore, the method does not relate to how to increase the rate of degradation of PLLA.

Metal-Organic Frameworks (MOFs) are crystalline porous materials formed by self-assembly of Metal ions or Metal clusters and Organic ligands. The porous carbon material has the characteristics of huge surface area, various structures, adjustable pore size, modifiable material and the like, and has attracted extensive attention in the fields of hydrogen energy storage, catalysis, gas adsorption and biology in recent years.

However, there is no report of using MOF-modified PLLA for the preparation of composite bone scaffolds.

Disclosure of Invention

Aiming at the problems of insufficient mechanical strength, slow degradation rate, low cell activity and the like of PLLA used as a bone implant material in the prior art, the invention aims to provide a PLLA/ZIF-8 composite bone scaffold with excellent mechanical property, proper degradation rate and high cell activity and a preparation method thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

The invention relates to a PLLA/ZIF-8 composite bone scaffold which comprises the following components in percentage by mass: PLLA 97-99.5 wt% and ZIF-80.5-3 wt%.

the invention provides a zinc element-constructed MOF material, namely a zeolite imidazole framework material 8(ZIF-8) -reinforced composite bone scaffold of L-polylactic acid (PLLA). The inventor finds that the organic component of ZIF-8 is well combined with a polymer, so that ZIF-8 and PLLA have excellent interface compatibility, and in addition, ZIF-8 has good thermal stability and excellent heterogeneous nucleation effect, can be used as a nucleation site in a polymer matrix, and can induce a high molecular chain to rapidly nucleate on the nucleation site and refine the grain size, so that the crystallinity of the polymer matrix is improved, and the ZIF-8-reinforced PLLA has excellent mechanical properties under the synergistic action; secondly, the inventor finds that as ZIF-8 is degraded in an acidic environment, holes generated in a matrix after degradation can accelerate the permeation of water molecules, and further accelerate the degradation of PLLA. In addition, zinc ions released by ZIF-8 degradation are used as essential trace elements of human bodies, participate in the biosynthesis of proteins and various enzymes, and provide favorable conditions for the growth of cells.

in the invention, the components of the composite bone scaffold need to be effectively controlled, the improvement of PLLA performance is limited due to too low ZIF-8 content, and the excessive ZIF-8 content can cause the excessive zinc ion content released by the PLLA/ZIF-8 composite bone scaffold and inhibit the proliferation of cells.

In a preferred scheme, the composite bone scaffold comprises the following components in percentage by mass: PLLA 97-99 wt% and ZIF-81-3 wt%.

As a further optimization, the composite bone scaffold comprises the following components in percentage by mass: PLLA 97-98 wt% and ZIF-82-3 wt%.

In a preferable scheme, the ultimate tensile strength of the composite bone scaffold is 20-40 MPa; the ultimate compressive strength is 30-50 MPa.

More preferably, the ultimate tensile strength of the composite bone scaffold is 28.4-40 MPa; the ultimate compressive strength is 37.8 to 50 MPa.

The invention relates to a preparation method of a PLLA/ZIF-8 composite bone scaffold, which comprises the following steps: dropwise adding the ethanol solution A dispersed with PLLA powder into the ethanol solution B dispersed with ZIF-8 powder or dropwise adding the ethanol solution B dispersed with ZIF-8 powder into the ethanol solution A dispersed with PLLA powder, stirring under ultrasound to form ZIF-8/PLLA mixed suspension, performing solid-liquid separation, drying and grinding the obtained solid phase to obtain composite powder, and selectively performing laser sintering on the composite powder to obtain the PLLA/ZIF-8 composite bone scaffold.

In a preferred scheme, the particle size of the PLLA powder is 100-150 mu m, and the melting point is 175-180 ℃.

In the preferable scheme, the particle size of the ZIF-8 powder is 0.5-4 mu m, and the purity is more than or equal to 98%.

The PLLA/ZIF-8 composite bone scaffold is prepared by adopting a selective laser sintering process, the particle size of the PLLA powder is too large, and the too large powder easily forms gaps in the sintering process under the condition of the same viscosity, so that incomplete sintering is caused, and the molding quality is influenced. If the particle size of the powder is too small, although the powder can be rapidly melted in the sintering process, the powder is not easy to spread, the powder is easy to fly, the layering thickness is easy to be uneven, and the forming quality is reduced. For ZIF-8 powder, the particle size of the powder is too large to achieve the effect of reinforcing the nanoparticles, and if the particle size is too small, agglomeration is easily caused due to the action of the huge surface area of the powder, and the mechanical property is also influenced.

Preferably, in the ethanol solution A dispersed with PLLA powder, the solid-liquid mass volume ratio of the PLLA powder to ethanol is 0.3-0.5 g: 1 ml.

In the preferable scheme, in the ethanol solution B dispersed with the ZIF-8 powder, the solid-liquid mass volume ratio of the ZIF-8 powder to ethanol is 0.005-0.02 g: 1 ml.

In the actual operation process, the PLLA powder and the ZIF-8 powder are respectively added into ethanol according to the solid-to-liquid ratio, then the ethanol solution A and the ethanol solution B are obtained through high-speed strong stirring and ultrasonic dispersion, then the ethanol solution A is dropwise added into the ethanol solution B, and the ZIF-8/PLLA mixed suspension is formed through stirring and ultrasonic dispersion, so that the PLLA powder and the ZIF-8 powder can be fully dispersed and uniformly mixed without agglomeration. If the operations are not carried out as above, for example, after the PLLA and the ZIF-8 are simultaneously added into the ethanol solution for magnetic stirring and ultrasonic dispersion, the obtained composite powder has poor dispersion effect, and further has certain influence on the comprehensive performance of the stent.

In a preferable scheme, the stirring time under ultrasonic is 60-120 min, the rotating speed is 800-1200 r/min, and the temperature is 30-60 DEG C

the inventor finds that effective uniform dispersion of powder can be realized by adopting high-speed strong stirring and ultrasound, and the dispersion effect is influenced by excessively high stirring speed and excessively low stirring speed, so that the performance of the material is influenced. Meanwhile, the inventor finds that the powder can be dispersed more uniformly by simultaneously stirring and ultrasonic treatment than by stirring first and then ultrasonic treatment, or by stirring first and then ultrasonic treatment.

In a preferable scheme, in the composite powder, the mass fraction of the PLLA powder is 97-99.5 wt%, and the mass fraction of the ZIF-8 powder is 0.5-3 wt%.

More preferably, in the composite powder, the mass fraction of the PLLA powder is 97-99 wt%, and the mass fraction of the ZIF-8 powder is 1-3 wt%.

More preferably, in the composite powder, the mass fraction of the PLLA powder is 97-98 wt%, and the mass fraction of the ZIF-8 powder is 2-3 wt%.

In the preferred scheme, the selective laser sintering process parameters are as follows: the laser power is 1.5-4W, the scanning speed is 100-200 mm/s, the scanning interval is 0.5-1.5 mm, the spot diameter is 0.3-0.5 mm, the thickness of the powder layer is 0.1-0.2 mm, and the preheating temperature of the powder bed is 130-160 ℃.

The inventor finds that the technological parameters of laser sintering have certain influence on the performance of the composite material, and the PLLA/ZIF-8 composite bone scaffold with the best performance can be finally obtained only by the synergistic effect of the laser power, the scanning speed and the spot diameter in a reasonable range, because the laser power, the scanning speed and the spot diameter jointly determine the energy density of the laser sintering in the laser sintering process, if the energy density is too low, the sintering is not compact, the mechanical property is not enough, and if the energy density is too high, the overburning phenomenon, including carbonization and burning loss, bubbling and cracking, can occur, and the mechanical property of the bone scaffold is seriously reduced.

The preparation method of the PLLA/ZIF-8 composite bone scaffold comprises the following main steps:

(1) And designing a three-dimensional model according to the bone tissue structure of the bone defect part.

(2) According to the solid-liquid mass-volume ratio of ZIF-8 powder to ethanol of 0.005-0.02 g: 1ml, adding the ZIF-8 powder into an ethanol cup, and mechanically stirring and ultrasonically dispersing to obtain an ethanol solution B in which the ZIF-8 powder is uniformly dispersed; according to the solid-liquid mass volume ratio of the PLLA powder to the ethanol of 0.3-0.5 g: 1ml, adding PLLA powder into an ethanol cup, mechanically stirring and ultrasonically dispersing to obtain an ethanol solution A in which the PLLA powder is uniformly dispersed,

(3) Dropwise adding the ethanol solution A dispersed with the PLLA powder into the ethanol solution B dispersed with the ZIF-8 powder or dropwise adding the ethanol solution B dispersed with the ZIF-8 powder into the ethanol solution A dispersed with the PLLA powder, and uniformly stirring and mixing under ultrasound to obtain a mixed suspension, wherein the stirring and ultrasound time is 60-120 min, the rotation speed is 800-1200 r/min, and the temperature is 30-60 DEG C

(4) After carrying out liquid-solid separation on the mixed suspension, drying the obtained solid phase to obtain mixed powder, and grinding the mixed powder to obtain PLLA/ZIF-8 composite powder;

(5) Placing the PLLA/ZIF-8 composite powder in a selective laser sintering system, sintering layer by layer according to a three-dimensional model, and removing unsintered powder after sintering to obtain the PLLA/ZIF-8 composite bone scaffold, wherein the selective laser sintering process parameters are as follows: the laser power is 1.5-4W, the scanning speed is 100-200 mm/s, the scanning interval is 0.5-1.5 mm, the spot diameter is 0.3-0.5 mm, the thickness of the powder layer is 0.1-0.2 mm, and the preheating temperature of the powder bed is 130-160 ℃.

Compared with the prior art, the invention has the advantages and beneficial effects that:

(1) The invention utilizes the good combination effect of ZIF-8 and PLLA matrix, improves the interface combination ability of ZIF-8 and PLLA matrix, and promotes the dispersion of ZIF-8 in PLLA matrix, thereby enhancing the mechanical property of PLLA scaffold.

(2) By utilizing the good heterogeneous nucleation effect of ZIF-8, the nucleation rate of PLLA is accelerated, the crystallinity of PLLA is improved, PLLA crystal grains are refined, and the mechanical property of the PLLA is synergistically improved.

(3) The degradation of PLLA is synergistically accelerated by utilizing the degradation characteristic of ZIF-8 in an acidic environment.

(4) Zinc ions released by ZIF-8 degradation participate in synthesis of various enzymes, so that adhesion and proliferation of cells on the scaffold are facilitated, and the biological performance of the composite scaffold is improved.

Drawings

FIG. 1 is an SEM image of a PLLA/ZIF-8 composite stent made in example 1;

FIG. 2 is an SEM image of a PLLA/ZIF-8 composite stent made in example 2;

FIG. 3 is an SEM image of a PLLA/ZIF-8 composite stent made in comparative example 1.

Detailed Description

the following further describes embodiments of the present invention with reference to specific examples, but the present invention is not limited thereto.