CN101781815A - Preparation method of porous fiber with controllable degradation rate for tissue engineering scaffold - Google Patents

Abstract

The invention relates to a method for preparing a porous fiber with a controllable degradation rate for tissue engineering scaffolds. The pore-forming agent is removed in distilled water, and after vacuum drying, a porous fiber with micropores with a diameter of 10-100 μm uniformly distributed on the surface is obtained. The preparation method of the invention is simple and suitable for industrial production; the micropore diameter of the obtained fiber matches the size of the cells, so that the cells are easy to adhere and grow in the micropores on the surface of the fiber, and the degradation rate is controllable at the same time.

Description

Preparation method of porous fiber with controllable degradation rate for tissue engineering scaffold

technical field

The invention belongs to the field of preparation of porous fibers, in particular to a method for preparing porous fibers with controllable degradation rate for tissue engineering scaffolds.

Background technique

So far, the clinical applications in the field of biomedical polymer materials are mainly polyester materials, such as polyglycolic acid (PGA), polycaprolactone (PCL), polylactic acid (PLA), polydioxane Hexanone (PDO), etc. Therefore, aliphatic polyesters have been more and more widely used in the fields of implant materials in vivo and tissue engineering. In order to control the biodegradability of aliphatic polyesters, new biomedical polymer materials with different biodegradation rates can be prepared by changing the polymer structure, composition and morphology, which can significantly improve the physical and chemical properties of aliphatic polymers such as degradation and thermodynamics. So far, there is no single biomaterial that can meet all the needs of tissue engineering for scaffold materials. It is necessary to combine the advantages of existing biomaterials and organically integrate them to prepare biocompatible scaffolds that can guide tissues. Cell growth, a tissue engineering scaffold that can support tissue growth and ensure a controllable degradation rate in vivo.

The degradation time of PGA, PLA, and PDO is 60 days, 220 days and 182 days respectively. The degradation time of PGA is very fast, which has a great impact on its application. It is very important to adjust its degradation rate through molecular weight and molecular weight distribution. Therefore, the crystallinity and hydrophilicity of PGA can be changed by blending or copolymerization, so as to achieve the purpose of controlling the degradation rate of PGA composite materials. In addition, since the degradation cycle of block copolymers is among the polymers, the degradation behavior can also be controlled by adjusting the ratio of each block component. Li S.M. etc. made a systematic study on the in vivo degradation properties of PLA, PGA, PCL copolymers and homopolymers, and found that lactide (LA), glycolide (GA) and caprolactone (CL) can be adjusted to adjust the rate of degradation. [LiSM, VertM. The Encyclopedia of Controlled Drug Delivery. Mathiowitz E.ed, John Wiley & Sons, New York, 1999]. By copolymerizing GA and LA, the degradation properties of PLGA can be regulated by adjusting the feed ratio of LA and GA. The degradation times of PGLA (LA/GA=10/90, 25/75, 50/50, 75/25) were 90, 100, 120, 180, respectively.

In terms of blending, PLA has been studied more because of its hydrophobicity, which affects its biocompatibility and degradation performance. In the PLA fully biodegradable blend system, PLA can change the mechanical properties, processing properties and degradation of composite materials by blending with poly 3-hydroxybutyrate (PHB), PCL, polyoxyethylene (PEO), starch, etc. speed. But there is no report about the blending compound of PGA and PLA or PDO.

In addition to simply using degradable fibers, tissue engineering composite scaffolds can also be used by weaving fibers into a certain shape and structure. Scaffolds prepared by fiber weaving are commonly used in tissue engineering tendon, cartilage, blood vessel and nerve repair. Jin Yiming et al. used PDO fiber warp-knitted extravascular stents. The results showed that the PDO stent structure was stable and had good compression recovery performance. The in vitro degradation test showed that it maintained a relatively stable degradation rate and good mechanical properties within 8 weeks. [Jin Yiming, Wang Wenzu. In vitro degradation performance of warp-knitted extravascular stents. Chinese Tissue Engineering Research and Clinical Rehabilitation, 2008, 12(27): 5248-5252]. Single-component degradable fiber fabrics usually cannot meet the requirements of tissue repair for mechanical support and degradation time. Wu Shuangquan et al. used polylactic acid and polyglycolic acid filaments with different component ratios to weave four kinds of braided wires, and found that in the degradation process , with the increase of the proportion of PGA fiber in the braided wire, the degradation rate of the braided wire is also accelerated, the mass loss rate of the braided wire increases, and the strength gradually decreases. [Wu Shuangquan, Zhang Peihua, Guo Zheng. In vitro degradation performance of PGA/PLA braided wire with different ratios. Journal of Donghua University (Natural Science Edition), 2009, 35(3): 274-303]. Yuan Xiaoyan and others disclosed a method for preparing a multi-component hybrid three-dimensional braided tendon scaffold material, using polyglycolide, polylactide or their copolymer aliphatic polyester fibers each containing a certain proportion as the material, and 1× 1 The four-step circular three-dimensional weaving method is used to weave a column-braided rope-packed three-dimensional braided tendon scaffold material, which has the advantages of good tensile strength, adjustable degradation rate, and good cell affinity. [Yuan Xiaoyan et al. Preparation method of multi-component hybrid three-dimensional braided tendon scaffold (CN 1194774C)].

Porous fibers have structures fabricated using some conventional phase separation methods. These methods generally involve mixing the polymer resin with a diluent or plasticizer, cooling the polymer solution in a liquid medium to induce phase separation, and then rinsing the diluent away to leave a cross-linked porous structure; in A certain amount of inorganic particles are added to the polyester spinning melt for spinning, and the inorganic particles are removed by alkali reduction after stretching, leaving micropores on the surface of the fibers. The capillary action of the micropores can improve the moisture absorption of the fibers Sex and get a cool feel.

A kind of microporous polyester fiber is characterized in that it is composed of conventional resin and water-soluble modified polymeric resin, uniformly blended according to the ratio of 70-50%: 30-50%, and dissolves 8-12% after melt spinning % of the water-soluble modified polymeric resin has a large number of micropores with a diameter of about 0.5-2 μm evenly distributed on the surface and inside. [Qian Jianhua et al. A microporous polyester fiber and its preparation method (CN 101144206A)]. A microcellular foam fiber in which a supercritical fluid is introduced as the polymers used to form the fiber are melted and mixed in the extruder, and the unidirectional solution of melt and gas passes through the spinnerets of the spin pack Extruded to form micropores, the ratio of the length to diameter of the micropores is greater than 1, the diameter of the monofilament is greater than 5 μm, and the diameter of the micropores is less than 10 μm. [Cui Rongbai et al. Microporous foam fiber and its preparation method (CN 1304652C)]. Yang Enning et al. used calcium carbonate as a pore-forming agent, stretched it into a hollow fiber by mixing it with polypropylene, and performed post-treatment with hydrochloric acid. The calcium carbonate mixed in the hollow fiber was dissolved to form pores. [Yang Enning, Guo Jing. CaCO ₃ /polypropylene blending preparation of porous polypropylene fibers. Synthetic Fibers, 2006, 2:25-27].

At present, there is no single polymer or copolymer of PGA, PLA, PDO or a mixture of polymers in China to prepare porous fibers and fabrics for tissue engineering scaffolds.

Contents of the invention

The technical problem to be solved by the present invention is to provide a preparation method of a porous fiber with a controllable degradation rate for tissue engineering scaffolds. The method is simple, low in cost, and suitable for industrial production; the micropore diameter of the obtained fiber matches the cell size, It makes it easy for cells to adhere and grow in the micropores on the surface of the fiber, while the degradation rate is controllable.

A method for preparing a porous fiber with controllable degradation rate for a tissue engineering scaffold of the present invention, comprising:

The biodegradable polymer and the pore-forming agent are uniformly mixed at a weight percentage of 90-99%: 1-10%, vacuum-dried for 21-48 hours, melt-spun, stretched, and then immersed in hydrochloric acid or distilled water to remove the pores After vacuum drying, porous fibers with micropores with a diameter of 10-100 μm uniformly distributed on the surface are obtained.

The biodegradable polymer is a mixture of two or three of single polymers of polyglycolic acid PGA, polylactic acid PLA and polydioxanone PDO.

The biodegradable polymer is a copolymer of polyglycolic acid PGA, polylactic acid PLA or polydioxanone PDO.

The biodegradable polymer is a mixture of two or three of polyglycolic acid PGA, polylactic acid PLA and polydioxanone PDO.

The molecular weight of the PGA is 100,000-150,000, the molecular weight of PLA is 100,000-150,000, and the molecular weight of PDO is 100,000-150,000.

The biodegradable polymer is PGLA with a GA/LA mass ratio of 1-99/99-1.

The pore-forming agent is calcium carbonate or polyvinylpyrrolidone (PVP) particles with a particle size of 10-80 μm.

The concentration of described hydrochloric acid is 6%.

The porous fiber is woven to obtain a porous fiber fabric, and the weaving method is the same kind of fiber weaving or interweaving of fibers with different proportions.

The porous fibrous fabric is in the form of threads, tubes or planar.

According to the different objects of tissue engineering repair, the present invention selects PGA, PLA and PDO fibers with different weight ratios for mixed weaving, so that the degradation time of the fiber scaffold matches the growth rate of cells, and promotes tissue repair.

The composite of tissue engineered cells and scaffolds requires that the scaffold materials have good compatibility with the cells, which can facilitate the attachment and growth of cells on the scaffolds. In general, the surface of the fiber prepared by melt spinning is relatively dense and smooth. In order to improve the adhesion of cells on the degradable fiber, micropores corresponding to the size of the cell can be prepared on the surface of the fiber so that the cell can fall. In these micropores, it is not easy to peel off the scaffold, and at the same time, the roughness of the fiber surface can be increased to improve the affinity between cells and scaffold materials.

The diameter range of the cells is 10-100 μm. In order to prepare micropores in this pore size range on the fiber surface, the diameter of the micropores obtained by the dissolution method of water-soluble modified polymer resin and the method of introducing supercritical fluid to make holes is too small , the cells cannot fall into the micropores, and it is not easy to control the size of the pores. Therefore, particles with known diameters are selected as pore-forming agents, and fibers are prepared by blending with degradable polymers. Finally, pore-forming agents are dissolved to prepare micropores with a certain diameter. Holes, this method is simple and easy, will not pollute the environment, and the cost of raw materials is low, and the reproducibility is good.

Beneficial effect

(1) The preparation method of the present invention is simple, low in cost, and suitable for industrialized production;

(2) The micropore diameter of the obtained fiber of the present invention matches the cell size, so that the cells are easy to adhere and grow in the micropores on the surface of the fiber, and the degradation rate is controllable at the same time, so that the decay rate of the mechanical properties of the material is comparable to the healing rate of the tissue Matching is conducive to the compound culture of tissue engineering cells and scaffolds, and can be used as scaffolds for tissue engineering cells such as nerves or blood vessels.

Detailed ways

Below in conjunction with specific embodiment, further illustrate the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Example 1

PGA with a molecular weight of 100,000, slices of PLA with a molecular weight of 100,000 (the mass ratio of GA/LA is 75/25) and the pore-forming agent calcium carbonate with a particle diameter of 50 μm are in a ratio of 95% by weight: 5%. Mix evenly, dry in vacuum for 24 hours, then carry out melt spinning and stretching, then immerse the prepared fiber in 6% hydrochloric acid to remove the pore-forming agent, during which the hydrochloric acid solution is replaced every 6 hours, take out the fiber after 24 hours, vacuum After drying, porous fibers with uniform surface distribution and micropores with a diameter of 50-60 μm are obtained.

Example 2

PGA with a molecular weight of 120,000, slices of PLA with a molecular weight of 120,000 (the mass ratio of GA/LA is 90/10) and the pore-forming agent calcium carbonate with a particle diameter of 20 μm are in a ratio of 98%: 2% by weight Mix evenly, dry in vacuum for 24 hours, then carry out melt spinning and stretching, then immerse the prepared fiber in 6% hydrochloric acid to remove the pore-forming agent, during which the hydrochloric acid solution is replaced every 6 hours, take out the fiber after 24 hours, vacuum After drying, a porous fiber with micropores with a diameter of 20-35 μm uniformly distributed on the surface is obtained.

Example 3

The PGA with a molecular weight of 100,000, the slices of PDO with a molecular weight of 100,000 (the weight ratio of PGA and PDO is 50/50) and the pore-forming agent PVP with a particle size of 80 μm are uniformly mixed in a ratio of 99%:1% by weight , after vacuum drying for 24 hours, carry out melt spinning and stretching, and then immerse the prepared fiber in distilled water to remove the pore-forming agent, during which the distilled water is replaced every 6 hours, take out the fiber after 24 hours, and obtain a surface uniformly distributed after vacuum drying. Porous fibers with micropores with a diameter of 80-100 μm.

Example 4

The slices of PGLA (GA/LA mass ratio is 75/25) and the porogen PVP with a particle size of 10 μm are uniformly mixed in a ratio of 93%: 7% by weight, melt-spun after vacuum drying for 24 hours, and drawn , and then immerse the prepared fiber in distilled water to remove the pore-forming agent, during which the distilled water was replaced every 6 hours, and the fiber was taken out after 24 hours, and after vacuum drying, the porous fiber with micropores with a diameter of 10-15 μm uniformly distributed on the surface was obtained.

Example 5

PGA with a molecular weight of 100,000, slices of PLA with a molecular weight of 100,000, and a pore-forming agent PVP with a particle size of 10 μm in a weight percentage of 98%: 2% are evenly mixed, and vacuum-dried for 24 hours to carry out melt spinning. Stretching, then immersing the prepared fiber in distilled water to remove the pore-forming agent, changing the distilled water every 6 hours during this period, taking out the fiber after 24 hours, and drying in vacuum to obtain a porous fiber with micropores with a diameter of 10-15 μm evenly distributed on the surface. Select 4 PGA porous filaments and 2 PLA porous filaments to weave on a 6-spindle vertical spindle braiding machine, change gears with 30 teeth, and weave a process angle of 54.5° to obtain a 4PGA/2PLA braided wire. The diameter of the braided wire is 0.18mm, breaking strength 1276.2cN, friction coefficient 0.72.

Example 6

PGA with a molecular weight of 150,000 and slices of PLA with a molecular weight of 150,000 are uniformly mixed with a pore-forming agent PVP with a particle size of 10 μm in a weight percentage of 98%: 2%, and melt-spun after vacuum drying for 24 hours. Stretching, then immersing the prepared fiber in distilled water to remove the pore-forming agent, changing the distilled water every 6 hours during this period, taking out the fiber after 24 hours, and drying in vacuum to obtain a porous fiber with micropores with a diameter of 10-15 μm uniformly distributed on the surface. Select 2 PGA porous filaments and 4 PLA porous filaments to weave on a 6-spindle vertical spindle braiding machine, change gears with 30 teeth, and weave a process angle of 54.5° to obtain a 2PGA/4PLA braided wire. The diameter of the braided wire is 0.22mm, breaking strength 1061.1cN, friction coefficient 0.72.

Claims (8)

1. A method for preparing a porous fiber with controllable degradation rate for a tissue engineering scaffold, comprising: The biodegradable polymer and the pore-forming agent are uniformly mixed at a weight percentage of 90-99%: 1-10%, vacuum-dried for 21-48 hours, melt-spun, stretched, and then immersed in hydrochloric acid or distilled water to remove the pores After vacuum drying, porous fibers with micropores with a diameter of 10-100 μm uniformly distributed on the surface are obtained. 2. the preparation method of a kind of porous fiber with controllable degradation rate for tissue engineering scaffold according to claim 1, it is characterized in that: described biodegradable polymer is polyglycolic acid PGA, polylactic acid PLA, polyparaffin Mixture of two or three in a single polymer of dioxanone PDO. 3. The preparation method of a porous fiber with controllable degradation rate for a tissue engineering scaffold according to claim 1, characterized in that: the biodegradable polymer is polyglycolic acid PGA, polylactic acid PLA or polyparaffin Copolymer of dioxanone PDO. 4. The preparation method of a porous fiber with controllable degradation rate for a tissue engineering scaffold according to claim 1, wherein said biodegradable polymer is polyglycolic acid PGA, polylactic acid PLA, polyparaffin A blend of two or three of the polymers of dioxanone PDO. 5. The preparation method of a porous fiber with controllable degradation rate for a tissue engineering scaffold according to claim 4, characterized in that: the molecular weight of the PGA is 100,000 to 150,000, and the molecular weight of the PLA is 100,000 to 150,000 , The molecular weight of PDO is 100,000 to 150,000. 6. The method for preparing a porous fiber with a controllable degradation rate for a tissue engineering scaffold according to claim 4, wherein the biodegradable polymer is GA/LA with a mass ratio of 1 to 99/99 ~1 PGLA. 7. The preparation method of a porous fiber with controllable degradation rate for a tissue engineering scaffold according to claim 1, characterized in that: the pore-forming agent is calcium carbonate or polyvinylpyrrolidone PVP, and the particle size is 10～ 80 μm. 8 . The method for preparing a porous fiber with a controllable degradation rate for tissue engineering scaffolds according to claim 1 , wherein the concentration of the hydrochloric acid is 6%.