CN109847103B - Artificial blood vessel and preparation method thereof - Google Patents
Artificial blood vessel and preparation method thereof Download PDFInfo
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Abstract
The invention relates to an artificial blood vessel and a preparation method thereof, wherein the artificial blood vessel is of a hollow round tube structure and comprises a base layer, a bonding layer and a bioglass layer which are sequentially connected from inside to outside, wherein the base layer is a styrene-isobutylene block copolymer. The preparation method comprises injection molding, cleaning and drying to form the bonding layer, the bioglass layer and the like. The artificial blood vessel prepared by the invention stably exists in a human body, has good surgical bypass suturing property, is not easy to form thrombus, can be quickly received by human tissues and compatibly form tissue fixation, and has wide application prospect.
Description
Technical Field
The invention relates to the field of medical treatment and health, in particular to an artificial blood vessel and a preparation method thereof.
Background
The development of artificial blood vessels (artiFIcial blood vessels) began in the early part of the last century. When the blood vessel of a certain part of a human body can not ensure normal blood supply of the human body due to arteriosclerosis, embolism or damage and the like, the blood vessel needs to be treated by surgical operations such as replacement, bypass or intervention and the like. At first, autologous blood vessels were used for transplantation, but the source thereof was greatly limited, and for this reason, scientists began to study artificial blood vessels.
Various scholars firstly adopt tubular objects made of metal, glass, polyethylene, silicon rubber and other materials to carry out a large number of animal experiments, but the tubular objects are not widely applied clinically because the tubular objects are easy to cause intracavity thrombus in a short period. Here we briefly introduce the artificial blood vessel materials commonly used at present: in 1952, Voorhees first studied the vascular prosthesis made of vinylon, which was successful in animal experiments and worked clinically in the second year, and changed the impermeability of the vascular wall of the previous vascular prosthesis.
The dacron artificial blood vessel is the earliest used blood vessel material, and is successfully used for replacing a large blood vessel for a long time due to high patency rate, but cannot completely meet the manufacturing requirement of a small-caliber artificial blood vessel. The later developed artificial real silk blood vessel is easy to cause the blood vessel to be shriveled due to the unstable spiral shrinkage, and has poor shape retention and lower strength, thereby limiting the clinical application.
The expanded polytetrafluoroethylene artificial blood vessel has good biocompatibility and anticoagulation, but has poor compliance, the patency rate of the graft is only 30 percent, and particularly, the defects of the ePTFE artificial blood vessel with the diameter less than 6mm are more obvious, and the long-term patency rate is extremely poor.
Polyurethane PU artificial blood vessel material has better biocompatibility than ePTFE, and artificial blood vessels made of PU material are thought to solve the above problems, so it is the direction of current research by many foreign researchers. PU has excellent fatigue resistance, abrasion resistance, high elasticity and high strength, and thus is widely used in the field of biomedical materials. However, the existing PU materials can not meet the high standard of clinical application of artificial blood vessels so far. For example, the PU is found to have aging degradation and calcification phenomena in vivo and cracks or even total damage to the material in the long-term use process. When the material is modified to improve the histocompatibility, the mechanical property and even the blood compatibility of the material are often negatively influenced.
The materials of the artificial blood vessels which are used in large quantity at present are taken from artificial compounds such as polyester fibers, and the like, and the tubes are hard, lack the elasticity like true blood vessels, are easy to generate thrombus, so the diameter cannot be less than 6 mm. Artificial blood vessels of natural silk appear.
Natural mulberry silk, the artificial blood vessel of this kind of silk has adopted the silk through special processing, rolls into the tube-shape with unique knitting technique, and the outside is with other kind of silk and is made the protective layer, prevents the blood and leaks outward, can say that silk and the best combination of weaving technique. The diameter of the silk artificial blood vessel can be 1mm, thrombus is not easy to form, the protein component of the silk artificial blood vessel can be compatible with the internal tissue of the body, and the silk artificial blood vessel is also very practical for the young patients needing to replace the blood vessel. But its durability in use is relatively short, increasing the number of surgeries and the risk of replacement over long periods of time.
Among the original medical materials for in vivo implantation, polyurethanes are most frequently used. The polyurethane has good mechanical processing performance and biocompatibility, but fragments formed by the uncontrollable degradation of the polyurethane in vivo continuously attract granulocytes, macrophages, leukocytes and giant cells of foreign bodies to diffuse to the implanted material. The fragmented material is degraded by film-forming encapsulation and phagocytosis of the fragments. Thereby forming a blockage around and on the surface of the implant and potentially risking accelerated degradation of the implant. Similarly, silica gel implants degrade in acidic environments with low pH, and polytetrafluoroethylene materials face the same problems.
Bioglass (Bioglass) is a Na-Ca-Si series glass which can generate a series of special surface reactions with biological environment after being implanted into a human body, so that the material and natural tissues form firm chemical bonds to be combined and have biological activity. The Bioglass generation generally refers to bioactive glass of composition 45S 5. Bioglass has become the interdiscipline of material science, biochemistry and molecular biology at present, and because bioglass has the characteristics of bioactivity and the like, the bioglass has considerable application prospects in the aspects of tissue engineering scaffold materials, orthopedics, dentistry, middle ear, cancer treatment, drug carriers and the like, and mainly has the following characteristics:
1. application of bioglass in dental treatment
Bioglass has been used in clinical repair of bone, articular cartilage, skin and vascular injuries since 1985. The artificial middle ear bone MEP is the earliest product of bioglass material, can be connected with soft tissue (eardrum) and bone, and has better clinical results than other bioceramic and metal materials. The second generation bioglass material ERMI can be used for filling the vacancy of the tooth root and avoiding the atrophy of the gum. The ERMI is tightly connected to the gum bone and has a better therapeutic effect than other materials for preventing gum atrophy. The third generation biological glass material early product PerioGlas is mainly used for bone defect reconstruction caused by periodontal diseases and local filling after tooth extraction. Long-term clinical research shows that the PerioGlas has good clinical effect and no adverse reaction to human bodies. Bioglass containing 50% phosphoric acid can be used for treating dentin hypersensitivity and early enamel caries. The reason is that when the bioactive glass particles are implanted into the medullary cavity perforation and contacted with blood and alveolar bone tissues, complex ion exchange can be generated between the bioactive glass particles and the tissues instantly, a silicon-rich gel layer is formed on the surface of the bioglass and is aggregated to form a carbonic acid hydroxyapatite layer, and the bioactive glass particles are rapidly formed through a calcium-phosphorus layer and deposited in the periodontal tissues in the perforation area and are finally calcified to form cementum and new attachment of periodontal. Bakry et al research on bioglass containing 50% phosphoric acid shows that the bioglass is good in biocompatibility and is a safe biological material.
2. Application of bioglass in bone repair
After the biological glass has good clinical effect in preventing and treating dental diseases, the biological glass is also applied to orthopedics immediately, and the product has the function of skeleton growth (NovaBone). The bioglass has poor mechanical strength and is mainly used for repairing bone defects of non-bearing parts. The bioglass surface can generate a series of chemical reactions in the physiological environment of a human body and can directly participate in the metabolism and repair process of human bone tissues, and finally inorganic mineral components, namely hydroxyapatite carbonate (HA) CO (2OH) (PO- [ CaO-23-6410) which are the same as the human body can be formed on the surface of the bioglass material, and the growth of the bone tissues is induced, so the bioglass surface can be used for filling and repairing human bone defects. The America and the like report that biological glass and autologous iliac crest bone transplantation are respectively adopted in posterior spinal fusion orthopedics of adolescent idiopathic scoliosis patients, and the fact that the clinical effect of a biological glass group is the same as that of an autologous iliac crest bone transplantation group and the complication caused by the autologous iliac crest bone transplantation can be reduced is found in the postoperative average follow-up visit of 34.7 months (the shortest 24 months). Seddighi et al reported the use of titanium mesh filled with bioglass and autologous bone in cervical spondylopathy anterior fusion, and the average follow-up of 14.3 months showed spinal fusion rates that were substantially the same as those of titanium mesh filled with autologous bone alone.
3. Application of bioglass in drug carriers
Drug therapy carriers are also one of the most promising applications of bioglass. Various medicines are stored in the porous bioglass and then implanted into relevant key parts of a human body, and the medicines are released along with the progress of the surface reaction of the bioglass, so that the aim of treating diseases in a targeted way is fulfilled.
4. Application of bioglass in wound healing
The use of bioactive glass to promote wound healing is also a research direction today. Some patents at home and abroad are concerned with this. For example, U.S. d.c. grinspan et al, in its patent, describes a tissue for accelerating wound and burn healing, which contains active glass. The mechanism of accelerating the promotion of wound healing of the bioactive glass is as follows: when the material is implanted into a human body, ions with high activity such as Na, 2Ca and the like are firstly dissolved out under the action of body fluid, H in the body fluid enters the surface of glass to form Si-OH, then a random network is dissolved due to the damage of Si-O-Si bonds, soluble silicon is released in the form of silanol, and a hydroxyapatite cementing layer is quickly formed on the surface of a material body. The soluble silicon has the metabolism and structural action of molecular level connective tissue, after the bioglass is dissolved, the increase of local Si concentration can promote the internal response of cells of cell metabolism, stimulate the autocrine reaction of the factor for promoting wound healing, accelerate the growth and division of all the cells participating in wound healing under the stimulation of the factor for promoting wound healing, and gather in the hydroxyapatite cementing layer formed on the surface of the material, so that the new tissue can smoothly creep and cover the whole wound surface.
The Chinese patent application CN109009561A discloses an artificial blood vessel and a preparation method thereof, which comprises a blood vessel stent and inoculated cells, wherein the blood vessel stent sequentially comprises an inner layer stent, an intermediate layer stent and an outer layer stent which are tightly connected, and the inner layer stent is a layer of porous fiber tubular structure consisting of polyethylene glycol succinate and anticoagulant; the middle layer bracket is a layer of porous fiber round tubular structure consisting of hydrogel materials, biological ceramic materials (such as biological glass) and growth factors, and the seeded cells are adhered and filled in pores of the middle layer bracket; the outer layer bracket is a layer of porous fiber round tubular structure formed by poly butylene succinate. Such vessels still do not address the degradation and occlusion issues.
Disclosure of Invention
The invention aims to solve the problem that the conventional artificial blood vessel is degraded in a human body to generate various adverse reactions, and provides an artificial blood vessel and a preparation method thereof. The artificial blood vessel of the invention utilizes tertiary carbon type copolymer with extremely high chemical stability and biological stability to manufacture the artificial blood vessel, and combines with biological glass with unique structure to achieve the high biological safety and high biological compatibility of the product, thereby forming a novel artificial blood vessel which is physically and chemically stable, has good surgical bridging and suturing properties, is not easy to form thrombus, can be quickly accepted by human tissues and can be compatibly formed into tissue fixation and other products for replacing the structure of the body lumen.
The choice of substrate material is critical to vascular prostheses. The main reason for the limited application of artificial blood vessels is the biocompatibility of artificial blood vessel materials, and the anti-aging capacity must be considered. Among the materials approved in the medical field at present, materials with good biocompatibility are more, but reliable materials with aging resistance and in-vivo degradation, fracture and damage resistance are not easy to find. This biological or chemical degradation is derived from free radical attack in the body and the chain reaction initiated. The inventor selects a styrene-isobutylene block copolymer (SIBS) according to the generation mechanism of free radicals and the mechanism of polymers, and the structural formula of the SIBS is shown as follows.
SIBS is a copolymer of isobutylene and styrene whose tertiary carbon structure naturally blocks the formation of free radicals, and in the polymer structure there are no chemical bonds that can be degraded: ether bonds (C-O-C), ester bonds (O-CO-C), amides (N-CO-C), amino acid esters (N-CO-O), urea bonds (N-CO-N), carbonates (O-CO-O), single bonds (C-C), double bonds (C ═ C-C), thus avoiding in vivo degradation of SIBS polymers and subsequent in vivo stress. There was no visible cracking or molecular weight loss after two years of SIBS implantation in vivo, regardless of microscopic slice observation and molecular weight re-determination. The polyisobutylene does not contain any of the above labile bonds, and more preferably, a dimethyl group is present on every other carbon, which prevents oxidation of the backbone to form double bonds. Many polyolefins, such as polyethylene and polypropylene propane, the presence of double bonds in the polymer backbone leads to embrittlement, low flex fatigue life and degradation. The conversion of polyisobutenes to elastomers requires crosslinking with permanent or fusible pseudo-crosslinks. To process the material into a moldable or extrudable medical device, a SIBS polymer is formed that combines non-degradable, plastic properties by incorporating polystyrene into both ends of a polyisobutylene central block to bind amorphous (elastomeric/rubbery) polyisobutylene segments together. The current application of SIBS to glaucoma shunt and paclitaxel in vivo delivery vehicles has proven to be very safe, and the inventors first attempted to apply SIBS materials to a wider range of vascular prosthesis fields.
The proportion of the polystyrene block in the styrene-isobutylene block copolymer as the base layer is 10 to 30% by weight, and outside this range, the rigidity of the blood vessel is affected, and 20% by weight is preferable.
Although SIBS has various advantages, it is not well compatible with the human body, for example, it cannot form a stable connection with the blood vessels of the human body to which it is connected, and thus cannot achieve a satisfactory bridging effect. For this reason, the inventor selects bioglass as an intermediate medium to combine the implanted blood vessel and human tissue safely and perfectly.
The thickness of the bioglass layer is 50-250 μm, and is determined according to the position of the blood vessel and the size of bioglass particles. The bioglass particles are selected from five of 50 μm, 100 μm, 150 μm, 200 μm and 250 μm. The applicable range is adjusted according to the implanted area of the human body and the size of the vessel diameter.
The specific scheme is as follows:
the artificial blood vessel is of a hollow round tube structure and comprises a base layer, a bonding layer and a bioglass layer which are sequentially connected from inside to outside, wherein the base layer is a styrene-isobutylene block copolymer.
Further, the polystyrene block proportion in the base layer is 10 to 30 wt%.
Further, the adhesive layer is a SILASTIC adhesive series, preferably dow corning SILASTIC.
Further, the bioglass layer is a thin layer formed by bioactive glass 45S5, and the particle diameter of the bioactive glass 45S5 is 50-720 mu m.
Furthermore, the inner diameter of the base layer is 4mm-15mm, and the thickness of the base layer is 0.5mm-2 mm.
Further, the thickness of the bonding layer is 50-100 μm.
The invention also provides a preparation method of the artificial blood vessel, which comprises the following steps:
step 1: injecting the styrene-isobutylene segmented copolymer into a blood vessel by using an injection molding machine at the temperature of 180 ℃ and 240 ℃, wherein the inner diameter is 4mm-15mm, and the thickness is 0.5mm-2 mm;
step 2: sequentially cleaning the blood vessel injection-molded in the step 1 with acetone and ethanol, and drying;
and step 3: sleeving the dried blood vessel in the step 2 on one end of a stainless steel rod with the diameter equal to the inner diameter of the blood vessel, fixing the other end of the stainless steel rod on a rotary stirring head, and coating a layer of silica gel adhesive on the surface of the blood vessel by means of the rotation of the rotary stirring head to form a bonding layer;
and 4, step 4: spreading the bioglass powder in a clean polytetrafluoroethylene disc, enabling blood vessels containing bonding layers to roll in the bioglass powder, uniformly adhering the bioglass powder, and vibrating the blood vessels to remove loose and unfixed bioglass powder on the surface;
and 5: drying the blood vessel coated with the bioglass powder at normal temperature for 12-20 hours to obtain the artificial blood vessel.
Further, the step 1 comprises: 1a, selecting a single-vertical or double-vertical injection molding machine, firstly filling the styrene-isobutylene segmented copolymer at the temperature of 180-; 1b, carrying out pressure maintaining treatment, continuously applying pressure of 1000-2000psi, compacting the melt, and increasing the melt density to compensate the shrinkage of the melt in a cooling stage; 1c, cooling by water or air, and demolding after the product is cooled and solidified to be proper in rigidity so as to avoid deformation of the product caused by external force, wherein organic siloxane is preferably used as the demolding agent.
Further, the step 2 comprises: 2a, immersing the blood vessel injection-molded in the step 1 into acetone to ensure that the inside and the outside of the vessel wall are completely immersed into the acetone, and stirring for 20-40 seconds by using a glass rod to remove impurities and release agents adhered to the surface of the blood vessel in the injection molding process; 2b, taking out the blood vessel, placing the blood vessel in a clean beaker, adding ethanol to immerse the inner wall and the outer wall of the vessel in the ethanol, stirring the mixture for 30 seconds by using a glass rod, and cleaning the blood vessel by using the ethanol; 2c finally, the washed blood vessels are taken out and placed in a clean glass dish, and are dried for 0.5 to 1.5 hours at room temperature, and then are dried for 1 to 3 hours in a vacuum oven at the temperature of between 38 and 42 ℃.
Further, the rotation speed of the rotary stirring head in the step 3 is 15-20rpm, and the thickness of the formed bonding layer is 50-100 μm.
Has the advantages that:
the artificial blood vessel combines the safety characteristic of the long-term implantation of the SIBS with the excellent biological performance of the bioglass, and is suitable for short-term implantation into blood vessels and long-term implantation as well. The artificial blood vessel guides peripheral tissues of the artificial blood vessel to gather towards the blood vessel wall, and the formation of a normal microenvironment similar to the body is particularly important. The formation of a gap between the artificial tube wall and the muscle tissue can be avoided, and effusion is avoided. Similarly, the guiding tissue and the blood vessel wall can be fused with each other to fix the blood vessel wall and maintain normal infiltration and tissue metabolism.
In addition, the preparation method of the artificial blood vessel provided by the invention utilizes an injection molding machine to prepare the blood vessel base layer, the inner diameter is 4mm-15mm, the thickness is 0.5mm-2mm, and the artificial blood vessel base layer has a stable structure and wide applicability.
Furthermore, the preparation method of the artificial blood vessel skillfully realizes the formation of the bonding layer and the bioglass layer by means of the stainless steel bar and the rotary stirring head, and has convenient operation.
In a word, the artificial blood vessel prepared by the invention stably exists in a human body, has good surgical bypass suturing property, is not easy to form thrombus, can be quickly received by human tissues and can be compatibly used for forming tissue fixation, thereby having wide application prospect.
Drawings
In order to illustrate the technical solution of the present invention more clearly, the drawings will be briefly described below, and it is apparent that the drawings in the following description relate only to some embodiments of the present invention and are not intended to limit the present invention.
Fig. 1 is a schematic cross-sectional view of a vascular prosthesis according to an embodiment 1 of the present invention.
Detailed Description
Preferred embodiments of the present invention will be described in more detail below. While the following describes preferred embodiments of the present invention, it should be understood that the present invention may be embodied in various forms and should not be limited by the embodiments set forth herein. The examples do not specify particular techniques or conditions, and are performed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available. In the following examples, "%" means weight percent, unless otherwise specified.
The following main reagents were used:
SIBS 102T-FD has a molecular weight of 10,000 daltons and a polystyrene block proportion of 20%. Other SIBS lot numbers that can be used are: 062A, 062M, 062H, 062T, 072T, 073T, 102T, 103T, 103T-FD, 102T-FC, 103T-FC. The product is Kaneka North America LLC product.
Biological glass: 45S5Bioglass, particle diameter ranges are applicable: a,50-300 μm; or B, 300-500 μm; or C, 500-720 μm.
Adhesive agent: dow Corning Silastic, Medical Adhesive Type A. The same series of SILASTIC adhesives can be used, but dow corning SILASTIC has the best effect on the coupling of SIBS and bioglass.
Example 1
Referring to fig. 1, the artificial blood vessel is a hollow circular tube structure, and is composed of a base layer 1, a bonding layer 2 and a Bioglass layer 3 which are sequentially connected from inside to outside, wherein the base layer 1 is a styrene-isobutylene block copolymer, the polystyrene block proportion is 20 wt%, the inner diameter is 4mm, the thickness is 1.6mm, the bonding layer 2 is a dow corning SILASTIC thin layer, the thickness is 60 μm, and the Bioglass layer 3 is a thin layer formed by adsorbing 45S5Bioglass (particle diameter is 50-300 μm) on the surface of the bonding layer 2.
The artificial blood vessel stably exists in a human body, has good surgical bridging and suturing properties, is not easy to form thrombus, can be quickly accommodated by human tissues and can be compatibly formed into tissue fixation, and has wide application prospect.
Example 2
An artificial blood vessel is a hollow circular tube structure and consists of a base layer 1, an adhesive layer 2 and a biological glass layer 3 which are sequentially connected from inside to outside, wherein the base layer 1 is a styrene-isobutylene block copolymer, the polystyrene block proportion is 15 wt%, the inner diameter is 10mm, the thickness is 1mm, the adhesive layer 2 is a Dow Corning SILASTIC thin layer, the thickness is 70 mu m, and the biological glass layer 3 is a thin layer formed by adsorbing 45S5Bioglass (the particle diameter is 300-500 mu m) on the surface of the adhesive layer 2.
Example 3
An artificial blood vessel is a hollow circular tube structure and consists of a base layer 1, an adhesive layer 2 and a biological glass layer 3 which are sequentially connected from inside to outside, wherein the base layer 1 is a styrene-isobutylene block copolymer, the polystyrene block proportion is 25 wt%, the inner diameter is 12mm, the thickness is 0.8mm, the adhesive layer 2 is a Dow Corning SILASTIC thin layer, the thickness is 80 mu m, and the biological glass layer 3 is a thin layer formed by adsorbing 45S5Bioglass (the particle diameter is 500-720 mu m) on the surface of the adhesive layer 2.
Example 4
An artificial blood vessel is a hollow circular tube structure and comprises a base layer 1, a bonding layer 2 and a Bioglass layer 3 which are sequentially connected from inside to outside, wherein the base layer 1 is a styrene-isobutylene block copolymer, the proportion of a polystyrene block is 18 wt%, the inner diameter is 15mm, the thickness is 0.5mm, the bonding layer 2 is a Dow Corning SILASTIC thin layer, the thickness is 100 mu m, and the Bioglass layer 3 is a thin layer formed by adsorbing 45S5Bioglass (the particle diameter is 50-300 mu m) on the surface of the bonding layer 2.
Example 5
An artificial blood vessel is a hollow circular tube structure and is composed of a base layer 1, an adhesive layer 2 and a Bioglass layer 3 which are sequentially connected from inside to outside, wherein the base layer 1 is a styrene-isobutylene block copolymer, the proportion of polystyrene blocks is 20 wt%, the inner diameter is 8mm, the thickness is 2mm, the adhesive layer 2 is SILASTIC adhesive series silica gel adhesive, the thickness is 50 mu m, and the Bioglass layer 3 is a thin layer formed by adsorbing 45S5Bioglass (the particle diameter is 500-720 mu m) on the surface of the adhesive layer 2.
Example 6
Preparing the artificial blood vessel by the following steps:
step 1: and (3) injection molding of the SIBS.
Selecting a single-vertical-face or double-vertical-face injection molding machine, and selecting the injection molding temperature according to different materials, wherein the range is 180-240 ℃. Filling is the first step in the overall injection cycle, from the time the mold is closed to start injection until the mold cavity is filled to about 95% by volume.
Then, the pressure is maintained, the pressure is continuously applied, the melt is compacted, and the density of the plastic is increased (densified) to compensate the shrinkage of the plastic, wherein the pressure is 1000-2000 psi.
Finally, cooling is carried out, and in an injection molding mold, the design of a cooling system is very important. The reason is that the formed plastic product can not be deformed due to external force after being demoulded until the formed plastic product is cooled and solidified to certain rigidity. The cooling is preferably both water-cooled and air-cooled. Some products use organosiloxanes as release agents during the release process.
Parameters of a finished product: the inner diameter is 4mm-15mm, and the wall thickness of the blood vessel is 0.5mm-2 mm.
Step 2: and (3) immersing the injection-molded SIBS blood vessel finished product into acetone to ensure that the inside and the outside of the vessel wall are completely immersed into the acetone, and cleaning impurities, release agents and other components possibly adhered to the surface of the blood vessel in the injection molding process. Stir with a glass rod for 30 seconds and remove the vessel into a clean beaker. Adding ethanol to immerse the inner and outer walls of the vessel wall in the ethanol, and cleaning the blood vessel with the ethanol. Stir with a glass rod for 30 seconds and remove the washed vessel into a clean glass dish. The washed SIBS vessels were dried at room temperature for 1 hour and then dried in a vacuum oven at 40 ℃ for 2 hours. The advantages of drying at room temperature and then vacuum heating compared with direct heating are reduced heating time, avoiding the possibility of thermal instability of the polymer and saving production energy.
And step 3: sleeving the dried blood vessel in the step 2 on one end of a stainless steel rod with the diameter equal to the inner diameter of the blood vessel, fixing the other end of the stainless steel rod on a rotary stirring head, and coating a layer of silica gel adhesive on the surface of the blood vessel by means of the rotation of the rotary stirring head at a low rotation speed (15-20rpm) to form a bonding layer with the thickness of 50-100 microns.
And 4, step 4: spreading the bioglass powder in a clean polytetrafluoroethylene disc, enabling blood vessels containing bonding layers to roll in the bioglass powder, uniformly adhering the bioglass powder, and vibrating the blood vessels to remove loose and unfixed bioglass powder on the surface;
and 5: drying the blood vessel coated with the bioglass powder at normal temperature for 12-20 hours to obtain the artificial blood vessel. Completely drying, and placing in a sterilizing bag for later use.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various features described in the above embodiments may be combined in any suitable manner without departing from the scope of the invention. The invention is not described in detail in order to avoid unnecessary repetition.
In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as it does not depart from the spirit of the present invention.
Claims (11)
1. The utility model provides an artificial blood vessel, is hollow pipe structure which characterized in that: the artificial blood vessel comprises a base layer, a bonding layer and a bioglass layer which are sequentially connected from inside to outside, wherein the base layer is a styrene-isobutylene block copolymer, the proportion of a polystyrene block in the base layer is 10-30 wt%, and the structural formula of the styrene-isobutylene block copolymer is as follows:
2. the vascular prosthesis of claim 1, wherein: the adhesive layer is SILASTIC adhesive series silica gel adhesive.
3. The vascular prosthesis of claim 2, wherein: the adhesive layer is Dow Corning SILASTIC.
4. The vascular prosthesis of claim 1, wherein: the bioglass layer is a thin layer formed by bioactive glass 45S5, and the particle diameter of the bioactive glass 45S5 is 50-720 mu m.
5. The vascular prosthesis of any one of claims 1-4, wherein: the inner diameter of the base layer is 4mm-15mm, and the thickness is 0.5mm-2 mm.
6. The vascular prosthesis of claim 5, wherein: the thickness of the bonding layer is 50-100 μm.
7. The method for preparing the artificial blood vessel of any one of claims 1 to 6, comprising the steps of:
step 1: injecting the styrene-isobutylene segmented copolymer into a blood vessel by using an injection molding machine at the temperature of 180 ℃ and 240 ℃, wherein the inner diameter is 4mm-15mm, and the thickness is 0.5mm-2 mm;
step 2: sequentially cleaning the blood vessel injection-molded in the step 1 with acetone and ethanol, and drying;
and step 3: sleeving the dried blood vessel in the step 2 on one end of a stainless steel rod with the diameter equal to the inner diameter of the blood vessel, fixing the other end of the stainless steel rod on a rotary stirring head, and coating a layer of silica gel adhesive on the surface of the blood vessel by means of the rotation of the rotary stirring head to form a bonding layer;
and 4, step 4: spreading the bioglass powder in a clean polytetrafluoroethylene disc, enabling blood vessels containing bonding layers to roll in the bioglass powder, uniformly adhering the bioglass powder, and vibrating the blood vessels to remove loose and unfixed bioglass powder on the surface;
and 5: drying the blood vessel coated with the bioglass powder at normal temperature for 12-20 hours to obtain the artificial blood vessel.
8. The method for producing an artificial blood vessel according to claim 7, wherein: the step 1 comprises the following steps: 1a, selecting a single-vertical or double-vertical injection molding machine, firstly filling the styrene-isobutylene segmented copolymer at the temperature of 180-; 1b, carrying out pressure maintaining treatment, continuously applying pressure of 1000-2000psi, compacting the melt, and increasing the melt density to compensate the shrinkage of the melt in a cooling stage; 1c, cooling by water or air, and demolding after the product is cooled and solidified to proper rigidity so as to avoid deformation of the product caused by external force.
9. The method for producing an artificial blood vessel according to claim 8, wherein: the release agent used was organosiloxane.
10. The method for producing an artificial blood vessel according to claim 7, wherein: the step 2 comprises the following steps: 2a, immersing the blood vessel injection-molded in the step 1 into acetone to ensure that the inside and the outside of the vessel wall are completely immersed into the acetone, and stirring for 20-40 seconds by using a glass rod to remove impurities and release agents adhered to the surface of the blood vessel in the injection molding process; 2b, taking out the blood vessel, placing the blood vessel in a clean beaker, adding ethanol to immerse the inner wall and the outer wall of the vessel in the ethanol, stirring the mixture for 30 seconds by using a glass rod, and cleaning the blood vessel by using the ethanol; 2C finally, the washed blood vessels are taken out and placed in a clean glass dish, and are dried for 0.5 to 1.5 hours at room temperature, and then are dried for 1 to 3 hours at 38 to 42 ℃ in a vacuum oven.
11. The method for producing an artificial blood vessel according to claim 7, wherein: in the step 3, the rotating speed of the rotating stirring head is 15-20rpm, and the thickness of the formed bonding layer is 50-100 mu m.
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