CN110301997A - Biomaterial, intravascular stent and wound dressing - Google Patents
Biomaterial, intravascular stent and wound dressing Download PDFInfo
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- CN110301997A CN110301997A CN201810246115.7A CN201810246115A CN110301997A CN 110301997 A CN110301997 A CN 110301997A CN 201810246115 A CN201810246115 A CN 201810246115A CN 110301997 A CN110301997 A CN 110301997A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/02—Adhesive plasters or dressings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
- A61L15/325—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/50—Lubricants; Anti-adhesive agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/044—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/424—Anti-adhesion agents
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Materials Engineering (AREA)
- Biomedical Technology (AREA)
- Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The present invention provides biomaterial, intravascular stent and wound dressings.Wherein, biomaterial includes: substrate；Microstructured layers, the microstructured layers are arranged on a surface of the substrate, and multiple first grooves and multiple second grooves are provided on surface of the microstructured layers far from the substrate, first groove is spaced setting in a first direction, and extend in a second direction, second groove is spaced setting in this second direction, and extends along the first direction；Wherein, the first direction and the second direction intersect, the width of first groove and second groove is less than the size of cell to be attached, and the second spacing between the first spacing and two neighboring second groove between two neighboring first groove is less than the size of the cell to be attached.Inventors have found that above-mentioned microstructured layers can effectively inhibit the adherency and migration of cell, and then achieve the effect that cell or biological tissue is effectively inhibited to infiltrate.
Description
Technical field
The present invention relates to technical field of biological material, specifically, being related to biomaterial, intravascular stent and wound dressing.
Background technique
The phenomenon that biological tissue spreads to surrounding is known as infiltrating, and often betides tumor tissues, inflammation part and placenta and grows
Support layer etc..Many biomaterials utilization during, the damaged tissues of lesions position or as biomaterial intervention caused by
Injury tissue can be attached in biomaterial surface, growth is even spread, and form tissue infiltration.Carrying out intravascular stent implantation and expansion
Zhang Shi, rigid bracket will cause the damage of blood vessel and the destruction of inner membrance, thus a series of inflammatory reactions of bring and blood
The response of pipe reparation stimulates smooth muscle cell in the migration and proliferation of rack surface, and then causes neointimal hyperplasia, causes blood
The restenosis of pipe；In the use process of wound dressing, granulation tissue infiltrates dressing, causes wound adhesion, causes in dressing
Pain even secondary damage.Therefore, it is necessary to be improved to current biomaterial, to inhibit its surface to the energy of tissue infiltration
Power.
Summary of the invention
The present invention is directed to solve at least some of the technical problems in related technologies.For this purpose, of the invention
One purpose is to propose a kind of biomaterial that can effectively inhibit biological tissue to infiltrate.
In one aspect of the invention, the present invention provides a kind of biomaterials.According to an embodiment of the invention, the life
Object material includes: substrate；Microstructured layers, the microstructured layers are arranged on a surface of the substrate, and the micro-structure
Layer is far from multiple first grooves and multiple second grooves are provided on the surface of the substrate, and first groove is in a first direction
Upper interval setting, and extend in a second direction, second groove is spaced setting in this second direction, and along described first
Direction extends；Wherein, the first direction and the second direction intersect, first groove and second groove
Width is less than the size of cell to be attached, the first spacing and two neighboring described second between two neighboring first groove
The second spacing between groove is less than the size of the cell to be attached.Inventors have found that groove in above-mentioned microstructured layers
Be arranged so that microstructured layers have the size less than cell to be attached, the continuity of cell adherence can be destroyed so that cell with
The attaching of biomaterial dies down, the formation of focal adhension when so as to effectively cell be inhibited to be attached on biomaterial, effectively presses down
The adherency and migration of cell processed, and then achieve the effect that cell or biological tissue is effectively inhibited to infiltrate.
According to an embodiment of the invention, between first groove and second groove of arbitrary neighborhood, there are crossover regions
Domain, the spacing between the center of the two neighboring overlapping region are less than the size of cell to be attached.Thus, it is possible to effectively inhibit
The formation of focal adhension when cell is attached on biomaterial, effectively inhibits the adherency and migration of cell, and then reaches effective inhibition
Cell or the effect of biological tissue's infiltration.
According to an embodiment of the invention, the width of first groove or second groove is independent is
500nm-5 μm, first spacing and second spacing it is independent be 100nm-5 μm.Microstructured layers have Asia as a result,
The micro-structure of cell size inhibits the effect of cell adherence and migration preferable, inhibits the effect of cell or biological tissue's infiltration
Preferably.
According to an embodiment of the invention, the width of first groove or second groove is independent is 1 μm-
3μm.Cell filling can be effectively prevented in a groove in the width of the first groove or the second groove within the above range as a result,
And can effectively inhibit the formation of focal adhension, inhibit cell or the effect of biological tissue's infiltration preferable.
According to an embodiment of the invention, the depth of first groove and the second groove is 100nm~20 μm.As a result, may be used
It to effectively prevent cell filling in a groove, and can effectively inhibit the formation of focal adhension, inhibit cell or biological tissue's leaching
The effect of profit is preferable.
According to an embodiment of the invention, the depth of first groove and the second groove is 500nm~20 μm.Press down as a result,
The better effect that focal adhension processed is formed inhibits the better effect of cell or biological tissue's infiltration.
According to an embodiment of the invention, the material for forming the substrate and microstructured layers is independent including metal, pottery
At least one of porcelain, macromolecule.Material source is wider as a result, and cost is relatively low, the biomaterial better quality of formation, uses
Performance is preferable.
According to an embodiment of the invention, the method for forming the microstructured layers includes the self assembly of latex microparticle, etching, sinks
At least one of area method and template.It is simple to operate as a result, it is easy to accomplish.
According to an embodiment of the invention, the biomaterial further include: biocompatible molecules layer, the biocompatible molecules
Layer covers the surface of the microstructured layers far from the substrate.Thus, it is possible to the biocompatibility of the biomaterial is effectively improved,
Effectively reduce the rejection between cell and biomaterial.
According to an embodiment of the invention, the material for forming the biocompatible molecules layer include protein, antibody, polypeptide,
At least one of nucleic acid, synthesis macromolecule.Material source is extensive as a result, can be effectively formed on the surface of microstructured layers, mention
The effect of high biomaterial biocompatibility is preferable, can reduce when the material for forming biocompatible molecules layer is protein non-
The adherency of specific biological molecules, service performance are preferable.
According to an embodiment of the invention, the protein includes fibronectin, collagen, laminin, serum egg
It is at least one of white.The biocompatibility of the biocompatible molecules layer formed as a result, more preferably, reduces non-specific biological molecule
The better effect of adherency.
According to an embodiment of the invention, the antibody includes at least one of people, animal, virus, the antibody of bacterium.By
This, the biocompatibility of the biocompatible molecules layer of formation more preferably, is conducive to repair endodermis.
According to an embodiment of the invention, the nucleic acid include double-stranded DNA segment, single stranded DNA segment, RNA segment at least
One of.The biocompatibility of the biocompatible molecules layer formed as a result, is more preferably.
According to an embodiment of the invention, the synthesis macromolecule include but is not limited to ethylene glycol, polylactic acid, polycaprolactone,
At least one of polyphosphazene.The biocompatibility of the biocompatible molecules layer formed as a result, is more preferably.
In another aspect of this invention, the present invention provides a kind of intravascular stents.According to an embodiment of the invention, the blood
Pipe holder includes mentioned-above biomaterial.Inventors have found that the intravascular stent that is formed by above-mentioned biomaterial and blood vessel
Biocompatibility is preferable, inhibits the effect infiltrated with the vascular tissue of biomaterial contact preferable, and then effectively cell is inhibited to exist
The migration or proliferation on intravascular stent surface effectively avoid In-stent Restenosis, and when in biomaterial including antibody,
Be conducive to repair endodermis, service performance is preferable.
In another aspect of this invention, the present invention provides a kind of wound dressings.According to an embodiment of the invention, the wound
Mouth dressing includes mentioned-above biomaterial.Inventors have found that the wound dressing formed by above-mentioned biomaterial and wound
Tissue biocompatibility it is preferable, inhibit it is preferable with the effect of the tissue infiltration of biomaterial contact, effectively avoid wound glue
Even, pain or secondary damage caused by when and can reduce dressing, service performance are preferable.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of biomaterial in one embodiment of the invention.
Fig. 2 is the sectional view of biomaterial in another embodiment of the present invention.
Fig. 3 is the sectional view of biomaterial in another embodiment of the present invention.
Fig. 4 is the top view of biomaterial in one embodiment of the invention.
Fig. 5 is the structural schematic diagram of biomaterial in another embodiment of the present invention.
Fig. 6 is the atomic force microscopy diagram of the biomaterial in embodiment 1.
Fig. 7 is the micro-image that the in-vitro simulated group of infiltration being woven on biomaterial changes over time in embodiment 1.
Fig. 8 is the in-vitro simulated group of wetting velocity result figure being woven on different biomaterials.
Fig. 9 is the in-vitro simulated group of wetted area result figure being woven on different biomaterials.
Figure 10 is the atomic force microscopy diagram of the biomaterial in embodiment 2.
Figure 11 is the atomic force microscopy diagram of the biomaterial in embodiment 3.
Figure 12 is the micro-image that the in-vitro simulated group of infiltration being woven on biomaterial changes over time in comparative example 1.
Specific embodiment
The embodiment of the present invention is described below in detail.The embodiments described below is exemplary, and is only used for explaining this hair
It is bright, and be not considered as limiting the invention.Particular technique or condition are not specified in embodiment, according to text in the art
It offers described technology or conditions or is carried out according to product description.Reagents or instruments used without specified manufacturer,
For can be with conventional products that are commercially available.
The present invention is following understanding based on inventor and discovery and completes:
Currently, needing to use biomaterial in the treatment of some diseases, biomaterial surface can be produced in some cases
Raw tissue infiltration be it is harmful even cause a disease, such as the tissue infiltration on intravascular stent surface will lead in intravascular stent again
It is narrow, pain or secondary damage when tissue infiltration will cause dressing in the use process of wound dressing.In view of the above technology
Problem, inventor conduct in-depth research, and find after research, and the micro-structure of subcellular scale can destroy the company of cell adherence
Continuous property, makes the attaching of cell and biomaterial die down, to hinder cell migration, and then can reduce histiocytic leaching
Profit, therefore, can adjust cell in bioelectric interface by constructing the micro-structure with subcellular scale in biomaterial surface
Adherency and migratory behaviour.
In view of this, in one aspect of the invention, the present invention provides a kind of biomaterials.Implementation according to the present invention
Example, (wherein, A1 is the top view of biomaterial in Fig. 1, and A2 is sectional view of the A1 along aa ', and A3 is A1 cutting along bb ' referring to Fig.1
Face figure), the biomaterial includes: substrate 100；The substrate 100 is arranged in microstructured layers 200, the microstructured layers 200
Multiple first grooves 210 and more are provided on one surface, and on surface of the microstructured layers 200 far from the substrate 100
A second groove 220, first groove 210 is spaced setting in a first direction, and extends in a second direction, and described second is recessed
Slot 220 is spaced setting in this second direction, and extends along the first direction；Wherein, the first direction and described
Two directions intersect, the width of first groove 210 and second groove 220 and the size less than cell to be attached,
The second spacing between the first spacing and two neighboring second groove 220 between two neighboring first groove 210
Less than the size of the cell to be attached.Inventors have found that the setting of the groove in above-mentioned microstructured layers is so that microstructured layers have
The standby size for being less than cell to be attached, can destroy the continuity of cell adherence, so that the attaching of cell and biomaterial dies down,
The formation of focal adhension when so as to effectively cell be inhibited to be attached on biomaterial effectively inhibits the adherency and migration of cell,
And then achieve the effect that cell or biological tissue is effectively inhibited to infiltrate.
It should be noted that the angle between above-mentioned first direction and second direction arranged in a crossed manner is not particularly limited,
As long as can satisfy requirement, those skilled in the art can flexible choice according to actual needs；First groove or the second groove
Width refer to the first groove or the second groove perpendicular to the maximum width on substrate direction；Implementation according to the present invention
Example, limits lug boss between two neighboring first groove or the second groove, when biological tissue is along the direction parallel with substrate
When laying, the lug boss and contact biological tissue will form contact area, the first spacing between two neighboring first groove or
The second spacing between two neighboring second groove of person refers to that the maximum value of the width of the contact area, the maximum value are less than cell
Scale.It is understood that when lug boss is semicircle perhaps triangle, the first spacing or the second spacing are point, when convex
When the portion of rising is rectangle, the first spacing or the second spacing are rectangular side length.According to an embodiment of the invention, above-mentioned first
The width of groove or the second groove it can be appreciated that between two neighboring lug boss not with the region of contact biological tissue
Width maximum value, and the maximum value be less than cell dimensions.
According to an embodiment of the invention, the micro-structure in microstructured layers can be regularly arranged, it can also be with irregular alignment, only
It can satisfy requirement, those skilled in the art can flexible choice according to actual needs.For example, microstructured layers can be by more
The compositions such as a close-packed arrays or spaced hemispherical, spherical shape, pyramid, terrace with edge or polygon column, first is recessed as a result,
The shape in the section of slot or the second groove can be " people " font of handstand, " V " font, U-shaped, trapezoidal etc..Of the invention
In some embodiments, referring to Fig.1, when microstructured layers are made of multiple hemisphericals closely arranged, the first groove or second recessed
The shape in the section of slot is " people " font to stand upside down.In other embodiments of the invention, referring to Fig. 2, when microstructured layers by
When multiple rectangular pyramid compositions closely arranged, the shape in the section of the first groove or the second groove is " V " font.Of the invention
In other embodiments, referring to Fig. 3, when microstructured layers are made of multiple spaced quadrangulars, the first groove or the
The shape in the section of two grooves is U-shaped.It has the advantages of simple structure and easy realization as a result,.
According to an embodiment of the invention, referring to Fig. 4, first groove 210 and second groove 220 of arbitrary neighborhood
Between there are overlapping region 230, it is two neighboring described overlapping in order to further increase the effect that biomaterial inhibits tissue infiltration
Spacing between the center in region 230 is less than the size of cell to be attached.Thus, it is possible to effectively cell be inhibited to be attached to biological material
The formation of focal adhension when on material, effectively inhibits the adherency and migration of cell, and then reaches and effectively inhibit cell or biological tissue
The effect of infiltration.
It should be noted that when the section of the first groove or the second groove is " people " font or " V " font to stand upside down
Whens equal, the overlapping region between the first groove and the second groove of arbitrary neighborhood in substrate is a point, two neighboring at this time
Spacing between the center of the overlapping region be adjacent intersection point the distance between；When the first groove or the second groove
Section whens being U-shaped or trapezoidal equal, the overlapping region between the first groove and the second groove of arbitrary neighborhood in substrate is
Polygon, the spacing between the center of the overlapping region two neighboring at this time is between the center of two neighboring polygon
Distance.It is understood that the center of the polygon is the regular polygon when above-mentioned polygon is the polygon of rule
The cornerwise intersection point of shape, when above-mentioned polygon is irregular polygon, the midpoint of the polygon is that this is irregular more
While shape it is each while perpendicular bisector intersection point.
According to an embodiment of the invention, in order to achieve the effect that preferably to inhibit tissue infiltration, first groove or
The width of second groove independent is 500nm-5 μm, such as the width of the first groove or the second groove can be each
From being independently 500nm, 700nm, 900nm, 1 μm, 1.5 μm, 2 μm, 2.5 μm, 3 μm, 3.5 μm, 4 μm, 4.5 μm, 5 μm etc.；Institute
It states the first spacing and second spacing is independent for 100nm-5 μm, such as the first spacing and the second spacing can be respective
It is independently 100nm, 150nm, 200nm, 250nm, 300nm, 350nm, 400nm, 450nm, 500nm, 700nm, 900nm, 1 μ
M, 1.5 μm, 2 μm, 2.5 μm, 3 μm, 3.5 μm, 4 μm, 4.5 μm, 5 μm etc..In some currently preferred embodiments of the present invention, described
The width of one groove perhaps second groove independent is 1 μm -3 μm for example described first grooves or described second
The width of groove can independent be 1 μm, 1.2 μm, 1.4 μm, 1.5 μm, 1.6 μm, 1.8 μm, 2 μm, 2.2 μm, 2.4 μm,
2.5 μm, 2.6 μm, 2.8 μm, 3 μm etc..Microstructured layers have the micro-structure of subcellular size as a result, inhibit cell adherence and move
The effect of shifting is preferable, inhibits cell or the effect of biological tissue's infiltration preferable.When the first groove or the width of the second groove
When too small, the aggregation of attachment proteins can not be effectively obstructed, causes the inhibitory effect to adherency and infiltration poor, but be an advantage over not
The effect of biomaterial containing microstructured layers；When the width of the first groove or the second groove is excessive, cell turgidity is not enough to
Overcome gravity, is easy to cause a part filling of cell to form three-dimensional adherency in a groove, but be an advantage over without microstructured layers
The effect of biomaterial；When the first spacing or too small the second spacing, the supporting role of microstructured layers is bad, is easy to cause micro-
The effect that the collapsing of structure sheaf causes biomaterial to inhibit infiltration in turn is poor, but is an advantage over the biomaterial without microstructured layers
Effect；When the first spacing or excessive the second spacing, it can make cell attachment is easy to form in micro-structure surface to stick together
Spot, and then weaken inhibiting effect, but be an advantage over the effect of the biomaterial without microstructured layers.
According to an embodiment of the invention, in order to further suppress tissue infiltration, the depth of first groove and the second groove
Spend it is independent for 100nm~20 μm, such as the first groove and the second groove depth can it is independent for 100nm,
200nm, 400nm, 500nm, 1 μm, 2 μm, 4 μm, 6 μm, 8 μm, 10 μm, 12 μm, 14 μm, 16 μm, 18 μm, 20 μm etc..In this hair
In bright some preferred embodiments, the depth of first groove and the second groove is 500nm~20 μm.Thus, it is possible to effectively
It prevents cell filling in a groove, and can effectively inhibit the formation of focal adhension, inhibit the effect of cell or biological tissue's infiltration
Fruit is preferable.When the depth of the first groove or the second groove is too low, groove is easy to be filled by cell, so as to cause focal adhension
It is formed, inhibits the ineffective of infiltration, but be an advantage over the effect of the biomaterial without microstructured layers；When the first groove or
When the depth of two grooves is excessively high, micro-structure draw ratio is excessive, is easy to cause structural mechanics intensity small, influences making for biomaterial
With.
It should be noted that the depth of the first groove or the second groove refers to the first groove or the second groove vertical
In the maximum value of the depth on the direction of substrate.
According to an embodiment of the invention, the biomaterial for having any of the above-described kind of structure inhibits the principle of tissue infiltration can be with
Are as follows: micro-structure in the microstructured layers of above-mentioned biomaterial is subcellular scale, and the biomaterial for having above-mentioned micro- knot layer can be with
The continuity for destroying cell adherence, makes the attaching of cell and biomaterial die down, is unfavorable for the formation of focal adhension, to hinder
The migration of cell, and then histiocytic infiltration can be reduced.
According to an embodiment of the invention, forming the material of substrate and microstructured layers may be the same or different, as long as energy
It enough meets the requirements, those skilled in the art can flexible choice according to actual needs.According to an embodiment of the invention, described in being formed
The material of substrate and microstructured layers independent includes at least one of metal, ceramics, macromolecule.Material source as a result,
Relatively wide, cost is relatively low, the biomaterial better quality of formation, and service performance is preferable.
According to an embodiment of the invention, the method for forming microstructured layers is not particularly limited, as long as can satisfy requirement, this
Field technical staff can flexible choice according to actual needs.In some embodiments of the invention, the microstructured layers are formed
Method include the self assembly of latex microparticle, etching (including chemical etching, ion etching, photoengraving etc.), sedimentation (including change
At least one of learn vapor deposition, physical vapour deposition (PVD), liquid deposition etc.) and template.It is simple to operate as a result, easily
In realization.In some embodiments of the invention, the methods of mechanical grinding, chemical etching or vapor deposition be can use
The microstructured layers with the micro-structure of irregular alignment are obtained, or can use the formation of latex microparticle self-assembly method to have
The microstructured layers of the micro-structure of sequence arrangement.
According to an embodiment of the invention, referring to Fig. 5, the biomaterial further include: biocompatible molecules layer 300, it is described
Biocompatible molecules layer 300 covers surface of the microstructured layers 200 far from the substrate 100.Thus, it is possible to effectively improve this
The biocompatibility of biomaterial effectively reduces the rejection between cell and biomaterial.
According to an embodiment of the invention, in order to enable the biocompatibility of raising biomaterial, forms the bio-compatible
The material of molecular layer includes at least one of protein, antibody, polypeptide, nucleic acid, synthesis macromolecule.Material source is wide as a result,
It is general, it can be effectively formed on the surface of microstructured layers, the effect of raising biomaterial biocompatibility is preferable, when formation biofacies
The material for holding molecular layer can raise biomolecule or cell with specific function when being antibody, and service performance is preferable.At this
In some specific embodiments of invention, the protein includes fibronectin, collagen, laminin, haemocyanin
At least one.The biocompatibility of the biocompatible molecules layer formed as a result, more preferably, reduces the adherency of non-specific biological molecule
Better effect.In other specific embodiments of the invention, the antibody include people, animal, virus, bacterium antibody extremely
It is one of few.The biocompatibility of the biocompatible molecules layer formed as a result, will include the biomaterial of antibody applied to blood more preferably
In pipe holder, is conducive to endothelial progenitor cells to wound face, accelerates to repair endodermis, to prevent smooth muscle excessive infiltration.At this
Invention other specific embodiments in, the nucleic acid include double-stranded DNA segment, single stranded DNA segment, RNA segment at least it
One.The biocompatibility of the biocompatible molecules layer formed as a result, is more preferably.In other specific embodiments of the invention, institute
Stating synthesis macromolecule includes but is not limited at least one of ethylene glycol, polylactic acid, polycaprolactone, polyphosphazene.The life formed as a result,
The biocompatibility of the compatible molecular layer of object is more preferably.
In another aspect of this invention, the present invention provides a kind of methods for preparing mentioned-above biomaterial.According to
The embodiment of the present invention, the method for preparing above-mentioned biomaterial may include:
S100: the pretreatment of substrate.
According to an embodiment of the invention, substrate is consistent with the description of front, no longer excessively repeat herein.
The pretreated concrete operations of substrate are described so that the material for forming substrate is glass as an example below, need to illustrate
, following methods are merely to illustrate the application, and should not be understood as the limitation to the application:
Sheet glass is cut into required size, is placed in ultrapure water and is cleaned by ultrasonic 20min, is taken out；According to the concentrated sulfuric acid and double
The volume ratio of oxygen water is the ratio of 7:3, and the concentrated sulfuric acid and hydrogen peroxide are added in beaker, obtains Piranha solution, will be ultrasonically treated
Sheet glass afterwards, which is put into 120 DEG C of Piranha solution, impregnates 2h, takes out, and is cleaned by ultrasonic 3 times with ultrapure water.Before use, by glass
Glass piece is dried with nitrogen, and with 200W 5~10min of oxygen plasma treatment, obtains the sheet glass of surface active.
S200: microstructured layers are formed on a surface of substrate.
According to an embodiment of the invention, the microstructured layers are consistent with the description of front, no longer excessively repeat herein.
In some embodiments of the invention, preparing microstructured layers using latex microparticle self-assembly method may include
The preparation of latex microparticle self-assembled film or the fixation of latex microparticle self-assembled film.According to an embodiment of the invention,
In order to enable biomaterial inhibits the effect of tissue infiltration preferable, the latex microparticle self-assembled film of single layer can be prepared.
According to an embodiment of the invention, can also include disappearing to above-mentioned material before forming biocompatible molecules layer
The mode of malicious processing step, the disinfection treatment is not particularly limited, as long as can satisfy requirement, those skilled in the art can be with
Flexible choice is carried out according to actual needs.Such as the mode of disinfection treatment can impregnate for alcohol, ultraviolet illumination or γ are penetrated
One or more of linear light photograph.
S300: biocompatible molecules layer is formed far from the surface of substrate in microstructured layers.
According to an embodiment of the invention, biocompatible molecules layer is consistent with the description of front, no longer excessively repeat herein.Root
According to the embodiment of the present invention, when preparing biocompatible molecules layer, the solution concentration for forming the material of biocompatible molecules layer can
Think 5~100 μ g/ml, the preferably Fibronectin solution of 10 μ g/ml.
According to an embodiment of the invention, in order to enable after the surface of microstructured layers covers one layer of biocompatible molecules layer
The structure of microstructured layers is not destroyed, and the thickness of biocompatible molecules layer is uniform.
In another aspect of this invention, the present invention provides a kind of biomaterials to inhibit the assessment side in tissue infiltration
Method.According to an embodiment of the invention, this method comprises:
1, in-vitro simulated tissue is provided.
According to an embodiment of the invention, the preparation method of in-vitro simulated tissue can be as follows:
The agarose that 2 parts are sterilized is added in 100 parts of water, is completely dissolved with microwave stove heating 2~5 minutes to agarose,
Solution is colorless and transparent.When above-mentioned agarose temperature drops to 50~70 DEG C, take 500 μ l that Sigma-Aldrich is added public
Take charge of the 3D Petri of productionIn (article No.: Z764000-6EA), 5 minutes are stood to the cooling plastic of agarose solution.It takes out
Agarose aquogel is formed, is put into 12 orifice plates, is impregnated 15 minutes, is repeated 2 times with culture medium.Agar syrup is siphoned away with liquid-transfering gun
Culture medium about and within gel.Configuration concentration is 7.5 × 105The Hep G2 cell suspending liquid of/ml takes 190 μ l that fine jade is added
In lipolysaccharide water-setting sealing rubber die, 15 minutes are stood to cell settlement.2ml culture medium is added around agarose again, is put into cell training
It supports and is cultivated 72 hours in case, the in-vitro simulated tissue that diameter is 100~200 μm can be obtained.
It should be noted that above-mentioned culture medium is DMEM complete medium, condition of culture is regular growth culture
Condition no longer excessively repeats herein.
2, in-vitro simulated tissue is planted on biomaterial.
According to an embodiment of the invention, the method for planting in-vitro simulated tissue on biomaterial includes by in-vitro simulated group
It knits and is added on above-mentioned biological coating, stationary culture is for a period of time.Specific method can be as follows:
Simulated tissue is drawn out from agarose aquogel with liquid-transfering gun, and is cleaned 2~3 times with culture medium.It takes out and prepares
Good biomaterial is put into the burnt culture dish of copolymerization.1~2ml simulated tissue suspension is taken to be added in the burnt culture dish of copolymerization.It will
Above-mentioned copolymerization coke culture dish is put into cell incubator and stands 1 hour, and simulated tissue is deposited on material, and with material formed compared with
Weak adherency.
3, the wetting velocity of in-vitro simulated tissue is measured.
According to an embodiment of the invention, the wetting velocity for measuring in-vitro simulated tissue includes that will plant in-vitro simulated tissue
Biomaterial be put into cell and cultivate observation device in real time, observe and record image in real time with microscope, measure wetting velocity.Specifically
, adjusting cell matched with microscope and cultivating observation unit temp in real time is 37 DEG C, and is passed through the CO containing 5%2Gaseous mixture
Body forms stable cell culture environment, keeps 1h.The biomaterial for being stained with simulated tissue is taken out, above-mentioned dress is placed in
In setting, 12 hours are observed in real time with inverted phase contrast microscope, record image, measure wetting velocity.
It should be noted that wetting velocity refers to the ratio that the area in tissue infiltration region is increased speed with initial radium.
Wetting velocity is smaller, indicates that biomaterial inhibits the effect of tissue infiltration better.
Thus, it is possible to judge that biomaterial inhibits tissue infiltration's effect according to the wetting velocity of cell, and this method is grasped
Make simply, conveniently, it is easy to accomplish.
In another aspect of this invention, the present invention provides a kind of intravascular stents.According to an embodiment of the invention, the blood
Pipe holder includes mentioned-above biomaterial.Inventors have found that the intravascular stent that is formed by above-mentioned biomaterial and blood vessel
Biocompatibility is preferable, inhibits the effect infiltrated with the vascular tissue of biomaterial contact preferable, and then effectively cell is inhibited to exist
The migration or proliferation on intravascular stent surface effectively avoid In-stent Restenosis, and when in biomaterial including antibody,
Be conducive to repair endodermis, service performance is preferable.
In another aspect of this invention, the present invention provides a kind of wound dressings.According to an embodiment of the invention, the wound
Mouth dressing includes mentioned-above biomaterial.Inventors have found that the wound dressing formed by above-mentioned biomaterial and wound
Tissue biocompatibility it is preferable, inhibit it is preferable with the effect of the tissue infiltration of biomaterial contact, effectively avoid wound glue
Even, pain or secondary damage caused by when and can reduce dressing, service performance are preferable.
Embodiment
Material used in following embodiment and comparative examples and reagent, if commercially being obtained without specified otherwise.
Calculation method of the biomaterial to the inhibiting rate of tissue infiltration are as follows: group is woven on the biomaterial of microstructured layers
The ratio of wetting velocity on wetting velocity and the biomaterial without microstructured layers.
Embodiment 1
1, the preparation of biomaterial
(1.1) pretreatment of substrate.
Sheet glass is cut into required size, is placed in ultrapure water and is cleaned by ultrasonic 20min, is taken out；According to the concentrated sulfuric acid and double
The volume ratio of oxygen water is the ratio of 7:3, and the concentrated sulfuric acid and hydrogen peroxide are added in beaker, obtains Piranha solution, will be ultrasonically treated
Sheet glass afterwards, which is put into 120 DEG C of Piranha solution, impregnates 2h, takes out, and is cleaned by ultrasonic 3 times with ultrapure water.Before use, by glass
Glass piece is dried with nitrogen, and with 200W 5~10min of oxygen plasma treatment, obtains the sheet glass of surface active.
(1.2) preparation of microstructured layers:
The preparation of (1.2.1) single layer latex beads self-assembled film
Ultrapure water is poured into culture dish.Take the polystyrene microsphere that mass fraction is 30% surface carboxylation suspended
Liquid, ultrasonic disperse 30min.The above-mentioned polystyrene microsphere turbid liquid of 10 μ l is drawn with liquid-transfering gun, is slowly added dropwise several times in water
Layer surface is creamy white until the water surface is covered by whole polystyrene microspheres, and promotes latex micro- by slight shake culture ware
Ball is evenly distributed, monolayer alignment.The Triton X-100 aqueous solution of volume fraction 10% is dipped with copper wire, is put in water surface side,
Polystyrene microsphere is promoted to form close continuous film in the water surface other side.By the glass of surface active described in step (1.1)
Glass oblique cutting enters in water, quickly picks up upwards, and dries in the culture dish edge vertical display for being lined with filter paper, obtains being attached to one layer
The sheet glass of spherical polyethylene microballoon self-assembled film.Spherical polystyrene microsphere diameter used is 1500nm.
The fixation of (1.2.2) latex beads self-assembled film
The hydrochloric acid solution for configuring 0.1M, mixes according to the ratio of volume ratio 1:9 with ethyl alcohol.By above-mentioned hydrochloric acid/ethanol solution
It is mixed according to the ratio of volume ratio 88:12 with ethyl orthosilicate.The 10 above-mentioned solution of μ l are taken slowly to drip in step with liquid-transfering gun
On single layer spherical polyethylene microballoon self-assembled film described in (1.2.1), when film color becomes colorless and transparent, show liquid
Infiltration process has been completed.It is dry in 40 DEG C of temperature, the climatic chamber of humidity 60%, obtain spherical polystyrene microballoon certainly
Assemble coating.
(1.3) preparation of biocompatible molecules layer
Spherical polystyrene microballoon self-assembled coating described in step (1.2.2) is cleaned with medicinal alcohol and to impregnate 1 small
When, after being dried in Biohazard Safety Equipment, with 200W oxygen plasma treatment 5 minutes.By treated, coating is immersed in 10 μ g/ again
4 hours in the Fibronectin solution of ml.It is finally cleaned 3 times with the Tris-HCl buffer solution of 0.05M, be inhibited tissue infiltration
Biological coating.
The biomaterial atomic force microscopy diagram of the present embodiment is found in Fig. 6, it can be seen that microstructured layers have periodically
The ordered structure that height rises and falls.
2, biomaterial is inhibiting the assessment in tissue infiltration
(2.1) in-vitro simulated tissue is provided
The agarose that 2 parts are sterilized is added in 100 parts of water, is completely dissolved with microwave stove heating 2~5 minutes to agarose,
Solution is colorless and transparent.When above-mentioned agarose temperature drops to 50~70 DEG C, take 500 μ l that Sigma-Aldrich is added public
Take charge of the 3D Petri of productionIn (article No.: Z764000-6EA), 5 minutes are stood to the cooling plastic of agarose solution.It takes out
Agarose aquogel is formed, is put into 12 orifice plates, is impregnated 15 minutes, is repeated 2 times with culture medium.Agar syrup is siphoned away with liquid-transfering gun
Culture medium about and within gel.Configuration concentration is 7.5 × 105The Hep G2 cell suspending liquid of/ml takes 190 μ l that fine jade is added
In lipolysaccharide water-setting sealing rubber die, 15 minutes are stood to cell settlement.2ml culture medium is added around agarose again, is put into cell training
It supports and is cultivated 72 hours in case, the in-vitro simulated tissue that diameter is 100~200 μm can be obtained.
(2.2) in-vitro simulated tissue is planted on biomaterial
Simulated tissue is drawn out from agarose aquogel with liquid-transfering gun, and is cleaned 2~3 times with culture medium.It takes out and prepares
Good biomaterial is put into the burnt culture dish of copolymerization.1~2ml simulated tissue suspension is taken to be added in the burnt culture dish of copolymerization.It will
Above-mentioned copolymerization coke culture dish is put into cell incubator and stands 1 hour, and simulated tissue is deposited on material, and with material formed compared with
Weak adherency.
(2.3) wetting velocity of in-vitro simulated tissue is measured
First 1 hour of observation, adjusting cell matched with microscope and cultivating observation unit temp in real time is 37 DEG C, and is passed through and contains
5% CO2Mixed gas, form stable cell culture environment.By the biology for being stained with simulated tissue in step (2.2)
Material takes out, and is placed in above-mentioned apparatus, observes 12 hours in real time with inverted phase contrast microscope, records image, measurement infiltration speed
Degree.
The micro-image of in-vitro simulated tissue infiltration is found in Fig. 7 in the present embodiment, and wetting velocity is found in Fig. 8, infiltration
Area is 48.2% to the inhibiting rate of tissue infiltration referring to Fig. 9, biomaterial.
Embodiment 2
1, the preparation of biomaterial
In the present embodiment, the preparation method is the same as that of Example 1 for biomaterial, the difference is that the preparation method of microstructured layers
Difference, specific as follows:
The preparation of microstructured layers:
(1) preparation of single layer latex beads self-assembled film
Ultrapure water is poured into culture dish.Take the polystyrene microsphere that mass fraction is 25% surface carboxylation suspended
Liquid, ultrasonic disperse 30min.The above-mentioned polystyrene microsphere turbid liquid of 10 μ l is drawn with liquid-transfering gun, is slowly added dropwise several times in water
Layer surface is creamy white until the water surface is covered by whole polystyrene microspheres, and promotes latex micro- by slight shake culture ware
Ball is evenly distributed, monolayer alignment.The Triton X-100 aqueous solution of volume fraction 10% is dipped with copper wire, is put in water surface side,
Polystyrene microsphere is promoted to form close continuous film in the water surface other side.The glass oblique cutting of surface active is entered in water, fastly
Speed picks up upwards, and dries in the culture dish edge vertical display for being lined with filter paper, obtains being attached to one layer of spherical polyethylene microballoon
The sheet glass of self-assembled film.Spherical polystyrene microsphere diameter used is 1000nm.
(2) fixation of latex beads self-assembled film
The hydrochloric acid solution for configuring 0.1M, mixes according to the ratio of volume ratio 1:9 with ethyl alcohol.By above-mentioned hydrochloric acid/ethanol solution
It is mixed according to the ratio of volume ratio 9:1 with ethyl orthosilicate.The 10 above-mentioned solution of μ l are taken slowly to drip with liquid-transfering gun described in step (1)
Single layer spherical polyethylene microballoon self-assembled film on, when film color becomes colorless and transparent, shown liquid penetrate into process
Through completing.It is dry in 40 DEG C of temperature, the climatic chamber of humidity 60%, obtain spherical polystyrene microballoon self-assembled coating.
The atomic force microscopy diagram of the biomaterial of the present embodiment is found in Figure 10, it can be seen that microstructured layers have the period
Property height rise and fall ordered structure.
2, biomaterial is inhibiting the assessment in tissue infiltration
Appraisal procedure of the biomaterial in inhibition tissue infiltration is the same as embodiment 1.
The wetting velocity of in-vitro simulated tissue is found in Fig. 8 in the present embodiment, and wetted area can refer to Fig. 9, biomaterial
Inhibiting rate to tissue infiltration is 23.6%.
Embodiment 3
1, the preparation of biomaterial
In the present embodiment, the preparation method is the same as that of Example 1 for biomaterial, the difference is that the preparation method of microstructured layers
Difference, specific as follows:
The preparation of microstructured layers:
(1) preparation of single layer latex beads self-assembled film
Ultrapure water is poured into culture dish.Take the polystyrene microsphere that mass fraction is 20% surface carboxylation suspended
Liquid, ultrasonic disperse 30min.The above-mentioned polystyrene microsphere turbid liquid of 10 μ l is drawn with liquid-transfering gun, is slowly added dropwise several times in water
Layer surface is creamy white until the water surface is covered by whole polystyrene microspheres, and promotes latex micro- by slight shake culture ware
Ball is evenly distributed, monolayer alignment.The Triton X-100 aqueous solution of volume fraction 10% is dipped with copper wire, is put in water surface side,
Polystyrene microsphere is promoted to form close continuous film in the water surface other side.The glass oblique cutting of surface active is entered in water, fastly
Speed picks up upwards, and dries in the culture dish edge vertical display for being lined with filter paper, obtains being attached to one layer of spherical polyethylene microballoon
The sheet glass of self-assembled film.Spherical polystyrene microsphere diameter used is 500nm.
(2) fixation of latex beads self-assembled film
The hydrochloric acid solution for configuring 0.1M, mixes according to the ratio of volume ratio 1:9 with ethyl alcohol.By above-mentioned hydrochloric acid/ethanol solution
It is mixed according to the ratio of volume ratio 92:8 with ethyl orthosilicate.The 10 above-mentioned solution of μ l are taken slowly to drip in step (1) institute with liquid-transfering gun
On the single layer spherical polyethylene microballoon self-assembled film stated, when film color becomes colorless and transparent, show that liquid penetrates into process
It has completed.It is dry in 40 DEG C of temperature, the climatic chamber of humidity 60%, obtain spherical polystyrene microballoon self assembly painting
Layer.
The atomic force microscopy diagram of the biomaterial of the present embodiment is found in Figure 11, it can be seen that microstructured layers have the period
Property height rise and fall ordered structure.
2, biomaterial is inhibiting the assessment in tissue infiltration
Appraisal procedure of the biomaterial in inhibition tissue infiltration is the same as embodiment 1.
The wetting velocity of in-vitro simulated tissue is found in Fig. 8 in the present embodiment, and wetted area can refer to Fig. 9, biomaterial
Inhibiting rate to tissue infiltration is 4.1%.
Comparative example 1
1, the preparation of biomaterial
In the present embodiment, the preparation of biomaterial is with embodiment 1, the difference is that the biomaterial in the present embodiment is not
Including microstructured layers.
The micro-image of in-vitro simulated tissue infiltration in the present embodiment is found in Figure 12.
2, biomaterial is inhibiting the assessment in tissue infiltration
Appraisal procedure is the same as embodiment 1.
The in-vitro simulated group of wet-out rate for being woven in biomaterial surface in the present embodiment can refer to Fig. 8, and wetted area can
Referring to Fig. 9.
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means specific features, structure, material or spy described in conjunction with this embodiment or example
Point is included at least one embodiment or example of the invention.In the present specification, schematic expression of the above terms are not
It must be directed to identical embodiment or example.Moreover, particular features, structures, materials, or characteristics described can be in office
It can be combined in any suitable manner in one or more embodiment or examples.In addition, without conflicting with each other, the skill of this field
Art personnel can tie the feature of different embodiments or examples described in this specification and different embodiments or examples
It closes and combines.
Although the embodiments of the present invention has been shown and described above, it is to be understood that above-described embodiment is example
Property, it is not considered as limiting the invention, those skilled in the art within the scope of the invention can be to above-mentioned
Embodiment is changed, modifies, replacement and variant.
Claims (10)
1. a kind of biomaterial characterized by comprising
Substrate；
Microstructured layers, the microstructured layers are arranged on a surface of the substrate, and the microstructured layers are far from the base
Multiple first grooves and multiple second grooves are provided on the surface at bottom, first groove is spaced setting in a first direction,
And extend in a second direction, second groove is spaced setting in this second direction, and extends along the first direction；
Wherein, the first direction and the second direction intersect, the width of first groove and second groove
Less than the size of the cell to be attached, the first spacing between two neighboring first groove and two neighboring described second
The second spacing between groove is less than the size of the cell to be attached.
2. biomaterial according to claim 1, which is characterized in that first groove of arbitrary neighborhood and described second
There are overlapping region between groove, the spacing between the center of the two neighboring overlapping region is less than the ruler of cell to be attached
It is very little.
3. biomaterial according to claim 1, which is characterized in that the width of first groove or second groove
Spend it is independent for 500nm-5 μm, first spacing and second spacing it is independent be 100nm-5 μm；
Optional, the width of first groove or second groove independent is 1 μm -3 μm.
4. biomaterial according to claim 1, which is characterized in that the depth of first groove and the second groove is respectively
It is independently 100nm~20 μm；
Preferably, the depth of first groove and the second groove is 500nm~20 μm.
5. biomaterial according to claim 1, which is characterized in that form the material of the substrate and microstructured layers respectively
Independent includes at least one of metal, ceramics, macromolecule.
6. biomaterial according to claim 1, which is characterized in that the method for forming the microstructured layers includes that latex is micro-
At least one of particles self assemble, etching, sedimentation and template.
7. biomaterial according to claim 1, which is characterized in that further include:
Biocompatible molecules layer, the biocompatible molecules layer cover surface of the microstructured layers far from the substrate.
8. biomaterial according to claim 7, which is characterized in that the material for forming the biocompatible molecules layer includes
At least one of protein, antibody, polypeptide, nucleic acid, synthesis macromolecule,
Optional, the protein includes at least one of fibronectin, collagen, laminin, haemocyanin；
Optional, the antibody includes at least one of people, animal, virus, the antibody of bacterium；
Optional, the nucleic acid includes at least one of double-stranded DNA segment, single stranded DNA segment, RNA segment；
Optional, the synthesis macromolecule includes but is not limited at least one of ethylene glycol, polylactic acid, polycaprolactone, polyphosphazene.
9. a kind of intravascular stent, which is characterized in that the intravascular stent includes the described in any item biological materials of claim 1-8
Material.
10. a kind of wound dressing, which is characterized in that the wound dressing includes the described in any item biological materials of claim 1-8
Material.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115192774A (en) * | 2022-07-20 | 2022-10-18 | 四川大学 | Wear-resistant multifunctional cell membrane coating and preparation method thereof |
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