阅读说明：本技术 一种用于4d打印的生物可降解体温感应材料和可降解体温感应记忆生物支架的制备方法 (A kind of preparation method for remembering biological support for the biodegradable body temperature inductive material of 4D printing and the induction of degradable body temperature ) 是由 李兴建 于 2019-09-11 设计创作，主要内容包括：本发明公开了一种用于4D打印的生物可降解体温感应材料和可降解体温感应记忆生物支架的制备方法,材料制备方法包括步骤：以末端为羟基的生物可降解高分子为主体,制备末端为巯基或降冰片烯基的多组分生物可降解高分子；生物支架的制备方法包括步骤：多官能团巯基小分子或降冰片烯小分子与生物可降解体温感应材料通过4D打印发生降冰片烯-巯基光聚合反应得到生物支架；将生物支架加热到熔点温度或玻璃化温度以上并沿着直径方向压缩降低尺寸,然后在零度附近固定临时形状,即得可降解体温感应记忆生物支架。本发明具备打印速度快、无氧阻聚和无收缩性的特点,具有热转变峰宽狭窄、回复速度快、回复温度精确、兼顾可控的降解速率等优势。(The invention discloses the preparation methods of a kind of biodegradable body temperature inductive material for 4D printing and degradable body temperature induction memory biological support, material preparation method is comprising steps of using end as based on the Biodegradable high-molecular of hydroxyl, preparation end is the multicomponent biodegradable macromolecule of sulfydryl or norbornene；The preparation method of biological support is comprising steps of polyfunctional group sulfydryl small molecule or norbornene small molecule and biodegradable body temperature inductive material print generation norbornene-sulfydryl photopolymerization reaction by 4D and obtain biological support；Biological support is heated to melting temperature or glass transition temperature or more and diametrically compression reduction size, then incudes memory biological support in the fixed temporary shapes of near zero to get degradable body temperature.The present invention have print speed it is fast, without oxygen inhibition and the characteristics of shrinkage-void, have that heat deflection peak width is narrow, it is fast to reply speed, recovery temperature is accurate, takes into account the advantages such as controllable degradation rate.)

1. a kind of preparation method of the biodegradable body temperature inductive material for 4D printing, it is characterised in that: comprising steps of with Based on the Biodegradable high-molecular that physiological temp lower end is hydroxyl, by the processing of body ends sealing endization, preparation The multicomponent biodegradable macromolecule that the degradable, end under physiological temp is sulfydryl or norbornene is obtained, is made Biodegradable body temperature inductive material for 4D printing uses.

2. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 1, Be characterized in that: the glass transition temperature or melting temperature of the main body are 20 DEG C -40 DEG C.

3. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 2, Be characterized in that: the preparation method of the main body includes: with D, and L- lactide or caprolactone are main monomer；L- lactide, caprolactone, One of glycolide, cyclic acid anhydride, cyclic carbonate ester, cyclic phosphorus or Lanthanum Isopropoxide are a variety of as comonomer；Through being catalyzed Copolymerization obtains multicomponent copolymer after agent, initiator effect.

4. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 3, Be characterized in that: the initiator is dihydroxylic compound, multi-hydroxy compound or oligomer.

5. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 3, Be characterized in that: the initiator is ethylene glycol, pentaerythrite, small molecule polyhydroxy-alcohol, oligomeric two arms polyethylene glycol, the poly- second of multi-arm Glycol, oligomeric two arms polycaprolactone polyol, multi-arm polycaprolactone polyol, oligomeric two arms polyether polyol, three arm polyethers are more First alcohol, cyclodextrin or sugar alcohol.

6. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 3, Be characterized in that: the catalyst is stannous octoate.

7. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 6, Be characterized in that: when the main body that preparation glass transition temperature is 20 DEG C -40 DEG C, the main monomer of use and the mass fraction of comonomer are pressed It is determined according to formula (1):

T_gBased on glass transition temperature；T_g1、T_g2…T_gnThe segment glass transition temperature of respectively each monomer for participating in reaction；n For the positive integer more than or equal to 2；W₁、W₂…W_nRespectively each monomer for participating in reaction accounts for the mass fraction of all monomers.

8. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 7, Be characterized in that: when the main body that preparation glass transition temperature is 20 DEG C -40 DEG C, the mole of initiator accounts for all monomer integral molar quantities 0.02mol%.

9. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 8, Be characterized in that: the molecular weight for the main body that the glass transition temperature is 20 DEG C -40 DEG C is 400-2000.

10. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 6, Be characterized in that: when preparing the main body that fusing point is 20 DEG C -40 DEG C, the molar ratio of initiator and each monomer is 20 according to the fusing point The molecular weight of DEG C -40 DEG C of main body determines.

11. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 10, It is characterized by: initiator amount is the 0.1wt% of the gross weight of all monomers when preparing the main body that fusing point is 30 DEG C -40 DEG C；It is main The molecular weight of body is 1000-4000.

12. a kind of biodegradable body temperature inductive material for 4D printing described in -11 any one according to claim 1 Preparation method, which is characterized in that the body ends sealing endization processing is norbornene termination process, the norbornene Termination process is comprising steps of it is drop ice that main body, norbornene acyl chlorides and triethylamine solvent, which are mixed reaction end is prepared, The multicomponent biodegradable macromolecule of piece alkenyl.

13. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 12, It is characterized in that, the solvent is methylene chloride；The molar ratio of the norbornene acyl chlorides, triethylamine and main body hydroxyl is 1.2: 1.2:1；Reaction time is 48h；Reaction temperature is room temperature.

14. a kind of biodegradable body temperature inductive material for 4D printing described in -11 any one according to claim 1 Preparation method, which is characterized in that the body ends sealing endization processing is sulfydryl termination process, and the sulfydryl termination process includes Step: by main body, thioacetic acid, catalysts and solvents, back flow reaction obtains the multicomponent biological that end is sulfydryl under nitrogen atmosphere Degradable macromolecule.

15. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 14, It is characterized in that, the hydroxyl of the main body and the molar ratio of thioacetic acid are 1:10 in the body ends sealing endization processing.

16. a kind of preparation method of biodegradable body temperature inductive material for 4D printing according to claim 15, It is characterized in that, catalyst is a water p-methyl benzenesulfonic acid in the body ends sealing endization processing；One water p-methyl benzenesulfonic acid accounts for list The mass fraction of weight is 1wt%；The temperature of the reaction is 120 DEG C -126 DEG C, and the reaction time is for 24 hours.

17. a kind of print degradable body using biodegradable body temperature inductive material 4D described in claim 1-16 any one Warming should remember the preparation method of biological support, which is characterized in that comprising steps of the biodegradable body temperature is incuded material After material, solvent, photoinitiator and polyfunctional group sulfydryl small molecule or the mixing of norbornene small molecule are adjusted to suitable printing viscosity, The polyfunctional group sulfydryl small molecule or norbornene small molecule and biodegradable body temperature inductive material are printed by 4D to be occurred Biological support is obtained after norbornene-sulfydryl photopolymerization reaction；By biological support be heated to melting temperature or glass transition temperature with Compressing above and diametrically reduces size, then fixes temporary shapes near zero to get the induction of degradable body temperature is arrived Remember biological support.

18. biodegradable body temperature inductive material 4D according to claim 17 prints degradable body temperature induction memory biology The preparation method of bracket, which is characterized in that the biological support is intravascular stent, and the print conditions of the 4D printing are ultraviolet light Intensity 30mW/cm^-2；Print speed: 50mm/h, print carriage size: length 40mm, outer diameter 4mm, internal diameter 2mm.

19. biodegradable body temperature inductive material 4D according to claim 17 prints degradable body temperature induction memory biology The preparation method of bracket, which is characterized in that the biodegradable body temperature inductive material is the multiple groups that end is norbornene Decomposing biological degradable macromolecule；The preparation of the biological support includes the following steps: the biodegradable body temperature incuding material After material, solvent, photoinitiator and the mixing of polyfunctional group sulfydryl small molecule are adjusted to suitable printing viscosity, are printed and given birth to by 4D Object bracket；The polyfunctional group sulfydryl small molecule is four (3- mercaptopropionic acid) pentaerythritol esters.

20. biodegradable body temperature inductive material 4D according to claim 17 prints degradable body temperature induction memory biology The preparation method of bracket, which is characterized in that the biodegradable body temperature inductive material is the multicomponent biological that end is sulfydryl Degradable macromolecule；The preparation of the biological support includes the following steps: the biodegradable body temperature inductive material, molten After agent, photoinitiator and the mixing of norbornene small molecule are adjusted to suitable printing viscosity, print to obtain biological support by 4D；Institute Stating norbornene small molecule is 5- norbornene -2- carboxylic acid trimethylolpropane triester.

21. biodegradable body temperature inductive material 4D described in 7-20 any one prints degradable body temperature according to claim 1 The preparation method of induction memory biological support, which is characterized in that the photoinitiator is 2,4,6 (trimethylbenzoyl) hexichol Base phosphine oxide；The solvent is chloroform；The mass fraction that photoinitiator accounts for each substance gross weight is 0.5wt%.

Technical field

The invention belongs to 4D printed material technical fields, and in particular to a kind of biodegradable body temperature sense for 4D printing Material and degradable body temperature is answered to incude the preparation method of memory biological support.

Background technique

Cardiovascular disease has become No.1 Health Killer in world wide.Treatment maximally efficient for this disease at present Means are the intracavitary Balloon Angioplasties of coronary artery (PTCA), i.e., provide radial support to blood vessel using timbering material, prevent again narrow It is narrow, to achieve the purpose that treatment.The implantation of presently the most common balloon-expandable bracket is that bracket pressure is held on end band Have on the seal wire of sacculus, sent bracket to Coronary Artery Lesions by foley's tube, then utilizes the pressure expanded release branch of sacculus Frame.It shows according to statistics, in the annual cardiovascular interventional operation about 2,400,000 in the whole world in 2006, and every year with 40% speed Degree increases.Therefore, there is very high scientific value and social effect for the exploration of new timbering material and technology.

Intravascular stent experienced revolutionary development three times at present, be first generation bare metal stent, second generation drug respectively FirebirdTM and third generation biodegradable polymer stent.Discovered in recent years, current most reliable method are using completely may be used Degradation bracket, after playing a supporting role in a short time, does not leave any metal or polymer, while drug release in human body It finishes.Thus the concept for proposing Wholly-degradable bracket, is considered as third time revolution in cardiovascular disease interventional therapy.

The implantation of current biodegradable stent can only can be just implanted under the conditions of assisting operation using adminiclies such as sacculus Human body, operation is highly inconvenient, and surgical procedure is cumbersome, and needs the circumscribed wound of mask placement device larger when treatment.It can drop Bracket manufacture view is solved, intravascular stent generallys use the modes such as traditional injection molding, braiding, laser processing, and equipment is complicated, technique is multiple It needs to reject burr after miscellaneous, waste material, molding and forms the problems such as capilary bracket is difficult, personalized customization difficult to realize is set Meter.3D printing forming technique is the novel digital forming technique for quickly manufacturing arbitrarily complicated 3 dimensional coil geometry object, is had Precision is high, speed is fast and can flexible design the features such as.Currently, the degradable thermoplastics bio-medical material such as polylactic acid, polycaprolactone Material has used fused glass pellet method 3D printing to prepare various bio-medical materials.

It 2013, holds in TED (Technology, Entertainment, Design) conference, comes from California, USA The Skylar Tibbits of the Massachusetts Institute of Technology is first public to demonstrate 4D printing technique.The cardinal principle of 4D printing technique be On the basis of 3D printing technique, using intelligent alterable shape material (shape-memory material is most widely used) as driving execution unit, Using the deformability characteristics of material, the design parameter of shaped component, moulding process, deformational behavior and final structure target etc. are believed Breath is designed into initial configuration.It is stimulated after molding using outfield excitable media, by bending, distortion, expansion etc., self deformation is obtained Three-dimensional space configuration must be preset, is the innovative technology that a kind of design of integrated products, manufacture, assembly are integrated, i.e. 4D Method of printing.

For degradable polymer bracket presently, there are technical bottleneck problem, newest 4D printing technique can prepare The intelligentized complete absorbable polymer intravascular stent with shape memory function.Using the blood of 4D printing technique machine-shaping Pipe holder self deformation such as can expand under the excitation of body temp, be finally reached preset three-dimensional space configuration, make It can be deformed by self without balloon expandable when being implanted into human body and realize that bracket is bonded with the close stabilization of blood vessel, this Kind adaptivity can reduce intense impact, reduction vascular wall tearing risk of the balloon expandable process to vascular wall, greatly reduce The size of circumscribed wound mitigates sufferer pain.Meanwhile forming process is not limited by structural complexity, with classical production process It compares, it is easier to meet mechanical property and the requirement with medical performance.

There are pertinent literature report and patented technology using 4D printing technique printing shape memory vascular stent material.Specially Sharp a kind of 201410344228.2 (methods of 4D printing shaping artificial blood vessel bracket) are prepared for shape memory using 3D printing and gather Object intravascular stent is closed, using fusion sediment 3D printing, intravascular stent does not have degradability.Patent 201410832997.7 (a kind of to can absorb macromolecule intravascular stent and preparation method thereof completely) is prepared for degradable shape memory using melting extrusion 3D Bracket, the timbering material do not have body temperature induction shape memory function.(one kind is based on 3D printing skill to patent 201610232704.0 The method that art prepares biodegradable polymer self-expanding type blood vessel dilator) it is prepared for gathering cream using melting extrusion formula 3D printing Acid/ferric oxide nano composite material, shape memory respond temperature close to human body temperature.Patent 201710064389.X (is based on shape Degradable self expandable 4D intravascular stent of shape memory polyurethane and preparation method thereof) it is prepared for incuding temperature using melting extrusion 3D printing Spend the Biodegradable Shape-Memory Polyurethane close to human body temperature.(a kind of visualization shape memory is high by patent 201710215735.X The preparation method of molecule intravascular stent) using six terminal-modified arm degradable macromolecules of photocuring 3D printing double bond it is prepared for blood Pipe holder, since macromolecular end is the photocatalysis self-polymeric reaction of acrylic double bond, photopolymerization rate is slow, has oxygen inhibition and receipts The shortcomings that contracting.Document (ACS Appl.Mater.Interfaces, 2017,9,876-883) reports a kind of extrusion posterior photocuring Mode be prepared for polylactic acid/iron oxide intravascular stent, since preparation process is first to squeeze out to be crosslinked in illumination, preparation process is slow Slowly, processing step is complicated, and shape memory response temperature is much higher than human body temperature.

The degradable shape memory intravascular stent of achievable 4D printing is largely by melting extrusion 3D printing skill at present Art preparation, bracket is to be printed by piling up layer by layer, and be not crosslinked mutually, and mechanical property is relatively weak.For current The intravascular stent of direct photocuring 4D printing is to be prepared by the macromolecular of acrylate end functionalization by photo-crosslinking, due to The photopolymerization of acrylic acid ester bond, there are chance oxygen inhibitions, and photocuring is incomplete, and extend curing time.In addition, acrylate Key is an auto polymerization system, is easy to happen gel and occurs to early, and generates stress and concentrates, and can cause sample corrugation and warpage.Step Increasing sulfydryl-alkene light reaction not only has collaboration photopolymerization reaction and walks the advantage of Propagating Radical polymerization reaction, is also equipped with nothing Oxygen inhibition, unstressed concentration, the feature that initiator amount is few and polymerization rate is fast.

Light-initiated sulfydryl and can be in the photochemical reaction system of homopolymerization type double bond monomer a chain growth mechanism and by The photopolymerization reaction that step Growth Mechanism is vied each other, and be simple in sulfydryl and non-homopolymerizing type double bond monomer photochemical reaction system Gradually mechanism of polymerization.According to the double bond monomer reactivity of click-reaction sequence (J.Am.Chem.Soc.2012,134, 13804-13817), as shown in figure 11, at present only norbornene (Norbornene), vinyl ethers (Vinyl ether) and The monomer of the minority such as propenyl ether (Propenyl ether) takes simple gradually mechanism of polymerization, and norbornene group Sulfydryl alkene photopolymer reaction speed is most fast.

In consideration of it, also lacking at present, a kind of shaping speed is fast, prints degradable body temperature sense without oxygen inhibition and shrinkage-free 4D Answer material and using shape memory intravascular stent made of the material.

Summary of the invention

In order to solve the above problems existing in the present technology, it is an object of that present invention to provide a kind of biologies for 4D printing The preparation method of degradable body temperature inductive material and degradable body temperature induction memory biological support.

The technical scheme adopted by the invention is as follows:

A kind of preparation method of the biodegradable body temperature inductive material for 4D printing, comprising steps of in physiology temperature It spends based on the Biodegradable high-molecular that lower end is hydroxyl, by being prepared in life to the processing of body ends sealing endization Degradable at a temperature of reason, end is the multicomponent biodegradable macromolecule of sulfydryl or norbornene, is printed as 4D Biodegradable body temperature inductive material use.

Further, the glass transition temperature of the main body or melting temperature are 20 DEG C -40 DEG C.

Further, the preparation method of the main body includes: with D, and L- lactide or caprolactone are main monomer；L- third is handed over One of ester, caprolactone, glycolide, cyclic acid anhydride, cyclic carbonate ester, cyclic phosphorus or Lanthanum Isopropoxide are a variety of single as copolymerization Body；Copolymerization obtains multicomponent copolymer after catalyst, initiator effect.

Further, the initiator is dihydroxylic compound, multi-hydroxy compound or oligomer.

Further, the initiator be ethylene glycol, pentaerythrite, small molecule polyhydroxy-alcohol, oligomeric two arms polyethylene glycol, Multi-arm polyethylene glycol, oligomeric two arms polycaprolactone polyol, multi-arm polycaprolactone polyol, oligomeric two arms polyether polyol, three Arm polyether polyol, cyclodextrin or sugar alcohol.

Further, the catalyst is stannous octoate.

Further, when the main body that preparation glass transition temperature is 20 DEG C -40 DEG C, the main monomer of use and the matter of comonomer Score is measured to determine according to formula (1):

T_gBased on glass transition temperature；T_g1、T_g2…T_gnThe segment vitrifying temperature of respectively each monomer for participating in reaction Degree；N is the positive integer more than or equal to 2；W₁、W₂…W_nRespectively each monomer for participating in reaction accounts for the quality point of all monomers Number.

Further, when the main body that preparation glass transition temperature is 20 DEG C -40 DEG C, it is total that the mole of initiator accounts for all monomers The 0.02mol% of mole.

Further, the molecular weight for the main body that the glass transition temperature is 20 DEG C -40 DEG C is 400-2000.

Further, when preparing the main body that fusing point is 20 DEG C -40 DEG C, the molar ratio of initiator and each monomer is according to The molecular weight for the main body that fusing point is 20 DEG C -40 DEG C determines.

Further, when preparing the main body that fusing point is 30 DEG C -40 DEG C, initiator amount is the gross weight of all monomers 0.1wt%；The molecular weight of main body is 1000-4000.

Further, the body ends sealing endization processing is norbornene termination process, the norbornene envelope End processing is comprising steps of it is norborneol that main body, norbornene acyl chlorides and triethylamine solvent, which are mixed reaction end is prepared, The multicomponent biodegradable macromolecule of alkenyl.

Further, the solvent is methylene chloride；The molar ratio of the norbornene acyl chlorides, triethylamine and main body hydroxyl For 1.2:1.2:1；Reaction time is 48h；Reaction temperature is room temperature.

Further, the body ends sealing endization processing is sulfydryl termination process, and the sulfydryl termination process includes step It is rapid: can by main body, thioacetic acid, the catalysts and solvents multicomponent biological that back flow reaction obtains that end is sulfydryl under nitrogen atmosphere Degraded macromolecular.

Further, in the body ends sealing endization processing, the hydroxyl of the main body and the molar ratio of thioacetic acid are 1:10。

Further, catalyst is a water p-methyl benzenesulfonic acid in the body ends sealing endization processing；One water is to toluene sulphur The mass fraction that acid accounts for monomer mass is 1wt%；The temperature of the reaction is 120 DEG C -126 DEG C, and the reaction time is for 24 hours.

A kind of biodegradable body temperature inductive material 4D prints the preparation method of degradable body temperature induction memory biological support, Comprising steps of by the biodegradable body temperature inductive material, solvent, photoinitiator and polyfunctional group sulfydryl small molecule or drop ice The mixing of piece alkene small molecule is adjusted to be suitble to printing viscosity after, the polyfunctional group sulfydryl small molecule or norbornene small molecule and life Biodegradable body temperature inductive material obtains biological support after printing generation norbornene-sulfydryl photopolymerization reaction by 4D；It will give birth to Object bracket is heated to melting temperature or glass transition temperature or more and diametrically compression reduction size, then near zero Fixed temporary shapes remember biological support to get to the induction of degradable body temperature.

Further, the biological support is intravascular stent, and the print conditions of the 4D printing are ultraviolet ray intensity 30mW/ cm^-2；Print speed: 50mm/h, print carriage size: length 40mm, outer diameter 4mm, internal diameter 2mm.

Further, the biodegradable body temperature inductive material is that the multicomponent biological that end is norbornene can drop Solve macromolecule；The preparation of the biological support includes the following steps: the biodegradable body temperature inductive material, solvent, light After initiator and the mixing of polyfunctional group sulfydryl small molecule are adjusted to suitable printing viscosity, print to obtain biological support by 4D；Institute Stating polyfunctional group sulfydryl small molecule is four (3- mercaptopropionic acid) pentaerythritol esters.

Further, the biodegradable body temperature inductive material is the multicomponent biodegradable high score that end is sulfydryl Son；The preparation of the biological support includes the following steps: the biodegradable body temperature inductive material, solvent, photoinitiator It is adjusted to the mixing of norbornene small molecule after being suitble to printing viscosity, prints to obtain biological support by 4D；The norbornene Small molecule is 5- norbornene -2- carboxylic acid trimethylolpropane triester.

Further, the photoinitiator is 2,4,6 (trimethylbenzoyl) diphenyl phosphine oxides；The solvent is three Chloromethanes；The mass fraction that photoinitiator accounts for each substance gross weight is 0.5wt%.

The invention has the benefit that a kind of biodegradable body temperature inductive material for 4D printing of the invention and can Degrade body temperature induction memory biological support preparation method, by end be hydroxyl Biodegradable high-molecular based on, lead to Cross the multicomponent biodegradable macromolecule for the processing of body ends sealing endization being prepared end is sulfydryl or norbornene The shortcomings that being printed for 4D, contraction can be generated when overcoming traditional 4D printing using acrylate monomer photopolymerization；The present invention Biological support is small for the multicomponent biodegradable macromolecule and sulfydryl or norbornene of sulfydryl or norbornene by end Molecule prepares the memory biological support of degradable body temperature induction by norbornene-sulfydryl photocuring printing；This norbornene- The printing of sulfydryl photocuring have the advantages that shaping speed fastly, without oxygen inhibition and shrinkage-free.Meanwhile with acrylate-based radical polymerization Conjunction is compared, and the polymer network that norbornene-sulfydryl step increases polymerization formation has regularity, and heat deflection peak width is narrow, shape It replys faster, the more accurate advantage of recovery temperature, in addition, it can also take into account controllable degradation rate；Biology branch of the invention Frame such as can expand at self deformation under the excitation of body temp, be finally reached preset three-dimensional space configuration, make its It can be deformed by self when being implanted into human body without balloon expandable and realize that bracket is bonded with the close stabilization of blood vessel.Due to life Object bracket has biodegradability, takes out without second operation, can mitigate sufferer pain significantly.

Detailed description of the invention

Fig. 1 is based on norbornene-sulfydryl photopolymerization 4D printing technique printing schematic diagram.

Fig. 2 norbornene blocks the poly- D of four arms, the nucleus magnetic hydrogen spectrum figure of L- lactide.

Fig. 3 sulfydryl blocks the poly- D of four arms, the nucleus magnetic hydrogen spectrum of L- lactide.

Fig. 4 norbornene blocks the poly- D of four arms, and L- lactide and four (3- mercaptopropionic acid) pentaerythritol esters are 10mW/m2's 1~2s forms the schematic diagram of gel under ultraviolet light.

Fig. 5 norbornene blocks the poly- D of four arms, and L- lactide and four (3- mercaptopropionic acid) pentaerythritol esters are crosslinked shape memory Polymer glass transition area figure (narrow half-peak breadth).

Fig. 6 norbornene blocks the poly- D of four arms, and L- lactide and four (3- mercaptopropionic acid) pentaerythritol esters are crosslinked shape memory Shape-memory properties figure of the polymer under differently strained.

Fig. 7 norbornene blocks the poly- D of four arms, and L- lactide and four (3- mercaptopropionic acid) pentaerythritol esters are crosslinked shape memory The memory cycle performance map of polymer.

Fig. 8 norbornene blocks the poly- D of four arms, and L- lactide and four (3- mercaptopropionic acid) pentaerythritol esters are crosslinked shape memory The shape memory of polymer replys display diagram (1s can be replied in the hot water of glass transition temperature).

Tan δ-temperature curve of Fig. 9 hydroxy-end capped four arms poly- D, L- lactide-co- trimethylene carbonate copolymer.

Figure 10 hydroxy-end capped poly- (caprolactone-co- trimethylene carbonate) melting point curve.

Figure 11 is double bond monomer reactivity precedence diagram in sulfydryl alkene reaction.

Specific embodiment

With reference to the accompanying drawing and specific embodiment does further explaination to the present invention.

A kind of biodegradable body temperature inductive material and the induction memory life of degradable body temperature for 4D printing of the invention The preparation method of object bracket, preparation method and degradable body temperature induction memory biology including biodegradable body temperature inductive material Two big technical solutions of preparation method of bracket.It is described as follows respectively:

The preparation method of biodegradable body temperature inductive material is the Biodegradable high-molecular of hydroxyl by using end (i.e. hydroxy-end capped Biodegradable high-molecular) is basic body material, that preparation can degrade under physiological temp, last End is the multicomponent biodegradable macromolecule of sulfydryl or norbornene, i.e. the multiple groups of sulfydryl or norbornene sealing end are mitogenetic Biodegradable macromolecule.The material application prints field to 4D, is the multicomponent biological blocked by sulfydryl or norbornene The degradable macromolecular that degradable macromolecule is blocked with corresponding two arm or multi-arm norbornene or sulfydryl, in photocatalysis Under, photocatalysis norbornene-sulfydryl click chemistry reaction occurs and realizes.The biological support as made from the reaction, such as blood vessel Bracket has shape design and replys the advantage that speed is fast, recovery temperature is more accurate and degradation rate is controllable.

In order to enable biodegradable body temperature inductive material of the invention (the i.e. biological intracorporal maintenance life under physiological temp Manage movable temperature) it degrades, the present invention is the Biodegradable high-molecular of hydroxyl to the end as material of main part first Degradable improvement is carried out.

Guarantee especially by the following two kinds mode.First is that by the glass transition temperature of control material of main part at 20 DEG C -40 ℃；Second is that being realized by the fusing point for controlling material of main part at 20 DEG C -40 DEG C.

Glass transition temperature of the invention is with D in 20 DEG C -40 DEG C of main body, and L- lactide or caprolactone are main monomer；L- One of lactide, caprolactone, glycolide, cyclic acid anhydride, cyclic carbonate ester, cyclic phosphorus or Lanthanum Isopropoxide are a variety of as altogether Polycondensation monomer；Copolymerization obtains multicomponent copolymer after catalyst, initiator effect, and the composition of product is controlled by formula (1) And molecular weight obtains.Specifically, it is exemplified below:

Using stannous octoate as catalyst, binary or multi-hydroxy compound or oligomer are initiator, with D, L- lactide For main monomer, in L- lactide, caprolactone, glycolide, cyclic acid anhydride, cyclic carbonate ester, cyclic phosphorus, Lanthanum Isopropoxide etc. one Kind, two or three the above are comonomers.Anhydrous and oxygen-free reaction is added in reactant needed for will be above-mentioned, initiator and catalyst Bottle, vacuumizes, and leads to nitrogen, repeatedly for three times.It is reacted for 24 hours under 130 DEG C of oil bath after reaction system sealing.After completion of the reaction, instead It answers system to be down to room temperature, suitable chloroform lysate is added.Reaction mixture is slowly dropped in cold methanol and is precipitated, Wherein the volume of methanol is the chloroform soln volume of 5-10 times of reactant, dissolves and precipitates again after filtering, continuous precipitation Three times, the final product obtained.Wherein, the mole dosage of initiator accounts for the mole percent of all monomer integral molar quantities and is 0.02mol%；The molar ratio of initiator and monomer is calculated according to required molecular weight, and the macromolecular molecular weight finally synthesized is 400 ~2000 or so；The proportion of main monomer and comonomer makes its glass transition temperature on 20~40 DEG C of left sides according to FOX equation calculation The right side, for example, the calculating of three kinds of monomers copolymerization is as follows:

In formula: T_g=34~37 DEG C, shape memory transition temperature is made to be close to human body temperature；T_g1、T_g2And T_g3It is D, The vitrifying of L- lactide (55-60 DEG C), L- lactide (60-65 DEG C) and Trimethylene Carbonate (- 15 DEG C) three kinds of segments Temperature；W₁、W₂And W₃It is D, the mass fraction of three kinds of L- lactide, L- lactide and Trimethylene Carbonate segments.

Fusing point of the invention is with D in 20 DEG C -40 DEG C of main body, and L- lactide or caprolactone are main monomer；L- lactide, One of caprolactone, glycolide, cyclic acid anhydride, cyclic carbonate ester, cyclic phosphorus or Lanthanum Isopropoxide are a variety of as comonomer； Copolymerization obtains multicomponent copolymer after catalyst, initiator effect, and the molecular weight of the main body finally synthesized by constraint is 1000-4000 or so, and the 0.1wt% for the gross weight that initiator amount is all monomers is controlled to realize.Concrete example is as follows:

Using stannous octoate as catalyst, binary or multi-hydroxy compound or oligomer are initiator, based on caprolactone Monomer, D, L- lactide, L- lactide, caprolactone, glycolide, cyclic acid anhydride, cyclic carbonate ester, cyclic phosphorus, Lanthanum Isopropoxide etc. One of, two or three the above are comonomers.Anhydrous and oxygen-free is added in reactant needed for will be above-mentioned, initiator and catalyst Reaction flask vacuumizes, and leads to nitrogen, repeatedly for three times.It is reacted for 24 hours under 130 DEG C of oil bath after reaction system sealing.End of reaction Afterwards, reaction system is down to room temperature, and suitable chloroform lysate is added.Reaction mixture is slowly dropped in cold methanol Precipitating, wherein the volume of methanol is the chloroform soln volume of 5-10 times of reactant, dissolves and precipitates again after filtering, continuously It precipitates three times, obtained final product.Wherein, initiator amount is the 0.1wt% of (all) monomers；Initiator and monomer Molar ratio is calculated according to required molecular weight, and the macromolecular molecular weight finally synthesized is 1000~4000 or so, and fusing point is 30~40 ℃。

The present invention end be hydroxyl Biodegradable high-molecular carried out degradable improved on the basis of, further into Row norbornene termination process and sulfydryl termination process, to obtain degradable 4D printed material.Concrete example is as follows:

The synthesis of norbornene sealing end Biodegradable high-molecular is added hydroxy-end capped degradable big in reaction flask Molecule, norbornene acyl chlorides and triethylamine.Wherein, the molar ratio of norbornene acyl chlorides, triethylamine and hydroxyl is 1.2:1.2:1, Solvent is dry methylene chloride, reacts at room temperature 48h, filters after the reaction was completed, filtrate is precipitated three times in cold methanol, room temperature Cryo-conservation is spare after vacuum drying.

The synthesis of sulfydryl sealing end Biodegradable high-molecular takes hydroxy-end capped degradable macromolecular to be placed in connection water segregator Two mouth flask in, be added 10 times of hydroxyl mole thioacetic acid and monomer mass 1wt% a water Catalyzed by p-Toluenesulfonic Acid Then solvent is added in agent, lead to nitrogen.Back flow reaction is for 24 hours under the conditions of 120~126 DEG C for reactant.After reaction, cooling, it is molten Liquid precipitates three times in methyl alcohol, stored refrigerated after room temperature in vacuo is dry.

After the completion of degradable 4D printed material, biological support is prepared by 4D printing.The basic skills of the printing be by The biodegradable body temperature inductive material, solvent, photoinitiator and polyfunctional group sulfydryl small molecule or norbornene small molecule Mixing is adjusted to be suitble to printing viscosity after, the polyfunctional group sulfydryl small molecule or norbornene small molecule and biodegradable body Warm inductive material is printed by 4D, and norbornene-sulfydryl photopolymerization reaction occurs under the catalysis of ultraviolet light；By biological support plus More than heat to melting temperature or glass transition temperature and diametrically compressing reduces size, then fixed interim near zero Shape remembers biological support to get to the induction of degradable body temperature.

After the biological support is implanted to human body, it self deformation such as can expand under the excitation of body temp, finally Reach preset three-dimensional space configuration, make its when being implanted into human body without balloon expandable can by self deform realize bracket with The close of blood vessel stablizes fitting.

The polymer network of the biological support is the three-dimensional network of crosslinking, has excellent shape memory fixed rate, replys Rate, memory cycle performance, height can recovery strain and degradabilities.

The printing principle that 4D of the invention prints degradable body temperature induction shape memory intravascular stent is dropped based on photocatalysis The reaction of bornylene-sulfydryl click chemistry, have the advantages that print speed fastly, without oxygen inhibition and shrinkage-free.It is prepared based on the method Shape memory vascular stent material have recovery of shape speed it is fast, the more accurate and controllable degradation rate of recovery temperature.

Print conditions after optimization are as follows: the print conditions of the 4D printing are ultraviolet ray intensity 30mW/cm^-2；Printing speed Degree: 50mm/h, print carriage size: length 40mm, outer diameter 4mm, internal diameter 2mm.

The different biodegradable body temperature inductive materials of above-mentioned synthesis can be respectively adopted such as under type, progress 4D Printing and making biological support.

When biodegradable body temperature inductive material is the multicomponent biodegradable macromolecule that end is norbornene, institute The preparation for stating biological support includes the following steps: the biodegradable body temperature inductive material, solvent, photoinitiator and more officials Sulfydryl small molecule can be rolled into a ball and mix to be adjusted to and be suitble to printing viscosity (such as the solid content of solution when printing is made to be maintained at 40% or so) Afterwards, it prints to obtain biological support by 4D；The polyfunctional group sulfydryl small molecule is four (3- mercaptopropionic acid) pentaerythritol esters.It is excellent Selection of land, photoinitiator 2,4,6 (trimethylbenzoyl) diphenyl phosphine oxide；Solvent is chloroform；Photoinitiator accounts for respectively The mass fraction of substance gross weight is 0.5wt%.

When biodegradable body temperature inductive material is the multicomponent biodegradable macromolecule that end is sulfydryl, biological support Preparation include the following steps: the biodegradable body temperature inductive material, solvent, photoinitiator and norbornene small molecule After mixing is adjusted to suitable printing viscosity, print to obtain biological support by 4D；The norbornene small molecule is 5- norborneol Alkene -2- carboxylic acid trimethylolpropane triester.Preferably, photoinitiator 2,4,6 (trimethylbenzoyl) diphenyl phosphine oxides； Solvent is chloroform；The mass fraction that photoinitiator accounts for each substance gross weight is 0.5wt%.