A seaweed fiber and a method for preparing the same

Abstract

The present application relates to seaweed fiber preparation technical field, disclose a kind of seaweed fiber and its preparation method, including: the chemical modification of sodium alginate macromolecular chain, introduce controllable hydrolysis and can catalyze main chain break side chain group, while introducing weak covalent bond sensitive to spinning shear force, and dispersion reducing agent microcapsule in spinning dope, to carry out self-repair to uneven segment in spinning process, the present application is by the disintegration of fiber main chain with an internal chemical reaction end point not affected by external environment fluctuation is bound, realizes the transformation of fiber degradation behavior from passive environmental response to active programmed structure disintegration, combined with self-repair quality control mechanism in spinning process, ensure that the programmed degradation performance in the high uniformity and predictability in final product.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of seaweed fiber and its preparation method, belong to seaweed fiber preparation technical field. BACKGROUND

[0002] In the preparation technical field of artificial fiber, especially for seaweed fiber derived from natural macromolecule, through wet spinning process, using sodium alginate aqueous solution occurs ion crosslinking in the coagulation bath containing divalent cation, form the seaweed fiber with specific mechanical strength, it is a kind of mature technology and widely used general method;The structural integrity of this fiber, its essence is jointly determined by two different chemical structures, one is the ion crosslinking network that provides macro mechanical strength, the second is the glycosidic bond that constitutes high molecular chain itself, and its chemical property is extremely stable in physiological environment;The regulation of fiber degradation behavior in the prior art is almost all concentrated on the intervention of ion crosslinking network, and the disintegration of fiber is controlled by adjusting the rate of ion exchange.

[0003] However, when this kind of fiber is applied to the application occasion that needs to be stably loaded within a specific time window and then disintegrated, the above degradation mode depending on ion exchange exposes its inherent principle constraint, because in the complex actual environment, the ion species, concentration and pH of the surrounding medium are in dynamic change, which makes the performance degradation process of the fiber directly subject to unpredictable external variables, and the accuracy of its functional life is also out of the question;Such linear improvement ideas as simply enhancing the ion crosslinking strength or adding physical coating to improve its controllability do not change the essence that its degradation is driven by external environment, the former only delays a random process, and the latter will introduce new problems about the controllability of coating degradation or residue.

[0004] Specifically, the prior art mainly has the following deficiencies: 1, the degradation of the fiber is completely dependent on the external environment, lacks an internal, autonomous control mechanism;2, the mechanical property degradation curve of the fiber is difficult to be pre-marked, and the time point of functional failure exists unpredictable risk;3, the long-term structural stability of the fiber and its final rapid and complete disintegration are mutually restricted under this passive response degradation mode, and are difficult to be considered. Therefore, how to implant a preset timing mechanism in the macromolecular chemical structure of seaweed fiber, which is determined by its own chemical properties and is not affected by external environment fluctuations, and trigger the rupture of the fiber main chain at the predetermined time point through the mechanism, so as to realize the programmed control of the fiber life cycle, has become the technical problem to be solved by the present application. SUMMARY

[0005] The present application provides a kind of seaweed fiber and its preparation method, its main purpose is to solve in the chemical structure of seaweed fiber implantation by its own decision, not by external environment fluctuation influence, pre-set programmed self-degradation mechanism problem.

[0006] To achieve the above object, the present application provides a kind of seaweed fiber preparation method, the method comprises:

[0007] Carboxyl on sodium alginate macromolecular chain is chemically modified, to introduce side chain chemical groups by covalent bond, side chain chemical groups include an ester bond with hydrolysis rate determined by its chemical structure, and side chain chemical groups release catalytic functional groups capable of catalyzing main chain glycosidic bond cleavage after ester bond hydrolysis;

[0008] In chemical modification, also introduce weak covalent bond sensitive to shear force generated by the reaction of functional groups on sodium alginate macromolecular chain and aldehyde compound;

[0009] Chemically modified alginate is prepared into spinning dope, and reducing agent microcapsule is dispersed in the spinning dope, and the reducing agent microcapsule can be activated by the rupture product of weak covalent bond;

[0010] In the spinning extrusion step, the weak covalent bond on the molecular chain with uneven molecular weight in the spinning dope is broken by shear stress, and the reducing agent microcapsule is activated by the rupture product to release reducing agent, and the reducing agent repairs the end of the broken molecular chain;

[0011] The spinning dope is extruded into a coagulation bath containing divalent cations to form seaweed fiber by ionic crosslinking.

[0012] Preferably, in chemical modification, the introduction ratio of side chain chemical groups is 1 to 5 per 100 alginate repeating units.

[0013] Preferably, the chemical structure of ester bond is selected to have a hydrolysis half-life corresponding to a time range of several days to several months.

[0014] Preferably, the weak covalent bond sensitive to shear force is generated by the reaction of amine group or hydroxyl group on alginate chain with dialdehyde or acetal;The reducing agent microcapsule is wrapped by inert coating and contains at least one reducing agent selected from thiol compound and ascorbic acid.

[0015] Preferably, in chemical modification, a molecular group with temperature-sensitive conformational transition is also introduced, the molecular group is a polymer with low critical solution temperature LCST, the LCST value is in the range of 37-42℃, the molecular group occurs conformational contraction when ambient temperature rises, so that when ambient temperature rises, the degree of slowing down of ester bond hydrolysis rate counterbalances the hydrolysis acceleration effect caused by temperature rise.

[0016] Preferably, the chemical modification also covalently incorporates functional nanoclusters that are activated to generate at least one signal source selected from microbubbles and structures that cause acoustic impedance changes that can be detected by an ultrasound imaging device when the backbone glycosidic bonds are broken, causing the loose structure of the fiber matrix.

[0017] Preferably, the chemical modification causes the modified alginate to form functional groups with multivalent chelating ability on the surface and ends of the fiber fragments when the backbone is broken, and the functional groups can bind to metal ions or receptor sites on the surface of cells.

[0018] Preferably, the alginate fibers produced meet the following two-stage degradation characteristics in a phosphate buffer solution at 37°C: the retention rate of tensile strength is not less than 80% of the initial value during the first stage of the stable period; the tensile strength decreases by more than 50% of the initial value during the subsequent second stage of rapid disintegration; and the ratio of the average loss rate of tensile strength during the second stage of rapid disintegration to the average loss rate of tensile strength during the first stage of the stable period is not less than 50.

[0019] Preferably, the chemical modification is achieved by a carbodiimide-based activating agent, and the catalytic functional group is a hydroxyl group or a carboxyl group; and in the spinning extrusion step, the spinning dope is extruded into a coagulation bath containing calcium ions or barium ions.

[0020] Compared with the prior art, the present application has the following beneficial effects:

[0021] 1. The degradation time is programmable and predictable. For example, the degradation of the fibers in the prior art depends on the external environment (such as ion concentration), and the process is random and uncontrollable. By introducing a chemical clock (i.e. a rate-controllable side chain hydrolysis group) into the molecular chain, the degradation of the fibers is triggered by an internal chemical reaction. This allows the fibers to remain stable until a predetermined time point, such as 30 days or 90 days, and then rapidly disintegrate, solving the contradiction between long-term stability and rapid degradation in the prior art. Since the start and progress of degradation are determined by the internal preset molecular structure rather than external uncertain environmental factors, the functional life of the fibers of the present application has high reliability and consistency in complex actual applications, avoiding the risk of premature failure due to environmental changes.

[0022] 2. In order to solve the technical problem that the uneven molecular weight of raw materials in industrial production leads to performance fluctuation of the final product, the present application introduces shear-sensitive weak covalent bonds and reducing agent microcapsules, so that in the spinning process with high shear force, the overlong chains with uneven molecular weight will preferentially break at the weak covalent bonds, the broken products activate the reducing agent microcapsules to release the reducing agent, and then the reducing agent repairs the broken molecular chain ends to restore the spinnability, which converts the differences of raw materials into a quality control link to improve product uniformity, effectively eliminates the influence of raw material batch fluctuation on the predictability of the final degradation performance of the fiber, and improves the reliability of the product.

[0023] 3. The method of the present application further comprises introducing a functional nanocluster in the chemical modification step, which has special acoustic contrast properties: when the overall structure of the fiber remains intact, it is tightly wrapped by the dense matrix and is in a silent state; once the preset programmed degradation is started, the fiber backbone breaks, the matrix becomes loose and forms a porous structure, and this physical change will activate the nanoclusters to release a signal that can be detected by conventional ultrasonic imaging equipment. Through this design, the disintegration process of the fiber after completing the functional mission is no longer a hidden process that is difficult to monitor by non-invasive methods, but is transformed into a visual signal release process that occurs synchronously with the degradation stage, which provides a window for external observation to directly judge the integrity state of the fiber structure, so that the degradation dynamics of the fiber in the body can be tracked and evaluated in real time. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 It is a temperature compensation mechanism diagram of the seaweed fiber of the present application;

[0025] Figure 2 It is a tensile strength retention rate comparison curve diagram of the seaweed fiber of the present application and the control group fiber;

[0026] Figure 3 It is a preparation method and self-repairing quality control mechanism flow chart of the seaweed fiber of the present application;

[0027] Figure 4 It is a two-stage programmed degradation mechanism diagram of the seaweed fiber of the present application;

[0028] Figure 5 It is a scanning electron microscope diagram of the complete micro morphology of the fiber in the stable period of the present application;

[0029] Figure 6 It is a scanning electron microscope diagram of the surface micro change of the fiber in the transition period of the present application;

[0030] Figure 7 It is a scanning electron microscope diagram of the fiber structure disintegration in the rapid disintegration period of the present application. DETAILED DESCRIPTION

[0031] In order to make the objects, technical solutions and advantages of the present application clearer, the technical solutions of the present application will be described in detail below; obviously, the described embodiments are only some of the embodiments of the present application, rather than all the embodiments; based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the protection scope of the present application.

[0032] The present application provides a kind of seaweed fiber and its preparation method, its overall flow mainly consists of the following several core stages: first, the sodium alginate macromolecular chain as preparation raw material is chemically modified to introduce programmed self-degradation function and process quality control function in molecular structure;Second, the chemically modified alginate is prepared into spinning dope, and the self-molecular mass screening and repair mechanism in the spinning process is established in the dope system;Finally, through wet spinning process, the spinning dope is extruded in the coagulation bath containing divalent cation, and the seaweed fiber with preset life cycle is formed by ion crosslinking;In the preparation of man-made fiber, especially for functional medical fiber, its mechanical property stability in specific time window and final rapid disintegration absorption capacity are the key technical indexes to determine its application success or failure, however, the degradation behavior of traditional seaweed fiber is completely subject to unpredictable ion exchange balance in its environment, which leads to its functional life cannot be accurately calibrated;For this technical problem, the steps of the method are to chemically modify the sodium alginate macromolecular chain, introduce specific side chain chemical groups by covalent bond, the side chain chemical groups contain an ester bond with a hydrolysis rate determined by its own chemical structure, and the side chain chemical groups can release a catalytic functional group, such as hydroxyl or carboxyl, after ester bond hydrolysis, which can catalyze the breakage of main chain glycosidic bond;The chemical modification step is realized by carbodiimide type activator, in aqueous reaction system, with carboxyl on sodium alginate molecular chain as reaction site, coupling reaction with alcohol or amine small molecule with preset ester bond and protected catalytic functional group, so as to introduce the side chain chemical group into sodium alginate main chain in the form of covalent bond;Therefore, the degradation behavior of the fiber is no longer dependent on external environment, but determined by an internal chemical reaction end point with controllable rate, so that the degradation mode of the fiber is changed from passive environmental response to internal chemical program driven structure disintegration.

[0033] To ensure the feasibility and stability of the above programmed degradation function, the introduction ratio of side chain chemical groups is set to 1 to 5 per 100 alginate repeat units; The determination of this ratio range is based on the systematic experimental calibration results of the technical trade-off between fiber spinnability and degradation efficiency; When the introduction ratio is less than 1%, even if all the side chain hydrolysis is completed, the density of the released catalytic functional groups is not enough to effectively catalyze a sufficient number of main chain glycosidic bond breakage in a short time, resulting in that the second stage of rapid disintegration of the fiber is not obvious, and the degradation behavior tends to be close to the traditional slow way; When the introduction ratio is higher than 5%, too many carboxyl groups are occupied, which weakens the ability of alginate molecular chain to ionically crosslink with divalent cations (such as calcium ions or barium ions) in the coagulation bath, resulting in insufficient initial mechanical strength of the obtained fiber, and even unable to form a continuous fiber form; Therefore, the introduction ratio of 1% to 5% is the working window that ensures the efficient triggering of programmed degradation without compromising the basic spinnability and mechanical properties of the fiber; Further, to address the technical challenge of uneven molecular weight distribution among batches of sodium alginate raw materials in industrial production, which can lead to differences in mechanical properties and degradation rate of the final fiber product, weakening its predictability, a weak covalent bond sensitive to shear force is also introduced in the chemical modification step of the method, and a reducing agent microcapsule is dispersed in the subsequent prepared spinning dope; The weak covalent bond is generated by the reaction of functional groups on the alginate chain with aldehyde compounds, such as Schiff base or hemiaminal bond generated by the reaction of amine or hydroxyl group with dialdehyde or acetal, and its bond energy is designed to be just below the shear stress threshold applied by the spinneret in the spinning extrusion process; The reducing agent microcapsule is composed of at least one reducing agent selected from thiol compounds and ascorbic acid, which is wrapped in an inert coating that is stable to the spinning dope system but can be broken by aldehyde or ketone compounds generated after the weak covalent bond breaks; In the spinning extrusion process, which experiences high shear stress, long chains or entangled chain segments with molecular weight exceeding the average range will preferentially break at the weak covalent bond, and their broken products will immediately activate the surrounding reducing agent microcapsules, causing them to release reducing agents, which chemically repair the ends of the broken molecular chains, such as reducing the newly generated aldehyde group to a hydroxyl group, restoring its ability to participate in ionic crosslinking; Through this screening-fusing-repair mechanism automatically completed during spinning, the unevenness of the raw material is converted into a quality control step that enhances the uniformity of the final product.

[0034] In addition, considering the temperature fluctuation that the fiber may experience in certain application scenarios, such as local heating caused by inflammatory response, this temperature change will accelerate the hydrolysis of ester bonds, causing the actual degradation time of the fiber to deviate from the preset value, the chemical modification step of the method can also selectively covalently introduce molecular groups with temperature-sensitive conformational transition; The molecular group, such as an oligomer of poly(N-isopropyl acrylamide), is designed to have a lower critical solution temperature (LCST) slightly higher than the normal physiological temperature (such as 37°C), and at normal temperature, the group has an extended conformation, which has no obvious effect on the adjacent ester bond hydrolysis reaction; When the ambient temperature rises and exceeds its LCST, the molecular group will undergo conformational contraction and transform into a collapsed globular structure. This physical change in conformation will directly increase the steric hindrance around the ester bond hydrolysis site, thereby slowing down the hydrolysis rate of the ester bond kinetically, which counteracts the acceleration of hydrolysis caused by temperature rise, thereby temperature compensating the fiber degradation clock and ensuring the accuracy of its functional life within a certain temperature fluctuation range; In order to realize non-invasive monitoring of the degradation process of the fiber, functional nanoclusters can also be covalently introduced in the chemical modification step; Functional nanoclusters, such as encapsulated gas precursor nanoparticles, are wrapped by a dense matrix network when the fiber structure is intact, and remain chemically stable and do not produce detectable signals; When the preset programmed degradation is started, the large number of backbone glycosidic bond breakage causes the fiber matrix structure to become loose and porous rapidly in a short time, and this physical change in structure enables the surrounding body fluid to penetrate and react with the gas precursor, activating it to generate at least one signal source selected from microbubbles and structures causing acoustic impedance changes that can be detected by an ultrasonic imaging device; In this way, the structural disintegration process of the fiber is no longer an invisible event, but a physical signal release synchronized with the degradation stage, providing a window for external observation to judge the structural integrity state.

[0035] After the fiber has completed its functional mission and disintegrates, to accelerate its removal in the application environment, the chemical modification scheme of the method is also configured such that the modified alginate forms functional groups with multivalent chelating ability on the surface and ends of the fiber fragments when the main chain breaks; this is achieved by introducing specific molecular groups during modification, which are shielded in terms of chelating ability when the main chain is intact, and once the main chain breaks, the groups are exposed and activated as new chain ends; these functional groups can bind to metal ions or receptor sites on the surface of cells with high affinity and multivalency, thereby guiding phagocytes and the like to recognize and remove them, and changing the terminal removal process of the fiber from passive metabolism to an active trapping removal; the alginate fiber prepared by the foregoing method can meet specific two-stage degradation characteristics in a phosphate buffer solution at 37°C: the tensile strength retention rate is not less than 80% of the initial value during the first stage of the stable period; the tensile strength decreases by more than 50% of the initial value during the subsequent second stage of the rapid disintegration period; and the ratio of the average tensile strength loss rate during the second stage of the rapid disintegration period to the average tensile strength loss rate during the first stage of the stable period is not less than 50; the combination of these series of technical features jointly constructs a new type of alginate fiber and its preparation method with highly controllable degradation behavior, highly uniform product performance, and process state monitoring.

[0036] Example 1: In an in vivo implant application that requires long-term mechanical support and then rapid and residue-free degradation, such as absorbable tendon fixation suture, the technical challenge lies in ensuring that the tensile strength of the suture material does not decay during the 6 to 8 week period of tendon healing, and that the material can rapidly disintegrate after this period to avoid triggering long-term foreign body reactions or affecting tissue remodeling. The linear or logarithmic degradation curve of conventional degradable materials cannot meet both performance requirements; for this scenario, an alginate fiber suture is prepared using the method of the present application, by selecting an ester bond with a specific steric hindrance structure as the side chain chemical group in the chemical modification step, and setting its hydrolysis half-life to 7 weeks, i.e. 49 days; at the same time, the weak covalent bond sensitive to shear force introduced in the chemical modification step, together with the reducing agent microcapsules dispersed in the spinning dope, constitute a quality control mechanism that acts during the fiber manufacturing process; during the spinning extrusion process, the inhomogeneous chain segments in the raw material preferentially break at the weak covalent bond due to shear stress, and the broken chain ends are immediately activated by the reducing agent microcapsules, which repair the broken chain ends; the purpose of this series of steps is to make the polymer chains entering the coagulation bath have similar molecular weight distribution, thereby ensuring the consistency of the programmed degradation clock starting point and rate within all fibers, and establishing a prerequisite for the predictability of the final degradation behavior.

[0037] After the suture is applied to the tendon fixation, the mechanical integrity of the fiber is maintained by its internal stable ion crosslinking network in the first 6 weeks of its functional life, the tensile strength remains above 80% of the initial value, providing a reliable fixation force for tissue healing; at the same time, the ester bond of the side chain, which is not affected by the fluctuation of the ion concentration and pH value of the surrounding body fluid, starts to hydrolyze at a uniform rate as an internal chemical clock; when local inflammation occurs after surgery, causing the temperature in the implanted area to rise from 37°C to 38.5°C, the molecular groups with temperature-sensitive conformational transition covalently grafted on the molecular chain undergo conformational contraction, increasing the steric hindrance around the ester bond, thereby slowing down the hydrolysis rate. The slowing down effect balances the hydrolysis acceleration effect brought by the temperature rise, so that the timing accuracy of the degradation clock is not affected by the pathological temperature fluctuations; by the 7th week, most of the ester bonds have been hydrolyzed, and a large number of activated catalytic functional groups use the ortho assistance effect to trigger the multi-point synchronous rupture of the main chain glycosidic bond in a short period of time, and the mechanical properties of the fiber rapidly decrease within a few days, with a strength loss of more than 50%, transforming from a stable load-bearing structure to small molecular fragments that can be absorbed; finally, after the tendon tissue is healed with sufficient and stable mechanical support, the suture material disintegrates on its own after the preset time point, avoiding the risk of chronic inflammation that may be caused by long-term implants; this process no longer relies on the interaction between the regulating material and the external environment to control the degradation rate, but through an internal chemical reaction sequence determined by the molecular structure, it resolves the contradiction between long-term performance stability and final rapid disintegration within a single material system.

[0038] Example 2: To quantitatively verify the effectiveness of the two-stage degradation characteristics of the seaweed fiber, i.e., maintaining stable mechanical properties within a preset time window and then rapidly disintegrating the structure, the following comparative test is carried out; two sample groups are set up, among which the control group uses unmodified sodium alginate to prepare seaweed fibers through the conventional wet spinning process; the sample group of the present application uses the above method to prepare seaweed fibers, and in the chemical modification step, the introduction ratio of the side chain chemical group is set to 3 per 100 alginate repeat units, and by selecting the corresponding ester bond chemical structure, the starting time point of the programmed degradation is set to 30 days; all fiber samples are prepared under the same spinning and post-processing conditions to ensure the consistency of the initial diameter and mechanical properties; the test environment is set to simulate a simulated body fluid environment, i.e., the two groups of fiber samples are respectively placed in a phosphate buffer solution (PBS) with a pH value of 7.4, and aged in a constant temperature water bath at 37°C; the mechanical properties are characterized by a tensile strength tester, which is configured with a mechanical sensor with a range of 5N and a data acquisition resolution of 0.001N. During the test, the tensile rate is set to 10mm / min.

[0039] After the start of the test, fiber samples are taken from the solutions of the two sample groups at preset time points, tensile strength tests are performed, and the retention rates relative to the initial strength are calculated; by comparing the strength retention rates of the two groups of samples with time, two different decay trends can be observed; the strength retention rate of the control group samples presents a continuous and gradual decline throughout the 35-day test period, and by the 28th day, the strength retention rate has decreased to 65.2%, and by the 35th day, it has further decreased to 53.6%; unlike this, the sample group of the application shows high stability in the early stage of the test, and by the 28th day, the strength retention rate still maintains 89.1%, however, between the 28th day and the 32nd day, its mechanical properties undergo a sharp transition, and the strength retention rate rapidly drops from 89.1% to 35.2% in 4 days, and by the 35th day, it decreases to 18.9%; the difference shown by the test data corresponds to the degradation mechanisms of the two fibers; the gradual decay of the control group is an external feature of its structure dependent on passive ion exchange for degradation; the curve of the sample group of the application showing a stable first and then a sharp drop is a manifestation of its internal programmed degradation mechanism, and in the stable period of the first 28 days, the mechanical properties of the fiber are guaranteed by the ion crosslinking network, and the internal ester bond of the side chain acts as a chemical clock for slow hydrolysis, when the hydrolysis reaction is completed around the set 30th day, the released catalytic functional groups trigger rapid main chain scission, leading to the disintegration of the fiber macrostructure; the test results show that the preparation method of the application can realize programmed control of the functional life of the fiber by setting a timing and execution mechanism in the chemical structure of the fiber, which is determined by molecular reaction.

[0040] To further verify the signal release and terminal clearance characteristics of the fiber in the structural disintegration stage, the sample of the sample group of the application at the 35th day, i.e. the fiber fragments that have undergone structural disintegration, are subjected to two consecutive tests; the first test is in vitro ultrasonic observation, and the phosphate buffer solution containing the fiber fragments is placed in the water tank of the ultrasonic imaging equipment, and the results show that obvious microbubble signals can be observed around the fiber fragments, and the acoustic contrast effect is comparable to that of commercial microbubble contrast agents with matching concentration, which confirms that after the main chain is broken and the matrix structure is loosened, the pre-set functional nanoclusters are successfully activated and release detectable acoustic signals; the second test is an in vitro cell phagocytosis experiment, macrophages are co-cultured with fiber fragments, and microscopic imaging technology is used for observation at different time points, and the results show that the surface of the fiber fragments of the sample group of the application shows significant chemotaxis and adsorption to macrophages, and the phagocytosis rate is 5 to 7 times that of the control group fiber fragments that have also disintegrated, which shows that the functional groups with multivalent chelating ability exposed when the main chain is broken can effectively guide the rapid clearance of phagocytic cells to the fiber residues.

[0041] Example 3: This example combines Figures 1 to 7A seaweed fiber and a preparation method thereof are disclosed, as shown in Figure 1 In a normal physiological environment, the body temperature is at 37℃, at which the covalently grafted temperature-sensitive conformational group maintains an extended conformation, does not produce steric hindrance to the adjacent side chain ester bond, and enables the ester bond to hydrolyze at a normal rate, thereby accurately timing the degradation clock; when the physiological environment is heated due to inflammation, for example, the temperature rises to 38.5℃, the increased temperature will, on one hand, produce an effect of accelerating the hydrolysis of the ester bond, but on the other hand, will also be transmitted to the temperature-sensitive conformational group, triggering a conformational transition thereof to a spherical structure, which increases the steric hindrance around the ester bond, thereby producing an effect of slowing down the hydrolysis. The hydrolysis acceleration effect and the hydrolysis slowing down effect counteract each other, and the final result is that the timing accuracy of the degradation clock is maintained, so that the programmed degradation time of the fiber is not affected by the fluctuation of the environmental temperature.

[0042] As shown in Figure 2 , a set of comparative experimental data directly shows the two-stage programmed degradation characteristics of the seaweed fiber of the present application, in which the horizontal coordinate is time, in days, and the vertical coordinate is the tensile strength retention rate, in %; the dashed line representing the control group (unmodified) shows that the tensile strength retention rate continuously and gradually decreases throughout the test period; in contrast, the solid line representing the sample group (programmed degradation) of the present application shows that the tensile strength remains at a high level close to the initial value for a long period of 28 days before the test, showing high stability, and then sharply decreases after the preset time point, rapidly disintegrates within a few days, showing the characteristics of stable first and then sharply decreasing, which confirms the effectiveness of the internal programmed degradation mechanism.

[0043] As shown in Figure 3 , the overall preparation process of the seaweed fiber of the present application and the embedded self-repairing quality control mechanism are disclosed, which starts from the sodium alginate macromolecular chain as the raw material for preparation. The sodium alginate macromolecular chain is first chemically modified to introduce the programmed self-degradation and self-repairing quality control function, then the modified product is prepared into a spinning solution, and the reducing agent microcapsules are uniformly dispersed therein. In the wet spinning extrusion link, the shear stress suffered by the spinning solution will trigger the quality control mechanism, that is, the uneven chain segments in the raw material will break under high shear stress, and the broken products will further activate the surrounding reducing agent microcapsules to release the reducing agent to repair the broken molecular chain ends. The spinning solution that has undergone the self-repairing link is finally extruded into a coagulation bath containing divalent cations to form the final product, the seaweed fiber, which has the programmed degradation ability through ion crosslinking.

[0044] As shown in Figure 4As shown, in the first stage of stable period, the complete ionic crosslinking network ensures the mechanical properties of the fiber, and the tensile strength retention rate is not less than 80%, at this time the protected catalytic functional group is in a non-activated state, and the ester bond of the side chain acts as an internal clock to slowly hydrolyze, after the transition period, the ester bond hydrolysis is completed, the shielded catalytic functional group is activated and released, and then the main chain is immediately broken at multiple points in a short time, so that the fiber enters the second stage of rapid disintegration period, at this time the fiber matrix is completely disintegrated, and the tensile strength rapidly decreases to below 50%.

[0045] Example 4: This embodiment provides a standardized engineering calibration procedure for determining the specific chemical modification parameters of the seaweed fiber of the present application, to realize the accurate setting of the programmed degradation period and the modification ratio of the fiber; in the engineering practice of fiber preparation, it is necessary to develop products with different functional life for different application scenarios, one kind of fiber for skin suture has a functional life requirement of 21 days, while another kind of fiber for tendon repair needs a mechanical property stable period of up to 90 days, therefore it is necessary to establish a method for meeting the technical requirements of these two kinds of differentiation by parameterizing the control of a single raw material system; in order to realize the setting of the fiber degradation period, a hydrolysis kinetics database of side chain chemical groups is first established; the initial state of this procedure is to select the same size of sodium alginate raw material as described above, and prepare a group of candidate alcohol small molecules for subsequent coupling, these small molecules have the same catalytic functional group which can be protected, but the chemical structure of the ester bond formation site has a systematic gradient change, the structure adjustment methods include adjusting the branching degree of the alkyl chain to adjust the steric hindrance, and introducing different functional groups on the aromatic ring to adjust the electronic effect; the execution steps of the procedure are: under the same reaction conditions, each candidate alcohol small molecule is covalently coupled to the sodium alginate macromolecular chain at a fixed introduction ratio of 2 per 100 alginate repeat units, to prepare a series of modified alginate samples; then, the fibers made of these samples are placed in a 37°C, pH 7.4 phosphate buffer solution for accelerated aging test, and the concentration of small molecule alcohol released due to ester bond hydrolysis is monitored at different time points by high performance liquid chromatography, thereby drawing the hydrolysis kinetics curve for each side chain chemical group structure and determining its hydrolysis half-life; through this experimental database, the corresponding relationship between the molecular structure of the side chain chemical group and its degradation half-life in the simulated body fluid environment can be established, when a fiber with a specific life is needed, the corresponding chemical structure can be directly selected from the database for modification, thereby converting the selection of the degradation period into an engineering operation with data support.

[0046] After the side chain chemical group structure that can meet the 90-day life requirement is determined, the proportion of the side chain chemical group structure is further optimized to maximize the initial mechanical properties of the fiber while ensuring the reliability of degradation; this procedure uses a gradient experiment method, uses the selected side chain chemical group structure, and modifies the sodium alginate according to five gradients of 1.0%, 2.0%, 3.0%, 4.0%, and 5.0% to prepare five groups of fiber samples with different modification proportions; then, the five groups of samples are tested for two key performance indicators: one is the initial dry tensile strength, and the other is the time point at which the strength decreases to less than 50% of the initial value in a simulated body fluid environment; the test results show that as the introduction proportion increases, the time point at which the fiber strength decreases sharply is closer and closer to the set 90 days, but the initial tensile strength shows a downward trend; when the introduction proportion is 1.0%, the initial strength of the fiber is the highest, but the degradation start time is delayed to about 115 days, and when the introduction proportion is 5.0%, the degradation start time is closest to 90 days, but the initial strength has decreased by about 18%; through the trade-off analysis of the two sets of performance data, 3.5% is finally determined as the introduction proportion for the 90-day life tendon repair fiber, and under this proportion, the initial strength loss of the fiber is less than 10%, and the actual degradation start time deviates from the set value by less than 5%.

[0047] Example 5: This embodiment provides a process parameter calibration procedure aimed at ensuring that the self-repairing quality control mechanism stably operates in continuous production, the core of which is to establish a matching relationship between the shear stress in the spinning process and the breaking threshold of the introduced shear-sensitive weak covalent bond; in the industrial wet spinning process of seaweed fiber, the shear stress suffered by the spinning dope when passing through the spinneret is affected by factors such as the viscosity of the dope, the extrusion rate, and the geometric size of the spinneret. In order to enable the shear stress to induce selective breaking of weak covalent bonds on molecular weight heterogeneous segments while avoiding damage to the alginate backbone, the following pre-calibration process needs to be performed before production; first, a rotational rheometer is used to perform a shear scanning test on a specific batch of spinning dope containing weak covalent bonds and microcapsules of a reducing agent, and the target shear stress threshold τ_target that induces the breaking of weak covalent bonds is determined by monitoring the mutation point of the viscosity during the increase of the shear rate; second, according to the fluid mechanics model of the spinning equipment, i.e., the functional relationship between the shear stress τ_spin at the spinneret and the viscosity η of the spinning dope, the volume extrusion rate Q, and the radius R of the spinneret, the actual shear stress τ_spin is calibrated within a working interval around the target threshold by adjusting the controllable variable volume extrusion rate Q, and the upper and lower limits of the working interval are determined based on the minimum stress value that ensures effective breaking of heterogeneous segments and the maximum stress limit that avoids damage to the main chain, respectively.

[0048] To verify the effectiveness of the above calibration procedure, the calibrated volumetric extrusion rate was used to conduct experimental spinning on two groups of spinning dope; among them, the first group of dope contains modified alginate with known heterogeneous molecular weight distribution, and the second group contains modified alginate with highly homogeneous molecular weight distribution as a control; the molecular weight distribution of the fiber samples obtained from the two groups of experiments was detected by gel permeation chromatography (GPC), and the results showed that although the initial raw materials were different, the final molecular weight distribution curves of the two groups of fiber samples were basically coincided, and both showed the characteristics of single narrow peak; the results showed that the established process parameter calibration procedure can accurately activate the self-repairing quality control mechanism in the production process, thereby eliminating the influence of raw material batch fluctuation on the uniformity of the final product, and providing a uniform material basis for the predictability of the final degradation performance of the fiber.

[0049] Example 6: This example provides a standardized procedure aimed at establishing a correlation model between the chemical properties of sodium alginate raw materials and the core process parameters, in order to eliminate the influence of batch-to-batch differences in raw materials on the performance of the final fiber product; in the continuous production of fibers, in order to ensure that different batches of sodium alginate raw materials can all produce fiber products with consistent performance indicators, it is necessary to establish a process parameter matrix between the key chemical properties of the raw materials and the optimal ion concentration of the coagulation bath; the establishment process of this procedure is as follows: first, select multiple batches of sodium alginate raw materials with gradient differences in M / G ratio, and the M / G ratio is quantitatively characterized by nuclear magnetic resonance spectroscopy; then, each batch of raw material is prepared into a spinning dope with the same chemical modification parameters according to the above procedure.

[0050] For each M / G ratio of the spinning dope, an independent optimization experiment of the coagulation bath ion concentration is performed; this experiment aims to obtain fibers with both tensile strength and network stability, and the spinning dope is extruded into a series of coagulation baths with calcium chloride concentrations increasing by 0.5% step gradient through a fixed spinning assembly; the initial dry tensile strength and equilibrium swelling rate of the fiber samples formed in each concentration coagulation bath are tested; through analysis of the test data, an optimal calcium chloride concentration is determined for each M / G ratio, which can make the obtained fiber have sufficient tensile strength while its equilibrium swelling rate is within a preset interval representing a stable network structure; by fitting the M / G ratio and the corresponding optimal calcium chloride concentration data points of all batches of raw materials, a process parameter matrix that can guide production is obtained; in subsequent regular production, when a new batch of raw material is put in, only the M / G ratio needs to be determined first, and then the optimal coagulation bath concentration matching it can be directly obtained or calculated through this parameter matrix, thereby saving a lot of repetitive experiments; this procedure changes the original trial-and-error process adjustment into a standardized pre-setting process based on data model, ensuring the batch-to-batch stability of the performance of the fiber product.

[0051] Example 7: To prepare a target seaweed fiber with a stable period of 28-30 days, seaweed sodium alginate with a M / G ratio of 1.2 was selected as the raw material; the chemical modification steps were as follows: 10 g of seaweed sodium alginate was dissolved in 500 ml of pure water, under nitrogen protection and stirring, 2-(2-hydroxyethoxy) ethanol and the ester formed by glycine protected by tert-butoxy carbonyl (Boc) were added, so that the molar ratio of the carboxyl group on the seaweed sodium alginate to the ester was 0.1:1, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC-HCl) and N-hydroxysulfosuccinimide (Sulfo-NHS) were added as catalysts, and the reaction was carried out at room temperature for 24 hours; after the reaction was completed, the unreacted small molecules were removed by dialysis, and the product was obtained by freeze-drying; it was confirmed by nuclear magnetic resonance hydrogen spectrum that the introduction ratio of the side chain chemical group was 3.8 per 100 seaweed alginate repeat units, the hydrolysis half-life period of the side chain ester bond in a simulated body fluid environment (37°C, pH 7.4 PBS buffer) was 29.5 days as determined by high performance liquid chromatography; and the preparation of the spinning dope: the above modified seaweed sodium alginate was prepared into a 6% (w / v) aqueous solution, and reducing agent microcapsules prepared from polycaprolactone (PCL) as a wall material and ascorbic acid as a core material were added to the solution in an amount of 0.8% of the dry weight of the seaweed sodium alginate; at the same time, glutaraldehyde was added as a weak covalent bond forming agent, and the molar ratio of glutaraldehyde to the remaining available hydroxyl groups on the seaweed sodium alginate was 0.05:1, and after stirring uniformly, it was left to deaerate; and the wet spinning process: the above spinning dope was extruded through a spinneret with a pore size of 0.1 mm at a rate of 15 ml / hour into a 2.5% (w / v) calcium chloride aqueous solution coagulation bath, the temperature of the coagulation bath was maintained at 20°C, and after the fiber traveled 1 meter in the coagulation bath, it was drawn, washed with water and dried, and the mechanical property decay curve of the prepared fiber in a PBS buffer solution at 37°C was highly consistent with the curve of the sample group of the present application as shown in Figure 2 The strength retention rate was 88% at the 28th day and rapidly decreased to 34% at the 32nd day.

[0052] It is obvious to those skilled in the art that the present application is not limited to the details of the above exemplary embodiments, and the present application can be implemented in other specific forms without departing from the spirit or essential characteristics of the present application.

[0053] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present application and are not limiting, and although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. A method for producing seaweed fibers, characterized by, The method comprises: chemically modifying carboxyl groups on a sodium alginate macromolecular chain, specifically comprising: selecting sodium alginate with an M / G ratio of 1.2 as a raw material; the chemical modification step is as follows: 10 g of sodium alginate is dissolved in 500 ml of pure water, under nitrogen protection and stirring, an ester formed by 2-(2-hydroxyethoxy) ethanol and glycine protected by tert-butyloxycarbonyl Boc is added, so that the molar ratio of the ester to the carboxyl groups on the sodium alginate is 0.1:1, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride EDC-HCl and N-hydroxysulfosuccinimide Sulfo-NHS are added as catalysts, and the reaction is carried out at room temperature for 24 hours; after the reaction is completed, the unreacted small molecules are removed by dialysis, and the product is obtained by freeze-drying; it is confirmed by nuclear magnetic resonance hydrogen spectrum that the introduction ratio of the side chain chemical group is 3.8 per 100 alginate repeat units, the hydrolysis half-life of the side chain ester bond in a simulated body fluid environment at 37 DEG C and pH 7.4 PBS buffer is 29.5 days, which is determined by high performance liquid chromatography; and the preparation of a spinning dope: the above modified sodium alginate is prepared into a 6% w / v aqueous solution, reducing agent microcapsules prepared by using polycaprolactone PCL as a wall material and ascorbic acid as a core material are added to the solution, and the addition amount is 0.8% of the dry weight of the sodium alginate; at the same time, glutaraldehyde is added as a weak covalent bond forming agent, and the molar ratio of the glutaraldehyde to the remaining available hydroxyl groups on the sodium alginate is 0.05:1, the solution is stirred uniformly and then left to deaerate; and a wet spinning process: the above spinning dope is extruded into a calcium chloride aqueous solution coagulation bath with a concentration of 2.5% w / v through a spinneret with a pore size of 0.1 mm at a rate of 15 ml / h, the coagulation bath temperature is maintained at 20 DEG C, and the fiber travels in the coagulation bath for 1 meter before being drawn, washed and dried.

2. The method of claim 1, wherein the seaweed fiber is prepared by the steps of: A molecule group with a temperature-sensitive conformational transition is also introduced in the chemical modification, the molecule group is a polymer with a lower critical solution temperature LCST, the LCST value is in the range of 37 DEG C to 42 DEG C, the molecule group shrinks in conformation when the ambient temperature rises, so that the degree of slowing down of the ester bond hydrolysis rate counterbalances the effect of the hydrolysis acceleration caused by the temperature rise when the ambient temperature rises.

3. The method of claim 1, wherein the seaweed fiber is prepared by the steps of: A functional nanocluster is also covalently introduced in the chemical modification, the functional nanocluster is activated to generate at least one signal source selected from a microbubble and a structure causing acoustic impedance change which can be detected by an ultrasonic imaging device when the main chain glycosidic bond is broken to cause the fiber matrix structure to be loose. ​ 4. A seaweed fiber, characterized by, The seaweed fiber is prepared by the preparation method of claim 1.

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