Polymer solution, electrospun nanofibrous membrane and preparation method therefor

Abstract

The present disclosure relates to a polymer solution, an electrospun nanofibrous membrane and a preparation method therefor, pertaining to the technical field of electrospinning. The polymer solution includes, in parts by weight, 5-20 parts by weight of an amorphous in vivo-degradable polymer, 0.5-3 parts by weight of a water-soluble polymer, 0.01-1.5 parts by weight of an antibacterial agent and a solvent. In the above, a weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand. After the polymer solution forms the electrospun nanofibrous membrane, the electrospun nanofibrous membrane can make the antimicrobial agent well released and effectively suppress bacterial growth, thereby optimizing antibacterial efficacy of the electrospun nanofibrous membrane.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a U.S. National Stage under 35 U.S.C. § 371 of Chinese Application No. PCT / CN2025 / 072129 filed on Jan. 13, 2025, which claims priority to Chinese Application No. 202410083511.8 filed with the Chinese Patent Office on Jan. 19, 2024 and entitled “POLYMER SOLUTION, ELECTROSPUN NANOFIBROUS MEMBRANE AND PREPARATION METHOD THEREFOR”, the contents of which are incorporated herein by reference in entirety.TECHNICAL FIELD

[0002] The present disclosure relates to the technical field of electrospinning, and particularly to a polymer solution, an electrospun nanofibrous membrane (film) and a preparation method therefor.BACKGROUND ART

[0003] In the prior art, an electrospun nanofibrous membrane can be applied to a damaged tissue site so as to promote tissue repair. As the damaged tissue site is accompanied by inflammation, antibacterial components are typically incorporated into the electrospun nanofibrous membrane to suppress bacterial growth.

[0004] However, in practical applications, the inventors have found from researches that the effect of antibacterial agents inside the membrane is often suboptimal, leading to excessive bacterial proliferation at the damaged tissue site and delayed healing of damaged tissues.SUMMARY

[0005] In view of shortcomings of the prior art, objective of embodiments of the present disclosure includes providing a polymer solution, an electrospun nanofibrous membrane and a preparation method therefor. After the polymer solution forms the electrospun nanofibrous membrane, the electrospun nanofibrous membrane effectively suppresses bacterial growth, thereby enhancing antibacterial efficacy of the electrospun nanofibrous membrane.

[0006] In the first aspect, embodiments of the present disclosure provide a polymer solution, including, in parts by weight, 5-20 parts by weight of an amorphous in vivo-degradable polymer, 0.5-3 parts by weight of a water-soluble polymer, 0.01-1.5 parts by weight of an antibacterial agent and a solvent. In the above, a weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand.

[0007] In the above technical solution, the amorphous in vivo-degradable polymer has excellent biocompatibility and degradability. Therefore, in the polymer solution, the high-molecular-weight amorphous in vivo-degradable polymer has a higher content, and serves as a dominant component of the polymer solution, so as to enable the subsequently obtained electrospun nanofibrous membrane to have superior biocompatibility and degradability. The electrospun nanofibrous membrane with that component as a dominant component is likely to shrink after coverage or occlusion at a damaged tissue site, resulting in compromised efficacy of the antibacterial agent. Through investigations into the cause of shrinkage, the inventors have revealed that due to presence of exudate in a tissue damage environment, the amorphous in vivo-degradable polymer will absorb water and swell, causing amorphous molecular chain slippage, thereby reducing a glass transition temperature of the material to or below the human body temperature (36° C.-38° C.), and thus inducing shrinkage thereof. In the present disclosure, a small amount of the water-soluble polymer is incorporated into the polymer solution, then the exudate at the damaged tissue site will preferentially interact with the water-soluble polymer to swell, thus the exudate at the damaged site is less likely to interact with the amorphous in vivo-degradable polymer to alter the glass transition temperature thereof, which can restrict the shrinkage of the electrospun nanofibrous membrane to a certain extent, enable the antibacterial agent to well exert its efficacy, and effectively suppress the bacterial growth, thus resulting in enhanced antibacterial efficacy of the electrospun nanofibrous membrane.

[0008] In some embodiments, the water-soluble polymer includes a synthetic water-soluble polymer, with a weight-average molecular weight not less than 50 thousand, and the antibacterial agent is a low-molecular-weight antibacterial agent, with a weight-average molecular weight not more than 10 thousand.

[0009] In the above technical solutions, the low-molecular-weight antibacterial agent fails to form fibrous structures on the electrospun nanofibrous membrane, it typically exists on the electrospun nanofibrous membrane in a granular or short linear shape, and after the electrospun nanofibrous membrane shrinks, the antibacterial agent is likely to be partially entrapped within the shrinking electrospun nanofibrous membrane, resulting in compromised performance of the antibacterial agent. Nevertheless, the incorporation of a small amount of the synthetic water-soluble polymer with a high molecular weight can solve this problem, that is, the polymer, which can form fibrous filaments with the amorphous in vivo-degradable polymer, can preferentially interact with the exudate at the damaged tissue site, and can also play a role in stabilizing fibrous structures, thereby making the electrospun nanofibrous membrane less prone to shrinkage, and optimizing the performance of the antibacterial agent.

[0010] In some embodiments, the polymer solution further includes 0.1-3 parts by weight of a bioactive substance.

[0011] In the above technical solutions, the bioactive substance incorporated can synergize with the low-molecular-weight antibacterial agent, thus enabling the electrospun nanofibrous membrane to promote cellular proliferation, effectively suppress bacterial growth, and facilitate tissue repair and regeneration.

[0012] In some embodiments, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; a weight-average molecular weight of the bioactive substance is greater than 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0013] In the above technical solutions, the weight-average molecular weights of the bioactive substance and the synthetic water-soluble polymer both range from 50 thousand to 500 thousand, the bioactive substance and the synthetic water-soluble polymer with high molecular weight can form fibrous filaments with the amorphous in vivo-degradable polymer during the electrospinning, so that the performance of the bioactive substance can be enhanced, the bioactive substance is synergized with the low-molecular-weight antibacterial agent, thus enabling the electrospun nanofibrous membrane to have excellent antibacterial and proliferation efficacies, and facilitating tissue repair and regeneration.

[0014] In some embodiments, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; a weight-average molecular weight of the bioactive substance ranges from 1 thousand to 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0015] In the above technical solutions, synergistic combination of the high-molecular-weight amorphous in vivo-degradable polymer and synthetic water-soluble polymer can endow the electrospun nanofibrous membrane with excellent biocompatibility and degradability along with anti-shrinkage property. Moreover, coordination with a small amount of the low-molecular-weight bioactive substance and antimicrobial agent enables optimization of their performance.

[0016] In some embodiments, the polymer solution includes: 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-2 parts by weight of the bioactive substance, 0.5-2 parts by weight of the synthetic water-soluble polymer, and 0.1-1.5 parts by weight of the antibacterial agent.

[0017] In the above technical solutions, incorporating a small amount of the synthetic water-soluble polymer can well suppress shrinkage of the electrospun nanofibrous membrane, thus enabling optimal functional performance of the bioactive substance and the antimicrobial agent following incorporation of a small amount of the two, thereby enhancing overall performance of the electrospun nanofibrous membrane.

[0018] In some embodiments, the parts by weight X of the amorphous in vivo-degradable polymer is greater than a sum Y of the parts by weight of the bioactive substance, the synthetic water-soluble polymer and the antibacterial agent.

[0019] In the above technical solutions, as a dominant component of the polymer solution, the amorphous in vivo-degradable polymer can endow the electrospun nanofibrous membrane with better biocompatibility and degradation effect, and it is synergized with the synthetic water-soluble polymer, to enable optimal performance of the antimicrobial agent and the bioactive substance even if they are incorporated in a small amount.

[0020] In some embodiments, X>5×Y.

[0021] In some embodiments, the amorphous in vivo-degradable polymer includes at least one of racemic polylactic acid and poly(lactic-co-glycolic acid) copolymer.

[0022] In the above technical solutions, the above materials selected have good in vivo degradability and biocompatibility, so as to serve as a dominant component of the electrospun nanofibrous membrane.

[0023] In some embodiments, the bioactive substance includes at least one of collagen, growth factor, silk fibroin, zein, gelatin and hyaluronic acid.

[0024] In the above technical solutions, the above choices of bioactive substance have favorable efficacy in promoting cellular proliferation, thereby enabling the electrospun nanofibrous membrane to promote tissue repair and regeneration.

[0025] In some embodiments, the synthetic water-soluble polymer includes at least one of polyethylene oxide, polyethylene glycol, polyvinyl alcohol, polyacrylamide and polyvinyl pyrrolidone.

[0026] In the above technical solutions, incorporation of a small amount of the above components can well improve an anti-shrinkage effect of the electrospun nanofibrous membrane, thereby ensuring optimal performance of the antibacterial agent and bioactive substance.

[0027] In some embodiments, the antibacterial agent includes an inorganic antibacterial agent and / or an organic antibacterial agent.

[0028] In the above technical solutions, the molecular weight of the antibacterial agent is low, and if the electrospun nanofibrous membrane shrinks, the efficacy of the antibacterial agent is compromised. Therefore, the antibacterial agent is synergized with other components in the polymer solution, thus enhancing the efficacy of the antibacterial agent.

[0029] In some embodiments, the organic antibacterial agent includes at least one of guanidine antibacterial agent, β-lactam antibacterial agent and quaternary ammonium salt antibacterial agent.

[0030] In some embodiments, the guanidine antibacterial agent includes at least one of polyhexamethylene guanidine, polyhexamethylene biguanide, polyaminopropyl biguanide and dodecylguanidine acetate.

[0031] In some embodiments, the β-lactam antibacterial agent includes penicillin and / or cephalosporin.

[0032] In some embodiments, the quaternary ammonium salt antibacterial agent includes at least one of alkyl trimethyl ammonium chloride, alkyl dimethyl benzyl ammonium chloride and tetradecyl-2-methylpyridinium ammonium bromide.

[0033] In some embodiments, a mass proportion of a solute in the polymer solution ranges from 5% to 30%

[0034] In the above technical solutions, when the mass proportion of the solute in the polymer solution is maintained within the above range, it facilitates stable formation of fibrous filaments by an electrospinning device, and a fibrous structure of the electrospun nanofibrous membrane can mimic extracellular matrix, thereby facilitating tissue repair and regeneration upon coverage or occlusion at the damaged tissue site.

[0035] In the second aspect, the present disclosure provides an electrospinning method, including: spraying the polymer solution according to any item in the first aspect onto a collector at an electrospinning voltage ranging from 5 kV to 30 kV, and a polymer solution flow rate ranging from 0.2 ml / h to 1 ml / h.

[0036] In the above technical solution, an electrospun nanofibrous membrane obtained under the above electrospinning parameters is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.

[0037] In some embodiments, an electrospinning environment maintains a temperature ranging from 20° C. to 35° C., and humidity ranging from 35% to 60%.

[0038] In the above technical solutions, the electrospinning conducted in the environment with such temperature and humidity enables electrospinning stability, and facilitates the formation of a stable electrospun nanofibrous membrane.

[0039] In some embodiments, the collector is a collection roller, and a rotational speed of the collection roller ranges from 300 r / min to 3000 r / min.

[0040] In the above technical solutions, it enables more uniform nanofiber distribution of the electrospun nanofibrous membrane, and facilitates evaporation of the solvent from the polymer solution during the electrospinning.

[0041] In the third aspect, the present disclosure provides an electrospun nanofibrous membrane, prepared by the electrospinning method provided by any item in the second aspect.

[0042] In the above technical solutions, the electrospun nanofibrous membrane prepared by the method is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.BRIEF DESCRIPTION OF DRAWING

[0043] In order to more clearly illustrate technical solutions of embodiments of the present disclosure, drawing which needs to be used in the embodiments will be briefly introduced below, and it should be understood that the drawing merely shows some embodiments of the present disclosure, and thus should not be construed as limitation to the scope. Those ordinarily skilled in the art still could obtain other relevant drawings according to the drawing, without using any inventive efforts.

[0044] FIG. 1 is diagrams of antibacterial performance of electrospun nanofibrous membranes provided by some examples and comparative examples of the present disclosure.DETAILED DESCRIPTION OF EMBODIMENTS

[0045] An electrospun nanofibrous membrane is a fibrous thin film fabricated by an electrospinning method, with high strength and flexibility. In order to impart some functions to the electrospun nanofibrous membrane, substances having corresponding functions are typically incorporated into an polymer solution for electrospinning. For example, if an electrospun nanofibrous membrane is to be imparted with an antibacterial efficacy, an antibacterial agent having an antibacterial efficacy is typically incorporated into the polymer solution, so as to suppress bacterial growth.

[0046] The electrospun nanofibrous membrane with antibacterial performance is usually applied to cover or occlude a damaged tissue site (for example, tissues may be skin, subcutaneous fascia, muscle, tendon sheath, ligament, peripheral nerve vessels, etc.). Thus, if the electrospun nanofibrous membrane has excellent in vivo absorption or metabolism properties along with remarkable biocompatibility, the electrospun nanofibrous membrane can exhibit optimal efficacy. Therefore, an amorphous in vivo-degradable polymer (for example, poly(lactic-co-glycolic acid) copolymer) can be used as a substrate material for the electrospun nanofibrous membrane. When the substrate material is formed into an electrospun nanofibrous membrane, and applied to cover or occlude a damaged tissue site, an issue of shrinkage often occurs over time, which compromises antibacterial agent efficacy in the electrospun nanofibrous membrane.

[0047] Through investigations into the cause of shrinkage of the electrospun nanofibrous membrane, the inventors have revealed that under a drying condition, a glass transition temperature of the poly(lactic-co-glycolic acid) copolymer is around 48° C. (its deformation temperature is higher than ambient temperature and human body temperature), while due to presence of certain exudate at the damaged tissue site, matrix components of the poly(lactic-co-glycolic acid) copolymer in electrospun nanofibrous membrane are likely to absorb water and swell, causing amorphous molecular chain slippage, and prolonged water absorption reduces the glass transition temperature of the material, thereby making the glass transition temperature align with or fall below the human body temperature (36° C.-38° C.), and inducing shrinkage thereof. Therefore, to address the shrinkage of the amorphous in vivo-degradable polymer during prolonged coverage or occlusion at the damaged tissue site, the polymer solution, the electrospinning method and the electrospun nanofibrous membrane are optimized, specifically as follows.Polymer Solution

[0048] The present disclosure provides a polymer solution, including, in parts by weight, 5-20 parts by weight of an amorphous in vivo-degradable polymer, 0.5-3 parts by weight of a water-soluble polymer, 0.01-1.5 parts by weight of an antibacterial agent and a solvent. In the above, a weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand.

[0049] Degradability encompasses in vitro biodegradation (for example, soil degradation, and environmental degradation) and in vivo biodegradation (in vivo absorption or metabolism). The in vitro biodegradation does not confer superior biocompatibility (meaning being safe, non-toxic and having low or no rejection reaction in human body), and in vivo biodegradation typically exhibits favorable biocompatibility, so as to facilitate coverage or occlusion of the formed electrospun nanofibrous membrane at the damaged tissue site. The amorphous in vivo-degradable polymer refers to that the polymer exhibits both in vivo absorption or metabolism and amorphous characteristics, demonstrating a certain swelling effect in a medium such as water or ethanol, which causes relative slippage of molecular chains. Therefore, the electrospun nanofibrous membrane formed from the amorphous in vivo-degradable polymer by electrospinning exhibits shrinkage after prolonged coverage or occlusion at the damaged tissue site. The present disclosure makes improvements in view of the shrinkage characteristic of the polymer. The weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand, and in the electrospun nanofibrous membrane formed from the polymer solution, the amorphous in vivo-degradable polymer is a primary component for forming fibrous filaments, and it serves as a matrix of the electrospun nanofibrous membrane.

[0050] The water-soluble polymer refers to a biological water-soluble polymer or / and a synthetic water-soluble polymer. The biological water-soluble polymer refers to that the polymer is derived from a biological raw material (such as bioactive substance). The synthetic water-soluble polymer refers to that the polymer is artificially synthesized, while natural biological materials do not contain that substance. The water-soluble polymer in the present disclosure may be biologically derived, artificially synthesized, or both, which is not limited in the present disclosure.

[0051] In such polymer solution, the amorphous in vivo-degradable polymer has excellent biocompatibility and degradability. Therefore, in the polymer solution, the high-molecular-weight amorphous in vivo-degradable polymer has a higher content, and serves as a dominant component of the polymer solution, so as to enable the subsequently obtained electrospun nanofibrous membrane to have superior biocompatibility and degradability. The electrospun nanofibrous membrane with that component as a dominant component is likely to shrink after coverage or occlusion at the damaged tissue site, resulting in compromised efficacy of the antibacterial agent. Through investigations into the cause of shrinkage, the inventors have revealed that due to presence of exudate in a tissue damage environment, the amorphous in vivo-degradable polymer will absorb water and swell, causing amorphous molecular chain slippage, thereby reducing the glass transition temperature of the material to or below the human body temperature (36° C.-38° C.), and thus inducing shrinkage thereof. In the present disclosure, a small amount of a water-soluble polymer is incorporated into the polymer solution, then the exudate at the damaged tissue site will preferentially interact with the water-soluble polymer to swell, thus the exudate at the damaged tissue site is less likely to interact with the amorphous in vivo-degradable polymer to alter the glass transition temperature thereof, which can restrict the shrinkage of the electrospun nanofibrous membrane to a certain extent, enable the antibacterial agent to well exert its efficacy, and effectively suppress the bacterial growth, thus resulting in enhanced antibacterial efficacy of the electrospun nanofibrous membrane.

[0052] In some embodiments, the water-soluble polymer includes a synthetic water-soluble polymer, with a weight-average molecular weight not less than 50 thousand; and the antibacterial agent is a low-molecular-weight antibacterial agent, with a weight-average molecular weight not more than 10 thousand. The synthetic water-soluble polymer with a high molecular weight can form fibrous filaments with the amorphous in vivo-degradable polymer. The antibacterial agent with a low molecular weight substantially cannot form fibrous filaments, and is typically in a granular or short linear shape.

[0053] As the antibacterial agent has a low molecular weight and fails to form fibrous structures on the electrospun nanofibrous membrane, it typically exists on the electrospun nanofibrous membrane in a granular or short linear shape, and after the electrospun nanofibrous membrane shrinks, the antibacterial agent is likely to be partially entrapped within the shrinking electrospun nanofibrous membrane, resulting in compromised performance of the antibacterial agent. Nevertheless, the incorporation of a small amount of the synthetic water-soluble polymer with a high molecular weight can solve this problem, that is, the polymer, which can form fibrous filaments with the amorphous in vivo-degradable polymer, can preferentially interact with the exudate at the damaged tissue site, and can also play a role in stabilizing fibrous structures, thereby making the electrospun nanofibrous membrane less prone to shrinkage, and optimizing the performance of the antibacterial agent.

[0054] In some embodiments, the polymer solution further includes 0.1-3 parts by weight of a bioactive substance. The bioactive substance incorporated can synergize with the low-molecular-weight antibacterial agent, thus enabling the electrospun nanofibrous membrane to promote cellular proliferation, effectively suppress bacterial growth, and facilitate tissue repair and regeneration.

[0055] The bioactive substance may or may not be water soluble. In some embodiments, the bioactive substance is a water-soluble bioactive substance, and the polymer solution includes 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.5-3 parts by weight of the water-soluble bioactive substance, 0.01-1.5 parts by weight of the antibacterial agent and the solvent. In the above, the weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand.

[0056] In some embodiments, the bioactive substance has a high weight-average molecular weight, and the polymer solution includes, in parts by weight, 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-3 parts by weight of the bioactive substance, 0.5-3 parts by weight of the synthetic water-soluble polymer, 0.01-1.5 parts by weight of the antibacterial agent and the solvent. The weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; the weight-average molecular weight of the bioactive substance is greater than 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0057] In the polymer solution, the amorphous in vivo-degradable polymer and the bioactive substance with a high weight-average molecular weight form fibrous filaments together, and an organic antibacterial agent with a low molecular weight fails to form fibrous filaments, and forms short linear or granular substances on the electrospun nanofibrous membrane. When the electrospun nanofibrous membrane is applied to cover or occlude a damaged tissue site, due to presence of exudate in the environment of the damaged tissue site, prolonged coverage or occlusion will cause water absorption and swelling of the amorphous in vivo-degradable polymer and amorphous molecular chain slippage, thereby reducing the glass transition temperature of the amorphous in vivo-degradable polymer to or below the human body temperature (36° C.-38° C.), which induces shrinkage of the electrospun nanofibrous membrane, and after the shrinkage, the short linear or granular organic antibacterial agent is partially encapsulated within the shrinking membrane, exhibits compromised performance, and fails to suppress the bacterial growth. While the bioactive substance forms fibrous filaments and co-shrinks with the electrospun nanofibrous membrane, and the properties of the bioactive substance still can be well utilized. Although the bioactive substance can promote cellular proliferation, it also promotes bacterial division, and suboptimal performance of the antibacterial agent in turn leads to increased bacterial load in the exudate. If the amount of the antibacterial agent is increased, the biocompatibility of the electrospun nanofibrous membrane is comprised. Therefore, the synthetic water-soluble polymer with a high weight-average molecular weight is incorporated in the present disclosure, and it can form filaments together with the amorphous in vivo-degradable polymer and the bioactive substance during the electrospinning, then the exudate at the damaged tissue site preferentially interacts with the synthetic water-soluble polymer to swell, and the exudate at the damaged tissue site is less likely to interact with the amorphous in vivo-degradable polymer to swell; and the synthetic water-soluble polymer also plays a role in stabilizing fibrous structures, mitigating the shrinkage of the electrospun nanofibrous membrane, and optimizing the performance of the antimicrobial agent. Moreover, the bioactive substance can promote cellular proliferation, thereby enabling the electrospun nanofibrous membrane to facilitate tissue repair and regeneration.

[0058] Exemplarily, the weight-average molecular weight of the amorphous in vivo-degradable polymer is 80 thousand, 100 thousand, 120 thousand, 140 thousand, 160 thousand, 180 thousand, 200 thousand, 220 thousand, 240 thousand, 260 thousand, 280 thousand or 300 thousand; the weight-average molecular weight of the synthetic water-soluble polymer is 50 thousand, 100 thousand, 150 thousand, 200 thousand, 250 thousand, 300 thousand, 350 thousand, 400 thousand, 450 thousand or 500 thousand; the weight-average molecular weight of the bioactive substance is 10 thousand, 50 thousand, 100 thousand, 150 thousand, 200 thousand, 250 thousand, 300 thousand, 350 thousand, 400 thousand, 450 thousand or 500 thousand; and the weight-average molecular weight of the organic antibacterial agent is 1 thousand, 2 thousand, 3 thousand, 4 thousand, 5 thousand, 6 thousand, 7 thousand, 8 thousand, 9 thousand or 10 thousand.

[0059] Optionally, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 100 thousand to 300 thousand; and the weight-average molecular weights of both the bioactive substance and the synthetic water-soluble polymer range from 50 thousand to 300 thousand. The three polymer substances forming fibrous filaments have relatively narrow weight-average molecular weight distribution, so as to form a relatively uniform electrospun nanofibrous membrane, which can further solve the problem of inadequate performance of the antibacterial agent due to the shrinkage of the electrospun nanofibrous membrane, thereby optimizing the performance of both the antibacterial agent and the bioactive substance. It should be noted that, the weight-average molecular weights of both the bioactive substance and the synthetic water-soluble polymer range from 50 thousand to 300 thousand, which does not mean that the weight-average molecular weights of the two are the same, while the weight-average molecular weights of the two may be the same, or different, which is not limited in the present disclosure.

[0060] In some other embodiments, the bioactive substance has a low weight-average molecular weight, and the polymer solution includes, in parts by weight, 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-3 parts by weight of the bioactive substance, 0.5-3 parts by weight of the synthetic water-soluble polymer, 0.01-1.5 parts by weight of the antibacterial agent and the solvent. The weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; the weight-average molecular weight of the bioactive substance ranges from 1 thousand to 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0061] In the polymer solution, the amorphous in vivo-degradable polymer forms fibrous filaments. The organic antibacterial agent and the bioactive substance with a low molecular weight fail to form fibrous filaments, and form short linear or granular substances on the electrospun nanofibrous membrane. When the electrospun nanofibrous membrane is applied to cover or occlude a damaged tissue site, due to presence of exudate in the environment of the damaged tissue site, prolonged coverage or occlusion will cause water absorption and swelling of the amorphous in vivo-degradable polymer and amorphous molecular chain slippage, thereby reducing the glass transition temperature of the amorphous in vivo-degradable polymer to or below the human body temperature (36° C.-38° C.), which induces shrinkage of the electrospun nanofibrous membrane, and after the shrinkage, the short linear or granular organic antibacterial agent and bioactive substance are partially encapsulated in the shrinking membrane, fail to exert optimal performance, and exhibit unfavorable effects in suppressing the bacterial growth and promoting the cellular proliferation. If the amounts of the antibacterial agent and the bioactive substance are increased, the biocompatibility of the electrospun nanofibrous membrane is comprised. Therefore, the synthetic water-soluble polymer with a high weight-average molecular weight is incorporated in the present disclosure, and it can form fibrous filaments together with the amorphous in vivo-degradable polymer and the bioactive substance during the electrospinning, then the exudate at the damaged tissue site preferentially interacts with the synthetic water-soluble polymer to swell, and the exudate at the damaged tissue site is less likely to interact with the amorphous in vivo-degradable polymer to swell; and the synthetic water-soluble polymer also plays a role in stabilizing fibrous structures, mitigating the shrinkage of the electrospun nanofibrous membrane, optimizing the performance of the antimicrobial agent and the bioactive substance, and suppressing the bacterial growth and promoting cellular proliferation, thereby enabling the electrospun nanofibrous membrane to facilitate tissue repair and regeneration.

[0062] Exemplarily, the weight-average molecular weight of the amorphous in vivo-degradable polymer is 80 thousand, 100 thousand, 120 thousand, 140 thousand, 160 thousand, 180 thousand, 200 thousand, 220 thousand, 240 thousand, 260 thousand, 280 thousand, or 300 thousand; the weight-average molecular weight of the synthetic water-soluble polymer is 50 thousand, 100 thousand, 150 thousand, 200 thousand, 250 thousand, 300 thousand, 350 thousand, 400 thousand, 450 thousand or 500 thousand; the weight-average molecular weight of the bioactive substance is 1 thousand, 3 thousand, 5 thousand, 7 thousand, 9 thousand or 10 thousand; and the weight-average molecular weight of the organic antibacterial agent is 1 thousand, 2 thousand, 3 thousand, 4 thousand, 5 thousand, 6 thousand, 7 thousand, 8 thousand, 9 thousand or 10 thousand.

[0063] Optionally, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 100 thousand to 300 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 100 thousand to 300 thousand; and the weight-average molecular weight of the bioactive substance ranges from 1 thousand to 10 thousand. The two polymer substances forming fibrous filaments have relatively narrow weight-average molecular weight distribution, so as to form a relatively uniform electrospun nanofibrous membrane, which can further solve the problem of inadequate performance of the antibacterial agent due to the shrinkage of the electrospun nanofibrous membrane, thereby optimizing the performance of both the antibacterial agent and the bioactive substance. It should be noted that, the weight-average molecular weights of both the amorphous in vivo-degradable polymer and the synthetic water-soluble polymer range from 100 thousand to 300 thousand, which does not mean that the weight-average molecular weights of the two are the same, while the weight-average molecular weights of the two may be the same, or different, which is not limited in the present disclosure.

[0064] In other embodiments, the weight-average molecular weight of the amorphous in vivo-degradable polymer further may be 320 thousand, 340 thousand, 360 thousand, 380 thousand, 400 thousand, 420 thousand, 440 thousand, 460 thousand, 480 thousand, 500 thousand, etc.; the weight-average molecular weight of the synthetic water-soluble polymer is 520 thousand, 540 thousand, 560 thousand, 580 thousand or 600 thousand, etc.; and the weight-average molecular weight of the organic antibacterial agent further may be 5 hundred, 6 hundred, 7 hundred, 8 hundred or 9 hundred, etc.; and the weight-average molecular weight of the bioactive substance further may be 550 thousand, 600 thousand, etc.

[0065] Exemplarily, in parts by weight, in the polymer solution, X parts by weight of the amorphous in vivo-degradable polymer may be 5 parts, 8 parts, 10 parts, 12 parts, 15 parts, 18 parts or 20 parts; Y1 parts by weight of the bioactive substance may be 0.1 parts, 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts or 3 parts; Y2 parts by weight of the water-soluble polymer may be 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts or 3 parts; Y3 parts by weight of the antibacterial agent may be 0.1 parts, 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts or 5 parts.

[0066] Optionally, the polymer solution includes, in parts by weight, 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-2 parts by weight of the bioactive substance, 0.5-2 parts by weight of the synthetic water-soluble polymer, and 0.1-1.5 parts by weight of the antibacterial agent. Incorporation of a small amount of the synthetic water-soluble polymer can well suppress the shrinkage of the electrospun nanofibrous membrane, so as to optimize the performance of the bioactive substance and antibacterial agent following a small amount of incorporation of the two, thereby enhancing comprehensive performance of the electrospun nanofibrous membrane.

[0067] Further, the parts by weight X of the amorphous in vivo-degradable polymer is greater than a sum Y (Y=Y1+Y2+Y3) of the parts by weight of the bioactive substance, the synthetic water-soluble polymer and the antibacterial agent. As a dominant component of the polymer solution, the amorphous in vivo-degradable polymer can endow the electrospun nanofibrous membrane with better biocompatibility and degradation effect, and it is synergized with the synthetic water-soluble polymer, to well exert the performance of the antibacterial agent and the bioactive substance even if they are incorporated in a small amount.

[0068] Further, X>5×Y, which enables both optimal efficacies of the bioactive substance and the antibacterial agent, and excellent biocompatibility and degradability of the electrospun nanofibrous membrane.

[0069] In some embodiments, the amorphous in vivo-degradable polymer includes at least one of racemic polylactic acid and poly(lactic-co-glycolic acid) copolymer. The materials selected have good in vivo degradability and biocompatibility, so as to serve as a dominant component of the electrospun nanofibrous membrane for repairing the damaged tissue site.

[0070] The present disclosure does not limit specific components of the amorphous in vivo-degradable polymer, as long as the amorphous polymer is biodegradable and biocompatible.

[0071] In some embodiments, the bioactive substance includes at least one of collagen, growth factor, silk fibroin, zein, gelatin and hyaluronic acid. The above choices of bioactive substance have favorable efficacy in promoting cellular proliferation, thereby enabling the electrospun nanofibrous membrane to promote tissue repair and regeneration.

[0072] The bioactive substance may or may not be soluble in water. In some embodiments, the bioactive substance may be soluble in water (for example, the bioactive substance soluble in water is one or more of growth factor, gelatin and hyaluronic acid), which can be incorporated as a bioactive substance in the polymer solution, and can also be incorporated as a water-soluble polymer in the polymer solution. A water-soluble polymer is also incorporated while incorporating the water-soluble bioactive substance, so that components of the polymer solution are simple. In other embodiments, even if a water-soluble bioactive substance is incorporated into the polymer solution, a synthetic water-soluble polymer can also be incorporated into the polymer solution.

[0073] In some embodiments, among the bioactive substances, collagen, silk fibroin, zein, gelatin and hyaluronic acid are bioactive substances with a weight-average molecular weight greater than or equal to 10 thousand. Among the bioactive substances, growth factor and enzyme digestion oligomeric sodium hyaluronate are bioactive substances with a weight-average molecular weight of less than 10 thousand.

[0074] The present disclosure does not limit specific components of the bioactive substance, as long as the bioactive substance can promote cellular proliferation.

[0075] In some embodiments, the synthetic water-soluble polymer includes at least one of polyethylene oxide, polyethylene glycol, polyvinyl alcohol, polyacrylamide and polyvinyl pyrrolidone. These polymers are synthetic water-soluble polymers, and incorporation of a small amount of the above components can well improve an anti-shrinkage effect of the electrospun nanofibrous membrane, thereby ensuring optimal performance of the antibacterial agent and bioactive substance.

[0076] The present disclosure does not limit components of the synthetic water-soluble polymer, as long as the polymer can mitigate the shrinkage property of the electrospun nanofibrous membrane with the amorphous in vivo-degradable polymer as a dominant component.

[0077] In some embodiments, the low-molecular-weight antibacterial agent includes an inorganic antibacterial agent and / or an organic antibacterial agent. The molecular weight of the antibacterial agent is low. If the electrospun nanofibrous membrane shrinks, the efficacy of the antibacterial agent is compromised. Therefore, the antibacterial agent is synergized with other components in the polymer solution, thus enhancing the efficacy of the antibacterial agent.

[0078] In the above, the inorganic antibacterial agent includes at least one of silver sulfate, zinc oxide, copper oxide, ammonium dihydrogen phosphate and lithium carbonate.

[0079] The organic antibacterial agent includes at least one of guanidine antibacterial agent, β-lactam antibacterial agent and quaternary ammonium salt antibacterial agent.

[0080] In some embodiments, the guanidine antibacterial agent includes at least one of polyhexamethylene guanidine, polyhexamethylene biguanide, polyaminopropyl biguanide and dodecylguanidine acetate. The β-lactam antibacterial agent includes penicillin and / or cephalosporin. The quaternary ammonium salt antibacterial agent includes at least one of alkyl trimethyl ammonium chloride, alkyl dimethyl benzyl ammonium chloride and tetradecyl-2-methylpyridinium ammonium bromide. As organic antibacterial agents, these antibacterial agents are predominantly formed into short linear structures after electrospinning, and the shrinkage of the electrospun nanofibrous membrane has a relatively small impact on the performance of the antibacterial agent (relative to the inorganic antibacterial agent). Therefore, synergistic combination with other components in the polymer solution (e.g., synthetic water-soluble polymer) can enhance the efficacy of the organic antibacterial agent.

[0081] The present disclosure does not limit specific components of the antibacterial agent, and all antibacterial agents with antibacterial performance applicable in the polymer solution fall within the scope of protection of the present disclosure.

[0082] In some embodiments, the solvent includes one or more of hexafluoroisopropanol, chloroform, dichloromethane, trifluoroacetic acid, dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, acetic acid, water, methanol, ethanol, and isopropanol. These solvents can well dissolve other components in the polymer solution, thus facilitating subsequent formation of the electrospun nanofibrous membrane by electrospinning. If the solvent is merely water, it cannot dissolve all components in the polymer solution, but can be synergized with other solvents to dissolve other components in the polymer solution. Selecting one or more solvents in the present disclosure is related to choices of other components in the polymer solution, and those skilled in the art could make adjustments according to actual situations.

[0083] The present disclosure does not limit the components of the solvent, and all solvents that can dissolve other components in the polymer solution fall within the scope of protection of the present disclosure.

[0084] In some embodiments, a mass proportion of a solute in the polymer solution ranges from 5% to 30%, where the solute is a substance other than the solvent in the polymer solution, and the mass proportion of the solute is solute / (solute+solvent)×100%.

[0085] When the mass proportion of the solute in the polymer solution is maintained within the above range, it facilitates formation of fibrous filaments by an electrospinning device, and a fibrous structure of the electrospun nanofibrous membrane can mimic extracellular matrix, thereby facilitating tissue repair and regeneration upon coverage or occlusion at the damaged tissue site.

[0086] Exemplarily, the mass proportion of the solute in the polymer solution is 5%, 10%, 15%, 20%, 25% or 30%. Optionally, the mass proportion of the solute in the polymer solution ranges from 10% to 20%.Preparation Method for the Polymer Solution

[0087] The present disclosure provides a preparation method for the polymer solution, with other components in the preceding polymer solution dispersed in the solvent. The components in the polymer solution are the preceding components and will not be reiterated herein. The preparation method is mainly described.

[0088] In some embodiments, the amorphous in vivo-degradable polymer is first dispersed in the solvent to form a mixed solution 1, and then the bioactive substance, the synthetic water-soluble polymer and the antibacterial agent are dispersed in the mixed solution 1 to form the polymer solution. The amorphous in vivo-degradable polymer is incorporated at a high amount, and it is first dissolved and dispersed in the solvent, followed by dissolution and dispersion of other components, so as to enable a better dissolving and dispersing effect of the polymer solution, thereby rendering a more uniform polymer solution.

[0089] In other embodiments, each component may be dispersed separately in the solvent and then mixed to form the polymer solution. Alternatively, other components are first dispersed in the solvent, followed by dispersion of the amorphous in vivo-degradable polymer.Electrospinning Method

[0090] The present disclosure provides an electrospinning method, using the preceding polymer solution for electrospinning, including: spraying the polymer solution onto a collector at an electrospinning voltage ranging from 5 kV to 30 kV, and a polymer solution flow rate ranging from 0.2 ml / h to 1 ml / h. An electrospun nanofibrous membrane obtained under such electrospinning parameters is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.

[0091] Exemplarily, the electrospinning voltage is 5 kV, 10 kV, 15 kV, 20 kV, 25 kV or 30 kV; and the polymer solution flow rate is 0.2 ml / h, 0.4 ml / h, 0.6 ml / h, 0.8 ml / h or 1 ml / h. Optionally, the electrospinning voltage ranges from 5 kV to 20 kV; and the polymer solution flow rate ranges from 0.4 ml / h to 0.8 ml / h.

[0092] In some embodiments, an electrospinning environment maintains a temperature ranging from 20° C. to 35° C., and humidity ranging from 35% to 60%. The electrospinning conducted in the environment with such temperature and humidity enables electrospinning stability, and facilitates the formation of a stable electrospun nanofibrous membrane.

[0093] Exemplarily, the temperature of the electrospinning environment is 20° C., 22° C., 25° C., 28° C., 30° C., 32° C. or 35° C., and the humidity is 35%, 40%, 45%, 50%, 55% or 60%.

[0094] In some embodiments, the collector is a collection roller, and a rotational speed of the collection roller ranges from 300 r / min to 3000 r / min, which enables more uniform nanofiber distribution of the electrospun nanofibrous membrane, and facilitates evaporation of the solvent from the polymer solution during the electrospinning.

[0095] Exemplarily, the rotational speed of the collection roller is 300 r / min, 500 r / min, 800 r / min, 1000 r / min, 1200 r / min, 1500 r / min, 1800 r / min, 2000 r / min, 2200 r / min, 2500 r / min, 2800 r / min or 3000 r / min. Optionally, the rotational speed of the collection roller ranges from 500 r / min to 2000 r / min.Electrospun Nanofibrous Membrane

[0096] The present disclosure provides an electrospun nanofibrous membrane, prepared with the above polymer solution by the preceding electrospinning method. The electrospun nanofibrous membrane prepared by the method has excellent biocompatibility, can mitigate the shrinkage of the electrospun nanofibrous membrane, is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.

[0097] In other embodiments, the polymer solution further can be formed on a collector by coating, so as to form a membrane material. The polymer solution in the present disclosure is not limited to electrospinning membrane formation, while membrane formation by other electrospinning methods or coating methods is also encompassed within the scope of protection of the present disclosure.

[0098] In order to make objectives, technical solutions and advantages of embodiments of the present disclosure clearer, the technical solutions in examples of the present disclosure will be described below clearly and completely. Examples, for which no concrete conditions are specified, are carried out according to conventional conditions or conditions recommended by manufactures. If manufacturers of reagents or apparatuses used are not specified, they are conventional products commercially available.Example 1

[0099] A polymer solution was provided, including, in parts by weight, 20 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.4 g of hydrolyzed collagen (Col, with weight-average molecular weight of 200 thousand), 1 g of polyethylene oxide (PEO, with weight-average molecular weight of 400 thousand), 0.3 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 78.3 g of hexafluoroisopropanol (HFIP).

[0100] A preparation method for the polymer solution included:

[0101] step 1: weighing 20 g of poly(lactic-co-glycolic acid) copolymer granules into 82.3 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0102] step 2: weighing 0.4 g of hydrolyzed collagen freeze-dried tablets, 1 g of polyethylene oxide powder, and 0.3 g of PHMB powder into the PLGA solution obtained in step 1 using the precision electronic balance, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PHMB / Col / PEO / PLGA polymer solution;

[0103] Step 3: loading the above PHMB / Col / PEO / PLGA polymer solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0104] Step 4: drying a nanofiber material prepared by the above electrospinning at room temperature for 12 h, so as to obtain a PHMB / Col / PLGA (PEO-containing) nanofiber membrane.Example 2

[0105] Example 2 was substantially identical to Example 1, except that the poly(lactic-co-glycolic acid) copolymer in Example 1 was replaced with racemic polylactic acid (PDLLA, Poly(D,L-lactide), D,L-polylactide, with weight-average molecular weight of 100 thousand) powder in Example 2; and the solvent hexafluoroisopropanol in Example 1 was replaced with tetrahydrofuran in Example 2.Example 3

[0106] Example 3 was substantially identical to Example 1, except that polyethylene oxide was not added.Example 4

[0107] Example 4 was substantially identical to Example 1, except that the polyethylene oxide powder in Example 1 was replaced with polyvinyl alcohol (PVA, with weight-average molecular weight of 80 thousand) powder in Example 4.Example 5

[0108] Example 5 was substantially identical to Example 1, except that the polyethylene oxide powder in Example 1 was replaced with polyvinyl pyrrolidone (PVP, with weight-average molecular weight of 60 thousand) powder in Example 5.Example 6

[0109] Example 6 was substantially identical to Example 1, except that the collagen freeze-dried tablets in Example 1 were replaced with 2 g of gelatin (Gel, with weight-average molecular weight of 80 thousand) particles in Example 6, and the amount of PHMB was 0.1 g.Example 7

[0110] Example 7 was substantially identical to Example 1, except that collagen in Example 1 was replaced with 0.5 g of fibroblast growth factor (FGF, with weight-average molecular weight of 6 thousand) freeze-dried powder in Example 7, and the amount of the poly(lactic-co-glycolic acid) copolymer was 10 g.Example 8

[0111] Example 8 was substantially identical to Example 1, except that PHMB in Example 1 was replaced with 0.01 g of amoxicillin (with molecular weight of 365.4) in Example 8, and the amount of poly(lactic-co-glycolic acid) copolymer was 10 g.Example 9

[0112] Example 9 was substantially identical to Example 1, except that PHMB in Example 1 was replaced with 0.01 g of silver sulfate (with molecular weight of 169.87) in Example 9, and the amount of poly(lactic-co-glycolic acid) copolymer was 18 g.Examples 10-11

[0113] Examples 10-11 were substantially identical to Example 1, except that the amounts of various components were different, specifically as listed in Table 1.Example 12

[0114] A polymer solution was provided, including, in parts by weight, 10 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.4 g of collagen (Col, with weight-average molecular weight of 200 thousand), 3 g of polyethylene oxide (PEO, with weight-average molecular weight of 400 thousand), 0.3 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 86.3 g of hexafluoroisopropanol (HFIP).

[0115] A preparation method for the polymer solution included:

[0116] step 1: weighing 10 g of poly(lactic-co-glycolic acid) copolymer granules into 86.3 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0117] step 2: weighing 0.4 g of collagen, 3 g of polyethylene oxide powder, and 0.3 g of PHMB powder into the PLGA solution obtained in step 1 using the precision electronic balance, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PHMB / Col / PEO / PLGA polymer solution;

[0118] step 3: loading the above PHMB / Col / PEO / PLGA polymer solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0119] step 4: drying a nanofiber material prepared by the above electrospinning method at room temperature for 12 h, so as to obtain a PHMB / Col / PLGA (PEO-containing) nanofiber membrane.Comparative Example 1

[0120] A polymer solution was provided, including, in parts by weight, 16 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer and 84 g of hexafluoroisopropanol (HFIP).

[0121] A preparation method for the polymer solution included:

[0122] step 1: weighing 16 g of poly(lactic-co-glycolic acid) copolymer granules into 84 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0123] step 2: loading the above PLGA solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0124] step 3: drying a nanofiber material prepared by the above electrospinning method at room temperature for 12 h, so as to obtain a PLGA nanofiber membrane.Comparative Example 2

[0125] A polymer solution was provided, including, in parts by weight, 16 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.5 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 83.5 g of hexafluoroisopropanol (HFIP).

[0126] A preparation method for the polymer solution included:

[0127] step 1: weighing 16 g of poly(lactic-co-glycolic acid) copolymer granules into 83.5 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0128] step 2: weighing 0.5 g of PHMB powder into the PLGA solution obtained in step 1 using the precision electronic balance, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PHMB / PLGA polymer solution;

[0129] step 3: loading the above PHMB / PLGA polymer solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0130] step 4: drying a nanofiber material prepared by the above electrospinning method at room temperature for 12 h, so as to obtain a PHMB / PLGA nanofiber membrane.Comparative Example 3

[0131] A polymer solution was provided, including, in parts by weight, 16 g of polyvinlbutaral (PVB, with weight-average molecular weight of 100 thousand) and 84 g of ethanol aqueous solution.

[0132] A preparation method for the polymer solution included:

[0133] step 1: weighing 16 g of polyvinlbutaral granules into 84 g of ethanol aqueous solution using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PVB solution;

[0134] step 2: loading the above PVB solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0135] step 3: drying a nanofiber material prepared by the above electrospinning at room temperature for 12 h, so as to obtain a PVB nanofiber membrane.Experimental Example 1

[0136] Performance of the electrospun nanofibrous membranes provided by Examples 1-12 and Comparative Examples 1-3 was tested, with results as listed in Table 1.

[0137] (1) Antibacterial performance was tested according to standard GB / T 20944.1-2007, with ATCC8739 Escherichia coli (E. coli) as test strain. The antibacterial performance was evaluated based on a size of an inhibition zone formed after a sample was added. The inhibition zone means that there are no bacteria growing in the area, and growth of bacteria around is suppressed. A larger inhibition zone indicates better antibacterial performance.

[0138] A specific method was as follows: all samples were first cut into a circle with a diameter of 3.55 cm, and were subjected to sterilization treatment under ultraviolet light irradiation for 2 h. Sterile nutrient agar was poured into a sterilized petri dish, and cooled and shaped under ultraviolet sterilization for later use. Subsequently 1501 of bacterial solution (at concentration of 10 CFU) was uniformly inoculated onto a culture medium, and the sterilized samples were placed at center of agar plates respectively, and put in a 37±1° C. biological incubator for 24 h.

[0139] Determination of the inhibition zone: Firstly, whether an area without bacterial growth appeared around the electrospun nanofibrous membrane was observed; if so, it indicated that the growth of bacteria was stopped when reaching an outer ring of the area, demonstrating a significant antibacterial efficacy, and a antibacterial area was an area of the outer ring; if not, the area of the electrospun nanofibrous membrane was further irradiated by a point light source to examine whether bacterial colonies appeared in a membrane-covered area, and if so, it indicated that the membrane had no antibacterial efficacy, and the antibacterial area was 0; if not, it indicated that bacteria failed to enter the membrane-covered area to grow, demonstrating that the membrane had certain antibacterial efficacy, and can prevent bacteria from entering the interior of dressing to grow.

[0140] The antibacterial performance of some samples is as shown in FIG. 1. In FIG. 1, an inner ring in the petri dishes represents the electrospun nanofibrous membrane, and a grey area surrounding the inner ring represents the inhibition zone. As can be seen from FIG. 1, compared with Examples 1 and 10, the PLGA electrospun nanofibrous membranes provided by Comparative Examples 1 and 2 had significant shrinkage, and failed to form the inhibition zone, thus having no antibacterial performance. Hence, it can be seen from Comparative Example 1 that the PLGA electrospun nanofibrous membrane provided by Comparative Example 1 was prone to shrinkage, and did not have antibacterial performance; and it can be seen from Comparative Example 2 that the PLGA electrospun nanofibrous membrane incorporated with the PHMB antibacterial agent still exhibited significant shrinkage, the performance of the antibacterial agent was compromised, and the antibacterial efficacy was still lacked. It can be seen from Example 1 and Example 10 that incorporating the synthetic water-soluble polymer polyethylene oxide into the electrospun nanofibrous membrane can significantly mitigate the shrinkage of the electrospun nanofibrous membrane, and the antibacterial efficacy of the electrospun nanofibrous membrane was effectively enhanced.(2) Cell Viability Experiment

[0141] A mouse fibroblast L929 cell line was selected for the cell viability experiment. Various test samples were set as experimental groups, and control groups did not contain any samples. First, the experimental groups were respectively placed into 12-well tissue culture plates, to be subjected to UV sterilization for 2 h, and subsequently L929 cells (1×105 / mL) were seeded into the 12-well tissue culture plates (12 parallel experiments were performed on each sample and test results were analyzed as in Table 1). The samples were all incubated in a 37° C., 5% CO2 incubator for 72 h. After the incubation period was ended, absorbance values at 570 nm were determined for each group by a microplate reader using the MTT method. By calculating an absorbance ratio, a cellular proliferation rate of each experimental group can be obtained, where a higher cellular proliferation rate indicates better cell viability, i.e., stronger tissue repair capability; and if the cellular proliferation rate is less than 100%, it is indicated that the sample is cytotoxic.TABLE 1Components of Polymer solutions and Performance of Electrospun nanofibrous membranesAmorphous inSyntheticArea of theCellularvivo-degradableBioactivewater-solubleAntibacterialinhibitionproliferationpolymersubstancepolymeragentSolventzone (cm2)rate (%)Example 120% PLGA0.4% Col1% PEO0.5% PHMBHFIP9.66 120.60 ± 10.09Example 216% PDLLA0.4% Col1% PEO0.3% PHMBTHF8.65166.47 ± 3.49Example 316% PLGA0.4% Col\0.3% PHMBHFIP4.62132.24 ± 1.75Example 416% PLGA0.4% Col1% PVA0.3% PHMBHFIP7.98146.90 ± 8.28Example 516% PLGA0.4% Col1% PVP0.3% PHMBHFIP7.49152.21 ± 5.52Example 616% PLGA2% gelatin1% PEO0.1% PHMBHFIP7.84138.61 ± 1.92Example 710% PLGA0.5% FGF1% PEO0.3% PHMBHFIP7.32141.44 ± 6.08Example 810% PLGA0.4% Col1% PEO0.01%HFIP8.51119.44 ± 5.18amoxicillinExample 918% PLGA0.4% Col1% PEO0.01% silverHFIP8.22119.13 ± 1.78sulfateExample 1016% PLGA0.4% Col1% PEO0.3% PHMBHFIP9.16132.05 ± 5.03Example 1120% PLGA0.4% Col2% PEO0.5% PHMBHFIP8.42135.06 ± 9.46Example 1210% PLGA0.4% Col3% PEO0.5% PHMBHFIP8.50121.37 ± 4.64Comparative16% PLGA\\\HFIP0133.65 ± 9.46Example 1Comparative16% PLGA\\0.5% PHMBHFIP0111.82 ± 4.40Example 2Comparative16% PVB\\\ethanol0 87.66 ± 1.80Example 3

[0142] It can be seen from Table 1 that, in Comparative Example 3, PVB caused certain cytotoxicity and affected cell growth activity. As can be seen from comparison between Comparative Example 1 and Comparative Example 2, PLGA had good biocompatibility, without cytotoxicity to cells, and the electrospun nanofiber structure also had a certain promoting effect on cell viability, but in the case where PLGA acted as a matrix of the polymer solution, even if the polymer solution was incorporated with the antibacterial agent PHMB, the resulting electrospun nanofibrous membrane substantially still exhibited no antibacterial efficacy. In Examples 1-12 of the present disclosure, in the case where the amorphous in vivo-degradable polymer acted as the matrix of the polymer solution, incorporating a small amount of the water-soluble polymer and the antibacterial agent can increase the antibacterial area of the electrospun nanofibrous membrane, thus optimizing the performance of the antibacterial agent.

[0143] As can be seen from comparison between Example 1 and Example 2, both PLGA and PDLLA selected as the amorphous in vivo-degradable polymer to synergize with the synthetic water-soluble polymer (PEO), the bioactive substance (Col, natural water-soluble polymer) and the antibacterial agent (PHMB) can enhance the performance of the antibacterial agent and the bioactive substance, suppress the bacterial growth (larger antibacterial area), and also promote cellular proliferation (higher cellular proliferation rate), thus facilitating tissue repair and regeneration.

[0144] Through comparison between Example 1 and Example 3, it can be seen that in the case where the amorphous in vivo-degradable polymer PLGA acted as a matrix of the polymer solution, compared with Example 3 merely incorporated with the bioactive substance (Col, natural water-soluble polymer), Example 1 was incorporated with both the synthetic water-soluble polymer (PEO) and the bioactive substance (Col, natural water-soluble polymer), the performance of the antibacterial agent and the bioactive substance can be further enhanced, the bacterial growth (larger antibacterial area) can be further suppressed, and cellular proliferation can further be promoted, thus facilitating tissue repair and regeneration.

[0145] Through comparison between Example 1, Example 4 to Example 9, it can be seen that selecting PEO, PVA or PVP as the synthetic water-soluble polymer, selecting Col, gelatin or FGF as the bioactive substance, and selecting PHMB, amoxicillin or silver sulfate as the antibacterial agent can well suppress the bacterial growth and promote cellular proliferation, thus facilitating tissue repair and regeneration.

[0146] The embodiments described above are only some but not all embodiments of the present disclosure. The detailed descriptions of the embodiments of the present disclosure are not intended to limit the scope of the present disclosure claimed, but merely illustrate chosen embodiments of the present disclosure. All of other embodiments obtained by those ordinarily skilled in the art based on the embodiments in the present disclosure without using any inventive efforts shall fall within the scope of protection of the present disclosure.

Examples

example 1

[0099]A polymer solution was provided, including, in parts by weight, 20 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.4 g of hydrolyzed collagen (Col, with weight-average molecular weight of 200 thousand), 1 g of polyethylene oxide (PEO, with weight-average molecular weight of 400 thousand), 0.3 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 78.3 g of hexafluoroisopropanol (HFIP).

[0100]A preparation method for the polymer solution included:[0101]step 1: weighing 20 g of poly(lactic-co-glycolic acid) copolymer granules into 82.3 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;[0102]step 2: weighing 0.4 g of hydrolyzed collagen freeze-dried tablets, 1 g of polyethylene oxide powder, and 0.3 g...

example 2

[0105]Example 2 was substantially identical to Example 1, except that the poly(lactic-co-glycolic acid) copolymer in Example 1 was replaced with racemic polylactic acid (PDLLA, Poly(D,L-lactide), D,L-polylactide, with weight-average molecular weight of 100 thousand) powder in Example 2; and the solvent hexafluoroisopropanol in Example 1 was replaced with tetrahydrofuran in Example 2.

example 3

[0106]Example 3 was substantially identical to Example 1, except that polyethylene oxide was not added.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a U.S. National Stage under 35 U.S.C. § 371 of Chinese Application No. PCT / CN2025 / 072129 filed on Jan. 13, 2025, which claims priority to Chinese Application No. 202410083511.8 filed with the Chinese Patent Office on Jan. 19, 2024 and entitled “POLYMER SOLUTION, ELECTROSPUN NANOFIBROUS MEMBRANE AND PREPARATION METHOD THEREFOR”, the contents of which are incorporated herein by reference in entirety.TECHNICAL FIELD

[0002] The present disclosure relates to the technical field of electrospinning, and particularly to a polymer solution, an electrospun nanofibrous membrane (film) and a preparation method therefor.BACKGROUND ART

[0003] In the prior art, an electrospun nanofibrous membrane can be applied to a damaged tissue site so as to promote tissue repair. As the damaged tissue site is accompanied by inflammation, antibacterial components are typically incorporated into the electrospun nanofibrous membrane to suppress bacterial growth.

[0004] However, in practical applications, the inventors have found from researches that the effect of antibacterial agents inside the membrane is often suboptimal, leading to excessive bacterial proliferation at the damaged tissue site and delayed healing of damaged tissues.SUMMARY

[0005] In view of shortcomings of the prior art, objective of embodiments of the present disclosure includes providing a polymer solution, an electrospun nanofibrous membrane and a preparation method therefor. After the polymer solution forms the electrospun nanofibrous membrane, the electrospun nanofibrous membrane effectively suppresses bacterial growth, thereby enhancing antibacterial efficacy of the electrospun nanofibrous membrane.

[0006] In the first aspect, embodiments of the present disclosure provide a polymer solution, including, in parts by weight, 5-20 parts by weight of an amorphous in vivo-degradable polymer, 0.5-3 parts by weight of a water-soluble polymer, 0.01-1.5 parts by weight of an antibacterial agent and a solvent. In the above, a weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand.

[0007] In the above technical solution, the amorphous in vivo-degradable polymer has excellent biocompatibility and degradability. Therefore, in the polymer solution, the high-molecular-weight amorphous in vivo-degradable polymer has a higher content, and serves as a dominant component of the polymer solution, so as to enable the subsequently obtained electrospun nanofibrous membrane to have superior biocompatibility and degradability. The electrospun nanofibrous membrane with that component as a dominant component is likely to shrink after coverage or occlusion at a damaged tissue site, resulting in compromised efficacy of the antibacterial agent. Through investigations into the cause of shrinkage, the inventors have revealed that due to presence of exudate in a tissue damage environment, the amorphous in vivo-degradable polymer will absorb water and swell, causing amorphous molecular chain slippage, thereby reducing a glass transition temperature of the material to or below the human body temperature (36° C.-38° C.), and thus inducing shrinkage thereof. In the present disclosure, a small amount of the water-soluble polymer is incorporated into the polymer solution, then the exudate at the damaged tissue site will preferentially interact with the water-soluble polymer to swell, thus the exudate at the damaged site is less likely to interact with the amorphous in vivo-degradable polymer to alter the glass transition temperature thereof, which can restrict the shrinkage of the electrospun nanofibrous membrane to a certain extent, enable the antibacterial agent to well exert its efficacy, and effectively suppress the bacterial growth, thus resulting in enhanced antibacterial efficacy of the electrospun nanofibrous membrane.

[0008] In some embodiments, the water-soluble polymer includes a synthetic water-soluble polymer, with a weight-average molecular weight not less than 50 thousand, and the antibacterial agent is a low-molecular-weight antibacterial agent, with a weight-average molecular weight not more than 10 thousand.

[0009] In the above technical solutions, the low-molecular-weight antibacterial agent fails to form fibrous structures on the electrospun nanofibrous membrane, it typically exists on the electrospun nanofibrous membrane in a granular or short linear shape, and after the electrospun nanofibrous membrane shrinks, the antibacterial agent is likely to be partially entrapped within the shrinking electrospun nanofibrous membrane, resulting in compromised performance of the antibacterial agent. Nevertheless, the incorporation of a small amount of the synthetic water-soluble polymer with a high molecular weight can solve this problem, that is, the polymer, which can form fibrous filaments with the amorphous in vivo-degradable polymer, can preferentially interact with the exudate at the damaged tissue site, and can also play a role in stabilizing fibrous structures, thereby making the electrospun nanofibrous membrane less prone to shrinkage, and optimizing the performance of the antibacterial agent.

[0010] In some embodiments, the polymer solution further includes 0.1-3 parts by weight of a bioactive substance.

[0011] In the above technical solutions, the bioactive substance incorporated can synergize with the low-molecular-weight antibacterial agent, thus enabling the electrospun nanofibrous membrane to promote cellular proliferation, effectively suppress bacterial growth, and facilitate tissue repair and regeneration.

[0012] In some embodiments, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; a weight-average molecular weight of the bioactive substance is greater than 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0013] In the above technical solutions, the weight-average molecular weights of the bioactive substance and the synthetic water-soluble polymer both range from 50 thousand to 500 thousand, the bioactive substance and the synthetic water-soluble polymer with high molecular weight can form fibrous filaments with the amorphous in vivo-degradable polymer during the electrospinning, so that the performance of the bioactive substance can be enhanced, the bioactive substance is synergized with the low-molecular-weight antibacterial agent, thus enabling the electrospun nanofibrous membrane to have excellent antibacterial and proliferation efficacies, and facilitating tissue repair and regeneration.

[0014] In some embodiments, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; a weight-average molecular weight of the bioactive substance ranges from 1 thousand to 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0015] In the above technical solutions, synergistic combination of the high-molecular-weight amorphous in vivo-degradable polymer and synthetic water-soluble polymer can endow the electrospun nanofibrous membrane with excellent biocompatibility and degradability along with anti-shrinkage property. Moreover, coordination with a small amount of the low-molecular-weight bioactive substance and antimicrobial agent enables optimization of their performance.

[0016] In some embodiments, the polymer solution includes: 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-2 parts by weight of the bioactive substance, 0.5-2 parts by weight of the synthetic water-soluble polymer, and 0.1-1.5 parts by weight of the antibacterial agent.

[0017] In the above technical solutions, incorporating a small amount of the synthetic water-soluble polymer can well suppress shrinkage of the electrospun nanofibrous membrane, thus enabling optimal functional performance of the bioactive substance and the antimicrobial agent following incorporation of a small amount of the two, thereby enhancing overall performance of the electrospun nanofibrous membrane.

[0018] In some embodiments, the parts by weight X of the amorphous in vivo-degradable polymer is greater than a sum Y of the parts by weight of the bioactive substance, the synthetic water-soluble polymer and the antibacterial agent.

[0019] In the above technical solutions, as a dominant component of the polymer solution, the amorphous in vivo-degradable polymer can endow the electrospun nanofibrous membrane with better biocompatibility and degradation effect, and it is synergized with the synthetic water-soluble polymer, to enable optimal performance of the antimicrobial agent and the bioactive substance even if they are incorporated in a small amount.

[0020] In some embodiments, X>5×Y.

[0021] In some embodiments, the amorphous in vivo-degradable polymer includes at least one of racemic polylactic acid and poly(lactic-co-glycolic acid) copolymer.

[0022] In the above technical solutions, the above materials selected have good in vivo degradability and biocompatibility, so as to serve as a dominant component of the electrospun nanofibrous membrane.

[0023] In some embodiments, the bioactive substance includes at least one of collagen, growth factor, silk fibroin, zein, gelatin and hyaluronic acid.

[0024] In the above technical solutions, the above choices of bioactive substance have favorable efficacy in promoting cellular proliferation, thereby enabling the electrospun nanofibrous membrane to promote tissue repair and regeneration.

[0025] In some embodiments, the synthetic water-soluble polymer includes at least one of polyethylene oxide, polyethylene glycol, polyvinyl alcohol, polyacrylamide and polyvinyl pyrrolidone.

[0026] In the above technical solutions, incorporation of a small amount of the above components can well improve an anti-shrinkage effect of the electrospun nanofibrous membrane, thereby ensuring optimal performance of the antibacterial agent and bioactive substance.

[0027] In some embodiments, the antibacterial agent includes an inorganic antibacterial agent and / or an organic antibacterial agent.

[0028] In the above technical solutions, the molecular weight of the antibacterial agent is low, and if the electrospun nanofibrous membrane shrinks, the efficacy of the antibacterial agent is compromised. Therefore, the antibacterial agent is synergized with other components in the polymer solution, thus enhancing the efficacy of the antibacterial agent.

[0029] In some embodiments, the organic antibacterial agent includes at least one of guanidine antibacterial agent, β-lactam antibacterial agent and quaternary ammonium salt antibacterial agent.

[0030] In some embodiments, the guanidine antibacterial agent includes at least one of polyhexamethylene guanidine, polyhexamethylene biguanide, polyaminopropyl biguanide and dodecylguanidine acetate.

[0031] In some embodiments, the β-lactam antibacterial agent includes penicillin and / or cephalosporin.

[0032] In some embodiments, the quaternary ammonium salt antibacterial agent includes at least one of alkyl trimethyl ammonium chloride, alkyl dimethyl benzyl ammonium chloride and tetradecyl-2-methylpyridinium ammonium bromide.

[0033] In some embodiments, a mass proportion of a solute in the polymer solution ranges from 5% to 30%

[0034] In the above technical solutions, when the mass proportion of the solute in the polymer solution is maintained within the above range, it facilitates stable formation of fibrous filaments by an electrospinning device, and a fibrous structure of the electrospun nanofibrous membrane can mimic extracellular matrix, thereby facilitating tissue repair and regeneration upon coverage or occlusion at the damaged tissue site.

[0035] In the second aspect, the present disclosure provides an electrospinning method, including: spraying the polymer solution according to any item in the first aspect onto a collector at an electrospinning voltage ranging from 5 kV to 30 kV, and a polymer solution flow rate ranging from 0.2 ml / h to 1 ml / h.

[0036] In the above technical solution, an electrospun nanofibrous membrane obtained under the above electrospinning parameters is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.

[0037] In some embodiments, an electrospinning environment maintains a temperature ranging from 20° C. to 35° C., and humidity ranging from 35% to 60%.

[0038] In the above technical solutions, the electrospinning conducted in the environment with such temperature and humidity enables electrospinning stability, and facilitates the formation of a stable electrospun nanofibrous membrane.

[0039] In some embodiments, the collector is a collection roller, and a rotational speed of the collection roller ranges from 300 r / min to 3000 r / min.

[0040] In the above technical solutions, it enables more uniform nanofiber distribution of the electrospun nanofibrous membrane, and facilitates evaporation of the solvent from the polymer solution during the electrospinning.

[0041] In the third aspect, the present disclosure provides an electrospun nanofibrous membrane, prepared by the electrospinning method provided by any item in the second aspect.

[0042] In the above technical solutions, the electrospun nanofibrous membrane prepared by the method is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.BRIEF DESCRIPTION OF DRAWING

[0043] In order to more clearly illustrate technical solutions of embodiments of the present disclosure, drawing which needs to be used in the embodiments will be briefly introduced below, and it should be understood that the drawing merely shows some embodiments of the present disclosure, and thus should not be construed as limitation to the scope. Those ordinarily skilled in the art still could obtain other relevant drawings according to the drawing, without using any inventive efforts.

[0044] FIG. 1 is diagrams of antibacterial performance of electrospun nanofibrous membranes provided by some examples and comparative examples of the present disclosure.DETAILED DESCRIPTION OF EMBODIMENTS

[0045] An electrospun nanofibrous membrane is a fibrous thin film fabricated by an electrospinning method, with high strength and flexibility. In order to impart some functions to the electrospun nanofibrous membrane, substances having corresponding functions are typically incorporated into an polymer solution for electrospinning. For example, if an electrospun nanofibrous membrane is to be imparted with an antibacterial efficacy, an antibacterial agent having an antibacterial efficacy is typically incorporated into the polymer solution, so as to suppress bacterial growth.

[0046] The electrospun nanofibrous membrane with antibacterial performance is usually applied to cover or occlude a damaged tissue site (for example, tissues may be skin, subcutaneous fascia, muscle, tendon sheath, ligament, peripheral nerve vessels, etc.). Thus, if the electrospun nanofibrous membrane has excellent in vivo absorption or metabolism properties along with remarkable biocompatibility, the electrospun nanofibrous membrane can exhibit optimal efficacy. Therefore, an amorphous in vivo-degradable polymer (for example, poly(lactic-co-glycolic acid) copolymer) can be used as a substrate material for the electrospun nanofibrous membrane. When the substrate material is formed into an electrospun nanofibrous membrane, and applied to cover or occlude a damaged tissue site, an issue of shrinkage often occurs over time, which compromises antibacterial agent efficacy in the electrospun nanofibrous membrane.

[0047] Through investigations into the cause of shrinkage of the electrospun nanofibrous membrane, the inventors have revealed that under a drying condition, a glass transition temperature of the poly(lactic-co-glycolic acid) copolymer is around 48° C. (its deformation temperature is higher than ambient temperature and human body temperature), while due to presence of certain exudate at the damaged tissue site, matrix components of the poly(lactic-co-glycolic acid) copolymer in electrospun nanofibrous membrane are likely to absorb water and swell, causing amorphous molecular chain slippage, and prolonged water absorption reduces the glass transition temperature of the material, thereby making the glass transition temperature align with or fall below the human body temperature (36° C.-38° C.), and inducing shrinkage thereof. Therefore, to address the shrinkage of the amorphous in vivo-degradable polymer during prolonged coverage or occlusion at the damaged tissue site, the polymer solution, the electrospinning method and the electrospun nanofibrous membrane are optimized, specifically as follows.Polymer Solution

[0048] The present disclosure provides a polymer solution, including, in parts by weight, 5-20 parts by weight of an amorphous in vivo-degradable polymer, 0.5-3 parts by weight of a water-soluble polymer, 0.01-1.5 parts by weight of an antibacterial agent and a solvent. In the above, a weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand.

[0049] Degradability encompasses in vitro biodegradation (for example, soil degradation, and environmental degradation) and in vivo biodegradation (in vivo absorption or metabolism). The in vitro biodegradation does not confer superior biocompatibility (meaning being safe, non-toxic and having low or no rejection reaction in human body), and in vivo biodegradation typically exhibits favorable biocompatibility, so as to facilitate coverage or occlusion of the formed electrospun nanofibrous membrane at the damaged tissue site. The amorphous in vivo-degradable polymer refers to that the polymer exhibits both in vivo absorption or metabolism and amorphous characteristics, demonstrating a certain swelling effect in a medium such as water or ethanol, which causes relative slippage of molecular chains. Therefore, the electrospun nanofibrous membrane formed from the amorphous in vivo-degradable polymer by electrospinning exhibits shrinkage after prolonged coverage or occlusion at the damaged tissue site. The present disclosure makes improvements in view of the shrinkage characteristic of the polymer. The weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand, and in the electrospun nanofibrous membrane formed from the polymer solution, the amorphous in vivo-degradable polymer is a primary component for forming fibrous filaments, and it serves as a matrix of the electrospun nanofibrous membrane.

[0050] The water-soluble polymer refers to a biological water-soluble polymer or / and a synthetic water-soluble polymer. The biological water-soluble polymer refers to that the polymer is derived from a biological raw material (such as bioactive substance). The synthetic water-soluble polymer refers to that the polymer is artificially synthesized, while natural biological materials do not contain that substance. The water-soluble polymer in the present disclosure may be biologically derived, artificially synthesized, or both, which is not limited in the present disclosure.

[0051] In such polymer solution, the amorphous in vivo-degradable polymer has excellent biocompatibility and degradability. Therefore, in the polymer solution, the high-molecular-weight amorphous in vivo-degradable polymer has a higher content, and serves as a dominant component of the polymer solution, so as to enable the subsequently obtained electrospun nanofibrous membrane to have superior biocompatibility and degradability. The electrospun nanofibrous membrane with that component as a dominant component is likely to shrink after coverage or occlusion at the damaged tissue site, resulting in compromised efficacy of the antibacterial agent. Through investigations into the cause of shrinkage, the inventors have revealed that due to presence of exudate in a tissue damage environment, the amorphous in vivo-degradable polymer will absorb water and swell, causing amorphous molecular chain slippage, thereby reducing the glass transition temperature of the material to or below the human body temperature (36° C.-38° C.), and thus inducing shrinkage thereof. In the present disclosure, a small amount of a water-soluble polymer is incorporated into the polymer solution, then the exudate at the damaged tissue site will preferentially interact with the water-soluble polymer to swell, thus the exudate at the damaged tissue site is less likely to interact with the amorphous in vivo-degradable polymer to alter the glass transition temperature thereof, which can restrict the shrinkage of the electrospun nanofibrous membrane to a certain extent, enable the antibacterial agent to well exert its efficacy, and effectively suppress the bacterial growth, thus resulting in enhanced antibacterial efficacy of the electrospun nanofibrous membrane.

[0052] In some embodiments, the water-soluble polymer includes a synthetic water-soluble polymer, with a weight-average molecular weight not less than 50 thousand; and the antibacterial agent is a low-molecular-weight antibacterial agent, with a weight-average molecular weight not more than 10 thousand. The synthetic water-soluble polymer with a high molecular weight can form fibrous filaments with the amorphous in vivo-degradable polymer. The antibacterial agent with a low molecular weight substantially cannot form fibrous filaments, and is typically in a granular or short linear shape.

[0053] As the antibacterial agent has a low molecular weight and fails to form fibrous structures on the electrospun nanofibrous membrane, it typically exists on the electrospun nanofibrous membrane in a granular or short linear shape, and after the electrospun nanofibrous membrane shrinks, the antibacterial agent is likely to be partially entrapped within the shrinking electrospun nanofibrous membrane, resulting in compromised performance of the antibacterial agent. Nevertheless, the incorporation of a small amount of the synthetic water-soluble polymer with a high molecular weight can solve this problem, that is, the polymer, which can form fibrous filaments with the amorphous in vivo-degradable polymer, can preferentially interact with the exudate at the damaged tissue site, and can also play a role in stabilizing fibrous structures, thereby making the electrospun nanofibrous membrane less prone to shrinkage, and optimizing the performance of the antibacterial agent.

[0054] In some embodiments, the polymer solution further includes 0.1-3 parts by weight of a bioactive substance. The bioactive substance incorporated can synergize with the low-molecular-weight antibacterial agent, thus enabling the electrospun nanofibrous membrane to promote cellular proliferation, effectively suppress bacterial growth, and facilitate tissue repair and regeneration.

[0055] The bioactive substance may or may not be water soluble. In some embodiments, the bioactive substance is a water-soluble bioactive substance, and the polymer solution includes 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.5-3 parts by weight of the water-soluble bioactive substance, 0.01-1.5 parts by weight of the antibacterial agent and the solvent. In the above, the weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand.

[0056] In some embodiments, the bioactive substance has a high weight-average molecular weight, and the polymer solution includes, in parts by weight, 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-3 parts by weight of the bioactive substance, 0.5-3 parts by weight of the synthetic water-soluble polymer, 0.01-1.5 parts by weight of the antibacterial agent and the solvent. The weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; the weight-average molecular weight of the bioactive substance is greater than 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0057] In the polymer solution, the amorphous in vivo-degradable polymer and the bioactive substance with a high weight-average molecular weight form fibrous filaments together, and an organic antibacterial agent with a low molecular weight fails to form fibrous filaments, and forms short linear or granular substances on the electrospun nanofibrous membrane. When the electrospun nanofibrous membrane is applied to cover or occlude a damaged tissue site, due to presence of exudate in the environment of the damaged tissue site, prolonged coverage or occlusion will cause water absorption and swelling of the amorphous in vivo-degradable polymer and amorphous molecular chain slippage, thereby reducing the glass transition temperature of the amorphous in vivo-degradable polymer to or below the human body temperature (36° C.-38° C.), which induces shrinkage of the electrospun nanofibrous membrane, and after the shrinkage, the short linear or granular organic antibacterial agent is partially encapsulated within the shrinking membrane, exhibits compromised performance, and fails to suppress the bacterial growth. While the bioactive substance forms fibrous filaments and co-shrinks with the electrospun nanofibrous membrane, and the properties of the bioactive substance still can be well utilized. Although the bioactive substance can promote cellular proliferation, it also promotes bacterial division, and suboptimal performance of the antibacterial agent in turn leads to increased bacterial load in the exudate. If the amount of the antibacterial agent is increased, the biocompatibility of the electrospun nanofibrous membrane is comprised. Therefore, the synthetic water-soluble polymer with a high weight-average molecular weight is incorporated in the present disclosure, and it can form filaments together with the amorphous in vivo-degradable polymer and the bioactive substance during the electrospinning, then the exudate at the damaged tissue site preferentially interacts with the synthetic water-soluble polymer to swell, and the exudate at the damaged tissue site is less likely to interact with the amorphous in vivo-degradable polymer to swell; and the synthetic water-soluble polymer also plays a role in stabilizing fibrous structures, mitigating the shrinkage of the electrospun nanofibrous membrane, and optimizing the performance of the antimicrobial agent. Moreover, the bioactive substance can promote cellular proliferation, thereby enabling the electrospun nanofibrous membrane to facilitate tissue repair and regeneration.

[0058] Exemplarily, the weight-average molecular weight of the amorphous in vivo-degradable polymer is 80 thousand, 100 thousand, 120 thousand, 140 thousand, 160 thousand, 180 thousand, 200 thousand, 220 thousand, 240 thousand, 260 thousand, 280 thousand or 300 thousand; the weight-average molecular weight of the synthetic water-soluble polymer is 50 thousand, 100 thousand, 150 thousand, 200 thousand, 250 thousand, 300 thousand, 350 thousand, 400 thousand, 450 thousand or 500 thousand; the weight-average molecular weight of the bioactive substance is 10 thousand, 50 thousand, 100 thousand, 150 thousand, 200 thousand, 250 thousand, 300 thousand, 350 thousand, 400 thousand, 450 thousand or 500 thousand; and the weight-average molecular weight of the organic antibacterial agent is 1 thousand, 2 thousand, 3 thousand, 4 thousand, 5 thousand, 6 thousand, 7 thousand, 8 thousand, 9 thousand or 10 thousand.

[0059] Optionally, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 100 thousand to 300 thousand; and the weight-average molecular weights of both the bioactive substance and the synthetic water-soluble polymer range from 50 thousand to 300 thousand. The three polymer substances forming fibrous filaments have relatively narrow weight-average molecular weight distribution, so as to form a relatively uniform electrospun nanofibrous membrane, which can further solve the problem of inadequate performance of the antibacterial agent due to the shrinkage of the electrospun nanofibrous membrane, thereby optimizing the performance of both the antibacterial agent and the bioactive substance. It should be noted that, the weight-average molecular weights of both the bioactive substance and the synthetic water-soluble polymer range from 50 thousand to 300 thousand, which does not mean that the weight-average molecular weights of the two are the same, while the weight-average molecular weights of the two may be the same, or different, which is not limited in the present disclosure.

[0060] In some other embodiments, the bioactive substance has a low weight-average molecular weight, and the polymer solution includes, in parts by weight, 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-3 parts by weight of the bioactive substance, 0.5-3 parts by weight of the synthetic water-soluble polymer, 0.01-1.5 parts by weight of the antibacterial agent and the solvent. The weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; the weight-average molecular weight of the bioactive substance ranges from 1 thousand to 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

[0061] In the polymer solution, the amorphous in vivo-degradable polymer forms fibrous filaments. The organic antibacterial agent and the bioactive substance with a low molecular weight fail to form fibrous filaments, and form short linear or granular substances on the electrospun nanofibrous membrane. When the electrospun nanofibrous membrane is applied to cover or occlude a damaged tissue site, due to presence of exudate in the environment of the damaged tissue site, prolonged coverage or occlusion will cause water absorption and swelling of the amorphous in vivo-degradable polymer and amorphous molecular chain slippage, thereby reducing the glass transition temperature of the amorphous in vivo-degradable polymer to or below the human body temperature (36° C.-38° C.), which induces shrinkage of the electrospun nanofibrous membrane, and after the shrinkage, the short linear or granular organic antibacterial agent and bioactive substance are partially encapsulated in the shrinking membrane, fail to exert optimal performance, and exhibit unfavorable effects in suppressing the bacterial growth and promoting the cellular proliferation. If the amounts of the antibacterial agent and the bioactive substance are increased, the biocompatibility of the electrospun nanofibrous membrane is comprised. Therefore, the synthetic water-soluble polymer with a high weight-average molecular weight is incorporated in the present disclosure, and it can form fibrous filaments together with the amorphous in vivo-degradable polymer and the bioactive substance during the electrospinning, then the exudate at the damaged tissue site preferentially interacts with the synthetic water-soluble polymer to swell, and the exudate at the damaged tissue site is less likely to interact with the amorphous in vivo-degradable polymer to swell; and the synthetic water-soluble polymer also plays a role in stabilizing fibrous structures, mitigating the shrinkage of the electrospun nanofibrous membrane, optimizing the performance of the antimicrobial agent and the bioactive substance, and suppressing the bacterial growth and promoting cellular proliferation, thereby enabling the electrospun nanofibrous membrane to facilitate tissue repair and regeneration.

[0062] Exemplarily, the weight-average molecular weight of the amorphous in vivo-degradable polymer is 80 thousand, 100 thousand, 120 thousand, 140 thousand, 160 thousand, 180 thousand, 200 thousand, 220 thousand, 240 thousand, 260 thousand, 280 thousand, or 300 thousand; the weight-average molecular weight of the synthetic water-soluble polymer is 50 thousand, 100 thousand, 150 thousand, 200 thousand, 250 thousand, 300 thousand, 350 thousand, 400 thousand, 450 thousand or 500 thousand; the weight-average molecular weight of the bioactive substance is 1 thousand, 3 thousand, 5 thousand, 7 thousand, 9 thousand or 10 thousand; and the weight-average molecular weight of the organic antibacterial agent is 1 thousand, 2 thousand, 3 thousand, 4 thousand, 5 thousand, 6 thousand, 7 thousand, 8 thousand, 9 thousand or 10 thousand.

[0063] Optionally, the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 100 thousand to 300 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 100 thousand to 300 thousand; and the weight-average molecular weight of the bioactive substance ranges from 1 thousand to 10 thousand. The two polymer substances forming fibrous filaments have relatively narrow weight-average molecular weight distribution, so as to form a relatively uniform electrospun nanofibrous membrane, which can further solve the problem of inadequate performance of the antibacterial agent due to the shrinkage of the electrospun nanofibrous membrane, thereby optimizing the performance of both the antibacterial agent and the bioactive substance. It should be noted that, the weight-average molecular weights of both the amorphous in vivo-degradable polymer and the synthetic water-soluble polymer range from 100 thousand to 300 thousand, which does not mean that the weight-average molecular weights of the two are the same, while the weight-average molecular weights of the two may be the same, or different, which is not limited in the present disclosure.

[0064] In other embodiments, the weight-average molecular weight of the amorphous in vivo-degradable polymer further may be 320 thousand, 340 thousand, 360 thousand, 380 thousand, 400 thousand, 420 thousand, 440 thousand, 460 thousand, 480 thousand, 500 thousand, etc.; the weight-average molecular weight of the synthetic water-soluble polymer is 520 thousand, 540 thousand, 560 thousand, 580 thousand or 600 thousand, etc.; and the weight-average molecular weight of the organic antibacterial agent further may be 5 hundred, 6 hundred, 7 hundred, 8 hundred or 9 hundred, etc.; and the weight-average molecular weight of the bioactive substance further may be 550 thousand, 600 thousand, etc.

[0065] Exemplarily, in parts by weight, in the polymer solution, X parts by weight of the amorphous in vivo-degradable polymer may be 5 parts, 8 parts, 10 parts, 12 parts, 15 parts, 18 parts or 20 parts; Y1 parts by weight of the bioactive substance may be 0.1 parts, 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts or 3 parts; Y2 parts by weight of the water-soluble polymer may be 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts or 3 parts; Y3 parts by weight of the antibacterial agent may be 0.1 parts, 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts or 5 parts.

[0066] Optionally, the polymer solution includes, in parts by weight, 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-2 parts by weight of the bioactive substance, 0.5-2 parts by weight of the synthetic water-soluble polymer, and 0.1-1.5 parts by weight of the antibacterial agent. Incorporation of a small amount of the synthetic water-soluble polymer can well suppress the shrinkage of the electrospun nanofibrous membrane, so as to optimize the performance of the bioactive substance and antibacterial agent following a small amount of incorporation of the two, thereby enhancing comprehensive performance of the electrospun nanofibrous membrane.

[0067] Further, the parts by weight X of the amorphous in vivo-degradable polymer is greater than a sum Y (Y=Y1+Y2+Y3) of the parts by weight of the bioactive substance, the synthetic water-soluble polymer and the antibacterial agent. As a dominant component of the polymer solution, the amorphous in vivo-degradable polymer can endow the electrospun nanofibrous membrane with better biocompatibility and degradation effect, and it is synergized with the synthetic water-soluble polymer, to well exert the performance of the antibacterial agent and the bioactive substance even if they are incorporated in a small amount.

[0068] Further, X>5×Y, which enables both optimal efficacies of the bioactive substance and the antibacterial agent, and excellent biocompatibility and degradability of the electrospun nanofibrous membrane.

[0069] In some embodiments, the amorphous in vivo-degradable polymer includes at least one of racemic polylactic acid and poly(lactic-co-glycolic acid) copolymer. The materials selected have good in vivo degradability and biocompatibility, so as to serve as a dominant component of the electrospun nanofibrous membrane for repairing the damaged tissue site.

[0070] The present disclosure does not limit specific components of the amorphous in vivo-degradable polymer, as long as the amorphous polymer is biodegradable and biocompatible.

[0071] In some embodiments, the bioactive substance includes at least one of collagen, growth factor, silk fibroin, zein, gelatin and hyaluronic acid. The above choices of bioactive substance have favorable efficacy in promoting cellular proliferation, thereby enabling the electrospun nanofibrous membrane to promote tissue repair and regeneration.

[0072] The bioactive substance may or may not be soluble in water. In some embodiments, the bioactive substance may be soluble in water (for example, the bioactive substance soluble in water is one or more of growth factor, gelatin and hyaluronic acid), which can be incorporated as a bioactive substance in the polymer solution, and can also be incorporated as a water-soluble polymer in the polymer solution. A water-soluble polymer is also incorporated while incorporating the water-soluble bioactive substance, so that components of the polymer solution are simple. In other embodiments, even if a water-soluble bioactive substance is incorporated into the polymer solution, a synthetic water-soluble polymer can also be incorporated into the polymer solution.

[0073] In some embodiments, among the bioactive substances, collagen, silk fibroin, zein, gelatin and hyaluronic acid are bioactive substances with a weight-average molecular weight greater than or equal to 10 thousand. Among the bioactive substances, growth factor and enzyme digestion oligomeric sodium hyaluronate are bioactive substances with a weight-average molecular weight of less than 10 thousand.

[0074] The present disclosure does not limit specific components of the bioactive substance, as long as the bioactive substance can promote cellular proliferation.

[0075] In some embodiments, the synthetic water-soluble polymer includes at least one of polyethylene oxide, polyethylene glycol, polyvinyl alcohol, polyacrylamide and polyvinyl pyrrolidone. These polymers are synthetic water-soluble polymers, and incorporation of a small amount of the above components can well improve an anti-shrinkage effect of the electrospun nanofibrous membrane, thereby ensuring optimal performance of the antibacterial agent and bioactive substance.

[0076] The present disclosure does not limit components of the synthetic water-soluble polymer, as long as the polymer can mitigate the shrinkage property of the electrospun nanofibrous membrane with the amorphous in vivo-degradable polymer as a dominant component.

[0077] In some embodiments, the low-molecular-weight antibacterial agent includes an inorganic antibacterial agent and / or an organic antibacterial agent. The molecular weight of the antibacterial agent is low. If the electrospun nanofibrous membrane shrinks, the efficacy of the antibacterial agent is compromised. Therefore, the antibacterial agent is synergized with other components in the polymer solution, thus enhancing the efficacy of the antibacterial agent.

[0078] In the above, the inorganic antibacterial agent includes at least one of silver sulfate, zinc oxide, copper oxide, ammonium dihydrogen phosphate and lithium carbonate.

[0079] The organic antibacterial agent includes at least one of guanidine antibacterial agent, β-lactam antibacterial agent and quaternary ammonium salt antibacterial agent.

[0080] In some embodiments, the guanidine antibacterial agent includes at least one of polyhexamethylene guanidine, polyhexamethylene biguanide, polyaminopropyl biguanide and dodecylguanidine acetate. The β-lactam antibacterial agent includes penicillin and / or cephalosporin. The quaternary ammonium salt antibacterial agent includes at least one of alkyl trimethyl ammonium chloride, alkyl dimethyl benzyl ammonium chloride and tetradecyl-2-methylpyridinium ammonium bromide. As organic antibacterial agents, these antibacterial agents are predominantly formed into short linear structures after electrospinning, and the shrinkage of the electrospun nanofibrous membrane has a relatively small impact on the performance of the antibacterial agent (relative to the inorganic antibacterial agent). Therefore, synergistic combination with other components in the polymer solution (e.g., synthetic water-soluble polymer) can enhance the efficacy of the organic antibacterial agent.

[0081] The present disclosure does not limit specific components of the antibacterial agent, and all antibacterial agents with antibacterial performance applicable in the polymer solution fall within the scope of protection of the present disclosure.

[0082] In some embodiments, the solvent includes one or more of hexafluoroisopropanol, chloroform, dichloromethane, trifluoroacetic acid, dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, acetic acid, water, methanol, ethanol, and isopropanol. These solvents can well dissolve other components in the polymer solution, thus facilitating subsequent formation of the electrospun nanofibrous membrane by electrospinning. If the solvent is merely water, it cannot dissolve all components in the polymer solution, but can be synergized with other solvents to dissolve other components in the polymer solution. Selecting one or more solvents in the present disclosure is related to choices of other components in the polymer solution, and those skilled in the art could make adjustments according to actual situations.

[0083] The present disclosure does not limit the components of the solvent, and all solvents that can dissolve other components in the polymer solution fall within the scope of protection of the present disclosure.

[0084] In some embodiments, a mass proportion of a solute in the polymer solution ranges from 5% to 30%, where the solute is a substance other than the solvent in the polymer solution, and the mass proportion of the solute is solute / (solute+solvent)×100%.

[0085] When the mass proportion of the solute in the polymer solution is maintained within the above range, it facilitates formation of fibrous filaments by an electrospinning device, and a fibrous structure of the electrospun nanofibrous membrane can mimic extracellular matrix, thereby facilitating tissue repair and regeneration upon coverage or occlusion at the damaged tissue site.

[0086] Exemplarily, the mass proportion of the solute in the polymer solution is 5%, 10%, 15%, 20%, 25% or 30%. Optionally, the mass proportion of the solute in the polymer solution ranges from 10% to 20%.Preparation Method for the Polymer Solution

[0087] The present disclosure provides a preparation method for the polymer solution, with other components in the preceding polymer solution dispersed in the solvent. The components in the polymer solution are the preceding components and will not be reiterated herein. The preparation method is mainly described.

[0088] In some embodiments, the amorphous in vivo-degradable polymer is first dispersed in the solvent to form a mixed solution 1, and then the bioactive substance, the synthetic water-soluble polymer and the antibacterial agent are dispersed in the mixed solution 1 to form the polymer solution. The amorphous in vivo-degradable polymer is incorporated at a high amount, and it is first dissolved and dispersed in the solvent, followed by dissolution and dispersion of other components, so as to enable a better dissolving and dispersing effect of the polymer solution, thereby rendering a more uniform polymer solution.

[0089] In other embodiments, each component may be dispersed separately in the solvent and then mixed to form the polymer solution. Alternatively, other components are first dispersed in the solvent, followed by dispersion of the amorphous in vivo-degradable polymer.Electrospinning Method

[0090] The present disclosure provides an electrospinning method, using the preceding polymer solution for electrospinning, including: spraying the polymer solution onto a collector at an electrospinning voltage ranging from 5 kV to 30 kV, and a polymer solution flow rate ranging from 0.2 ml / h to 1 ml / h. An electrospun nanofibrous membrane obtained under such electrospinning parameters is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.

[0091] Exemplarily, the electrospinning voltage is 5 kV, 10 kV, 15 kV, 20 kV, 25 kV or 30 kV; and the polymer solution flow rate is 0.2 ml / h, 0.4 ml / h, 0.6 ml / h, 0.8 ml / h or 1 ml / h. Optionally, the electrospinning voltage ranges from 5 kV to 20 kV; and the polymer solution flow rate ranges from 0.4 ml / h to 0.8 ml / h.

[0092] In some embodiments, an electrospinning environment maintains a temperature ranging from 20° C. to 35° C., and humidity ranging from 35% to 60%. The electrospinning conducted in the environment with such temperature and humidity enables electrospinning stability, and facilitates the formation of a stable electrospun nanofibrous membrane.

[0093] Exemplarily, the temperature of the electrospinning environment is 20° C., 22° C., 25° C., 28° C., 30° C., 32° C. or 35° C., and the humidity is 35%, 40%, 45%, 50%, 55% or 60%.

[0094] In some embodiments, the collector is a collection roller, and a rotational speed of the collection roller ranges from 300 r / min to 3000 r / min, which enables more uniform nanofiber distribution of the electrospun nanofibrous membrane, and facilitates evaporation of the solvent from the polymer solution during the electrospinning.

[0095] Exemplarily, the rotational speed of the collection roller is 300 r / min, 500 r / min, 800 r / min, 1000 r / min, 1200 r / min, 1500 r / min, 1800 r / min, 2000 r / min, 2200 r / min, 2500 r / min, 2800 r / min or 3000 r / min. Optionally, the rotational speed of the collection roller ranges from 500 r / min to 2000 r / min.Electrospun Nanofibrous Membrane

[0096] The present disclosure provides an electrospun nanofibrous membrane, prepared with the above polymer solution by the preceding electrospinning method. The electrospun nanofibrous membrane prepared by the method has excellent biocompatibility, can mitigate the shrinkage of the electrospun nanofibrous membrane, is suitable for coverage or occlusion at a damaged tissue site, promotes cellular proliferation, and can also effectively suppress bacterial growth, thereby accelerating tissue repair and regeneration.

[0097] In other embodiments, the polymer solution further can be formed on a collector by coating, so as to form a membrane material. The polymer solution in the present disclosure is not limited to electrospinning membrane formation, while membrane formation by other electrospinning methods or coating methods is also encompassed within the scope of protection of the present disclosure.

[0098] In order to make objectives, technical solutions and advantages of embodiments of the present disclosure clearer, the technical solutions in examples of the present disclosure will be described below clearly and completely. Examples, for which no concrete conditions are specified, are carried out according to conventional conditions or conditions recommended by manufactures. If manufacturers of reagents or apparatuses used are not specified, they are conventional products commercially available.Example 1

[0099] A polymer solution was provided, including, in parts by weight, 20 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.4 g of hydrolyzed collagen (Col, with weight-average molecular weight of 200 thousand), 1 g of polyethylene oxide (PEO, with weight-average molecular weight of 400 thousand), 0.3 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 78.3 g of hexafluoroisopropanol (HFIP).

[0100] A preparation method for the polymer solution included:

[0101] step 1: weighing 20 g of poly(lactic-co-glycolic acid) copolymer granules into 82.3 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0102] step 2: weighing 0.4 g of hydrolyzed collagen freeze-dried tablets, 1 g of polyethylene oxide powder, and 0.3 g of PHMB powder into the PLGA solution obtained in step 1 using the precision electronic balance, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PHMB / Col / PEO / PLGA polymer solution;

[0103] Step 3: loading the above PHMB / Col / PEO / PLGA polymer solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0104] Step 4: drying a nanofiber material prepared by the above electrospinning at room temperature for 12 h, so as to obtain a PHMB / Col / PLGA (PEO-containing) nanofiber membrane.Example 2

[0105] Example 2 was substantially identical to Example 1, except that the poly(lactic-co-glycolic acid) copolymer in Example 1 was replaced with racemic polylactic acid (PDLLA, Poly(D,L-lactide), D,L-polylactide, with weight-average molecular weight of 100 thousand) powder in Example 2; and the solvent hexafluoroisopropanol in Example 1 was replaced with tetrahydrofuran in Example 2.Example 3

[0106] Example 3 was substantially identical to Example 1, except that polyethylene oxide was not added.Example 4

[0107] Example 4 was substantially identical to Example 1, except that the polyethylene oxide powder in Example 1 was replaced with polyvinyl alcohol (PVA, with weight-average molecular weight of 80 thousand) powder in Example 4.Example 5

[0108] Example 5 was substantially identical to Example 1, except that the polyethylene oxide powder in Example 1 was replaced with polyvinyl pyrrolidone (PVP, with weight-average molecular weight of 60 thousand) powder in Example 5.Example 6

[0109] Example 6 was substantially identical to Example 1, except that the collagen freeze-dried tablets in Example 1 were replaced with 2 g of gelatin (Gel, with weight-average molecular weight of 80 thousand) particles in Example 6, and the amount of PHMB was 0.1 g.Example 7

[0110] Example 7 was substantially identical to Example 1, except that collagen in Example 1 was replaced with 0.5 g of fibroblast growth factor (FGF, with weight-average molecular weight of 6 thousand) freeze-dried powder in Example 7, and the amount of the poly(lactic-co-glycolic acid) copolymer was 10 g.Example 8

[0111] Example 8 was substantially identical to Example 1, except that PHMB in Example 1 was replaced with 0.01 g of amoxicillin (with molecular weight of 365.4) in Example 8, and the amount of poly(lactic-co-glycolic acid) copolymer was 10 g.Example 9

[0112] Example 9 was substantially identical to Example 1, except that PHMB in Example 1 was replaced with 0.01 g of silver sulfate (with molecular weight of 169.87) in Example 9, and the amount of poly(lactic-co-glycolic acid) copolymer was 18 g.Examples 10-11

[0113] Examples 10-11 were substantially identical to Example 1, except that the amounts of various components were different, specifically as listed in Table 1.Example 12

[0114] A polymer solution was provided, including, in parts by weight, 10 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.4 g of collagen (Col, with weight-average molecular weight of 200 thousand), 3 g of polyethylene oxide (PEO, with weight-average molecular weight of 400 thousand), 0.3 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 86.3 g of hexafluoroisopropanol (HFIP).

[0115] A preparation method for the polymer solution included:

[0116] step 1: weighing 10 g of poly(lactic-co-glycolic acid) copolymer granules into 86.3 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0117] step 2: weighing 0.4 g of collagen, 3 g of polyethylene oxide powder, and 0.3 g of PHMB powder into the PLGA solution obtained in step 1 using the precision electronic balance, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PHMB / Col / PEO / PLGA polymer solution;

[0118] step 3: loading the above PHMB / Col / PEO / PLGA polymer solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0119] step 4: drying a nanofiber material prepared by the above electrospinning method at room temperature for 12 h, so as to obtain a PHMB / Col / PLGA (PEO-containing) nanofiber membrane.Comparative Example 1

[0120] A polymer solution was provided, including, in parts by weight, 16 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer and 84 g of hexafluoroisopropanol (HFIP).

[0121] A preparation method for the polymer solution included:

[0122] step 1: weighing 16 g of poly(lactic-co-glycolic acid) copolymer granules into 84 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0123] step 2: loading the above PLGA solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0124] step 3: drying a nanofiber material prepared by the above electrospinning method at room temperature for 12 h, so as to obtain a PLGA nanofiber membrane.Comparative Example 2

[0125] A polymer solution was provided, including, in parts by weight, 16 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.5 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 83.5 g of hexafluoroisopropanol (HFIP).

[0126] A preparation method for the polymer solution included:

[0127] step 1: weighing 16 g of poly(lactic-co-glycolic acid) copolymer granules into 83.5 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;

[0128] step 2: weighing 0.5 g of PHMB powder into the PLGA solution obtained in step 1 using the precision electronic balance, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PHMB / PLGA polymer solution;

[0129] step 3: loading the above PHMB / PLGA polymer solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0130] step 4: drying a nanofiber material prepared by the above electrospinning method at room temperature for 12 h, so as to obtain a PHMB / PLGA nanofiber membrane.Comparative Example 3

[0131] A polymer solution was provided, including, in parts by weight, 16 g of polyvinlbutaral (PVB, with weight-average molecular weight of 100 thousand) and 84 g of ethanol aqueous solution.

[0132] A preparation method for the polymer solution included:

[0133] step 1: weighing 16 g of polyvinlbutaral granules into 84 g of ethanol aqueous solution using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PVB solution;

[0134] step 2: loading the above PVB solution into a syringe, securing the syringe to an injection pump of an electrospinning machine, attaching a needle connected to a positive electrode of a high-voltage power supply, and connecting a collection roller to a negative electrode of the high-voltage power supply. Electrospinning parameters were set as follows: an electrospinning voltage being 10 kV, a polymer solution flow rate being 0.5 ml / h, a rotational speed of the collection roller being 800 r / min, a temperature being 28° C., and humidity being 58%; and

[0135] step 3: drying a nanofiber material prepared by the above electrospinning at room temperature for 12 h, so as to obtain a PVB nanofiber membrane.Experimental Example 1

[0136] Performance of the electrospun nanofibrous membranes provided by Examples 1-12 and Comparative Examples 1-3 was tested, with results as listed in Table 1.

[0137] (1) Antibacterial performance was tested according to standard GB / T 20944.1-2007, with ATCC8739 Escherichia coli (E. coli) as test strain. The antibacterial performance was evaluated based on a size of an inhibition zone formed after a sample was added. The inhibition zone means that there are no bacteria growing in the area, and growth of bacteria around is suppressed. A larger inhibition zone indicates better antibacterial performance.

[0138] A specific method was as follows: all samples were first cut into a circle with a diameter of 3.55 cm, and were subjected to sterilization treatment under ultraviolet light irradiation for 2 h. Sterile nutrient agar was poured into a sterilized petri dish, and cooled and shaped under ultraviolet sterilization for later use. Subsequently 1501 of bacterial solution (at concentration of 10 CFU) was uniformly inoculated onto a culture medium, and the sterilized samples were placed at center of agar plates respectively, and put in a 37±1° C. biological incubator for 24 h.

[0139] Determination of the inhibition zone: Firstly, whether an area without bacterial growth appeared around the electrospun nanofibrous membrane was observed; if so, it indicated that the growth of bacteria was stopped when reaching an outer ring of the area, demonstrating a significant antibacterial efficacy, and a antibacterial area was an area of the outer ring; if not, the area of the electrospun nanofibrous membrane was further irradiated by a point light source to examine whether bacterial colonies appeared in a membrane-covered area, and if so, it indicated that the membrane had no antibacterial efficacy, and the antibacterial area was 0; if not, it indicated that bacteria failed to enter the membrane-covered area to grow, demonstrating that the membrane had certain antibacterial efficacy, and can prevent bacteria from entering the interior of dressing to grow.

[0140] The antibacterial performance of some samples is as shown in FIG. 1. In FIG. 1, an inner ring in the petri dishes represents the electrospun nanofibrous membrane, and a grey area surrounding the inner ring represents the inhibition zone. As can be seen from FIG. 1, compared with Examples 1 and 10, the PLGA electrospun nanofibrous membranes provided by Comparative Examples 1 and 2 had significant shrinkage, and failed to form the inhibition zone, thus having no antibacterial performance. Hence, it can be seen from Comparative Example 1 that the PLGA electrospun nanofibrous membrane provided by Comparative Example 1 was prone to shrinkage, and did not have antibacterial performance; and it can be seen from Comparative Example 2 that the PLGA electrospun nanofibrous membrane incorporated with the PHMB antibacterial agent still exhibited significant shrinkage, the performance of the antibacterial agent was compromised, and the antibacterial efficacy was still lacked. It can be seen from Example 1 and Example 10 that incorporating the synthetic water-soluble polymer polyethylene oxide into the electrospun nanofibrous membrane can significantly mitigate the shrinkage of the electrospun nanofibrous membrane, and the antibacterial efficacy of the electrospun nanofibrous membrane was effectively enhanced.(2) Cell Viability Experiment

[0141] A mouse fibroblast L929 cell line was selected for the cell viability experiment. Various test samples were set as experimental groups, and control groups did not contain any samples. First, the experimental groups were respectively placed into 12-well tissue culture plates, to be subjected to UV sterilization for 2 h, and subsequently L929 cells (1×105 / mL) were seeded into the 12-well tissue culture plates (12 parallel experiments were performed on each sample and test results were analyzed as in Table 1). The samples were all incubated in a 37° C., 5% CO2 incubator for 72 h. After the incubation period was ended, absorbance values at 570 nm were determined for each group by a microplate reader using the MTT method. By calculating an absorbance ratio, a cellular proliferation rate of each experimental group can be obtained, where a higher cellular proliferation rate indicates better cell viability, i.e., stronger tissue repair capability; and if the cellular proliferation rate is less than 100%, it is indicated that the sample is cytotoxic.TABLE 1Components of Polymer solutions and Performance of Electrospun nanofibrous membranesAmorphous inSyntheticArea of theCellularvivo-degradableBioactivewater-solubleAntibacterialinhibitionproliferationpolymersubstancepolymeragentSolventzone (cm2)rate (%)Example 120% PLGA0.4% Col1% PEO0.5% PHMBHFIP9.66 120.60 ± 10.09Example 216% PDLLA0.4% Col1% PEO0.3% PHMBTHF8.65166.47 ± 3.49Example 316% PLGA0.4% Col\0.3% PHMBHFIP4.62132.24 ± 1.75Example 416% PLGA0.4% Col1% PVA0.3% PHMBHFIP7.98146.90 ± 8.28Example 516% PLGA0.4% Col1% PVP0.3% PHMBHFIP7.49152.21 ± 5.52Example 616% PLGA2% gelatin1% PEO0.1% PHMBHFIP7.84138.61 ± 1.92Example 710% PLGA0.5% FGF1% PEO0.3% PHMBHFIP7.32141.44 ± 6.08Example 810% PLGA0.4% Col1% PEO0.01%HFIP8.51119.44 ± 5.18amoxicillinExample 918% PLGA0.4% Col1% PEO0.01% silverHFIP8.22119.13 ± 1.78sulfateExample 1016% PLGA0.4% Col1% PEO0.3% PHMBHFIP9.16132.05 ± 5.03Example 1120% PLGA0.4% Col2% PEO0.5% PHMBHFIP8.42135.06 ± 9.46Example 1210% PLGA0.4% Col3% PEO0.5% PHMBHFIP8.50121.37 ± 4.64Comparative16% PLGA\\\HFIP0133.65 ± 9.46Example 1Comparative16% PLGA\\0.5% PHMBHFIP0111.82 ± 4.40Example 2Comparative16% PVB\\\ethanol0 87.66 ± 1.80Example 3

[0142] It can be seen from Table 1 that, in Comparative Example 3, PVB caused certain cytotoxicity and affected cell growth activity. As can be seen from comparison between Comparative Example 1 and Comparative Example 2, PLGA had good biocompatibility, without cytotoxicity to cells, and the electrospun nanofiber structure also had a certain promoting effect on cell viability, but in the case where PLGA acted as a matrix of the polymer solution, even if the polymer solution was incorporated with the antibacterial agent PHMB, the resulting electrospun nanofibrous membrane substantially still exhibited no antibacterial efficacy. In Examples 1-12 of the present disclosure, in the case where the amorphous in vivo-degradable polymer acted as the matrix of the polymer solution, incorporating a small amount of the water-soluble polymer and the antibacterial agent can increase the antibacterial area of the electrospun nanofibrous membrane, thus optimizing the performance of the antibacterial agent.

[0143] As can be seen from comparison between Example 1 and Example 2, both PLGA and PDLLA selected as the amorphous in vivo-degradable polymer to synergize with the synthetic water-soluble polymer (PEO), the bioactive substance (Col, natural water-soluble polymer) and the antibacterial agent (PHMB) can enhance the performance of the antibacterial agent and the bioactive substance, suppress the bacterial growth (larger antibacterial area), and also promote cellular proliferation (higher cellular proliferation rate), thus facilitating tissue repair and regeneration.

[0144] Through comparison between Example 1 and Example 3, it can be seen that in the case where the amorphous in vivo-degradable polymer PLGA acted as a matrix of the polymer solution, compared with Example 3 merely incorporated with the bioactive substance (Col, natural water-soluble polymer), Example 1 was incorporated with both the synthetic water-soluble polymer (PEO) and the bioactive substance (Col, natural water-soluble polymer), the performance of the antibacterial agent and the bioactive substance can be further enhanced, the bacterial growth (larger antibacterial area) can be further suppressed, and cellular proliferation can further be promoted, thus facilitating tissue repair and regeneration.

[0145] Through comparison between Example 1, Example 4 to Example 9, it can be seen that selecting PEO, PVA or PVP as the synthetic water-soluble polymer, selecting Col, gelatin or FGF as the bioactive substance, and selecting PHMB, amoxicillin or silver sulfate as the antibacterial agent can well suppress the bacterial growth and promote cellular proliferation, thus facilitating tissue repair and regeneration.

[0146] The embodiments described above are only some but not all embodiments of the present disclosure. The detailed descriptions of the embodiments of the present disclosure are not intended to limit the scope of the present disclosure claimed, but merely illustrate chosen embodiments of the present disclosure. All of other embodiments obtained by those ordinarily skilled in the art based on the embodiments in the present disclosure without using any inventive efforts shall fall within the scope of protection of the present disclosure.

Examples

example 1

[0099]A polymer solution was provided, including, in parts by weight, 20 g of poly(lactic-co-glycolic acid (PLGA, with weight-average molecular weight of 100 thousand) copolymer, 0.4 g of hydrolyzed collagen (Col, with weight-average molecular weight of 200 thousand), 1 g of polyethylene oxide (PEO, with weight-average molecular weight of 400 thousand), 0.3 g of polyhexamethylene biguanide (PHMB, with weight-average molecular weight of 1500) hydrochloride and 78.3 g of hexafluoroisopropanol (HFIP).

[0100]A preparation method for the polymer solution included:[0101]step 1: weighing 20 g of poly(lactic-co-glycolic acid) copolymer granules into 82.3 g of hexafluoroisopropanol using a precision electronic balance, adding a magnetic stir bar, and stirring under a room-temperature condition until a clear and transparent solution was obtained, so as to render a PLGA solution;[0102]step 2: weighing 0.4 g of hydrolyzed collagen freeze-dried tablets, 1 g of polyethylene oxide powder, and 0.3 g...

example 2

[0105]Example 2 was substantially identical to Example 1, except that the poly(lactic-co-glycolic acid) copolymer in Example 1 was replaced with racemic polylactic acid (PDLLA, Poly(D,L-lactide), D,L-polylactide, with weight-average molecular weight of 100 thousand) powder in Example 2; and the solvent hexafluoroisopropanol in Example 1 was replaced with tetrahydrofuran in Example 2.

example 3

[0106]Example 3 was substantially identical to Example 1, except that polyethylene oxide was not added.

Claims

1. A polymer solution, comprising, in parts by weight, 5-20 parts by weight of an amorphous in vivo-degradable polymer, 0.5-3 parts by weight of a water-soluble polymer, 0.01-1.5 parts by weight of an antibacterial agent and a solvent,wherein a weight-average molecular weight of the amorphous in vivo-degradable polymer is no less than 80 thousand.

2. The polymer solution according to claim 1, wherein the water-soluble polymer comprises a synthetic water-soluble polymer, with a weight-average molecular weight not less than 50 thousand, and the antibacterial agent is a low-molecular-weight antibacterial agent, with a weight-average molecular weight not more than 10 thousand.

3. The polymer solution according to claim 2, wherein the polymer solution further comprises 0.1-3 parts by weight of a bioactive substance.

4. The polymer solution according to claim 3, wherein the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; a weight-average molecular weight of the bioactive substance is greater than 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

5. The polymer solution according to claim 3, wherein the weight-average molecular weight of the amorphous in vivo-degradable polymer ranges from 80 thousand to 300 thousand; a weight-average molecular weight of the bioactive substance ranges from 1 thousand to 10 thousand; the weight-average molecular weight of the synthetic water-soluble polymer ranges from 50 thousand to 500 thousand; and the weight-average molecular weight of the low-molecular-weight antibacterial agent ranges from 1 thousand to 10 thousand.

6. The polymer solution according to claim 3, wherein the polymer solution comprises, in parts by weight, 5-20 parts by weight of the amorphous in vivo-degradable polymer, 0.1-2 parts by weight of the bioactive substance, 0.5-2 parts by weight of the synthetic water-soluble polymer, and 0.1-1.5 parts by weight of the antibacterial agent.

7. The polymer solution according to claim 3, wherein the polymer solution meets at least one of following conditions:a) the amorphous in vivo-degradable polymer comprises at least one of racemic polylactic acid and poly(lactic-co-glycolic acid) copolymer;b) the bioactive substance comprises at least one of collagen, growth factor, silk fibroin, zein, gelatin and hyaluronic acid;c) the synthetic water-soluble polymer comprises at least one of polyethylene oxide, polyethylene glycol, polyvinyl alcohol, polyacrylamide and polyvinyl pyrrolidone; andd) the antibacterial agent comprises an organic antibacterial agent and / or an inorganic antibacterial agent.

8. The polymer solution according to claim 7, wherein the organic antibacterial agent comprises at least one of guanidine antibacterial agent, β-lactam antibacterial agent and quaternary ammonium salt antibacterial agent.

9. The polymer solution according to claim 8, wherein the organic antibacterial agent meets at least one of following conditions:e) the guanidine antibacterial agent comprises at least one of polyhexamethylene guanidine, polyhexamethylene biguanide, polyaminopropyl biguanide and dodecylguanidine acetate;f) the β-lactam antibacterial agent comprises penicillin and / or cephalosporin; andg) the quaternary ammonium salt antibacterial agent comprises at least one of alkyl trimethyl ammonium chloride, alkyl dimethyl benzyl ammonium chloride and tetradecyl-2-methylpyridinium ammonium bromide.

10. The polymer solution according to claim 1, wherein a mass proportion of a solute in the polymer solution ranges from 5% to 30%.

11. A preparation method for an electrospun nanofibrous membrane, comprising: spraying the polymer solution according to claim 1 onto a collector at an electrospinning voltage ranging from 5 kV to 30 kV, and a polymer solution flow rate ranging from 0.2 ml / h to 1 ml / h.

12. The preparation method for an electrospun nanofibrous membrane according to claim 11, wherein an electrospinning environment maintains a temperature ranging from 20° C. to 35° C., and a humidity ranging from 35% to 60%.

13. An electrospun nanofibrous membrane, prepared by the preparation method for an electrospun nanofibrous membrane according to claim 11.

14. The polymer solution according to claim 6, wherein the parts by weight X of the amorphous in vivo-degradable polymer is greater than a sum Y of parts by weight of the bioactive substance, the synthetic water-soluble polymer and the antibacterial agent.

15. The polymer solution according to claim 6, wherein X>5×Y.

16. The preparation method for an electrospun nanofibrous membrane according to claim 12, wherein the collector is a collection roller, and a rotational speed of the collection roller ranges from 300 r / min to 3000 r / min.

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