CN113827769A - Degradable medical biological patch material and preparation method and application thereof - Google Patents

Abstract

The invention belongs to the technical field of biomedical materials, and discloses a degradable medical biological patch material, a preparation method and application thereof, wherein the preparation method of the degradable medical biological patch material comprises the following steps: obtaining a copolymer PHBV of 3-hydroxybutyrate and 3-hydroxyvalerate by biological fermentation; physically blending polymers with different biological functions and small molecules; patches for different aperture requirements are personalized using continuous 3D printing techniques. The 3D printed patch can be used for individualized treatment, the treatment cost is reduced, and 3D printing is an innovation point of the patch applied to clinic; the degradation time and the mechanical strength of the PHBV raw material have certain advantages, and the patch can be added by different high polymer materials, so that the patch has better effect. The patch material can be individually customized by 3D printing for patches with different pore size requirements, and provides a new economic and safe choice for clinical hernia surgical treatment.

Description

Degradable medical biological patch material and preparation method and application thereof

Technical Field

The invention belongs to the technical field of biomedical materials, and particularly relates to a degradable medical biological patch material, and a preparation method and application thereof.

Background

Currently, hernia refers to the movement of an organ or tissue from its normal anatomical location into another location through a congenital or acquired weak point, defect, or aperture. Abdominal hernias are free organs within the abdominal cavity such as: the small intestine, the cecum, the omentum majus, the bladder, the ovary, the fallopian tube and other organs enter another part through the normal or abnormal weak points or defects and pores of the human body. The hernia patch serves to allow a more secure and reliable repair of the area of the tissue defect causing the hernia. Synthetic materials that have been used internationally for hernia repair are now divided into two main groups: the first type is non-absorbable polyester patch, polypropylene patch, expanded polytetrafluoroethylene patch; the second category is composite patches.

The non-absorbable patch is typically a woven, mesh material made of polypropylene (PP) -Polyester (PE) or expanded polytetrafluoroethylene (ePTFE). The pores of the patch cannot be smaller than 100 μm.

However, all polypropylene materials can cause severe intestinal adhesions that affect bowel function and even cause ileus and intestinal fistulas. The material is not contactable with the intestine.

1. Polyester mesh sheet: polyester meshes are more flexible than polypropylene meshes, but have a tensile strength of only 1/3. The long-term complications of repair by using the material are existed, and only France is widely applied.

2. Expanded polytetrafluoroethylene patch: the patch is a microporous biological material, and has the advantage that adhesion is not easy to form when the patch is contacted with abdominal viscera, but fibroblasts and macrophages are not easy to be incorporated into the patch.

3. Compounding a patch: the composite patch which is widely used at present is a composite patch which is formed by combining polypropylene and ePTFE, combines the advantages of the polypropylene and the ePTFE, such as anti-adhesion, retention and tension reinforcement, but the ePTFE anti-infection capability is not increased, and once infection occurs, the patch still needs to be removed.

4. Absorbable patch: polyglycolic acid (Polyglycolic acid); polylactic glycolic acid (PLGA) patch, both of which are absorbable patches, can not be used as a permanent repair material for 90 days, and can be used as a peritoneal defect repair material and a temporary repair material for abdominal incision hernia defect with contaminated wound surface.

In summary, there is a need for a new degradable biological patch material suitable for surgical hernia repair and a preparation method thereof, so as to solve the problems in the prior art and make up for the technical defects of the existing material.

Through the above analysis, the problems and defects of the prior art are as follows:

(1) all the existing polypropylene materials can cause severe intestinal adhesion to influence the intestinal function, even cause intestinal obstruction and intestinal fistula.

(2) Once the existing polypropylene material has rejection reaction and patch infection, the operation incision can be infected for a long time and is not healed permanently, and the incision healing can be realized only by removing the patch through the re-operation.

(3) Existing absorbable patches are not useful as permanent repair materials.

The difficulty in solving the above problems and defects is: the problems and defects of the existing surgical hernia repair patch are determined by the material defects of the patch, and the problems can be solved only by replacing the material components from the material.

The significance of solving the problems and the defects is as follows: the novel degradable surgical hernia repair patch is made of materials, and the components of the materials are changed, so that the patch has the functions of complete degradation and no adhesion with intestinal canals.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a degradable biological patch material, a preparation method and application, and particularly relates to a degradable biological patch material based on an additive technology, a preparation method and application.

The invention is realized in such a way that the preparation method of the degradable biological patch material comprises the following steps:

step one, obtaining a copolymer PHBV of 3-hydroxybutyrate and 3-hydroxyvalerate by utilizing biological fermentation;

step two, carrying out physical blending on polymers with different biological functions and small molecules;

and thirdly, carrying out personalized customization on patches with different aperture requirements by utilizing a continuous 3D printing technology.

Further, the preparation method of the degradable biological patch material further comprises the following steps: and a small molecular bacteriostatic agent is doped into the composite absorbable biological patch or the polymer substrate of the patch is subjected to antibacterial modification. The antibacterial modification is carried out by a phase transition lysozyme and polyurethane compound method.

The invention also aims to provide the degradable biological patch material prepared by the preparation method of the degradable biological patch material, and the degradable biological patch material is prepared from copolymer PHBV of 3-hydroxybutyrate and 3-hydroxyvalerate generated by biological fermentation.

Furthermore, the degradable biological patch material also comprises a bioactive macromolecule, a small molecule bacteriostatic agent and a small molecule additive.

Further, the preparation method of the degradable biological patch material comprises the following steps: biologically fermenting to produce PHBV; ② physically blending with micromolecular substances; thirdly, the polymer after physical blending is made into filaments which are used as printing raw materials and placed in a 3D printer; and fourthly, directly printing by the 3D printer.

Further, the polymers having different biological functions include: polyethylene glycol, polylactic acid, polylactone, poly (butylene adipate terephthalate) (PBAT).

The invention also aims to provide application of the degradable biological patch material in a medical patch for treating surgical hernia.

By combining all the technical schemes, the invention has the advantages and positive effects that: the invention develops a multifunctional surgical hernia biological patch by using a copolymer (PHBV) of 3-hydroxybutyrate and 3-hydroxyvalerate generated by biological fermentation as a raw material, physically blending the raw material with polymers and small molecules with different biological functions and using a continuous 3D printing method, and provides an economic and safe new choice for clinical hernia surgical treatment.

According to the degradable biological patch material provided by the invention, by utilizing the characteristics that PHBV has long in-vivo degradation time and good mechanical strength, bioactive polymers (polyethylene glycol, polylactic acid, polylactone and the like) are added to promote local fibrous tissue regeneration; the mechanical strength of the PHBV can be adjusted by introducing other polymers so as to meet the requirements of the repairing strength and toughness of the surgical hernia patch. Meanwhile, the small-molecule bacteriostatic agent is doped into the composite absorbable biological patch or antibacterial modification is carried out on a patch polymer substrate (preparing a PEG/PHBV composite material, preparing a Polycaprolactone (PCL)/PHBV composite material, preparing a PLA/PHBV composite material, preparing the composite material loaded with the small-molecule bacteriostatic agent, and preparing the hernia patch based on an optimization system by 3D printing, so that the aims of reducing local tissue inflammatory reaction and resisting infection are fulfilled.

The patch printed by the 3D printing technology can be treated individually, so that the treatment cost is reduced, and the 3D printing is an innovation point of applying the patch to clinic; the degradation time and the mechanical strength of the PHBV raw material have certain advantages, and the patch can be added by different high polymer materials, so that the patch has better effect. The material source of the patch is biological fermentation, and the patch with different pore size requirements can be customized in a personalized way by using a 3D printing technology.

The surgical hernia patch with good biocompatibility and biodegradability is an urgent clinical need at present and is a great challenge for application and research. Aiming at the defects of high crystallinity and brittleness of PHBV, the innovation point of the invention is that different high-molecular and small-molecular additives are introduced to improve the mechanical property, the toughness and the antibacterial property of the PHBV, and then the safe and efficient absorbable surgical hernia patch is obtained.

The surgical hernia repair patch prepared by applying the 3D printing technology is not clinically applied at present. According to the invention, the polymer composite material design and the 3D printing technology are innovatively combined, and the biosynthesis patch which is lighter in weight, different in shape and adjustable in pore size and can be completely degraded into carbon dioxide and water is prepared by combining the individual conditions of patients, so that the treatment effect is improved, the treatment cost is reduced, and a better choice is provided for clinical surgical hernia treatment.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments of the present invention will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.

Fig. 1 is a flow chart of a preparation method of a degradable biological patch material provided by an embodiment of the invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Aiming at the problems in the prior art, the invention provides a degradable biological patch material, a preparation method and application thereof, and the invention is described in detail with reference to the accompanying drawings.

The degradable biological patch material provided by the embodiment of the invention is prepared from copolymer PHBV of 3-hydroxybutyrate and 3-hydroxyvalerate generated by biological fermentation, a bioactive polymer, a small molecular bacteriostatic agent and a small molecular additive.

As shown in fig. 1, a preparation method of a degradable biological patch material provided by an embodiment of the present invention includes the following steps:

s101, obtaining a copolymer PHBV of 3-hydroxybutyrate and 3-hydroxyvalerate by utilizing biological fermentation;

s102, physically blending polymers with different biological functions and small molecules;

and S103, carrying out personalized customization on patches with different aperture requirements by using a continuous 3D printing technology.

The preparation method of the degradable biological patch material provided by the embodiment of the invention comprises the following steps: biologically fermenting to produce PHBV; ② physically blending with micromolecular substances; thirdly, the polymer after physical blending is made into filaments which are used as printing raw materials and placed in a 3D printer; and fourthly, directly printing by the 3D printer.

The polymers of the present invention having different biological functions include: polyethylene glycol, polylactic acid, polylactone, poly (butylene adipate terephthalate) (PBAT).

The technical solution of the present invention is further described below with reference to specific examples.

1. The invention develops a multifunctional surgical hernia biological patch by using a copolymer (PHBV) of 3-hydroxybutyrate and 3-hydroxyvalerate generated by biological fermentation as a raw material, physically blending the raw material with polymers and small molecules with different biological functions and using a continuous 3D printing method, and provides an economic and safe new choice for clinical hernia surgical treatment.

2. Scheme(s)

(1) By utilizing the characteristics of longer in-vivo degradation time and good mechanical strength of PHBV, adding bioactive polymers to promote local fibrous tissue regeneration;

(2) the mechanical strength of the PHBV can be adjusted by introducing other polymers so as to meet the requirements of the repairing strength and the toughness of the surgical hernia patch;

(3) according to the invention, a small molecular bacteriostatic agent is doped into the composite absorbable biological patch or antibacterial modification is carried out on a polymer substrate of the patch, so that the aims of reducing local tissue inflammatory reaction and resisting infection are achieved;

(4) surgical hernia patches with good biocompatibility and biodegradability are the urgent clinical needs at present and are a great challenge for application research. Aiming at the defects of high crystallinity and brittleness of PHBV, the invention improves the mechanical property, the toughness and the antibacterial property by introducing different high-molecular and small-molecular additives, thereby obtaining a safe and efficient absorbable surgical hernia biological patch.

(5) The surgical hernia repair patch prepared by applying the 3D printing technology is not clinically applied at present. The invention organically combines the design of the polymer composite material with the 3D printing technology, and combines the individual condition of a patient to manufacture the biosynthesis patch which has lighter weight, different shapes and adjustable pore diameter and can be completely degraded into carbon dioxide and water, thereby improving the treatment effect and reducing the treatment cost. This will provide a better choice for clinical surgical hernia treatment.

The 3D printed patch can be used for individualized treatment, so that the treatment cost is reduced; the degradation time and the mechanical strength of the PHBV raw material have certain advantages, and the patch can be added by different high polymer materials, so that the patch has a better effect; patches for different aperture requirements can be personalized with 3D printing.

The above description is only for the purpose of illustrating the present invention and the appended claims are not to be construed as limiting the scope of the invention, which is intended to cover all modifications, equivalents and improvements that are within the spirit and scope of the invention as defined by the appended claims.

Claims (7)

1. The degradable biological patch material is characterized by being prepared from a copolymer PHBV of 3-hydroxybutyrate and 3-hydroxyvalerate generated by biological fermentation.

2. The degradable biological patch material of claim 1, wherein the degradable biological patch material further comprises a bioactive polymer, a small molecule bacteriostatic agent, and a small molecule additive.

3. The preparation method of the degradable biological patch material as claimed in any one of claims 1-2, wherein the preparation method of the degradable biological patch material comprises the following steps:

step one, obtaining a copolymer PHBV of 3-hydroxybutyrate and 3-hydroxyvalerate by utilizing biological fermentation;

step two, carrying out physical blending on polymers with different biological functions and small molecules;

and thirdly, carrying out personalized customization on patches with different aperture requirements by utilizing a continuous 3D printing technology.

4. The method of preparing a degradable biological patch material of claim 3, wherein the method of preparing a degradable biological patch material further comprises: and a small molecular bacteriostatic agent is doped into the composite absorbable biological patch or the polymer substrate of the patch is subjected to antibacterial modification.

5. The method of making a degradable biological patch material of claim 3, wherein the method of making the degradable biological patch material comprises: biologically fermenting to produce PHBV; ② physically blending with micromolecular substances; thirdly, the polymer after physical blending is made into filaments which are used as printing raw materials and placed in a 3D printer; and fourthly, directly printing by the 3D printer.

6. The method of preparing a degradable biological patch material of claim 3, wherein the polymers with different biological functions comprise: polyethylene glycol, polylactic acid, polylactone, poly (butylene adipate terephthalate) (PBAT).

7. Use of the degradable biological patch material according to any one of claims 1-2 in the preparation of a medical patch for treating surgical hernia.

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