CN113861518B - Hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis and preparation method thereof - Google Patents
Hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis and preparation method thereof Download PDFInfo
- Publication number
- CN113861518B CN113861518B CN202111203528.5A CN202111203528A CN113861518B CN 113861518 B CN113861518 B CN 113861518B CN 202111203528 A CN202111203528 A CN 202111203528A CN 113861518 B CN113861518 B CN 113861518B
- Authority
- CN
- China
- Prior art keywords
- hyaluronic acid
- solution
- sodium hyaluronate
- cross
- based thixotropic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/24—Materials or treatment for tissue regeneration for joint reconstruction
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2389/00—Characterised by the use of proteins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
- C08J2405/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2489/00—Characterised by the use of proteins; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dermatology (AREA)
- General Health & Medical Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a hyaluronic acid-based thixotropic hydrogel for lubricating joint prostheses and a preparation method thereof, and relates to the technical field of bionic lubricating liquid, wherein the hyaluronic acid-based thixotropic hydrogel is prepared from 1-16 vol.% of neutral cross-linked hyaluronic acid or sodium hyaluronate solution and 4-6 wt.% of protein solution, and the cross-linked hyaluronic acid or sodium hyaluronate solution is prepared by cross-linking reaction of 1-10 vol.% of cross-linking agent and 7-10 wt.% of hyaluronic acid or sodium hyaluronate alkaline solution. The preparation method of the hyaluronic acid based thixotropic hydrogel is simple in process and low in preparation cost; when the prepared hyaluronic acid-based thixotropic hydrogel is used as joint prosthesis lubricating liquid, the prepared hyaluronic acid-based thixotropic hydrogel has good lubricating performance, can effectively reduce the abrasion of the joint prosthesis and reduce the friction coefficient, and has excellent biocompatibility.
Description
Technical Field
The invention relates to the technical field of bionic lubricating liquid, in particular to hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis and a preparation method thereof.
Background
With age, the incidence of arthritis is increasing, but current data indicate that arthritis is moving towards younger age. When Osteoarthritis (OA), rheumatoid Arthritis (RA) or other infectious joint diseases occur, the composition of the joint lubricating fluid can be changed or the lubricating fluid can be reduced, the degree of friction of the joint is increased under the condition, a large amount of abrasion of the joint can be caused, so that the joint is diseased, the joint is painful, stiff and swollen, and the normal work of the joint is affected. Exogenous lubricating liquid can be injected into the early stage of pathological changes, which is beneficial to improving the friction condition of joints and inhibiting the pathological changes of the joints. Joint replacement operation is needed in the later stage of pathological changes, however, most of materials used for joint replacement are metal, ceramic, ultra-high molecular weight polyethylene and the like, friction and abrasion are inevitably generated due to the lack of a lubricating system of a normal joint, and abraded particles are a main reason for loosening of a joint prosthesis. In order to prolong the service life of the joint prosthesis, the bionic joint lubricating fluid is required to provide a lubricating effect, but the implantation of the joint prosthesis causes the joint capsule to be removed, the liquid bionic lubricating fluid cannot be stored, and the liquid lubricating fluid is not easy to adhere to the joint surface; further, the liquid bionic lubricating fluid is easy to pass, and in addition, the liquid bionic lubricating fluid has the problem of easy degradation (D.diamocoglu, K.Alptekin, B.Teksoz, et al.knee v.hip single-joint in-tissue with bone tip and knee osteo-arthritis: a pilot test, clin Rheumatol,2009,28, 1021-1024).
In view of the above problems, in order to increase the service life of the biomimetic lubricating fluid, it is required that the biomimetic lubricating fluid has excellent degradation resistance and easy storage property. Hyaluronic acid (also known as hyaluronic acid, abbreviated as HA) is a relatively common joint bionic lubricating fluid due to its good biocompatibility, but when hyaluronic acid is injected into a joint in vitro, the half-life of hyaluronic acid in the joint is about 12H under the degradation effect of in vivo enzymes, which greatly limits the lubrication time of HA in the joint (Kim H, jeong H, han S, et al, hyaluronic acid and its derivatives for stored biological applications [ J ] Biomaterials,2017, 123. In order to relieve the liquid lubricant from being easily degraded, the hydrogel is a good choice, and the hyaluronic acid crosslinked hydrogel is prepared by a chemical crosslinking method at present, but the crosslinked hydrogel prepared at present can only be lubricated under the condition of small stress (Kpa grade), and the hydrogel breaks with the increase of loading stress (Bonyadi S Z, dunn A C. Brittle or Ductle Abrasive Wear of polyacrylic Hydrogels sources Load-Dependent Wear mechanics [ J ]. Tribology Letters,2020,68 (1):.), so that the lubricating effect of the hydrogel is limited under the condition of human joint Load (stress is about 18 Gpa). Therefore, the development of the bionic joint lubricating liquid which has degradation resistance and storability and can realize the lubricating effect under the condition of human joint load has important scientific significance.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a hyaluronic acid-based thixotropic hydrogel for lubricating joint prostheses and a preparation method thereof, so as to solve the technical problem that the lubricating effect of the existing hyaluronic acid crosslinked hydrogel under the condition of human joint load is limited.
The technical scheme adopted by the invention is as follows:
a hyaluronic acid-based thixotropic hydrogel for lubrication of joint prostheses, which is prepared by crosslinking a neutral crosslinked hyaluronic acid or sodium hyaluronate solution and 4-6 wt.% of a protein solution in a volume ratio of 1-16, wherein the crosslinked hyaluronic acid or sodium hyaluronate solution is prepared by crosslinking reaction of a crosslinking agent and 7-10 wt.% of hyaluronic acid or sodium hyaluronate alkaline solution in a volume ratio of 1-10.
The thixotropic hydrogel prepared by the invention is a mechanical stimulus response hydrogel, and the state of the hydrogel is artificially controlled by utilizing the characteristics of stress dilution and force withdrawal recovery of the thixotropic hydrogel; the hydrogel shows a sol state under the condition of human joint load and provides a lubricating effect for joints, the hydrogel is changed from the sol state to a gel state under the condition of no load and is adhered to the surfaces of the joints, the passing speed of the lubricating liquid is slowed down, the effect of easy storage is further shown, and the service time of the lubricating liquid is prolonged.
The preparation method of the hyaluronic acid based thixotropic hydrogel comprises the following steps:
(1) Preparing a solution: dissolving hyaluronic acid or sodium hyaluronate powder in an alkaline solution with the pH of 12-14 to prepare a hyaluronic acid or sodium hyaluronate solution with the concentration of 7-10 wt.%, dissolving protein powder in deionized water to prepare a protein solution with the concentration of 4-6 wt.%, and preparing a 1mol/L hydrochloric acid solution;
(2) Crosslinking to form crosslinked hyaluronic acid or crosslinked sodium hyaluronate: uniformly mixing a cross-linking agent with the hyaluronic acid or sodium hyaluronate solution prepared in the step (1) according to a ratio, cross-linking for 3 hours under the condition of a water bath at 35-45 ℃, and then adjusting the pH of the mixed solution to be neutral by using the hydrochloric acid solution prepared in the step (1) to terminate the reaction, thus obtaining a cross-linked hyaluronic acid/sodium hyaluronate solution;
(3) Preparation of hyaluronic acid based thixotropic hydrogel: and (3) uniformly mixing the cross-linked hyaluronic acid/sodium hyaluronate solution prepared in the step (2) with the protein solution prepared in the step (1) according to the proportion to form a gel solution, and reacting for 60min under the water bath condition of 45-55 ℃ to obtain the hyaluronic acid-based thixotropic hydrogel.
Preferably, the alkaline solution in step (1) is one or more of ammonia water, sodium hydroxide solution or potassium hydroxide solution.
Preferably, the molecular weight range of the hyaluronic acid or the sodium hyaluronate in the step (1) is 6X 10 5 ～1.5×10 6 Da。
Preferably, the protein in step (1) is one or more of gelatin, silk fibroin or collagen.
Preferably, the crosslinking agent in step (2) is one or more of divinyl sulfone, 1, 4-butanediol diglycidyl ether, or genipin.
In summary, compared with the prior art, the invention has the following advantages and beneficial effects:
1. the thixotropy of the thixotropic hydrogel based on hyaluronic acid prepared by the invention is mainly derived from a supermolecule system in the components, mainly comprises electrostatic interaction and hydrogen bonds formed among the components, the supermolecule system is damaged when being subjected to external force, so that the hydrogel is converted into a sol state, and when the external force is removed, the components can rapidly re-form the electrostatic interaction and the hydrogen bonds to be recovered into a gel state. By utilizing the characteristic, when the shearing stress generated by the normal movement of the joint prosthesis acts on the thixotropic hydrogel, the thixotropic hydrogel can generate gel-sol transformation, so that a lubricating film is formed, and excellent lubricating performance is provided; when the joint prosthesis stops moving, the thixotropic hydrogel is subjected to sol-gel conversion, so that the thixotropic hydrogel is easily adhered to the surface of the joint prosthesis, the aim of protecting the joint capsule from lubricating liquid is indirectly fulfilled, the loss speed of the lubricating liquid is reduced, and the injection times are further reduced;
2. the raw materials of the invention are derived from proteins and hyaluronic acid/sodium hyaluronate in animal bodies in the nature, and have excellent biocompatibility, wherein the cross-linked hyaluronic acid has good viscoelasticity and long degradation time, and has the functions of protecting and inducing repair of articular cartilage of osteoarthritis, so the cross-linked hyaluronic acid is expected to be used for repairing the articular cartilage of a human body;
2. the preparation method of the hyaluronic acid based thixotropic hydrogel provided by the invention is simple in process, low in preparation cost and convenient to popularize and use.
Drawings
The invention will now be described, by way of example, with reference to the accompanying drawings, in which:
figure 1 is a graph of the results of amplitude sweep testing of hyaluronic acid-based thixotropic hydrogels prepared in example 1 using a rotary rheometer.
Fig. 2 is a graph of the results of a three step plot (3 ITT) test using a rotational rheometer on the hyaluronic acid-based thixotropic hydrogel prepared in example 1.
Figure 3 is a graph of the results of amplitude sweep testing of hyaluronic acid-based thixotropic hydrogels prepared in example 2 using a rotary rheometer.
Fig. 4 is a graph of the results of a three step plot (3 ITT) test using a rotational rheometer on the hyaluronic acid-based thixotropic hydrogel prepared in example 2.
Figure 5 is a graph of the results of amplitude sweep testing of the hyaluronic acid-based thixotropic hydrogel prepared in example 3 using a rotary rheometer.
Fig. 6 is a graph of the results of a three step plot (3 ITT) test using a rotational rheometer on hyaluronic acid-based thixotropic hydrogels prepared in example 3.
Figure 7 is a graph of the results of amplitude sweep testing of the hyaluronic acid-based thixotropic hydrogel prepared in example 4 using a rotary rheometer.
Fig. 8 is a graph of the results of a three step plot (3 ITT) test using a rotational rheometer on hyaluronic acid-based thixotropic hydrogels prepared in example 4.
Fig. 9 is a graph showing the results of an amplitude scan test using a rotational rheometer for the hyaluronic acid-based hydrogel prepared in comparative example 1.
Fig. 10 is a graph showing the results of the amplitude scan test using a rotational rheometer for the hyaluronic acid-based hydrogel prepared in comparative example 2.
Fig. 11 is a graph showing the results of an amplitude scan test using a rotational rheometer for the hyaluronic acid-based hydrogel prepared in comparative example 3.
FIG. 12 is a bar graph of the results of friction coefficients of a biomimetic joint system tested using a high speed reciprocating circular friction machine.
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 below with reference to the accompanying drawings and embodiments. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
A preparation method of hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis comprises the following steps:
(A) Pretreatment: dissolving sodium hydroxide in deionized water to prepare an alkaline solution with the pH value of 13; diluting 12mol/L hydrochloric acid solution into 1mol/L hydrochloric acid solution; molecular weight is 1X 10 6 Dissolving Da hyaluronic acid or sodium hyaluronate powder in the sodium hydroxide solution to prepare hyaluronic acid or sodium hyaluronate solution with the concentration of 8.5 wt%; gelatin powder was dissolved in deionized water to make a gelatin solution with a concentration of 5 wt.%.
(B) Preparation of cross-linked hyaluronic acid or sodium hyaluronate: mixing 1, 4-butanediol diglycidyl ether and the hyaluronic acid or sodium hyaluronate solution prepared in step A according to a volume ratio of 3.
(C) Preparation of hyaluronic acid based thixotropic hydrogel: and (3) mixing the gelatin solution prepared in the step A and the cross-linked hyaluronic acid or sodium hyaluronate solution prepared in the step B according to the volume ratio of 2.
The scanning test of the product obtained in this example is performed by using a rotational rheometer, and the results of the amplitude scanning test are shown in fig. 1, and as can be seen from fig. 1, G' (Storage module) and G "(Loss module) have an intersection, which indicates that a gel-sol transition point exists; the three-step diagram (3 ITT) test results are shown in fig. 2, and as can be seen from fig. 2, G' and G ″ have size mutation and can be restored to the initial state, which indicates that gel-sol-gel transition is realized, and the product obtained in this example has thixotropy.
Example 2
A method of preparing a thixotropic hyaluronic acid-based hydrogel for lubrication of joint prostheses, comprising the steps of:
(A) Pretreatment: dissolving potassium hydroxide in deionized water to prepare an alkaline solution with the pH value of 12.5; diluting 12mol/L hydrochloric acid solution into 1mol/L hydrochloric acid solution; molecular weight is 6X 10 5 Dissolving Da hyaluronic acid or sodium hyaluronate powder in the potassium hydroxide solution to prepare a hyaluronic acid or sodium hyaluronate solution with the concentration of 10 wt%; the collagen powder was dissolved in deionized water to prepare a collagen solution with a concentration of 7 wt.%.
(B) Preparation of cross-linked hyaluronic acid or sodium hyaluronate: and (2) mixing divinyl sulfone with the hyaluronic acid or sodium hyaluronate solution prepared in the step A according to a volume ratio of 1.
(C) Preparation of hyaluronic acid based thixotropic hydrogel: mixing the collagen solution prepared in the step A and the cross-linked hyaluronic acid or sodium hyaluronate solution prepared in the step B according to the volume ratio of 1.
The product obtained in this example was subjected to a scanning test using a rotational rheometer, and the results of the amplitude scanning test are shown in FIG. 3. As can be seen from FIG. 3, G' and G "have an intersection, indicating the presence of a gel-sol transition point; the three-step diagram (3 ITT) test results are shown in fig. 4, and as can be seen from fig. 4, G' and G ″ undergo size mutation and can be restored to the initial state, which indicates that gel-sol-gel transition is achieved, and the product obtained in this example has thixotropy.
Example 3
A preparation method of hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis comprises the following steps:
(A) Pretreatment: preparing ammonia water with pH of 14; diluting 12mol/L hydrochloric acid solution into 1mol/L hydrochloric acid solution; molecular weight is 1.5X 10 6 Da hyaluronic acid or sodium hyaluronate powder is dissolved in the ammonia water to prepare hyaluronic acid or sodium hyaluronate solution with the concentration of 5 wt%; silk fibroin powder was dissolved in deionized water to prepare a silk fibroin solution with a concentration of 4 wt.%.
(B) Preparation of crosslinked sodium hyaluronate: mixing a genipin cross-linking agent and the hyaluronic acid or sodium hyaluronate solution prepared in the step A according to a volume ratio of 1.
(C) Preparation of hyaluronic acid-based thixotropic hydrogel: and (2) mixing the silk fibroin solution prepared in the step A and the cross-linked hyaluronic acid or sodium hyaluronate solution prepared in the step B according to the volume ratio of 4.
The product obtained in this example was subjected to a scanning test using a rotational rheometer, and the results of the amplitude scanning test are shown in FIG. 5. As can be seen from FIG. 5, G' and G "have an intersection, indicating the presence of a gel-sol transition point; the results of the three-step diagram (3 ITT) test are shown in fig. 6, and as can be seen from fig. 6, G' and G ″ undergo size mutation and can be restored to the initial state, which indicates that the gel-sol-gel transition is realized, and the product obtained in this example has thixotropy.
Example 4
A preparation method of hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis comprises the following steps:
(A) Pretreatment: dissolving sodium hydroxide in deionized water to prepare an alkaline solution with the pH value of 13; diluting 12mol/L hydrochloric acid solution into 1mol/L hydrochloric acid solution; has a molecular weight of 1.5 × 10 7 Dissolving Da hyaluronic acid or sodium hyaluronate powder in the sodium hydroxide solution to prepare a hyaluronic acid or sodium hyaluronate solution with the concentration of 7 wt%; dissolving silk fibroin and collagen in deionized water according to the proportion of 1.
(B) Preparation of cross-linked hyaluronic acid: and (2) mixing a 1.4-butanediol diglycidyl ether cross-linking agent and the hyaluronic acid or sodium hyaluronate solution prepared in the step A according to a volume ratio of 7 to 500, stirring for 10min to prepare a uniformly distributed mixed solution, crosslinking the mixed solution for 3h under a water bath condition of 40 ℃, and then adjusting the pH of the mixed solution to be neutral by using 1mol/L hydrochloric acid to obtain a crosslinked hyaluronic acid solution.
(C) Preparation of hyaluronic acid based thixotropic hydrogel: and (3) mixing the silk fibroin/collagen solution prepared in the step A and the cross-linked hyaluronic acid solution prepared in the step B according to the volume ratio of 3.
The product obtained in this example was subjected to a scanning test using a rotational rheometer, and the results of the amplitude scanning test are shown in FIG. 7. It can be seen from FIG. 7 that G' and G "have an intersection, indicating that a gel-sol transition point exists; the three-step diagram (3 ITT) test result is shown in fig. 8, and as can be seen from fig. 8, G' and G ″ have size mutation and can be restored to the initial state, which indicates that gel-sol-gel transition is realized, and the product obtained in this example has thixotropy.
Comparative example 1
A preparation method of hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis comprises the following steps:
(A) Pretreatment: dissolving sodium hydroxide in deionized water to prepare an alkaline solution with the pH value of 13; diluting 12mol/L hydrochloric acid solution into 1mol/L hydrochloric acid solution; molecular weight is 1X 10 6 Dissolving Da hyaluronic acid or sodium hyaluronate powder in the sodium hydroxide solution to prepare hyaluronic acid or sodium hyaluronate solution with the concentration of 8.5 wt%; gelatin powder was dissolved in deionized water to make a gelatin solution with a concentration of 5 wt.%.
(B) Preparation of cross-linked hyaluronic acid or sodium hyaluronate: mixing 1, 4-butanediol diglycidyl ether and the hyaluronic acid or sodium hyaluronate solution prepared in step A according to a volume ratio of 3.
(C) Preparation of hyaluronic acid based thixotropic hydrogel: and (3) mixing the gelatin solution prepared in the step A and the cross-linked hyaluronic acid or sodium hyaluronate solution prepared in the step B according to the volume ratio of 1.
The product obtained in the comparative example was subjected to a scanning test using a rotational rheometer, and the results of the amplitude scanning test are shown in fig. 9, and as can be seen from fig. 9, G' and G ″ have no intersection, indicating that no gel-sol has occurred, and the product obtained in the comparative example has no thixotropy.
Comparative example 2
A preparation method of hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis comprises the following steps:
(A) Pretreatment: dissolving sodium hydroxide in deionized water to prepare an alkaline solution with the pH value of 13; diluting 12mol/L hydrochloric acid solution into 1mol/L hydrochloric acid solution; molecular weight is 1X 10 6 Da hyaluronic acid or sodium hyaluronate powder is dissolved in the sodium hydroxide solution to prepare hyaluronic acid or sodium hyaluronate solution with the concentration of 8.5 wt%; gelatin powder was dissolved in deionized water to make a gelatin solution with a concentration of 5 wt.%.
(B) Preparation of cross-linked hyaluronic acid or sodium hyaluronate: mixing 1, 4-butanediol diglycidyl ether and the hyaluronic acid or sodium hyaluronate solution prepared in step A according to a volume ratio of 3.
(C) Preparation of hyaluronic acid based thixotropic hydrogel: and (3) mixing the gelatin solution prepared in the step A and the cross-linked hyaluronic acid or sodium hyaluronate solution prepared in the step B according to the volume ratio of 9.
The scanning test of the product obtained in the comparative example was carried out using a rotational rheometer, and the results of the amplitude scanning test are shown in FIG. 10, and it can be seen from FIG. 10 that G 'and G' have no intersection, indicating that no gel-sol has occurred, and that the product obtained in the comparative example has no thixotropy
Comparative example 3
A method for preparing a hyaluronic acid-based hydrogel for lubrication of joint prostheses, comprising the steps of:
(A) Pretreatment: dissolving sodium hydroxide in deionized water to prepare an alkaline solution with the pH value of 13; diluting 12mol/L hydrochloric acid solution into 1mol/L hydrochloric acid solution; molecular weight is 1X 10 6 Dissolving Da hyaluronic acid or sodium hyaluronate powder in the sodium hydroxide solution to prepare hyaluronic acid or sodium hyaluronate solution with the concentration of 8.5 wt%; gelatin powder was dissolved in deionized water to make a gelatin solution with a concentration of 5 wt.%.
(B) Preparation of cross-linked hyaluronic acid or sodium hyaluronate/gelatin composite solution: and (3) mixing the 1.4-butanediol diglycidyl ether with the hyaluronic acid or sodium hyaluronate solution prepared in the step A according to the volume ratio of 3. And then mixing the gelatin solution prepared in the step A with the cross-linked hyaluronic acid or sodium hyaluronate mixed solution according to the volume ratio of 2.
(C) Preparation of hyaluronic acid-based hydrogel: crosslinking the crosslinked hyaluronic acid or the sodium hyaluronate/gelatin composite solution for 3 hours under the condition of water bath at 40 ℃, and then adjusting the pH of the mixed solution to be neutral by using 1mol/L hydrochloric acid to obtain the product.
The product obtained in the present comparative example was subjected to a scanning test using a rotational rheometer, and the results of the amplitude scanning test are shown in fig. 11, and as can be seen from fig. 11, G' and G ″ have no intersection, indicating that no gel-sol has occurred, and the product obtained in the present comparative example has no thixotropy.
Examples of the experiments
Constructing a bionic joint system: and (3) constructing a bionic joint system by using the prepared hyaluronic acid base thixotropic hydrogel and Ultrahigh molecular weight polyethylene (UHMWPE). Wherein the thixotropic hydrogel is spread and adhered on the surface of UHMWPE, which provides excellent lubricating property for the bionic joint system.
A bionic joint system is tested by adopting a high-speed reciprocating circulating friction machine, lubricating media are hyaluronic acid-based thixotropic hydrogel, calf serum (Calf serum, CS) and Normal Saline (NS) prepared in examples 1-4, the test result is shown in fig. 12, and the result shows that the friction coefficients of the hyaluronic acid-based thixotropic hydrogel are lower than those of the CS and the NS, which indicates that the human hyaluronic acid-based thixotropic hydrogel provided by the invention has good lubricating performance under a strong stress condition.
The above-mentioned embodiments only express the specific embodiments of the present application, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present application. It should be noted that, for those skilled in the art, without departing from the technical idea of the present application, several changes and modifications can be made, which all belong to the protection scope of the present application.
Claims (5)
1. A hyaluronic acid-based thixotropic hydrogel for use in joint prosthesis lubrication, characterized by: the hyaluronic acid-based thixotropic hydrogel is prepared from neutral cross-linked hyaluronic acid or a sodium hyaluronate solution and a protein solution, wherein the volume ratio of the neutral cross-linked hyaluronic acid or the sodium hyaluronate solution is 1-16, and the protein solution is 4-6 wt%, and the cross-linked hyaluronic acid or the sodium hyaluronate solution is prepared by cross-linking reaction of a cross-linking agent and an alkaline solution of hyaluronic acid or sodium hyaluronate, wherein the volume ratio of the cross-linked hyaluronic acid or the sodium hyaluronate solution is 1-10;
the protein in the protein solution is one or more of gelatin, silk fibroin or collagen.
2. A method of preparing the hyaluronic acid-based thixotropic hydrogel of claim 1, comprising the steps of:
(1) Preparing a solution: dissolving hyaluronic acid or sodium hyaluronate powder in an alkaline solution with the pH of 12-14 to prepare a hyaluronic acid or sodium hyaluronate solution with the concentration of 7-10 wt.%, dissolving protein powder in deionized water to prepare a protein solution with the concentration of 4-6 wt.%, and preparing 1mol/L hydrochloric acid solution;
(2) Crosslinking to form crosslinked hyaluronic acid or crosslinked sodium hyaluronate: uniformly mixing a cross-linking agent with the hyaluronic acid or sodium hyaluronate solution prepared in the step (1) according to a ratio, cross-linking for 3 hours under the water bath condition of 35-45 ℃, and then regulating the pH of the mixed solution to be neutral by using the hydrochloric acid solution prepared in the step (1) to terminate the reaction, so as to obtain a cross-linked hyaluronic acid/sodium hyaluronate solution;
(3) Preparation of hyaluronic acid based thixotropic hydrogel: and (3) uniformly mixing the cross-linked hyaluronic acid/sodium hyaluronate solution prepared in the step (2) with the protein solution prepared in the step (1) according to the proportion to form a gel solution, and reacting for 60min under the water bath condition of 45-55 ℃ to obtain the hyaluronic acid-based thixotropic hydrogel.
3. The method of preparing the hyaluronic acid-based thixotropic hydrogel of claim 2, wherein the basic solution in step (1) is one or more of aqueous ammonia, sodium hydroxide solution, or potassium hydroxide solution.
4. The method for preparing the hyaluronic acid-based thixotropic hydrogel of claim 2, wherein the molecular weight of the hyaluronic acid or the sodium hyaluronate in the step (1) is in a range of 6 x 105 to 1.5 x 106 Da.
5. The method of preparing the hyaluronic acid-based thixotropic hydrogel of claim 2, wherein the crosslinking agent of step (2) is one or more of divinylsulfone, 1, 4-butanediol diglycidyl ether, or genipin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111203528.5A CN113861518B (en) | 2021-10-15 | 2021-10-15 | Hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111203528.5A CN113861518B (en) | 2021-10-15 | 2021-10-15 | Hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113861518A CN113861518A (en) | 2021-12-31 |
| CN113861518B true CN113861518B (en) | 2023-01-06 |
Family
ID=78999794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111203528.5A Active CN113861518B (en) | 2021-10-15 | 2021-10-15 | Hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113861518B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103357066A (en) * | 2013-06-28 | 2013-10-23 | 陕西巨子生物技术有限公司 | Hydrogel with bioremediation activity and outstanding degradation performance and preparation method |
| CN104327311A (en) * | 2014-10-27 | 2015-02-04 | 天津科技大学 | Hyaluronic acid composite cross-linked hydrogel and preparation method thereof |
| KR101918452B1 (en) * | 2018-06-30 | 2018-11-13 | 구태훈 | Composition having Carboxymethyl Chitosan, cross-linked hyaluronic acid and collagen and, manufacturing methods for the same |
| WO2021134084A1 (en) * | 2019-12-26 | 2021-07-01 | Allergan, Inc. | Physical mix ha-collagen dermal fillers |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8697044B2 (en) * | 2007-10-09 | 2014-04-15 | Allergan, Inc. | Crossed-linked hyaluronic acid and collagen and uses thereof |
| US20130116411A1 (en) * | 2011-09-06 | 2013-05-09 | Allergan, Inc. | Methods of making hyaluronic acid/collagen compositions |
-
2021
- 2021-10-15 CN CN202111203528.5A patent/CN113861518B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103357066A (en) * | 2013-06-28 | 2013-10-23 | 陕西巨子生物技术有限公司 | Hydrogel with bioremediation activity and outstanding degradation performance and preparation method |
| CN104327311A (en) * | 2014-10-27 | 2015-02-04 | 天津科技大学 | Hyaluronic acid composite cross-linked hydrogel and preparation method thereof |
| KR101918452B1 (en) * | 2018-06-30 | 2018-11-13 | 구태훈 | Composition having Carboxymethyl Chitosan, cross-linked hyaluronic acid and collagen and, manufacturing methods for the same |
| WO2021134084A1 (en) * | 2019-12-26 | 2021-07-01 | Allergan, Inc. | Physical mix ha-collagen dermal fillers |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113861518A (en) | 2021-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108465128B (en) | Preparation method of cross-linked hyaluronic acid cell scaffold material | |
| US20220348745A1 (en) | Compositions and Methods for Treating a Disorder or Defect in Soft Tissue | |
| US6378527B1 (en) | Cell-culture and polymer constructs | |
| CN111892719B (en) | Hyaluronic acid supramolecular hydrogel for three-dimensional culture of chondrocytes, and preparation and application thereof | |
| JP4193917B2 (en) | Crosslinked polymer composition and method of use thereof | |
| EP1587945B1 (en) | Hydroxyphenyl cross-linked macromolecular network and applications thereof | |
| US5476666A (en) | Glycosaminoglycan-synthetic polymer conjugates | |
| JP5518709B2 (en) | Adjustable cross-linked hyaluronic acid composition | |
| JP2679409B2 (en) | Synthetic bone matrix | |
| CN102078227A (en) | Polyethylene artificial joint capable of improving biocompatibility and tribological property and preparation method thereof | |
| US20100233267A1 (en) | Composite hydrogel | |
| CN102772823A (en) | Preparation method of hyaluronic acid/gelatin/chondroitin sulfate bone repair bionic scaffold | |
| Young et al. | In situ-forming, mechanically resilient hydrogels for cell delivery | |
| CN109045354B (en) | In-situ forming injectable hydrogel for comprehensive repair of bone-cartilage | |
| CN113861518B (en) | Hyaluronic acid-based thixotropic hydrogel for lubricating joint prosthesis and preparation method thereof | |
| Wang et al. | Fabrication of a double-network hydrogel based on carboxymethylated curdlan/polyacrylamide with highly mechanical performance for cartilage repair | |
| CN113384753A (en) | Injectable temperature-sensitive composite hydrogel containing adipose-derived mesenchymal stem cells and preparation method and application thereof | |
| EP2983689B1 (en) | Composition comprising self-assembling peptides and a charged polysaccharide | |
| Guo et al. | Sustained-release application of PCEC hydrogel on laser-textured surface lubrication | |
| CN117915933A (en) | Cartilage regeneration using injectable in situ polymerizable collagen compositions containing chondrocytes or stem cells | |
| Sönmezer et al. | Production of Hydrogel with Alginate and Pericardial Fluid for use in Tissue Engineering Applications | |
| US10507178B2 (en) | Method for treating intervertebral disc degeneration | |
| Chawla et al. | Hydrogels with Ubiquitous Roles in Biomedicine and Tissue Regeneration | |
| Mishbak | Design and fabrication of scaffolds for cartilage applications through photopolymerization of hydrogels | |
| CN115737916A (en) | Functional polypeptide hydrogel and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |