A porous composite comprising a porous layer containing a calciumphosphateceramic, and a dense layer formed on part of the porous layer and having a smaller average pore size than that of the porous layer. The porous composite can be produced by (1) introducing a slurry containing a calciumphosphateceramic / collagen composite and collagen into a molding die having a high thermal conductivity, (2) rapidly freezing and drying the slurry in the molding die, to form a porous body comprising a porous layer and a dense layer formed on the porous layer, (3) cross-linking collagen in the porous body, and (4) removing the dense layer except for a portion thereof on a surface coming into contact with a soft tissue when implanted in a human body, so that the porous layer is exposed.
Disclosed are compounds and related methods useful for cross-linking collagen and stabilizing collagenous tissues using formaldehyde-donating compounds or nitrogenoxide-containing compounds such as β-Nitro Alcohols. Also disclosed are compounds and related methods for modulating the rate or degree of collagen cross-linking using nitrogenoxide-containing compounds such as β-Nitro Alcohols. The formaldehyde-donating, nitrogenoxide-containing and / or β-Nitro Alcohol compounds disclosed are capable of stabilizing collagenous tissues such as the corneal and scleral tissues and are useful in the treatment or prevention of diseases such as alterations in corneal curvature, keratoconus, keratectasia, progressive myopia and glaucoma.
The invention relates to a triple cross-linking collagen preparation method, which comprises: providing a soluble collagen sample, mixing the collagen sample and a first cross-linking agent to form a single cross-linking collagen, mixing the single cross-linking collagen and a second cross-linking agent to form a double cross-linking collagen, and mixing the double cross-linking collagen and a third cross-linking agent to form the triple cross-linking collagen, wherein the first cross-linking agent, the second cross-linking agent and the third cross-linking agent are separately selected from a group comprising an aldehyde cross-linking agent, an imine cross-linking agent and an epoxide cross-linking agent, the first cross-linking agent is different from the second cross-linking agent, and the third cross-linking agent is different from the first cross-linking agent and the second cross-linking agent.
A method for producing a cross-linked apatite / collagen porous body comprising the steps of gelling and then freeze-drying a dispersion containing an apatite / collagen composite and collagen to form a porous body, and further cross-linking collagen in the porous body, and a cross-linked apatite / collagen porous body produced by this method.
A method for producing a porous body comprising apatite / collagen composite fibers comprising the steps of gelling a dispersion comprising long apatite / collagen composite fibers having an average length of 10-75 mm, short apatite / collagen composite fibers having an average length of 0.05-1 mm, and a liquid; freezing and drying the resultant gel to form a porous body; and cross-linking collagen in the porous body.
The invention provides a bionic biomineralized artificial bonerepair material as well as a preparation method and an application thereof. The material consists of a cross-linked collagen matrix and biomineralized collagen / hydroxyapatite compositepowder dispersed in the matrix, wherein the mass ratio of the collagen matrix to the biomineralized collagen / hydroxyapatite compositepowder is (9-1) to(1-9). The bionic biomineralized artificial bonerepair material provided by the invention is a collage-based bionic biomineralized artificial bone, which can meet a demand of artificial bone and tissue suturing in a clinical GTR or GBR operation; the artificial bone repair material consists of hydroxyapatite and pure collagen, and the two ingredients are major ingredients of human natural tissues, so that the artificial bone repair material is free from toxicity; and influence to a material structure and an osteogenesis effect is avoided, and good biocompatibility is guaranteed. Due to the existence of the cross-linked collagen matrix, problems of a material which can get dispersed easily, and is too high in degradation speed, poor in mechanical performance and the like can be solved; and the bionic construction of nano-hydroxyapatite and collagen is achieved.
A porous composite comprising a porous layer containing a calciumphosphateceramic, and a dense layer formed on part of the porous layer and having a smaller average pore size than that of the porous layer. The porous composite can be produced by (1) introducing a slurry containing a calciumphosphateceramic / collagen composite and collagen into a molding die having a high thermal conductivity, (2) rapidly freezing and drying the slurry in the molding die, to form a porous body comprising a porous layer and a dense layer formed on the porous layer, (3) cross-linking collagen in the porous body, and (4) removing the dense layer except for a portion thereof on a surface coming into contact with a soft tissue when implanted in a human body, so that the porous layer is exposed.
A method for producing a porous body comprising apatite / collagen composite fibers comprising the steps of gelling a dispersion comprising long apatite / collagen composite fibers having an average length of 10-75 mm, short apatite / collagen composite fibers having an average length of 0.05-1 mm, and a liquid; freezing and drying the resultant gel to form a porous body; and cross-linking collagen in the porous body.
A method of cross-linking collagen present in a collagenous tissue comprising contacting the collagenous tissue with an amount of a formaldehyde releasing agent effective to crosslink the collagen is provided. A method of inhibiting loss of structural integrity of a collagenous tissue during transplantation-related transport comprising contacting the collagenous tissue with an amount of a formaldehyde releasing agent effective to inhibit loss of structural integrity of the collagenous tissue is also provided. A composition for ophthalmic administration comprising a formaldehyde releasing agent, sodiumbicarbonate, and ophthalmically suitable carriers or excipients is also provided. Finally, a method of altering the refractive power of a cornea comprising contacting the cornea with a formaldehyde releasing agent so as to effect cross-linking in the cornea and thereby alter the refractive power of the cornea is provided.
The invention discloses a collagenous fiber-based flexible pressure sensing material and a preparation method thereof, and belongs to the technical field of flexible sensing. The preparation method comprises the following steps: mixing a collagenous fiber suspension with a cross-linking agent, and carrying out a cross-linking reaction to prepare a cross-linked collagenous fiber suspension; adding an MXene dispersion liquid into the obtained cross-linked collagen fiber suspension liquid, and uniformly dispersing to obtain an MXene / collagen fiber composite suspension liquid; and carrying out freeze drying treatment on the obtained MXene / collagenous fiber composite suspension to obtain the collagenous fiber-based flexible pressure sensing material. The collagenous fiber-based flexible pressure sensing material has a spongy porous structure and comprises a collagenous fiber substrate material, and the surface of the substrate material is coated with MXene. According to the collagen fiber-based flexible pressure sensing material, the use of a traditional synthetic polymer as a substrate is avoided, and the collagen fiber-based flexible pressure sensing material has excellent air permeability and high sensitivity.
The invention relates to a triple cross-linking collagen preparation method, which comprises: providing a soluble collagen sample, mixing the collagen sample and a first cross-linking agent to form a single cross-linking collagen, mixing the single cross-linking collagen and a second cross-linking agent to form a double cross-linking collagen, and mixing the double cross-linking collagen and a third cross-linking agent to form the triple cross-linking collagen, wherein the first cross-linking agent, the second cross-linking agent and the third cross-linking agent are separately selected from a group comprising an aldehyde cross-linking agent, an imine cross-linking agent and an epoxide cross-linking agent, the first cross-linking agent is different from the second cross-linking agent, and the third cross-linking agent is different from the first cross-linking agent and the second cross-linking agent.
The invention discloses a collagen dermal implant and a preparation method thereof. The method comprises the following steps of dissolving collagen in ultrapure water; performing refrigeration; adding a chemical cross-linking agent; performing uniform stirring at a low temperature; performing refrigeration; performing heating in a water bath to start a cross-linking reaction, so as to prepare cross-linked collagen gel ;adding normal saline-ammonia water into the cross-linked collagen gel, and performing a blocking reaction; adding normal saline into the cross-linked collagen gel after the blocking reaction for purification; granulating the purified cross-linked collagen gel by a screening method; and dispersing the granulated cross-linked collagen gel particles in normal saline to prepare a cross-linked collagen suspension; filling the cross-linked collagen suspension into a pre-filling injector; and performing moist heat sterilization to prepare the collagen dermal implant. The collagen obtained through fermentation has a physical filling function through the cross-linking reaction, and in addition, the collagen dermal implant is free of immunotoxic reaction, has good biocompatibility and can be used as a body tissue filler in medical cosmetology.
The invention provides a controllable-degradation lacrimal passage suppository and a preparation method thereof. The lacrimal passage suppository is a novel slippage-preventing absorbable lacrimal passage suppository having multiple shapes and multiple degradation times and obtained with a cross-linked collagen matrix as a main raw material and through homogenization, freeze-drying molding and other processing steps. The multiple designed shapes not only all can be convenient to implant in surgery, but also can effectively prevent slippage; in addition, after implantation, the lacrimal passage suppository is swelled due to absorption of water, so that the stability of the product after implantation is more ensured, and the security is extremely high. In addition, with a specific micro-pore structure of the product, epiphora and other complications appearing after the product is implanted can be avoided. The method is simple in process and strong in operability. The prepared product can effectively relieve or treat xerophthalmia.
The invention relates to a tissue-guided regenerated collagen membrane and a preparation method thereof. The preparation method comprises the following steps: swelling type I collagen in an acetic acid solution, adding chondroitinsulfatesodium, and uniformly stirring to obtain collagen-chondroitinsulfatesodiumslurry; drying the collagen-chondroitinsulfatesodiumslurry to obtain a dried membrane; mixing the dried diaphragm with a crosslinking solution, and carrying out a crosslinking reaction to obtain a crosslinked collagen diaphragm after the crosslinking reaction is completed; and cleaning the cross-linked collagen membrane, carrying out secondary drying, and performing pressing after the secondary drying is completed. The preparation method comprises the following steps: firstly, swelling high-concentration I-type collagen in an acetic acid solution, adding sodium chondroitin sulfate, stirring, and then drying, cross-linking and secondarily drying, so that the obtained tissue-guided regenerated collagen membrane has excellent mechanical properties, and the pore size and porosity are beneficial to cell growth and repair; in addition, the degradation period is long, and sensitization is not prone to occurring; and the comprehensive effect is comprehensive, and the applicability is wide.
A method of cross-linking collagen present in a collagenous tissue comprising contacting the collagenous tissue with an amount of a formaldehyde releasing agent effective to crosslink the collagen is provided. A method of inhibiting loss of structural integrity of a collagenous tissue during transplantation-related transport comprising contacting the collagenous tissue with an amount of a formaldehyde releasing agent effective to inhibit loss of structural integrity of the collagenous tissue is also provided. A composition for ophthalmic administration comprising a formaldehyde releasing agent, sodiumbicarbonate, and ophthalmically suitable carriers or excipients is also provided. Finally, a method of altering the refractive power of a cornea comprising contacting the cornea with a formaldehyde releasing agent so as to effect cross-linking in the cornea and thereby alter the refractive power of the cornea is provided.
The invention discloses a plant extract and a method for cross-linking collagen by using the plant extract as a biological cross-linker. The plant extract is an amomum villosum extract, wherein the amomum villosum extract contains polyphenol effective components. The plant extract is prepared through the following steps: firstly, cleaning, drying and crushing amomum villosum; secondly, extracting crushed amomum villosumpowder in an extracting solution; thirdly, separating the extracting solution; fourthly, concentrating the extracting solution; fifthly, obtaining a concentrated plant extract solution or dehydrated plant extract powder. The plant extract has the benefits that by using the amomum villosum plant extract as the biological cross-linker, molecular chains of the collagen are cross-linked, the structure of the collagen can be stabilized, and the degradation resistance of the collagen is improved, so that the processing characteristics of a collagen product are improved, the physical properties and the texture characteristics are good, and the application prospect is wide.
The invention discloses a preparation method of a modified collagen membrane, the preparation method comprises the following steps: (1) preparing a collagen solution, and air-drying to obtain a collagen membrane; (2) repeatedly washing the collagen membrane with ultrapure water, soaking the collagen membrane in normal saline, and changing water for multiple times until the pH value of the soaked normal saline is kept unchanged, so as to obtain a rehydrated and swelled collagen membrane; and (3) soaking the rehydrated and swelled collagen membrane obtained in the step (2) in a solution of an activated multi-alkynyl cross-linking agent, and carrying out a cross-linking reaction to obtain the modified cross-linked collagen membrane. The invention also discloses the collagen membrane prepared by the preparation method and the activated multi-alkynyl cross-linking agent for modifying collagen. The collagen membrane is soaked in the solution of the activated multi-alkynyl cross-linking agent, so that cross-linking can be realized, the cross-linking method is simple, and the cross-linking effect is good; through the construction of a cross-linked network, the collagen with a disordered structure has an ordered structure similar to natural collagen fibers, so that the biological activity of the collagen is ensured, and the mechanical property of the collagen is enhanced.
The invention provides a calciumphosphatebioceramic compounded with collagen and its preparation and use method. The preparation method of the calciumphosphatebioceramic compounded with collagen comprises: using collagen solution from low to high concentration on the surface of calciumphosphateceramic particles Form a cross-linked collagen coating to obtain a cross-linked collagen coating wrapped on the surface of calcium phosphate ceramic particles, then mix with collagen solution and freeze-dry to obtain the precursor of calcium phosphate bioceramic composite collagen, and then use collagen solution to soak Freeze-dry after coating to obtain calcium phosphate bioceramics with collagen coating. The technical solution of the present invention improves the repair ability and degradation performance of the calcium phosphate bioceramics compounded with collagen, avoids aseptic inflammation caused by the shedding of calcium phosphate ceramic particles during clinical use, and utilizes the plasticity of shape and size and The convenience of use solves many problems encountered in the clinical application of bioceramics.