Search

CN-121668342-B - Intelligent developing measurement film for cartilage/meniscus defect and preparation method thereof

CN121668342BCN 121668342 BCN121668342 BCN 121668342BCN-121668342-B

Abstract

The invention provides an intelligent developing measurement film for cartilage/meniscus defect and a preparation method thereof, relating to the technical field of medicine, comprising the steps of carrying out low-temperature oxygen plasma treatment on one surface of a medical flexible substrate for surface activation to form an activation layer; forming a bionic anchoring substrate on the activation layer, depositing MMP response microcapsules on the bionic anchoring substrate, performing gas-phase crosslinking, and drying to obtain an MMP response function color development layer, and printing a measurement grid on the other surface of the medical flexible substrate. The method solves the technical problems that the cartilage/meniscus defect measuring method using medical images and intraoperative auxiliary measurement as cores in the prior art has poor adaptability to complex curved surfaces and irregular defects and high error rate, and can not quickly and accurately acquire morphological parameters of defects during the operation.

Inventors

  • NIE HONGTAO
  • WANG XINYI
  • Yang Kongyan
  • Zhai Sunli
  • WANG YUN
  • YANG MENGYU

Assignees

  • 北京邦塞科技有限公司

Dates

Publication Date
20260508
Application Date
20260210

Claims (10)

  1. 1. A method for preparing an intelligent imaging measurement film for cartilage/meniscus defects, comprising the steps of: A. Carrying out low-temperature oxygen plasma treatment on one surface of the medical flexible substrate to carry out surface activation to form an activation layer; B. soaking the medical flexible substrate treated in the step A in a first buffer solution containing catecholamine compounds of 1.0-5.0 mg/mL, performing self-polymerization reaction to form a bionic anchoring substrate on an activation layer, depositing MMP responsive microcapsules on the bionic anchoring substrate, performing gas-phase crosslinking, and drying to obtain an MMP responsive function chromogenic layer; The catecholamine compound is dopamine, and the pH value of the first buffer solution is 7.5-9.0; C. Printing a measurement grid on the other side of the medical flexible substrate; The preparation method of the MMP responsive microcapsule comprises the steps of adding a wall material solution into a core material oil phase at a high speed and homogenizing according to a volume ratio of 1:1.5-1:5, emulsifying to form an oil-in-water primary emulsion, adding the oil-in-water primary emulsion into a cold water solution containing a stabilizer according to a volume ratio of 1:5-1:20, stirring to form a water-in-oil-in-water double emulsion, adding a curing agent to separate out the wall material, adding a crosslinking agent to a final concentration of 0.5% (v/v), and collecting to obtain the MMP responsive microcapsule; the wall material solution contains 3-10% w/v MMP response material; the MMP responsive material is gelatin.
  2. 2. The method of claim 1, wherein the core oil phase comprises 0.1-2.0% w/v of a pH sensitive dye, 1-5% w/v of an acid precursor compound, and 1-5% w/v of an emulsifier; the concentration of the stabilizer in the cold water solution is 0.5-3.0% w/v; The addition amount of the curing agent is 10-30% of the total volume of the system; the rotating speed of the high-speed homogenization is 5000-15000 rpm; forming an oil-in-water primary emulsion, wherein the emulsification time is 3-10 min; The stirring speed for forming the water-in-oil-in-water double emulsion is 1000-3000 rpm; the stirring time for forming the water-in-oil-in-water double emulsion is 5-20 min.
  3. 3. The preparation method of claim 2, wherein the solvent of the wall material solution is a second buffer solution, and the pH of the second buffer solution is 6.5-8.0; the second buffer solution is selected from phosphate buffer solution or Tris-HCl buffer solution; the pH sensitive dye is at least one selected from bromocresol green, bromocresol purple, phenol red or Congo red; The acid precursor compound is selected from at least one of glucono-delta-lactone, gluconic acid, ascorbic acid or citric acid; The emulsifier is at least one selected from span 80, span 60 and tween 80; The solvent of the core material oil phase is at least one selected from octane, chloroform, ethyl acetate and dichloromethane; The stabilizer is at least one selected from acacia, polyvinyl alcohol or gelatin; The cross-linking agent in the preparation of MMP responsive microcapsules is at least one selected from glutaraldehyde, genipin or tannic acid.
  4. 4. The method of preparing of claim 1, wherein depositing the MMP responsive microcapsules on the biomimetic anchoring substrate comprises uniformly depositing a MMP responsive microcapsule suspension on the biomimetic anchoring substrate by coating; the solid content of the MMP responsive microcapsule suspension is 5-15% w/v; the MMP responsive microcapsule suspension has a particle size distribution of 10-50 μm; The coating mode comprises at least one of atomization spraying, spin coating or dip coating; The environmental temperature of the gas phase crosslinking is 20-50 ℃; the gas phase crosslinking time is 2-8 hours; the gas-phase crosslinking agent is selected from at least one of glutaraldehyde steam, formaldehyde steam or genipin steam; And the drying time is 12-48 h.
  5. 5. The preparation method according to claim 1, wherein the self-polymerization reaction is carried out under a condition of light shielding at 20-30 ℃ and at a speed of 40-80 rpm; the self-polymerization reaction time is 10-36 h; The first buffer is selected from Tris-HCl buffer, phosphate buffer or carbonate buffer.
  6. 6. The method according to claim 1, wherein the vacuum degree of the low-temperature oxygen plasma treatment is 5 to 50pa; the radio frequency power of the low-temperature oxygen plasma treatment is 100-500W; the time of the low-temperature oxygen plasma treatment is 30-180 s; the medical flexible substrate is made of thermoplastic polyurethane, polycaprolactone, polylactic acid-glycolic acid copolymer or silicone rubber; the low temperature oxygen plasma treated gas is selected from at least one of oxygen, air or argon.
  7. 7. The method of manufacturing according to claim 1, wherein the printing comprises printing and curing; the printing mode comprises screen printing, wherein the number of screen meshes is 200-600 meshes; the curing comprises ultraviolet light curing, heat curing or photo-thermal dual curing; The ultraviolet light main wavelength of ultraviolet light curing is 365-405 nm, the light intensity is 300-800 mW/cm < 2 >, and the irradiation time is 3-20 s; the line width of the measurement grid is 0.05-0.2 mm; the line material of the measurement grid is at least one of UV (ultraviolet) curing polyurethane ink, water-based polyurethane ink or medical silica gel ink; the measurement grid is a square grid; The size of the square grid is 1.0mm multiplied by 1.0mm; The measurement grid includes a coordinate scale and a digital identification.
  8. 8. The method of any one of claims 1-7, wherein the MMP comprises at least one of MMP-1, MMP-2, MMP-8, MMP-9, or MMP-13.
  9. 9. An intelligent imaging measurement film for cartilage/meniscus defects, which is prepared by the preparation method of any one of claims 1-8.
  10. 10. The intelligent development measurement film according to claim 9, comprising an MMP response function color developing layer arranged on one side of the medical flexible substrate and a measurement grid arranged on the other side of the medical flexible substrate; The MMP response function color development layer comprises a bionic anchoring substrate and MMP response microcapsules fixed on the bionic anchoring substrate; the MMP-responsive microcapsules are used for specifically recognizing MMP and releasing a chromogenic dye; the bionic anchoring substrate is used for in-situ deposition and fixation of chromogenic dye released by MMP responsive microcapsules.

Description

Intelligent developing measurement film for cartilage/meniscus defect and preparation method thereof Technical Field The invention relates to the technical field of medicines, in particular to an intelligent developing measurement film for cartilage/meniscus defects and a preparation method thereof. Background Osteoarthritis (Osteoarthritis, OA) is a worldwide high-frequency degenerative joint disease, particularly severe in knee joint damage, and in orthopedic clinical practice, knee joint is the most loaded and frequently movable joint, and its functional state is highly dependent on the integrity of cartilage and meniscus. The articular cartilage is covered on the surface of the bone end to provide a sliding interface with low friction, and the meniscus plays a key role in protecting the cartilage by enlarging the contact area, dispersing the mechanical load, absorbing shock and enhancing the stability of the joint. However, the inherent healing capacity of meniscus and cartilage tissue after injury is very limited due to its own structural characteristics. Once injury occurs, if effective intervention is not performed in time, the pathological changes can continuously progress, so that symptoms such as joint pain, limited movement and the like are aggravated, cartilage degeneration can be accelerated, and osteoarthritis is further induced or aggravated. In view of the core supporting role of cartilage and meniscus in knee joint function, accurate repair after injury has become an important research direction in the fields of orthopedics and sports medicine. With the development of tissue engineering and regenerative medicine, various repair techniques have been applied to clinical practice. For example, microfracture/microprill techniques for full-thickness cartilage damage, autologous Chondrocyte Transplantation (ACT) and osteochondral transplantation (OCT), as well as suturing techniques for meniscus repair and allogenic meniscus transplantation, and the like. The successful implementation of these advanced repair techniques, however, relies largely on the accurate morphological assessment of cartilage and meniscus defects. Research shows that parameters such as the area, geometric outline, depth, specific parts and the like of the defect are key bases for formulating an individual repair scheme. For example, cartilage defects smaller than 2cm2 may be suitable for microfracture, while larger or morphologically complex defects require consideration of implantation techniques. Therefore, accurate morphological evaluation not only affects the selection of the surgical mode, but also relates to the preparation and matching quality of the implant, thereby determining the tissue integration and function recovery effect after the operation. Currently, cartilage/meniscus defect assessment methods, which are based on medical imaging and intraoperative auxiliary measurements, have become clinical criteria, and these techniques have significant value in providing quantitative data, assisting preoperative planning, as compared to pure visual estimates. However, the existing mainstream technologies have inherent defects which are difficult to overcome, so that the existing mainstream technologies do not reach ideal conditions in terms of accuracy, real-time performance and convenience. Although medical image measurement (such as MRI and CT) has the advantages of morphological display, the measurement error (such as the measurement error of MRI on cartilage defect area can reach 15% -20%) and the dislocation from the actual defect morphology in the operation limit the reliability of the measurement as the basis of accurate decision in the operation, the arthroscopic probe measurement technology, although being applicable to the operation to a certain extent, relies on subjective estimation of operators in the measurement process, has poor adaptability to complex curved surfaces and irregular defects, has low measurement repeatability and high error rate, and is a 'sterile wrapper rubbing method' occasionally used as a non-standard technology, but the whole process lacks objectivity and standardization and cannot provide digital and recordable results although the measurement is relatively convenient. In view of this, the present invention has been made. Disclosure of Invention The invention aims to provide a preparation method of an intelligent development measurement film for cartilage/meniscus defects, which aims to solve the technical problems that the cartilage/meniscus defect measurement method taking medical images and intraoperative auxiliary measurement as cores in the prior art has poor adaptability to complex curved surfaces and irregular defects, has high error rate and can not quickly and accurately acquire morphological parameters of defects in the operation. It is a second object of the present invention to provide an intelligent visualization measuring membrane for cartilage/meniscus defects. In orde