Search

CN-122005944-A - Osteochondral repair hydrogel with dynamic repair performance and preparation method thereof

CN122005944ACN 122005944 ACN122005944 ACN 122005944ACN-122005944-A

Abstract

The invention discloses an osteochondral repair hydrogel with dynamic repair performance and a preparation method thereof, wherein the hydrogel has a double-layer structure, the upper layer is obtained by photocuring a solution containing silk fibroin, benzoyl peroxide, riboflavin and acylated chondroitin sulfate, and the lower layer is obtained by performing ultrasonic treatment on the solution containing the silk fibroin, the benzoyl peroxide, the riboflavin and amorphous calcium phosphate, and then photocuring. The hydrogel provided by the invention has good elasticity in the upper layer, higher hardness and good supportability in the lower layer, good interface bonding capability between the two layers, and the oxygen release amount of the upper layer and the lower layer can be adjusted by adjusting the content of benzoyl peroxide, so that the hydrogel can simultaneously meet the oxygen conditions required by cartilage tissue and bone tissue repair, in addition, the hydrogel has antibacterial and anti-inflammatory functions, the mineralization process of the amorphous calcium phosphate component in the hydrogel is perfectly matched with the bone repair process, and the dynamic bone repair induced in the wound surface in the bone repair process is realized.

Inventors

  • HUANG YING
  • WANG YILEI
  • ZHANG QIANG
  • YAN SHUQIN
  • Luo zuwei

Assignees

  • 武汉纺织大学

Dates

Publication Date
20260512
Application Date
20260317

Claims (10)

  1. 1. The osteochondral repair hydrogel with dynamic repair performance is characterized by having a double-layer structure, wherein the upper layer is obtained by photocuring a solution containing silk fibroin, benzoyl peroxide, riboflavin and acylated chondroitin sulfate, and the lower layer is obtained by performing ultrasonic treatment on the solution containing the silk fibroin, benzoyl peroxide, riboflavin and amorphous calcium phosphate, and then photocuring.
  2. 2. The osteochondral repair hydrogel with dynamic repair performance according to claim 1, wherein the preparation method of the acylated chondroitin sulfate is characterized in that the chondroitin sulfate is added into deionized water, the mixture is sufficiently stirred under ice bath condition to enable the chondroitin sulfate to be sufficiently dissolved to obtain a chondroitin sulfate solution, methacrylic anhydride is slowly dripped into the chondroitin sulfate solution under the conditions of light shielding and sufficient stirring, then the acylation reaction is carried out, and the acylated chondroitin sulfate is obtained after the reaction is finished, wherein the acylation rate of the acylated chondroitin sulfate is 40-60%.
  3. 3. The osteochondral repair hydrogel with dynamic repair performance according to claim 2, wherein the concentration of the chondroitin sulfate solution is 0.01-0.04g/mL, the mass-volume ratio of the chondroitin sulfate to the methacrylic anhydride is 0.2-0.3g/mL, and the acylation reaction condition is that the pH value of a system is 8-9, and the reaction is carried out for 24-48 hours at room temperature under the condition of full stirring and light shielding.
  4. 4. The osteochondral repair hydrogel with dynamic repair performance according to claim 1, wherein the hydrogel has an upper layer thickness of 1-3mm, an upper layer pore size of 50-200 μm, a maximum compressive stress of 50-80kPa, a lower layer thickness of 2-6mm, a lower layer pore size of 10-100 μm, and a maximum compressive stress of 450-650kPa.
  5. 5. A method for preparing the osteochondral repair hydrogel with dynamic repair performance according to any one of claims 1 to 4, which comprises the following specific steps: 1) The preparation of silk fibroin solution comprises dispersing silk fiber obtained by degumming silk and oven drying in lithium bromide solution, heating for dissolving, stirring thoroughly, dialyzing, filtering, centrifuging, and diluting supernatant to obtain silk fibroin solution; 2) Preparing an upper layer silk fibroin/chondroitin sulfate mixed solution, namely preparing a photoinitiator solution, dispersing acylated chondroitin sulfate in the photoinitiator solution to obtain an acylated chondroitin sulfate-containing solution, adding benzoyl peroxide and riboflavin solution into the silk fibroin solution obtained in the step 1) to obtain a benzoyl peroxide and riboflavin-containing silk fibroin solution, adding the acylated chondroitin sulfate-containing solution into the benzoyl peroxide and riboflavin-containing silk fibroin solution, and uniformly stirring in a dark place to obtain an upper layer silk fibroin/chondroitin sulfate mixed solution; 3) Adding benzoyl peroxide and riboflavin solution into the silk fibroin solution obtained in the step 1), adding amorphous calcium phosphate to obtain a lower mixed solution, performing ultrasonic treatment, immediately placing under an ultraviolet lamp to perform first light curing after the treatment, and adding the upper silk fibroin/chondroitin sulfate mixed solution prepared in the step 2) when the gel is not completely cured to continuously perform second light curing to obtain the bone cartilage repair hydrogel with the dynamic repair performance.
  6. 6. The method for preparing an osteochondral repair hydrogel with dynamic repair performance according to claim 5, wherein the photoinitiator solution in step 2) is obtained by dissolving a photoinitiator Irgacure 2959 in water, the concentration is 0.1-0.5wt%, the concentration of the acylated chondroitin sulfate in the solution containing the acylated chondroitin sulfate is 1-5wt%, and the concentration of the riboflavin solution is 0.01-0.5mmol/L.
  7. 7. The method for preparing an osteochondral repair hydrogel with dynamic repair performance according to claim 5, wherein in the step 2), the mass of benzoyl peroxide is 0.3-3.0% of that of a silk fibroin solution, the volume ratio of the silk fibroin solution to a riboflavin solution is 50-100:1, and the volume ratio of the silk fibroin solution containing benzoyl peroxide and riboflavin to the solution containing acylated chondroitin sulfate is 0.25-4:1.
  8. 8. The method for preparing the osteochondral repair hydrogel with dynamic repair performance according to claim 5, wherein the mass of benzoyl peroxide in the step 3) is 0.3-3.0% of that of a silk fibroin solution, the concentration of the riboflavin solution in the step 3) is 0.01-0.5mmol/L, the volume ratio of the silk fibroin solution to the riboflavin solution is 50-100:1, the mass of the amorphous calcium phosphate is 15-50% of that of silk fibroin in the silk fibroin solution, and the volume ratio of the lower mixed solution to the upper mixed solution of silk fibroin/chondroitin sulfate is 1-2:1.
  9. 9. The method for preparing the osteochondral repair hydrogel with the dynamic repair performance according to claim 5, wherein the ultrasonic treatment in the step 3) is carried out under the process conditions of 100-200W of ultrasonic power and 3-30s of ultrasonic treatment time, the first light curing condition is that the light curing reaction is carried out under the irradiation of an ultraviolet lamp, the power of the ultraviolet lamp is 100-900W, the light curing reaction time is 1-2 minutes, the second light curing condition is that the light curing reaction is carried out under the irradiation of the ultraviolet lamp, the power of the ultraviolet lamp is 100-900W, and the light curing reaction time is 5-10 minutes.
  10. 10. The use of the osteochondral repair hydrogel with dynamic repair performance according to any one of claims 1 to 4 in osteochondral repair, wherein the method of application is that the osteochondral repair hydrogel with dynamic repair performance is implanted between bone tissue and cartilage, the upper layer is attached to the cartilage tissue, and the lower layer is attached to the bone tissue.

Description

Osteochondral repair hydrogel with dynamic repair performance and preparation method thereof Technical Field The invention belongs to the technical field of prosthetic materials or prosthetic coating materials, and particularly relates to an osteochondral repair hydrogel with dynamic repair performance and a preparation method thereof. Background Osteochondral defects are clinically common joint diseases, and due to lack of blood vessels and innervation of cartilage tissues, the self-repair capacity of the cartilage defects is extremely limited, once damaged, the cartilage defects continuously worsen, joint pain, swelling and movement disorder are caused, and the life quality of patients is seriously influenced. The current common repair strategies in clinic mainly comprise microfracture surgery, autologous chondrocyte transplantation, autologous osteochondral transplantation and the like, however, the methods have obvious limitations. The fibrocartilage generated by microfracture surgery is not normal hyaline cartilage. Autologous osteochondral cell transplantation requires a secondary operation, increasing the risk of the operation. Autologous osteochondral grafting requires materials from healthy cartilage sites that can cause new damage. The hydrogel has good biocompatibility, can provide a proper environment for cell growth, and promotes regeneration of cartilage and bone. The double-layer hydrogel can simulate the layered structure of natural bone cartilage, respectively provide different growth conditions for cartilage and bone tissue, and improve the repair efficiency, wherein the upper layer simulates the softness and elasticity of cartilage, and the lower layer simulates the hardness and supportability of subchondral bone, thereby being beneficial to realizing more natural repair effect. The mechanical properties of the double-layer hydrogel can be adjusted according to requirements, the upper layer is soft and can bear joint pressure, and the lower layer is hard and can provide support, so that the double-layer hydrogel is better suitable for the mechanical environment of the joint, and the risk of repair failure is reduced. The oxygen release hydrogel can continuously release oxygen, improve local anoxic environment, promote survival, proliferation and differentiation of chondrocytes and stem cells, and accelerate tissue regeneration. Oxygen is critical for cellular metabolism and energy synthesis. The oxygen-releasing hydrogel can enhance the metabolic activity of cells by providing oxygen, support chondrocytes to synthesize matrix components such as collagen and proteoglycan, and promote cartilage repair. The oxygen-releasing hydrogel can create a more favorable microenvironment for tissue repair by improving oxygen supply, reducing inflammatory factor release and reducing inflammatory reaction in the anoxic environment. Oxygen released by the oxygen-releasing hydrogel can stimulate angiogenesis, increase blood supply in a damaged area, provide nutrition and oxygen for repairing subchondral bone and promote osteochondral integration. The damaged areas of osteochondral are often hypoxic, affecting cell survival and repair. In view of the above, the invention provides an osteochondral repair hydrogel with dynamic repair performance and a preparation method thereof, and the double-layer oxygen-releasing silk fibroin-based hydrogel has remarkable advantages in the aspects of bionic structure, double oxygen release, synchronous cartilage and bone repair, biocompatibility, anti-inflammatory performance, antibacterial performance, mechanical performance and the like, and can more effectively promote the repair of osteochondral defects. Disclosure of Invention Aiming at the defects in the prior art, the invention provides the bone cartilage repair hydrogel with dynamic repair performance and the preparation method thereof, wherein the hydrogel has a double-layer structure, can adjust the mechanical properties and oxygen release properties of an upper layer and a lower layer according to different requirements of bone tissues and cartilage tissues on mechanical properties and O 2, meets the requirements of the two tissues, can continuously provide Amorphous Calcium Phosphate (ACP) in the bone repair process, induces the dynamic repair of bone on a wound surface, can continuously lead the mineralization process to last for 90 days under the wrapping of the hydrogel, and perfectly matches the bone repair process to realize the dynamic repair of bone and cartilage tissues. The first aspect of the present application provides an osteochondral repair hydrogel with dynamic repair performance, wherein the hydrogel has a double-layer structure, the upper layer is obtained by photocuring a solution containing silk fibroin, benzoyl Peroxide (BPO), riboflavin and acylated chondroitin sulfate, and the lower layer is obtained by performing ultrasonic treatment on the solution containing silk fibroin, benzoyl peroxi