CN-122005936-A - Application of triple network hydrogel in preparation of osteochondral defect repair material

Abstract

The invention provides a PRP@OSA-GEL three-network composite hydrogel system based on PRP, OSA and gelatin, wherein in the system, a dynamic covalent network of OSA and gelatin, a physical network of fibrin and an egg-box model formed between Ca 2+ and OSA form an IPN network with enhanced mechanical properties, the dynamic crosslinking system of the IPN network can support cell infiltration and tissue regeneration, and also brings self-repairing capability to the hydrogel, can lead to rapid recovery of the hydrogel network after the hydrogel breaks, protects the vulnerable biological activity of the PRP, and the nascent cartilage of the PRP@OSA-GEL is complete, and cartilage tissue regenerated in a defect area is almost completely fused with surrounding normal cartilage, so that the PRP has the effect of obviously enhancing cartilage regeneration through the PRP@OSA-GEL and has effectiveness in promoting the enhancement of bone cartilage regeneration.

Inventors

• LIU MIN
• CAI CHUNYUAN

Assignees

• 瑞安市人民医院(瑞安市人民医院医疗服务集团瑞安市红十字医院)

Dates

Publication Date

20260512

Application Date

20251230

Claims (10)

1. 1. The application of the triple-network hydrogel in preparing the osteochondral defect repair material is characterized in that the triple-network hydrogel is a triple-network hydrogel PRP@OSA-GEL obtained by crosslinking gelatin and Oxidized Sodium Alginate (OSA) in Ca 2+ and then loading Platelet Rich Plasma (PRP).
2. 2. The use according to claim 1, wherein the volume ratio of gelatin to Oxidized Sodium Alginate (OSA) in the triple network hydrogel is 1:1.
3. 3. The use according to claim 1, wherein the Platelet Rich Plasma (PRP) content of the triple network hydrogel is 20% v/v.
4. 4. The use according to claim 1, wherein the gelatin concentration is 10-15% w/v.
5. 5. The use according to claim 1, wherein the concentration of Oxidized Sodium Alginate (OSA) is 10-20% w/v.
6. 6. The use according to claim 1, wherein the triple network hydrogel comprises a first layer of dynamic covalent network formed by Oxidized Sodium Alginate (OSA) and gelatin, a second layer of IPN network between Ca 2+ and Oxidized Sodium Alginate (OSA), and a third layer of covalent cross-linked network formed by fibrin converted from Platelet Rich Plasma (PRP).
7. 7. The use according to claim 1, wherein the Oxidized Sodium Alginate (OSA) is prepared by slowly adding dropwise sodium periodate solution to sodium alginate, stirring and reacting under dark room temperature condition, dialyzing the product with deionized water to remove unreacted chemicals and lyophilizing water to obtain Oxidized Sodium Alginate (OSA).
8. 8. The use according to claim 7, wherein the concentration of sodium alginate is 5% w/v.
9. 9. The use according to claim 7, characterized in that the dialysis has a molecular weight cut-off of 3500Da.
10. 10. The use according to claim 1, wherein the triple network hydrogel is in situ gelling after injection into the damaged site of the osteochondral defect.

Description

Application of triple network hydrogel in preparation of osteochondral defect repair material Technical Field The invention relates to the technical field of biological materials, in particular to application of triple network hydrogel in preparation of a bone cartilage defect repair material. Background The joint tissue is a multi-layer structure composed of cartilage and subchondral bone, has different anisotropic characteristics, and can guide the specific differentiation of different cartilage cells and bone cells. Articular cartilage is elastic connective tissue in joints, and is susceptible to acute trauma and chronic strain. Studies have also shown that articular cartilage damage often extends to subchondral bone, ultimately leading to full-thickness osteochondral defects in the knee joint. Clinically, osteochondral defects (OCDs) of joints are one of the most common diseases of orthopedics, and are mainly manifested by joint pain, swelling and mobility decline, which seriously affect quality of life. Cartilage, an avascular tissue with limited metabolic activity and lacking regenerative capacity, is essentially irreversible in its injury. Without proper intervention, cartilage defects can rapidly deteriorate, eventually leading to deterioration of Osteoarthritis (OA) and even total joint destruction. Repair of cartilage therefore requires complex therapeutic strategies aimed at restoring the biomechanical function and biological environment of the affected joint. The commonly used methods of cartilage defect treatment in clinic include non-operative treatments such as physical treatments and drugs, and operative treatments such as microfracture, autograft of osteochondral and autologous chondrocyte implantation, or even total joint replacement, etc. But the non-operative method does not correct structural damage, and the operative treatment faces challenges such as foreign body reaction, abnormal growth of fibrocartilage, difficulty in maintaining stable state of regenerated cartilage, and the like, which greatly increases the repair difficulty of cartilage injury. Thus, achieving high quality and rapid cartilage regeneration and maintaining cartilage homeostasis remains an urgent problem and a difficult challenge to address. The physiology of osteochondral defect repair is very complex, involving chondrocyte self-repair, such as proliferation of chondrocytes, secretion of cartilage-specific ECM (type II collagen, proteoglycans), and stem cell differentiation, including migration to the site of injury and chondrogenic differentiation. Among them, MSCs are the dominant force of regeneration, migrate to the damaged site through homing effect, differentiate into chondrocytes and secrete trophic factors. The regeneration of cartilage requires the precise regulation of growth factors such as TGF-beta, FGF and the like, but the vascular structure does not cause the microenvironment of a damaged area to be incapable of enriching the substances, thus forming a core bottleneck of regeneration failure. At present, platelet Rich Plasma (PRP) is a promising autologous derivative, and can be used for treating diseases such as cartilage injury, osteoarthritis and the like due to the fact that the PRP is rich in various growth factors and cytokines. PRP is a concentrated plasma of high level platelets obtained by blood centrifugation, and is rapidly degranulated to release Platelet Derived Growth Factor (PDGF), vascular Endothelial Growth Factor (VEGF), transforming growth factor after activation by calcium and thrombin addition1 (TGF-. Beta.1), insulin-like growth factor (IGF), and the like, all of which have a positive effect on cartilage regeneration. PRP also contains chemoattractants, which recruit stem cells to the site of injury. These properties enable PPR to modulate cellular processes such as migration, adhesion, proliferation and differentiation while promoting the production of extracellular matrix, thereby promoting tissue repair and remodeling. However, its clinical utility is hampered by poor stability and inefficient use due to sudden release of growth factors, which often requires multiple intra-articular injections to achieve the desired effect, increasing patient pain and increasing time, cost and risk of infection. Thus, to overcome these challenges, optimizing PRP application or extending the duration of action is critical to the success of OCDs treatments. Hydrogels are one of the ideal materials for cell growth and tissue regeneration after OCDs. Hydrogels form three-dimensional porous networks very similar to human tissue, which are ideal scaffolds for supporting cell survival and function, and because of their unique properties, including biocompatibility, adjustable mechanical properties, and good permeability to key elements such as oxygen, nutrients, and water-soluble metabolites, have become attractive scaffolds for cartilage tissue engineering. In view of the shortcomings of PRP, comb