Preparation method of bi-crosslinking stem cell sphere hydrogel for osteoarthritis

Abstract

The invention discloses a preparation method of bi-crosslinking stem cell sphere hydrogel for osteoarthritis, and belongs to the field of biological material preparation. The hydrogel can be used as a viscous substitute for synovial fluid after a cartilage operation, and is used for treating osteoarthritis, subchondral injury, osteoporosis, synovitis, tenosynovitis, tendinitis, tendon degeneration and interstitial cystitis. The hydrogel is injectable bi-crosslinking hydrogel and is prepared by modifying hyaluronic acid from an articular cavity matrix and chondroitin sulfate through hydroxyl groups and activating bi-crosslinking through EDC (Ethylene Dichloride). The bi-crosslinking stem cell sphere hydrogel obtained through reaction has good mechanical performance and controllable degradation rate, facilitates survival of 3D cell spheres, can moisturize, lubricate and slowly release biological factors for a long time, has high drug loading rate and light responsiveness, and has potential application value in the fields of injectable drug slow release carriers, minimally invasive therapy and the like.

Description

technical field [0001] The invention relates to the technical field of biomaterials, in particular to a method for preparing a double-crosslinked stem cell sphere hydrogel for osteoarthritis. [0002] technical background [0003] Osteoarthritis affects 80% of people over the age of 55. There are currently about 110 million patients with knee osteoarthritis in China. Its high prevalence and high disability rate have become a heavy medical and economic burden for the country. Due to the limited ability of articular cartilage to regenerate and repair. Current drug treatments can only relieve the pain but cannot cure it. Arthritis has developed to the end stage, and the only option is joint replacement surgery. [0004] Sodium hyaluronate (HA) and chondroitin sulfate (ChS) are a kind of glucuronic acid, which has no species specificity, and widely exists in the placenta, amniotic fluid, articular cartilage and other tissues, and plays the role of lubrication and nourishment....

AI Technical Summary

Problems solved by technology

However, one of the main limitations of using natural hydrogels to design injectable drug-loaded / cell systems is their weak mechanical properties, uncontrollable rheological properties and degradable properties, which greatly limit their sustained release and therapeutic effects, so Comprehensively improving the mechanical properties and degradation properties of injectable hydrogels has become a research hotspot in the field of biomedical hydrogels

[0005] However, traditional degradable natural polymer hydrogels have the following disadvantages: the mechanical properties of hydrogels are poor, and it is difficult to adapt to various mechanical environments in joints, which limits their application as osteochondral replacement materials; secondly, the cartilage layer Thickness is limited, cartilage damage will cause damage to subchondral bone, and damage to subchondral bone can affect the metabolism of the cartilage layer. Simple cartilage replacement materials are not conducive to the repair of cartilage morphology and structural functions; The structure of cartilage is similar, which is helpful for the repair of osteocartilage. However, current studies have shown that the interface between the upper and lower layers of the double-layer hydrogel is poorly bonded, and gradient functional repair cannot be achieved. At the same time, the upper layer of hydrogel is prone to short-term release through swelling and soaking adsorption factors. High volume, long-term activity reduction and other problems

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