Biomimetic photo-responsive hydrogels for articular cartilage defects repair
Item statusRestricted Access
Embargo end date24/11/2023
Osteoarthritis (OA) is one of the most prevalent chronic diseases and severely impacts the quality of patients’ life and brings burdens to society. Cartilage defects are important pathological features of OA. Challenges remain in both partial-thickness cartilage defects and osteochondral defects: it is difficult to fix the materials used for partial-thickness cartilage defects and the scaffolds for osteochondral defects require high performance in biological properties as well as structural properties. As a three-dimensional polymer network containing a large amount of water, hydrogels have become widespread in cartilage repair and other biomedical applications for their biomimetic properties and multifunctionalities. Here, based on the cartilage matrix, biomimetic hydrogels for articular cartilage defects repairment were developed. For partial-thickness cartilage defects, a two-step biomimetic adhesive hydrogel was developed; besides, a one-step adhesive hydrogel was developed by improving the components design of the previous strategy; for osteochondral defects, high-precision 3D hydrogel bioprinting system was developed for the preparation of biomimetic scaffolds. The research mainly includes the following contents: 1. ‘Two-step’ photo-responsive biomimetic tissue-adhesive hydrogel for partial-thickness cartilage defect repair. Partial-thickness cartilage defect is the most common symptom of OA but till now it is less focused with no proven clinical treatments and relatively less research on partial-thickness cartilage defect repair. Mimicking the natural cartilage, the tissue adhesive hydrogel “joint paint” is comprised of a gelatin methacrylate (GelMA)/ hyaluronic acid (HA) surface layer and a chondroitin sulfate (CS) layer that can bridge the surface layer and the cartilage. The joint paint can rapidly gel at the defect area under light exposure and the formed binding is tight enough for long-term maintenance. Being able to keep main cartilage matrix components such as glycosaminoglycan and inhibit cell apoptosis, this hydrogel functions well in rabbit partial-thickness cartilage defect models with good tissue integration and regeneration capability. 2. One-step photoresponsive biomimetic tissue adhesive hydrogel for partial-thickness cartilage defect repair Based on the strategy of in situ photoresponsive adhesive hydrogels for partial-thickness cartilage defects repairment, the material formulation was improved to avoid the two-step usage in Chapter 3, making it more suitable for clinical application and translation. The photoinduced imine crosslinking strategy was used to provide the adhesion ability between hydrogels and tissues. O-nitrobenzyl compound NB was grafted onto CS, and hydrogels containing GelMA, CSNB, and HA were prepared according to the proportion of natural cartilage matrix components. This double-network hydrogel can gel rapidly on cartilage surface in a single step and shows good efficacy for partial-thickness cartilage defects regeneration in large animal models. 3. High precision stereolithography 3D bioprinting system for the preparation of osteochondral tissue engineering scaffolds with biomimetic structure Osteochondral defect is one of the manifestations of the terminal progression of osteoarthritis. Structure-free hydrogels cannot meet the needs of osteochondral defect repair. However, due to technical limitations, the current osteochondral tissue engineering scaffolds rarely improve their performance through structures. 3D printing technology is a powerful means of creating complex structures. The application of CSNB in stereolithography 3D printing solves the problem that the printing resolution, the mechanical properties of products, and the cell-laden ability cannot be achieved simultaneously in the current 3D bioprinting technologies. CSNB system was used to print osteochondral scaffolds with a tidemark structure that could disperse mechanical load and the in vivo repair function of the scaffolds was assessed.