Injectable Cholesterol-Enhanced Stereocomplex Polylactide Thermogel Loading Chondrocytes for Optimized Cartilage Regeneration

Ideal cartilage tissue engineering requires scaffolds featuring good biocompatibility, large pore structure, high mechanical strength, as well as minimal invasion procedure. Although significant progress has been made in the development of polymer scaffolds, the construction of smart systems with all the desired properties is still emerging as a challenge. The thermogels of stereocomplex 4-arm poly(ethylene glycol)–polylactide (PEG–PLA) (scPLA_gel) and stereocomplex cholesterol-modified 4-arm PEG–PLA (scPLA–Chol_gel) from the equimolar enantiomeric 4-arm PEG–PLA and 4-arm PEG–PLA–Chol, respectively, are fabricated as scaffolds for cartilage tissue engineering. scPLA–Chol_gel shows lower critical gelation temperature, higher mechanical strength, larger pore size, better chondrocyte adhesion, and slower degradation compared to scPLA_gel as the benefit of cholesterol modification, which is more appropriate for cartilage regeneration. Moreover, the preservation of morphology, biomechanical property, cartilaginous specific matrix, as well as cartilaginous gene expressions of engineered cartilage mediated by scPLA–Chol_gel are proven superior to those by scPLA_gel. scPLA–Chol_gel serves as a promising chondrocyte carrier for cartilage tissue engineering and gives an alternative solution to clinical cartilage repair.