Cellular Capsule Delivery Bioink with Punicalagin‐Loaded Chondrocyte Membrane Vesicles for Tissue Engineering Therapy

Abstract The repair of injured cartilage in joints is a major challenge for clinic treatments, since pathological conditions impede cartilage regeneration caused by cytokines related to inflammation and the accumulation of reactive oxygen species (ROS). To overcome this challenge, a cellular capsule delivery bioink has been developed, which can gradually and continuously release membrane vesicles encapsulated with bioactive reagents for both scavenging ROS and enhancing cartilage regeneration. Chondrocyte membrane vesicles (CMVs) are loaded with punicalagin containing multiple reactive hydroxyl groups after they are modified with acrylates–poly(ethylene glycol)–succinimide ester, which acts as the cellular capsule. They are combined with methacrylated sericin (SerMA) to form a photocurable bioink precursor, and the combination bioink precursor exhibits excellent antioxidant properties, significant antibacterial activity, and strong chondroprotective effects. By using a digital light processing 3D bioprinter, all printed structures demonstrate high shape fidelity and maintain excellent cell viability and activity. This punicalagin (PUN)@SerMA─modified CMV bioink significantly enhances cartilage regeneration from both in vitro and in vivo animal tests, which result from uptake of the cellular capsule. Hence, this cellular capsule delivery bioink successfully integrates ROS scavenging with cartilage tissue repair, demonstrating the potential for 3D bioprinting applications in tissue regeneration.