3D Bioprinting Using Synovium-Derived MSC-Laden Photo-Cross-Linked ECM Bioink for Cartilage Regeneration

Abstract

In this study, inspired by the components of cartilage matrix, a photo-cross-linked extracellular matrix (ECM) bioink composed of modified proteins and polysaccharides was presented, including gelatin methacrylate, hyaluronic acid methacrylate, and chondroitin sulfate methacrylate. The systematic experiments were performed, including morphology, swelling, degradation, mechanical and rheological tests, printability analysis, biocompatibility and chondrogenic differentiation characterization, and RNA sequencing (RNA-seq). The results indicated that the photo-cross-linked ECM hydrogels possessed suitable degradation rate and excellent mechanical properties, and the three-dimensional (3D) bioprinted ECM scaffolds obtained favorable shape fidelity and improved the basic properties, biological properties, and chondrogenesis of synovium-derived MSCs (SMSCs). The strong stimulation of transforming growth factor-beta 1 (TGF-β1) enhanced the aggregation, proliferation, and differentiation of SMSCs, thereby enhancing chondrogenic ECM deposition. In vivo animal experiments and gait analysis further confirmed that the ECM scaffold combined with TGF-β1 could effectively promote cartilage regeneration and functional recovery of injured joints. To sum up, the photo-cross-linked ECM bioink for 3D printing of functional cartilage tissue may become an attractive strategy for cartilage regeneration.

3D printed osteochondral scaffolds: design strategies, present applications and future perspectives

“…For example, Sang et al presented a photo-cross-linked ECM bioink composed of modified proteins and polysaccharides, including gelatin methacrylate, hyaluronic acid methacrylate, and chondroitin sulfate methacrylate. The results indicated that the photo-cross-linked ECM hydrogels possessed a suitable degradation rate and excellent mechanical properties, and the 3D bioprinted ECM scaffolds obtained favorable shape fidelity and effectively promoted cartilage regeneration ( Sang et al, 2023 ). Bioceramics are often combined with natural or synthetic polymers to prepare 3D printable bioinks, which are more widely used in OC tissue engineering.…”

Integrating bioprinting, cell therapies and drug delivery towards in vivo regeneration of cartilage, bone and osteochondral tissue

“…rabbit, goat, porcine) and included in the bioink at a typical cell density ranging between 1 × 10 7 and 2 × 10 7 cells/mL [ 91 – 95 ]. In contrast, Sang et al [ 96 ] proposed synovium-derived MSCs (used at a lower cell density of 1 × 10 6 cells/mL) as a promising alternative, thanks to their high ability of proliferation and chondrogenic differentiation, promoted by the high expression of CD44 and CD105 receptors of these cells.…”

“…GeL-based bioinks are usually made by physically mixing GeL or GelMA with other components to achieve optimal mechanical properties [ 91 – 93 , 97 ]. For example, GelMA has been combined with other methacrylated polysaccharides, such as HAMA and chondroitin sulphate methacrylate (CSMA), or with Alg and Alg sulphate to form interpenetrating networks by combining UV-mediated chemical cross-linking with Ca 2+ ion–mediated physical gelation [ 93 , 96 ].…”

In Situ Bioprinting: Process, Bioinks, and Applications

“…In recent years, the advent of 3D bioprinting has brought about a revolutionary shift in the tissue engineering landscape. − This cutting-edge technology allows the precise creation of sophisticated tissues that closely replicate the structural and functional aspects of native tissues. − Despite their tremendous potential, the translation of bioprinting techniques into clinical applications has encountered several challenges. The key requirements for clinical viability include ensuring biocompatibility, pro-healing properties, spatial control, reliable fabrication, implantation feasibility, and accessibility. − A novel strategy known as in situ bioprinting has emerged to address these challenges and push the boundaries of clinical translation …”