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Three-dimensional (3D) printed skin substitutes have great potential for wound healing. However, current 3D printed skin models are limited in simulating heterogeneity and complexity of skin tissue due to the...

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.

Osteochondral defect caused by trauma or osteoarthritis exhibits a major challenge in clinical treatment with limited symptomatic effects at present. The regeneration and remodeling of subchondral bone play a positive effect on cartilage regeneration and further promotes the repair of osteochondral defects. Making use of the strengths of each preparation method, the combination of 3D printing and electrospinning is a promising method for designing and constructing multiscale scaffolds that mimic the complexity and hierarchical structure of subchondral bone at the microscale and nanoscale, respectively. In this study, the 3D printed-electrospun poly(ɛ-caprolactone)/nano-hydroxyapatites/multi-walled carbon nanotubes (PCL/nHA/MWCNTs) scaffolds were successfully constructed by the combination of electrospinning and layer-by-layer 3D printing. The resulting dual-scale scaffold consisted of a dense layer of disordered nanospun fibers and a porous microscale 3D scaffold layer to support and promote the ingrowth of subchondral bone. Herein, the biomimetic PCL/nHA/MWCNTs scaffolds enhanced cell seeding efficiency and allowed for higher cell-cell interactions that supported the adhesion, proliferation, activity, morphology and subsequently improved the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Together, this study elucidates that the construction of 3D printed-electrospun PCL/nHA/MWCNTs scaffolds provides an alternative strategy for the regeneration of subchondral bone and lays a foundation for subsequent in vivo studies.

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