The cartilage has poor ability to mount a sufficient healing response. Herein, kartogenin (KGN), an emerging stable non-protein compound with the ability to recruit bone marrow mesenchyme stem cells (BMSCs) to promote chondrogenic differentiation, was grafted onto dopamine-Fe(III) chelating nanoparticles, followed by involving a gelatin- and dextran-based injectable hydrogel to mimic the extracellular matrix to promote cartilage repair. The in vitro results demonstrated that KGN underwent long-term sustained release behavior and availably promoted the deep migration of BMSC cells in yielding hydrogels. Furthermore, in vivo New Zealand white rabbits’ cartilage defect model repairing results showed that cartilage defect obtained significant regeneration post operation in the 12th week, and the defect edge almost disappeared compared to adjacent normal cartilage tissue. Meanwhile, the T2-weighted magnetic resonance imaging (MRI) property resulting from dissociative Fe (III) can significantly monitor the degradation degree of the implanted hydrogels in the defect site. This integrated diagnosis and treatment system gives insight into cartilage regeneration.
Jia Liu,Chen Tang,Jian Huang,Jinhong Gu,Jingbo Yin,Guohua Xu,Shifeng Yan
Articular cartilage tissue is incapable of self-repair and therapies for cartilage defects are still lacking. Injectable hydrogels have drawn much attention in the field of cartilage regeneration. Herein, the novel design of nanofiber composite microchannel-containing hydrogels inspired by the tunnel-piled structure of subway tunnels is proposed. Based on the aldehydized polyethylene glycol/carboxymethyl chitosan (APA/CMCS) hydrogels, thermosensitive gelatin microrods (GMs) are used as a pore-forming agent, and coaxial electrospinning polylactic acid/gelatin fibers (PGFs) loaded with kartogenin (KGN) are used as a reinforcing agent and a drug delivery system to construct the nanofiber composite microchannel-containing injectable hydrogels (APA/CMCS/KGN@PGF/GM hydrogels). The in situ formation, micromorphology and porosity, swelling and degradation, mechanical properties, self-healing behavior, as well as drug release of the nanofiber composite microchannel-containing hydrogels are investigated. The hydrogel exhibits good self-healing ability, and the introduction of PGF nanofibers can significantly improve the mechanical properties. The drug delivery system can realize sustained release of KGN to match the process of cartilage repair. The microchannel structure effectively promotes bone marrow mesenchymal stem cell (BMSC) proliferation and ingrowth within the hydrogels. In vitro and animal experiments indicate that the APA/CMCS/KGN@PGF/GM hydrogels can enhance the chondrogenesis of BMSCs and promote neocartilage formation in the rabbit cartilage defect model.
A dual-layer biomimetic cartilage scaffold was prepared by mimicking the structural design, chemical cues and mechanical characteristics of mature articular cartilage. The surface layer was made from collagen (COL), chitosan (CS) and hyaluronic acid sodium (HAS). The transitional layer with microtubule array structure was prepared with COL, CS and silk fibroin (SF). The PLAG microspheres containing kartogenin (KGN) and the polylysine-heparin sodium nanoparticles containing TGF-β1 (TPHNs) were constructed for the surface, transitional layer, respectively. The SEM result showed that the dual-layer composite scaffold had a double structure similar to natural cartilage. The vitro biocompatibility experiment showed that the biomimetic cartilage scaffold with orientated porous structure was more conducive to the proliferation and adhesion of BMSCs. A rabbit KOA cartilage defect model was established and biomimetic cartilage scaffolds were implanted in the defect area. Compared with the surface layer and transitional layer scaffolds group, the results of dual-layer biomimetic cartilage scaffold group showed that the defects had been completely filled, the boundary between new cartilage and surrounding tissue was difficult to identify, and the morphology of cells in repair tissue was almost in accordance with the normal cartilage after 16 weeks. All those results indicated that the biomimetic cartilage scaffold could effectively repair the defect of KOA, which is related to the fact that the scaffold could guide the morphology, orientation, and proliferation and differentiation of BMSCs. This work could potentially lead to the development of multilayer scaffolds mimicking the zonal organization of articular cartilage.
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