Functionalization Of Theranostic Hydrogels With Kartogenin Grafted USPIO Nanoparticles To Enhance Cartilage Regeneration

Articular cartilage of human is subject to abrasion,injury,degradation and higher incidence of arthritis owning to the long-term activities and frequent use.Worse still,the articular cartilage suffering from injury will leave permanent lesions and cannot achieve cartilage regeneration by oneself due to the non-vascular,low cell density and low proliferation activity of cartilage.Existing clinical treatment methods are difficult to achieve regeneration of cartilage defect structure and function,but cell-based cartilage tissue engineering expands treatment of cartilage defects.Cartilage tissue engineering scaffolds loaded the relevant cell can achieve in situ repair of cartilage defects;however,the regulation of cell number and differentiation behavior will be a challenge.Meanwhile,cartilage tissue engineering often involves complex and time-consuming in vitro construction processes,so it is difficult to achieve clinical application.Cartilage regeneration can be achieved by recruiting stem cells in situ that will avoid many problems in the process of utilizing cells in cartilage tissue engineering.So far,factors that can recruit stem cells have been widely reported.However,based on the nature of these factors that have short half-life,and/or are susceptible to degeneration,it is difficult to induce long-term treatment.Excessive dose not only increases the burden of organs such as the liver and kidney,but also causes drug resistance in the body,stable inducing factors and slow release systems become an important problem.Based on the above problems,kartogenin(KGN),a non-protein chemokine factor,which can recruit bone marrow mesenchymal stem cells from host to the cartilage defect site and then induce differentiation into chondrocytes,grated onto the surface of ultrasmall superparamagnetic iron-oxide nanoparticles(USPIO),and followed by being combined with the cross-linking cellulose nanocrystals/dextran(CNC/Dex/USPIO-KGN)hydrogels to prepare the novel and functionalized CNC/Dex/USPIO-KGN composite hydrogels.Compared with CNC/Dex/KGN hydrogels,the CNC/Dex/USPIO-KGN hydrogels can keep better sustainable release effect.The prepared composite hydrogels meet the necessary mechanicalcharacteristics of cartilage repair,and the recruited bone mesenchymal stem cells can adhere,proliferate and differentiate well in the composite hydrogels.USPIO loaded into composite hydrogels can achieve MRI stability in vitro.After treatment for 12 weeks of rabbit cartilage defect,the new tissue of the defect site has a distinct cartilage structure,and new cartilage layer has evenly collagen II and glycosaminoglycan,consistent with natural cartilage.The morphology of the new cartilage obtained by non-invasive monitoring and the state of the implanted hydrogels are consistent with the observation results obtained from animal sacrifice.The results show that functionalization of the prepared novel composite hydrogels can promote cartilage regeneration and provide an effective diagnostic method.