ABSTRACT
BACKGROUND:There are many studies focusing on keloid scars,but the pathogenesis is not fully understood.In recent years,there have been some new research advances in the pathogenesis of keloids,including transforming growth factor-β(TGF-β)/Smad signaling pathway,ischemic hypoxia,hypoxia-inducible factor 1(HIF-1),and mitogen-activated protein kinase(MAPK)pathway.The TGF-β/Smad pathway is now more clearly studied,and activation of the TGF-β/Smad pathway promotes the development of keloid scars. OBJECTIVE:To review the TGF-β/Smad signaling pathway and evaluate the main therapeutic strategies targeting this pathway,with the aim of contributing to the development of more effective clinical treatments. METHODS:PubMed and Web of Science,CNKI and WanFang databases were searched by computer for relevant literature published from January 2017 to April 2023 with the search terms of"keloid,fibroblasts,TGF-β/Smad,extracellular matrix,collagen,treatment measures"in English and Chinese.Seventy-two articles were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The mechanism of TGF-β/Smad signaling pathway in the occurrence and development of keloids is summarized:TGF-β1 and TGF-β2 are overexpressed in keloids,while TGF-β3 shows antifibrotic effects.Smad2/3 and Smad1/5/8 are combined with Smad4 to form a complex that enters the nucleus and plays a fibrotic role,while Smad6/7 can inhibit keloid hyperplasia.The TGF-β/Smad signaling pathway is currently the most clearly studied pathway in keloids,and there are many pathways targeted to inhibit the activation of this pathway,which can inhibit the occurrence and development of keloids to a greater extent.Currently,there is no single clinical gold standard treatment for keloids,and inhibition of the TGF-β/Smad pathway alone cannot completely inhibit the development of keloids.A comprehensive consideration of the association between all systemic systems and keloids is needed.Although many promising targets have been identified in the fibrosis cascade,more research is needed to translate this into targeted therapies in the clinic.
ABSTRACT
Objective Aiming at the problem of significant anisotropy in the three-dimensional ( 3D) printed polyether-ether-ketone ( PEEK) bone substitutes manufactured by material extrusion technology, taking the femur, the main load-bearing long bone of the lower limb, as an example, the biomechanical properties of the femoral model under different direction in the build chamber were evaluated by the combination of finite element analysis and in-vitro mechanical experiment. Methods A left femoral model was obtained by reconstruction from CT data. The stress and displacement of the 3D printed PEEK femur with different directions in the build chamber under five physiological postures in the human gait cycle were simulated by varying the orthogonal anisotropy mechanical properties. An in-vitro mechanical experiment was conducted to investigate the safety and stability of the femur through a 3D printed PEEK femur. Results When the long axis of the femur model was perpendicular to the building platform of the 3D printer, a better mechanical property was obtained, and the maximum von Mises stress was 46. 56 MPa, which was lower than the yield stress of PEEK, while the maximum displacement was larger than that of the natural femur under same loading condition. Therefore, the 3D printed PEEK femur met the strength requirement, but the stability needs to be improved. Conclusions The long axis is recommended to be perpendicular to the building platform when the material extrusion technology was used for the substitute of the load-bearing long bone, and the effect of its anisotropy on service performance of the substitute should be carefully considered when the 3D printing technology is used for load-bearing bone substitute.