| As an important biomaterial,polymer materials have greatly influenced the development of modern medicine.Biodegradable materials have been widely used because of their excellent biocompatibility,biodegradability and processability,and have greatly promoted the development of biomedical field.With the development of biotechnology and medical technology,higher requirements have been put forward for biomedical materials,and biodegradable polymers with special properties have been widely demanded.Bone defect and rheumatoid arthritis are two common orthopaedic diseases,which have plagued people's lives for a long time.This study intends to use advanced environmental responsive polymer materials to effectively treat and real-time monitor these two orthopaedic diseases.The research contents are mainly divided into the following two parts:?1?Preparation and application in bone repair treatment and real-time monitoring of NaYF4:Ln3+/PLGA-PEG-PLGA composite thermosensitive hydrogelIn this study,NaYF4:Yb3+,Er3+upconversion hollow microtubules?UCHMs?were doped into poly?lactic acid-glycolic acid?-poly?ethylene glycol?-poly?lactic acid-glycolic acid??PLGA-PEG-PLGA?polymer hydrogels to prepare injectable thermosensitive composite hydrogels with upconversion imaging function to achieve noninvasive monitoring of bone repair process.The UCHMs/PLGA-PEG-PLGA composite hydrogel can effectively load protein drugs and achieve slow release,and which can promote the adhesion of bone marrow mesenchymal stem cells?BMSCs?in vitro.In addition,alkaline phosphatase detection and alizarin red S staining showed that osteogenic inducible factor bone morphogenetic protein 2?BMP-2?had good osteogenic activity.The composite hydrogel loaded with BMP-2 was implanted into the bone defect site of rats,and the process of bone repair?the degradation process of composite hydrogel scaffold material and the repair process of the defect site?was monitored in real time and noninvasively by upconversion imaging and CT imaging.The imaging results showed that the scaffold was completely degraded 4 weeks after injection and the defect site was completely repaired 8 weeks after injection.Therefore,UCHMs/PLGA-PEG-PLGA composite hydrogel has important clinical value in bone defect regeneration.?2?Application of RAPA/Cypate-loaded multi-responsive polymer nanomicelles in the treatment of rheumatoid arthritisIn this study,we prepared a multi-responsive polymer micelle loaded with rapamycin?RAPA?and Cypate?a carbocyanine dye?targeting the inflammatory site with high reactive oxygen species?ROS?,and the combined treatment of immunotherapy and photothermal therapy can alleviate the inflammatory symptoms.The prepared RAPA/Cypate-Se-Se-NPs have uniform particle size distribution,good ROS and near-infrared?NIR?responsiveness in vitro,which had obvious photothermal heating effect,and can produce a large amount of 1O2.Polymer micelle carriers have good cell compatibility,polymer micelles loaded with drugs have good cytotoxicity and photothermal cytotoxicity to inflammatory cells.Micelles mainly distribute in lysosomes after entering cells,and can produce a large number of ROS in cells after NIR irradiation.After successfully establishing the model of collagen-induced arthritis?CIA?in mice,fluorescence imaging showed that polymer micelles could be well enriched in inflammatory sites.Which has good photothermal killing effect under near infrared irradiation because of the enriched of micelles in inflammatory sites.At the same time,the immunosuppressive effect of RAPA could also inhibit the development of inflammation.Finally,the therapeutic effect was evaluated by measuring the thickness of the sole.Compared with the blank control group,the RAPA/Cypate-Se-Se-NPs+NIR group had the best therapeutic effect.It shows that the combination of photothermal therapy and immunotherapy can effectively alleviate the symptoms of rheumatoid arthritis,which has certain guiding significance for clinical treatment of rheumatoid arthritis. |
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