Poly(N-isopropylacrylamide-co-N-vinylpyrrolidone) [P(NIPAM-co-NVP)] copolymers with different content of N-vinylpyrrolidone (NVP) were synthesized, and reversible aggregation kinetics of the copolymers in aqueous solutions was investigated with elastic light scattering (ELS) spectra. The results indicated that the apparent activation energy of aggregation process during heating and dissociation process during cooling increased with the NVP content increasing. The phase transition temperature also increased as the content of NVP increased, suggesting that the hydrophilic nature of NVP strongly affected the phase behavior of the copolymer solutions. The higher the content of NVP, the higher the temperature required to break the balance between the hydrophilic and hydrophobic interaction. Besides, during heating and cooling process, the phase transition hysteresis of P(NIPAM-co-NVP) chains decreased when the hydrophilic comonomer increased.
目的采用micro-CT评价重组人BMP-2/壳聚糖/硫酸葡聚糖（recombinant human BMP-2/chitosan/dextran sulfate,rhBMP-2/CS/DS）复合微球诱导异位成骨情况。方法采用离子交联法制作rhBMP-2/CS/DS复合微球,扫描电镜观察其形态,ELISA法检测微球体外缓释效应。取6-8周龄雄性SD大鼠48只,随机分为4组（n=12）;制备股四头肌肌袋模型后,分别将相同体积明胶海绵（A组）、CS/DS微球（B组）、rhBMP-2（C组）及rhBMP-2/CS/DS复合微球（D组）植入肌袋肌间隙中。术后观察大鼠一般情况;于4、8、12、16周处死动物,取异位骨化组织块行micro-CT扫描及三维重建,检测组织骨密度（tissue mineral density,TMD）、骨体积分数（bone volume fraction,BVF）、骨小梁厚度（trabecular thickness,Tb.Th）、骨小梁数量（trabecular number,Tb.N）、皮质骨骨密度（bone mineral density,BMD）及组织矿含量（tissue mineral content,TMC）。结果扫描电镜观察示,制备的rhBMP-2/CS/DS复合微球球形较规整,分散较均匀,无团聚,微球表面较光滑;微球体外释放rhBMP-2于2 h后出现1个突释放期,2 d时达峰值,释放周期约20 d。各组大鼠均存活至实验完成,术后各时间点,A、B组CT扫描均未见放射性显影,三维重建未发现成骨;而C、D组放射性显影强度及三维重建骨组织逐渐增加,且D组强于C组。各时间点A、B组TMD、BVF、Tb.Th、Tb.N、BMD及TMC均为0。随时间延长,C、D组除Tb.N外,其余骨组织参数均呈总体增加趋势,各时间点与A、B组比较差异均有统计学意义（P〈0.05）;C、D组间4周时比较差异无统计学意义（P〉0.05）,8-16周时D组显著高于C组,比较差异有统计学意义（P〈0.05）。结论 rhBMP-2/CS/DS复合微球异位诱导成骨能力显著强于单独rhBMP-2。
