可降解生物材料不同特征化学官能团的体内外力化学降解机理研究

Physical factors play the same important role as chemical and biological factors in structures and properties of biodegradable materials. Although it can be achieved in a certain degree that regulating the biodegradable ability and improving the stability through chemical and biological modifications, the disagreement of in vitro and in vivo degradation dynamics induced by potential biomechanical microenvironment (mechanochemical degradation) is one of the most significant puzzles that prevent the successful clinical application of various biodegradable materials. Here, three representative biodegradable materials, chitosan (CS), poly(lactic acid) (PLA), and chitosan-graft-poly(lactic acid) (CS-g-PLA), are exposed to various levels of tensile, compressive, and shear stress loadings, respectively. The in vitro and in vivo degrading behaviors are widely investigated, focusing on the responses of corresponding glucosidic bonds (from CS), ester linkages (from PLA), and amido linkages (from CS-g-PLA), in order to illuminate the facts and mechanism of mechanochemical degradation from the point of chemical functional groups analyses. The present proposal expands and deepens our previous hypothesis. It can reveal the effects of biomechanical stimulation on degradation of various bioabsorbable materials, which would be helpful to fully understand the disagreement of in vitro and in vivo degradation and to enrich the knowledge of materials design, optimization and surface modification towards the clinical application., in order to illuminate the facts and mechanism of mechanochemical degradation from the point of chemical functional groups analysis. The present proposal expands and deepens our previous hypothesis. It can reveal the effects of biomechanical stimulation on degradation of various bioabsorbable materials, which would be helpful to fully understand the disagreement of in vitro and in vivo degradation and to enrich the knowledge of materials design, optimization and surface modification towards the clinical application.

物理因素和化学、生物学因素对可降解生物材料的结构和性能具有同等重要的影响。尽管通过化学改性和生物学修饰能在一定程度上达到调控材料降解特性并改善其体内稳定性的目的，但是由机体复杂力学环境所导致的体内外差异性降解（力化学降解）一直是阻碍可降解生物材料临床应用的关键科学问题。本项目以壳聚糖、聚乳酸、壳聚糖接枝聚乳酸三种可降解生物材料为研究对象，从化学官能团分析的角度探究力化学降解的过程及其调控机理。通过在体内外受控环境下施加不同水平的拉压和剪切应力，系统探讨糖苷键、酯键、酰胺键三种特征化学官能团对不同应力加载模式和加载参数的响应规律，揭示应力激活不同化学官能团的方式和阈值，建立力化学降解的耦合机理。本项目是申请人已结题项目的拓展和深化，研究结果有助于全面理解可降解生物材料体内外差异性降解的本质和规律，确定力学因素在其中的地位和作用，并为可降解内植入体的结构设计、构型优化、表面改性等提供理论依据。

针对生物体内复杂的力学微环境对可降解生物材料结构和性能的显著影响，本项目以壳聚糖（CS）、聚乳酸（PLA）、以及壳聚糖接枝聚乳酸（CS-g-PLA）三种典型的可降解生物材料为研究对象，从化学官能团分析的角度探究了力化学降解的过程及其调控机理。通过在受控环境下施加不同的力学载荷，系统探讨了材料理化结构对不同应力加载模式和加载参数的响应规律，研究了应力激活不同化学官能团的方式和阈值，建立了力化学降解的耦合机理。.研究内容主要分为两部分。首先是CS-g-PLA的制备和表征。本研究采用了两种不同的方法制备CS-g-PLA复合材料。乳液自组装法是利用油包水型乳化体系的原理，在表面活性剂Span-80的作用下，将CS的水溶液均匀分散在PLA的氯仿溶液中，进而用碳二亚胺使两相间发生交联反应，从而得到CS-g-PLA复合材料。FTIR、NMR等表征均验证了这种方法的可行性。为了进一步消除表面活性剂对产物的影响，我们又用乳酸替代PLA，在引发剂辛酸亚锡的催化作用下，采用非乳液自组装法制备了三种不同配比的CS-g-PLA复合材料，并对其理化结构、表面电荷、聚集行为等进行了表征。.其次是不同水平和不同模式应力加载对材料降解性能的影响。本研究利用自制的剪切应力加载装置，调节切应力大小分别为12、20和30 dyn/cm2，研究了不同应力水平对材料降解行为和力学性能的影响。结果发现，剪切应力会对降解液的粘度和试样的表面形貌产生显著影响，并会加速试样极限强度的丢失。进一步改变剪切应力的加载模式，设置了周期性正弦波和方波剪切应力，并与定常流剪切应力相比较。结果发现，在保持三者平均剪切应力相等的情况下，不同加载模式对材料降解的影响主要取决于最大剪切应力及其作用时间两个因素，二者均能加速试样体外降解时弹性模量和极限强度的丢失，并且前者在降解初期弹性模量的丢失中起主导作用。.通过本项目的实施，我们揭示了可降解生物材料体内外差异性降解的本质和规律，确定了力学因素在其中的作用，从而为可降解内植入体的结构设计、构型优化、表面改性等提供了理论依据。