环缩醛基多孔支架的制备及其体外降解行为研究

Biodegradable synthetic biopolymers have been widely used as scaffolds for tissue engineering; however, the degradation of traditional biodegradable polymer, such as poly lactic acid, could produce acidic products, which could not only elicit a high inflammatory response of the surrounding tissue, but also lead to too early loss in mechanical and structural properties by the autocatalytic effect during degradation. Synthetic biopolymer based on cyclic acetals is a novel class of biodegradable biomaterials with entirely non-acidic degradation products alcohols, carbonyls and aldehydes; therefore, such biomaterials have good application prospects as scaffolds for tissue engineering. In this study, we first synthesized a series of reactable monomers based on different cyclic acetals with the terminal groups of vinyl ether and vinyl carbonate, and the hydrophilic property of monomers was adjusted by monomer design. Then the scaffolds were prepared through photopolymerization-induced phase separation with different morphology and pore structure regulated by the concentration of solvent, the content of crosslinker and so on. Various properties of the obtained scaffolds were characterized, such as the porous structure and morphology, the conversation of polymerization, mechanical property and in vivo cytotoxicity, especially the degradation behavior. The degradation behavior, especially degradation rate, is the main property analyzed in this study which could be influenced by the structure of monomer, the pore size, porosity, specific surface area and crosslink density of scaffolds as it could significantly affect the final use of cyclic acetals based materials in the bone tissue engineering of orbital floor.

可降解的合成生物高分子作为组织工程支架材料被广泛应用，然而传统的可降解高分子（如聚乳酸）降解会产生酸性产物，不仅会刺激周围组织，而且其自加速降解效应会严重影响材料的机械性能。含环缩醛基团的合成聚合物是一种新型的可降解生物材料，完全不产生酸性降解产物,该类材料作为组织工程支架具有较好的应用前景。本工作拟首先合成一系列以乙烯基醚、乙烯基碳酸酯为端基的含不同环缩醛基团的可聚合单体，并通过单体的分子设计调节亲水性。然后采用光聚合诱导相分离的方法制备多孔支架，通过调节溶剂的浓度与性质、交联剂用量等调节支架的孔结构与形貌。最后对所得多孔支架的形态与结构 、孔隙率、聚合转化率、机械性能、体外细胞毒性等进行表征，并重点探讨单体的分子结构、支架的孔径、孔隙率、交联度、比表面积等因素对降解速率的影响，以掌握环缩醛基多孔支架的降解规律，从而更好地配合新生骨的形成，为最终用于眶底损伤的修复奠定基础。

可降解的合成生物高分子作为组织工程支架材料被广泛应用，然而传统的可降解高分子（如聚乳酸）降解会产生酸性产物，不仅会刺激周围组织，而且其自加速降解效应会严重影响材料的机械性能。含环缩醛基团的合成聚合物是一种新型的可降解生物材料，完全不产生酸性降解产物,该类材料作为组织工程支架具有较好的应用前景。将羟基磷灰石（HA）分散在环缩醛单体(EHD)中，通过原位光聚合的方法得到了HA/EHD复合材料，HA含量对EHD的光聚合动力学影响较少,EHD中HA含量越多支架材料的亲水性、机械性能增加，黏附在支架材料表面的细胞也增多。通过环缩醛单体(EHD)与甲氧基（聚乙二醇）单丙烯酸酯(mPEGA)在紫外线的照射得到的凝胶材料可以实现遇水不膨胀并改善表面亲水，解决了通常水凝胶膨胀导致破坏几何形状的完整性与机械性能下降问题，mPEGA的增加并不影响凝胶材料的光聚合性能、机械性能和热稳定性能；表面亲水性随着mPEGA的增加显著增强，含量达到30%时接触角达到37°，而且凝胶材料具有良好的生物相容性。低温相分离光聚合可以从单体一步形成2D或3D形状并孔形状可调的微孔交联聚合物，而且不需要任何模板和表面活性剂或其他添加剂，任何可以光聚合的单体都适用。当单体的浓度低于0.5%时，通过低温相分离光聚合可以得到交联的微米级的纤维，纤维直径在0.5-10μm范围，浓度从0.5%降低到0.1%时，纤维的平均直径逐渐降低。烯丙基碳酸酯类单体降解产物是二氧化碳和醇，将其引入到环缩醛结构中，可以完全避免酸性降解产物的产生，合成了烯丙基碳酸酯环缩醛（HEHDCAE），HEHDCAE与硫醇（PETMP）在引发剂存在的情况光照交联，光聚合动力学表明其具有高聚合速度和双键转化率。通过低温相分离光聚合制备了多孔交联支架，其孔径和孔隙率随溶剂的增加而增大，亲水基团PEG引入也能提高孔径和孔隙率，多孔交联支架在水和PBS (pH=7.4)呈现线性降解，并具有良好的生物相容性。