Jha Amit K, Hule Rohan A, Jiao Tong, Teller Sean S, Clifton Rodney J, Duncan Randall L, Pochan Darrin J, Jia Xinqiao
Departments of Materials Science and Engineering, Biological Sciences, and Mechanical Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19716, and Division of Engineering, Box D, Brown University, Providence, Rhode Island 02912.
Macromolecules. 2009;42(2):537-546. doi: 10.1021/ma8019442.
We have created a new class of hyaluronic acid (HA)-based hydrogel materials with HA hydrogel particles (HGPs) embedded in and covalently cross-linked to a secondary network. HA HGPs with an average diameter of ∼900 nm and narrow particle size distribution were synthesized using a refined reverse micelle polymerization technique. The average mesh size of the HGPs was estimated to be approximately 5.5 to 7.0 nm by a protein uptake experiment. Sodium periodate oxidation not only introduced aldehyde groups to the particles but also reduced the average particle size. The aldehyde groups generated were used as reactive handles for subsequent cross-linking with an HA derivative containing hydrazide groups. The resulting macroscopic gels contain two distinct hierarchical networks (doubly cross-linked networks, DXNs): one within individual particles and another among different particles. Bulk gels (BGs) formed by direct mixing of HA derivatives with mutually reactive groups were included for comparison. The hydrogel microstructures were collectively characterized by microscopy and neutron scattering techniques. Their viscoelasticity was quantified at low frequencies (0.1-10 Hz) using a controlled stress rheometer and at high frequencies (up to 200 Hz) with a home-built torsional wave apparatus. Both BGs and DXNs are stable elastic gels that become stiffer at higher frequencies. The HA-based DXN offers unique structural hierarchy and mechanical properties that are suitable for soft tissue regeneration.
我们制备了一类新型的基于透明质酸（HA）的水凝胶材料，其中HA水凝胶颗粒（HGPs）嵌入二级网络并与之共价交联。采用改进的反胶束聚合技术合成了平均直径约为900 nm且粒径分布窄的HA HGPs。通过蛋白质摄取实验估计HGPs的平均网孔尺寸约为5.5至7.0 nm。高碘酸钠氧化不仅在颗粒上引入了醛基，还减小了平均粒径。产生的醛基用作反应性基团，用于随后与含酰肼基的HA衍生物交联。所得的宏观凝胶包含两个不同的分级网络（双交联网络，DXNs）：一个在单个颗粒内部，另一个在不同颗粒之间。包括通过将具有相互反应性基团的HA衍生物直接混合形成的本体凝胶（BGs）用于比较。通过显微镜和中子散射技术对水凝胶微观结构进行了综合表征。使用控制应力流变仪在低频（0.1 - 10 Hz）下以及使用自制的扭转波装置在高频（高达200 Hz）下对它们的粘弹性进行了量化。BGs和DXNs都是稳定的弹性凝胶，在较高频率下会变得更硬。基于HA的DXN具有独特的结构层次和机械性能，适用于软组织再生。
