Schultz Kelly M, Baldwin Aaron D, Kiick Kristi L, Furst Eric M
Department of Chemical Engineering and Center for Molecular and Engineering Thermodynamics, University of Delaware, 150 Academy St., Newark, Delaware 19716.
Macromolecules. 2009 Jul 28;42(14):5310-5316. doi: 10.1021/ma900766u.
We study PEG-heparin hydrogels to identify compositions that lead to gel formation and measure the corresponding gelation kinetics. The material consists of a maleimide-functionalized high molecular weight heparin (HMWH) backbone covalently cross-linked with bis-thiol poly(ethylene glycol) (PEG). Using multiple particle tracking microrheology, we investigate a broad composition space, defined by the number of maleimide functional sites per HMWH (f = 3.9-11.8), the molecular weight of the PEG cross-linker (M(n) = 2000, 5000, and 10 000), and the concentrations of the heparin and PEG polymers. Gelation kinetics are characterized by time-cure superposition, yielding the gel time, t(c), and the critical relaxation exponent, n. Gelation times range from 5 < t(c) ≤ 45 min, with the fastest kinetics occurring for the highest HMWH maleimide functionalities. t(c) depends nonmonotonically on the PEG cross-linker molecular weight, suggesting that gelation is affected by the length of the cross-linker relative to intermolecular interactions between heparin molecules. The critical relaxation exponent decreases from n = 0.52 for PEG 2000 to n = 0.39 for PEG 10 000. Finally, 219 equilibrated samples taken over the entire composition space are identified as liquid or solid, defining the "gelation envelope". The boundaries of this empirical gelation envelope are in good agreement with Flory-Stockmayer theory. In all, microrheological measurements enable characterization over a large parameter space and provide crucial insight into the gelation of complex, multifunctional hydrogelators used in therapeutic applications.
我们研究聚乙二醇 - 肝素水凝胶，以确定能导致凝胶形成的成分，并测量相应的凝胶化动力学。该材料由与双硫醇聚乙二醇（PEG）共价交联的马来酰亚胺功能化高分子量肝素（HMWH）主链组成。使用多粒子追踪微观流变学，我们研究了一个广阔的成分空间，该空间由每个HMWH上马来酰亚胺功能位点的数量（f = 3.9 - 11.8）、PEG交联剂的分子量（M(n) = 2000、5000和10000）以及肝素和PEG聚合物的浓度定义。凝胶化动力学通过时间 - 固化叠加来表征，得出凝胶时间t(c)和临界松弛指数n。凝胶时间范围为5 < t(c) ≤ 45分钟，对于最高的HMWH马来酰亚胺功能，动力学最快。t(c)非单调地依赖于PEG交联剂的分子量，这表明凝胶化受交联剂长度相对于肝素分子间相互作用的影响。临界松弛指数从PEG 2000时的n = 0.52降至PEG 10000时的n = 0.39。最后，在整个成分空间采集的219个平衡样品被确定为液体或固体，定义了“凝胶化包络线”。这个经验性凝胶化包络线的边界与弗洛里 - 斯托克迈耶理论高度吻合。总之，微观流变学测量能够在大参数空间上进行表征，并为用于治疗应用的复杂多功能水凝胶剂的凝胶化提供关键见解。
