Institute of Interfacial Process Engineering and Plasma Technology IGVP, University of Stuttgart, Nobelstr. 12, 70569 Stuttgart, Germany.
Biomed Mater. 2018 Jul 19;13(5):055008. doi: 10.1088/1748-605X/aacdb2.
Gelatin hydrogels are used as tissue engineering scaffolds and systems for controlled release due to their inherent biodegradability and biocompatibility. In this study gelatin methacryloyl(-acetyl) (GM/A) with various degrees of methacryloylation (DM) and methacryl-modified heparin (HepM) were cross-linked radically via thermal-redox initiation. Investigation of gel yields (79.4%-85.8%) and equilibrium degrees of swelling (EDS; 564.8%-750.3%) by an experimental design approach suggested interaction effects between the applied HepM mass fraction and the DM of gelatin. HepM reduced the cross-linking effectivity (gel yield) only when added to GM with low DM (83% without HepM, 79% with HepM) but not when added to GM with high DM. For EDS combined impacts of the physical and chemical nature of the applied biopolymers are indicated: the elevated hydrophilicity and low cross-linking potential of HepM enhanced EDS in GM gels with low DM (Ø 1.1-fold increase), and lowered the storage moduli of all GM formulations (Ø 1.2-fold decrease). Vascular endothelial growth factor (VEGF) loading before cross-linking of gels resulted in major loss of functional growth factor (Ø 0.5% release), while loading after cross-linking was successful and significant release was detected over 28 days (6.4%-10.4% release). Release kinetics were mainly controlled by the VEGF concentration used for loading, and thus VEGF release and physico-chemical properties of the hydrogels can be tuned independently from each other in a broad range.
明胶水凝胶由于其固有生物降解性和生物相容性，被用作组织工程支架和控制释放系统。在这项研究中，具有不同程度甲基丙烯酰化（DM）的明胶甲基丙烯酰基（GM/A）和甲基丙烯酰化修饰的肝素（HepM）通过热-氧化还原引发自由基交联。通过实验设计方法研究凝胶产率（79.4%-85.8%）和平衡溶胀度（EDS；564.8%-750.3%），表明所应用的 HepM 质量分数与明胶的 DM 之间存在相互作用效应。只有当添加到低 DM 的 GM 时（无 HepM 为 83%，有 HepM 为 79%），HepM 才会降低交联效率（凝胶产率），而当添加到高 DM 的 GM 时则不会。对于 EDS，所应用的生物聚合物的物理和化学性质的综合影响表明：HepM 的高亲水性和低交联潜力增强了低 DM 的 GM 凝胶的 EDS（增加了 1.1 倍），并降低了所有 GM 配方的储能模量（降低了 1.2 倍）。在凝胶交联之前进行血管内皮生长因子（VEGF）负载会导致功能性生长因子大量损失（释放 0.5%），而交联后负载则成功，并且在 28 天内检测到明显的释放（释放 6.4%-10.4%）。释放动力学主要受用于负载的 VEGF 浓度控制，因此可以在很宽的范围内独立地调节 VEGF 释放和水凝胶的物理化学性质。
