Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210, USA.
Acta Biomater. 2010 Jun;6(6):1978-91. doi: 10.1016/j.actbio.2009.12.011. Epub 2009 Dec 23.
A family of injectable, rapid gelling and highly flexible hydrogel composites capable of releasing insulin-like growth factor (IGF-1) and delivering mesenchymal stromal cell (MSC) were developed. Hydrogel composites were fabricated from Type I collagen, chondroitin sulfate (CS) and a thermosensitive and degradable hydrogel copolymer based on N-isopropylacrylamide, acrylic acid, N-acryloxysuccinimide and a macromer poly(trimethylene carbonate)-hydroxyethyl methacrylate. The hydrogel copolymer was gellable at body temperature before degradation and soluble at body temperature after degradation. Hydrogel composites exhibited LCSTs around room temperature. They could easily be injected through a 26-gauge needle at 4 degrees C, and were capable of gelling within 6s at 37 degrees C to form highly flexible gels with moduli matching those of the rat and human myocardium. The hydrogel composites showed good oxygen permeability; the oxygen pressure within the hydrogel composites was similar to that in the air. The effects of collagen and CS contents on LCST, gelation time, injectability, mechanical properties and degradation properties were investigated. IGF-1 was loaded into the hydrogel composites for enhanced cell survival/growth. The released IGF-1 remained bioactive during a 2-week release period. Small fraction of CS in the hydrogel composites significantly decreased IGF-1 release rate. The release kinetics appeared to be controlled mainly by hydrogel composite water content, degradation and interaction with IGF-1. Human MSC adhesion on the hydrogel composites was comparable to that on the tissue culture plate. MSCs were encapsulated in the hydrogel composites and were found to grow inside during a 7-day culture period. IGF-1 loading significantly accelerated MSC growth. RT-PCR analysis demonstrated that MSCs maintained their multipotent differentiation potential in hydrogel composites with and without IGF-1. These injectable and rapid gelling hydrogel composites demonstrated attractive properties for serving as growth factor and cell carriers for cardiovascular tissue engineering applications.
研制了一种可注射、快速凝胶化和高度灵活的水凝胶复合材料，能够释放胰岛素样生长因子（IGF-1）并输送间充质基质细胞（MSC）。水凝胶复合材料由 I 型胶原、硫酸软骨素（CS）和基于 N-异丙基丙烯酰胺、丙烯酸、N-丙烯酰氧基琥珀酰亚胺和大分子聚（三亚甲基碳酸酯）-羟乙基甲基丙烯酸酯的热敏感和可降解水凝胶共聚物制成。水凝胶共聚物在降解前可在体温下凝胶化，在降解后可在体温下溶解。水凝胶复合材料的 LCST 在室温附近。它们可以在 4°C 下轻松通过 26 号针头注射，并且能够在 37°C 下在 6s 内凝胶化，形成与大鼠和人心肌相匹配的高柔韧性凝胶，模量。水凝胶复合材料具有良好的氧气渗透性；水凝胶复合材料内的氧气压力与空气中的氧气压力相似。研究了胶原和 CS 含量对 LCST、凝胶时间、可注射性、力学性能和降解性能的影响。将 IGF-1 载入水凝胶复合材料中以提高细胞存活率/生长。在 2 周的释放期内，释放的 IGF-1 保持生物活性。水凝胶复合材料中 CS 的小部分显著降低了 IGF-1 的释放速率。释放动力学似乎主要受水凝胶复合材料的含水量、降解和与 IGF-1 的相互作用控制。人 MSC 在水凝胶复合材料上的黏附性与组织培养板上的黏附性相当。MSC 被包封在水凝胶复合材料中，并在 7 天的培养期内发现其在内部生长。IGF-1 负载显著加速了 MSC 的生长。RT-PCR 分析表明，MSC 在有无 IGF-1 的水凝胶复合材料中保持其多能分化潜能。这些可注射和快速凝胶化的水凝胶复合材料具有作为心血管组织工程应用中生长因子和细胞载体的有吸引力的特性。
