Shin Hyeongho, Olsen Bradley D, Khademhosseini Ali
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA ; Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Mater Chem B. 2014 May 7;2(17):2508-2516. doi: 10.1039/C3TB20984A.
The relatively weak mechanical properties of hydrogels remain a major drawback for their application as load-bearing tissue scaffolds. Previously, we developed cell-laden double-network (DN) hydrogels that were composed of photocrosslinkable gellan gum (GG) and gelatin. Further research into the materials as tissue scaffolds determined that the strength of the DN hydrogels decreased when they were prepared at cell-compatible conditions, and the encapsulated cells in the DN hydrogels did not function as well as they did in gelatin hydrogels. In this work, we developed microgel-reinforced (MR) hydrogels from the same two polymers, which have better mechanical strength and biological properties in comparison to the DN hydrogels. The MR hydrogels were prepared by incorporating stiff GG microgels into soft and ductile gelatin hydrogels. The MR hydrogels prepared at cell-compatible conditions exhibited higher strength than the DN hydrogels and the gelatin hydrogels, the highest strength being 2.8 times that of the gelatin hydrogels. MC3T3-E1 preosteoblasts encapsulated in MR hydrogels exhibited as high metabolic activity as in gelatin hydrogels, which is significantly higher than that in the DN hydrogels. The measurement of alkaline phosphatase (ALP) activity and the amount of mineralization showed that osteogenic behavior of MC3T3-E1 cells was as much facilitated in the MR hydrogels as in the gelatin hydrogels, while it was not as much facilitated in the DN hydrogels. These results suggest that the MR hydrogels could be a better alternative to the DN hydrogels and have great potential as load-bearing tissue scaffolds.
水凝胶相对较弱的力学性能仍然是其作为承重组织支架应用的一个主要缺点。此前，我们开发了由可光交联的结冷胶（GG）和明胶组成的载细胞双网络（DN）水凝胶。对这些材料作为组织支架的进一步研究表明，当在细胞兼容条件下制备时，DN水凝胶的强度会降低，并且DN水凝胶中封装的细胞功能不如在明胶水凝胶中那样好。在这项工作中，我们用相同的两种聚合物开发了微凝胶增强（MR）水凝胶，与DN水凝胶相比，其具有更好的机械强度和生物学特性。MR水凝胶是通过将刚性的GG微凝胶掺入柔软且有延展性的明胶水凝胶中制备而成。在细胞兼容条件下制备的MR水凝胶表现出比DN水凝胶和明胶水凝胶更高的强度，最高强度是明胶水凝胶的2.8倍。封装在MR水凝胶中的MC3T3-E1前成骨细胞表现出与在明胶水凝胶中一样高的代谢活性，这明显高于在DN水凝胶中的代谢活性。碱性磷酸酶（ALP）活性和矿化量的测量表明，MC3T3-E1细胞在MR水凝胶中的成骨行为与在明胶水凝胶中一样得到促进，而在DN水凝胶中则没有得到那么大的促进。这些结果表明，MR水凝胶可能是DN水凝胶的更好替代品，并且作为承重组织支架具有巨大潜力。
