Institute of Health and Biomedical Innovation (IHBI), QUT, 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia.
Institute of Health and Biomedical Innovation (IHBI), QUT, 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia.
Acta Biomater. 2015 Nov;27:66-76. doi: 10.1016/j.actbio.2015.08.038. Epub 2015 Aug 28.
Photocrosslinkable hydrogels are frequently used in cartilage tissue engineering, with crosslinking systems relying on cytotoxic photoinitiators and ultraviolet (UV) light to form permanent hydrogels. These systems are rarely assessed in terms of optimization of photoinitiator or UV dosage, with non-cytotoxic concentrations from literature deemed sufficient. We hypothesized that the number of reactive functional groups present within a hydrogel polymer is highly relevant when crosslinking, affording cytoprotection to chondrocytes by preferentially interacting with the highly reactive radicals that are formed during UV-mediated activation of a photoinitiator. This was tested using two photocrosslinkable hydrogel systems: gelatin methacrylamide (GelMA) and gellan gum methacrylate (GGMA). We further assessed the effects of two different UV dosages on chondrocyte differentiation while subject to a single photoinitiator dosage in the GGMA system. Most notably, we found that a higher ratio of reactive groups to photoinitiator molecules offers cytoprotective effects, and future developments in photocrosslinkable hydrogel technology may involve assessment of such ratios. In contrast, we found there to be no effect of UV on chondrocyte differentiation at the two chosen dosages. Overall the optimization of photocrosslinkable systems is of great value in cartilage tissue engineering and these data provide a groundwork for such concepts to be developed further.
Photocrosslinkable hydrogels, which use photoinitiators and predominantly ultraviolet light to form stable matrices for cell encapsulation and tissue development, are promising for cartilage tissue engineering. While both photoinitiators and ultraviolet light can damage cells, these systems have generally not been optimized. We propose that the ratio of reactive functional groups within a polymer to photoinitiator molecules is a critical parameter for optimization of photocrosslinkable hydrogels. Using photocrosslinkable gelatin and gellan gum, we found that a higher ratio of reactive groups to photoinitiator molecules protected chondrocytes, but did not affect chondrocyte differentiation. The principle of cytoprotection by functional groups developed in this work will be of great value in optimizing photocrosslinkable hydrogel systems for cartilage and other tissue engineering applications.
光交联水凝胶常用于软骨组织工程，交联系统依赖于细胞毒性光引发剂和紫外线 (UV) 光来形成永久性水凝胶。这些系统很少根据光引发剂或 UV 剂量的优化进行评估，文献中的非细胞毒性浓度被认为是足够的。我们假设，在交联过程中，水凝胶聚合物中存在的反应性官能团的数量非常重要，通过优先与在光引发剂的 UV 介导激活过程中形成的高反应性自由基相互作用，为软骨细胞提供细胞保护。这是使用两种光交联水凝胶系统：明胶甲基丙烯酰胺 (GelMA) 和结冷胶甲基丙烯酰胺 (GGMA) 进行测试的。我们进一步评估了在 GGMA 系统中单一光引发剂剂量下，两种不同 UV 剂量对软骨细胞分化的影响。最值得注意的是，我们发现，反应性基团与光引发剂分子的比例越高，提供细胞保护效果越好，光交联水凝胶技术的未来发展可能涉及此类比例的评估。相比之下，我们发现在所选择的两种剂量下，UV 对软骨细胞分化没有影响。总的来说，光交联系统的优化在软骨组织工程中具有重要价值，这些数据为进一步发展这些概念提供了基础。
光交联水凝胶可使用光引发剂和主要的紫外线光形成用于细胞包封和组织发育的稳定基质，在软骨组织工程中很有前景。虽然光引发剂和紫外线光都可能损伤细胞，但这些系统通常没有得到优化。我们提出，聚合物内的反应性官能团与光引发剂分子的比例是优化光交联水凝胶的关键参数。使用光交联明胶和结冷胶，我们发现，反应性基团与光引发剂分子的比例越高，对软骨细胞的保护作用越好，但不影响软骨细胞的分化。本工作中通过官能团开发的细胞保护原理对于优化用于软骨和其他组织工程应用的光交联水凝胶系统将具有重要价值。
