Roy J. Carver Department of Biomedical Engineering, The University of Iowa, 5601 Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, 52242, USA; Institute for Vision Research, The University of Iowa, USA.
Institute for Vision Research, The University of Iowa, USA.
Exp Eye Res. 2021 Jun;207:108566. doi: 10.1016/j.exer.2021.108566. Epub 2021 Apr 7.
Emerging treatment strategies for retinal degeneration involve replacing lost photoreceptors using supportive scaffolds to ensure cells survive the implantation process. While many design aspects of these scaffolds, including material chemistry and microstructural cues, have been studied in depth, a full set of design constraints has yet to be established. For example, while known to be important in other tissues and systems, the influence of mechanical properties on surgical handling has not been quantified. In this study, photocrosslinked poly(ethylene glycol) dimethacrylate (PEGDMA) was used as a model polymer to study the effects of scaffold modulus (stiffness) on surgical handling, independent of material chemistry. This was achieved by modulating the molecular weight and concentrations of the PEGDMA in various prepolymer solutions. Scaffold modulus of each formulation was measured using photo-rheology, which enabled the collection of real-time polymerization data. In addition to measuring scaffold mechanical properties, this approach gave insight on polymerization kinetics, which were used to determine the polymerization time required for each sample. Scaffold handling characteristics were qualitatively evaluated using both in vitro and ex vivo trials that mimicked the surgical procedure. In these trials, scaffolds with shear moduli above 35 kPa performed satisfactorily, while those below this limit performed poorly. In other words, scaffolds below this modulus were too fragile for reliable transplantation. To better compare these results with literature values, the compressive modulus was measured for select samples, with the lower shear modulus limit corresponding to roughly 115 kPa compressive modulus. While an upper mechanical property limit was not readily apparent from these results, there was increased variability in surgical handling performance in samples with shear moduli above 800 kPa. Overall, the knowledge presented here provides important groundwork for future studies designed to examine additional retinal scaffold considerations, including the effect of scaffold mechanical properties on retinal progenitor cell fate.
用于视网膜变性的新兴治疗策略包括使用支持性支架替代丢失的光感受器，以确保细胞在植入过程中存活。尽管这些支架的许多设计方面，包括材料化学和微观结构线索，已经进行了深入研究，但尚未建立完整的设计约束条件。例如，尽管在其他组织和系统中被认为很重要，但机械性能对手术处理的影响尚未量化。在这项研究中，光交联的聚乙二醇二甲基丙烯酸酯 (PEGDMA) 被用作模型聚合物，以研究支架模量（刚度）对手术处理的影响，而与材料化学无关。这是通过调节各种预聚物溶液中 PEGDMA 的分子量和浓度来实现的。使用光流变学测量每个配方的支架模量，这使得能够收集实时聚合数据。除了测量支架机械性能外，这种方法还提供了关于聚合动力学的见解，可用于确定每个样品所需的聚合时间。通过体外和体内试验定性评估支架处理特性，这些试验模拟了手术过程。在这些试验中，剪切模量高于 35 kPa 的支架表现良好，而低于此限值的支架表现不佳。换句话说，低于此模量的支架太脆弱，无法进行可靠的移植。为了更好地将这些结果与文献值进行比较，对选定样品进行了压缩模量测量，较低的剪切模量限值对应于大约 115 kPa 的压缩模量。虽然从这些结果中不易看出上限机械性能，但在剪切模量高于 800 kPa 的样品中，手术处理性能的可变性增加。总体而言，这里提出的知识为未来旨在检查其他视网膜支架考虑因素的研究提供了重要基础，包括支架机械性能对视网膜祖细胞命运的影响。
