Kim Sung-Won, Im Gwang-Bum, Jeong Gun-Jae, Baik Sangyul, Hyun Jiyu, Kim Yu-Jin, Pang Changhyun, Jang Young Charles, Bhang Suk Ho
School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea.
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Biomaterials. 2021 Aug;275:120954. doi: 10.1016/j.biomaterials.2021.120954. Epub 2021 Jun 7.
Low cell engraftment is a major problem in tissue engineering. Although various methods related with cell sheets have been attempted to resolve the issue, low cell viability due to oxygen and nutrient depletion remains an obstacle toward advanced therapeutic applications. Cell therapy using fibroblasts is thought of as a good alternative due to the short doubling times of fibroblasts together with their immunomodulatory properties. Furthermore, three-dimensional (3D) fibroblasts exhibit unique angiogenic and inflammation-manipulating properties that are not present in two-dimensional (2D) forms. However, the therapeutic effect of 3D fibroblasts in tissue regeneration has not been fully elucidated. Macrophage polarization has been widely studied, as it stimulates the transition from the inflammation to the proliferation phase of wound healing. Although numerous strategies have been developed to achieve better polarization of macrophages, the low efficacy of these strategies and safety issues remain problematic. To this end, we introduced a biocompatible flat patch with specifically designed holes that form a spheroids-incorporated human dermal fibroblast sheet (SIS) to mediate the activity of inflammatory cytokines for M2 polarization and increase angiogenic efficacy. We further confirmed in vivo enhancement of wound healing with an SIS-laden skin patch (SISS) compared to conventional cell therapy.
低细胞植入是组织工程中的一个主要问题。尽管已经尝试了各种与细胞片相关的方法来解决这个问题，但由于氧气和营养物质耗尽导致的低细胞活力仍然是先进治疗应用的一个障碍。由于成纤维细胞的倍增时间短及其免疫调节特性，使用成纤维细胞的细胞疗法被认为是一种很好的替代方法。此外，三维（3D）成纤维细胞表现出二维（2D）形式中不存在的独特血管生成和炎症调节特性。然而，3D成纤维细胞在组织再生中的治疗效果尚未完全阐明。巨噬细胞极化已被广泛研究，因为它刺激伤口愈合从炎症阶段向增殖阶段的转变。尽管已经开发了许多策略来实现巨噬细胞更好的极化，但这些策略的低效率和安全性问题仍然存在问题。为此，我们引入了一种具有专门设计孔的生物相容性扁平贴片，该贴片形成了包含球体的人真皮成纤维细胞片（SIS），以介导炎症细胞因子的活性以实现M2极化并提高血管生成功效。与传统细胞疗法相比，我们进一步证实了载有SIS的皮肤贴片（SISS）在体内对伤口愈合的促进作用。
