BIO-IT Foundry Technology Institute, Pusan National University, Busan, 46241, Republic of Korea.
Mechanical Engineering, Korea University, Seoul, 02841, Republic of Korea.
Biomaterials. 2022 Sep;288:121747. doi: 10.1016/j.biomaterials.2022.121747. Epub 2022 Aug 24.
The essential therapeutic cues provided by a nanofibrous arginine-glycine-aspartic acid-engineered M13 phage were exploited as extracellular matrix (ECM)-mimicking niches, contributing to de novo soft tissue niche engineering. The interplay of biomimetic phage cues with surrounding organ tissues was identified, and cells were implanted between tissues to achieve an appropriate soft tissue niche that enables the proper functioning of the implanted stem cells at the injured site. With the polyacrylamide (PA) hydrogel mimicking the soft tissue organ stiffness ranges, it was found that biochemical and topological cues in conjunction with the ∼1-2 kPa elastic and mechanical cues of engineered phage nanofibers in soft tissues efficiently enhance the desired response of implanted stem cells. This phage cue with angiogenic and antioxidant functions overcomes the pathological environment to support implanted cells and surrounding soft tissues at the ischemic site, thereby successfully decreasing myogenic degeneration, minimizing fibrosis, and enhancing blood vessel regeneration with M2 macrophage polarization by improving the survival of the implanted endothelial progenitor cells (EPC) in an ischemic mouse model. These biomimetic phage nanofiber cues are considerably supportive of cell therapy, as they establish promising therapeutic extracellular de novo soft tissue niches for curing ischemic diseases.
利用纳米纤维精氨酸-甘氨酸-天冬氨酸工程化 M13 噬菌体提供的基本治疗线索作为细胞外基质 (ECM)-模拟小生境，有助于新的软组织小生境工程。确定了仿生噬菌体线索与周围器官组织的相互作用，并将细胞植入组织之间，以实现适当的软组织小生境，使植入的干细胞在受伤部位正常发挥功能。聚丙酰胺 (PA) 水凝胶模拟软组织器官的弹性范围，研究发现，生化和拓扑线索以及工程化噬菌体纳米纤维在软组织中的约 1-2 kPa 弹性和机械线索有效地增强了植入干细胞的期望反应。这种具有血管生成和抗氧化功能的噬菌体线索克服了病理环境，支持缺血部位的植入细胞和周围软组织，从而成功减少肌源性退化、最小化纤维化，并通过改善植入血管内皮祖细胞 (EPC) 的生存能力促进血管再生在缺血性小鼠模型中，M2 巨噬细胞极化。这些仿生噬菌体纳米纤维线索对细胞治疗具有重要的支持作用，因为它们为治疗缺血性疾病建立了有前途的治疗性细胞外新的软组织小生境。
