한빛사논문
Kshitiz Raj Shrestha a,1, Do Hoon Lee b,1, Woojae Chung c, Seung-Wuk Lee d, Byung Yang Lee b,*, So Young Yoo a,*
a BIO-IT Foundry Technology Institute, Pusan National University, Busan, 46241, Republic of Korea b Mechanical Engineering, Korea University, Seoul, 02841, Republic of Korea c Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea d Bioengineering, University of California, Berkeley, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, United States
* Corresponding author.
1 These authors contributed equally to this work.
Abstract
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.
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