生体活性人工血管の開発と血管組織修復のための免疫調節の役割の解明

2022 Fiscal Year Annual Research Report

• Project/Area Number: 21F21353
• Allocation Type: Single-year Grants
• Research Institution: Kyushu University
• Principal Investigator: 井嶋 博之 九州大学, 工学研究院, 教授 (10274515)
• Co-Investigator(Kenkyū-buntansha): SHAFIQ MUHAMMAD 九州大学, 工学(系)研究科(研究院), 外国人特別研究員
• Project Period (FY): 2021-11-18 – 2024-03-31
• Keywords: Hybrid vascular graft / Decellularized ECM / Polycaprolactone / Nanofibrous Membrane / Tubular scaffold / Electrospun membrane

Outline of Annual Research Achievements

The objective of this research is to foster instructive biomaterials to promote in situ tissue repair. Soluble and tethered biological cues as well as extracellular matrix (ECM)-mimicking scaffolds hold great promise. Growth factors (GFs) as well as cytokines and chemokines play a pivotal role for tissue repair, however, they can be easily degraded in vitro and in vivo owing to their short half-life and poor stability. Short amino-acid sequences, which can fully recapitulate the bioactivity of full-length proteins while ensuring an easy manufacturing and good stability offer an alternative paradigm. Therefore, the overarching goal of research in this fiscal year was to fabricate ECM-mimicking scaffolds and to modify them with GFs and other bioactive cues for a functional tissue repair.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Vascular endothelial growth factor (VEGF) is a potent angiogenic cue, while stromal cell-derived factor-1 alpha (SDF-1α) is a stem cell inducing/recruiting factor. The levels of VEGF and SDF-1α transiently increase following tissue injury, however sharply decline owing to matrix metalloproteinases. We conjugated VEGF-recruiting prominin-1-derived peptide (PR1P) and SDF-1α peptide with polycaprolactone (PCL, Mw = 14 kDa) and blended them along with PCL (Mw = 80 kDa) to fabricate vascular grafts. In vivo evaluation in an abdominal aorta revealed marked effect of dual cues for endogenous cell mobilization/recruitment and in situ blood vessel regeneration. We also fabricated heparin-immobilized electrospun fibers; as well as decellularized extracellular matrix (dECM)-based core/shell fibers for GFs immobilization.

Strategy for Future Research Activity

The above findings indicated beneficial effect of GFs and bioactive cues. ECM confers instructive cues to tissues and organs, thanks to its composition and localization as well as its ability to harbor soluble and tethered ligands. Our preliminary studies have indicated beneficial effect of heparinization for GFs immobilization. ECM is also composed of glycosaminoglycans, which may also bind endogenous and exogenous biological cues. We have prepared dECM from different tissues, such as nerves and aorta and successfully fabricated core/shell fibers; the core was composed of PCL/gelatin, while the shell was comprised of dECM. A battery of in vitro and in vivo tests will be performed to reveal the potential of dECM-based fibers to promote GFs immobilization as well as tissue repair in vitro and in vivo.

Research Products

• [Journal Article] Decellularized liver as a small-scale scaffold for the creation of a miniaturized human liver (2023)
  • Author(s): Hiroyuki Ijima, Yukako Fukuda, Muhammad Shafiq, Mario Kokichi Uehara, Fanqi Wu, Jaeyong Cho, Yusuke Sakai, Tatsunori Miyata, Takanobu Yamao, Yosuke Nakao, Yo-ichi Yamashita, Hideo Baba
  • Journal Title: Journal of Chemical Engineering of Japan Volume: in press Pages: in press
  • DOI: 10.1080/00219592.2023.2204899
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Peptides-tethered vascular grafts enable blood vessel regeneration via endogenous cell recruitment and neovascularization (2023)
  • Author(s): Wu Yifan、Song Lili、Shafiq Muhammad、Ijima Hiroyuki、Kim Soo Hyun、Wei Ran、Kong Deling、Mo Xiumei、Wang Kai
  • Journal Title: Composites Part B: Engineering Volume: 252 Pages: 110504～110504
  • DOI: 10.1016/j.compositesb.2023.110504
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Combined effect of SDF-1 peptide and angiogenic cues in co-axial PLGA/gelatin fibers for cutaneous wound healing in diabetic rats (2023)
  • Author(s): Shafiq Muhammad、Yuan Zhengchao、Rafique Muhammad、Aishima Shinichi、Jing Hou、Yuqing Liang、Ijima Hiroyuki、Jiang Shichao、Mo Xiumei
  • Journal Title: Colloids and Surfaces B: Biointerfaces Volume: 223 Pages: 113140～113140
  • DOI: 10.1016/j.colsurfb.2023.113140
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti-inflammatory, Antibacterial, Antioxidative Bioactive Glass-Based Nanofibrous Dressing Enables Scarless Wound Healing (2023)
  • Author(s): Zhengchao Yuan a, 1, Lixiang Zhang b, 1, Shichao Jiang c, d, 1, Muhammad Shafiq, Youjun Cai, Yujie Chen, Jiahui Song, Xiao Yu, Hiroyuki Ijima, Yuan Xu, Xiumei Mo
  • Journal Title: Smart Materials in Medicine Volume: in press Pages: in press
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vascular endothelial growth factor-recruiting nanofiber bandages promote multifunctional skin regeneration via improved angiogenesis and immunomodulation (2023)
  • Author(s): Yi Chen, Zhengchao Yuan, Weiyan Suna, Muhammad Shafiq, Jun Zhu, Jiafei Chena, Hai Tang, Ling Hu Weikang Lin, Yanxi Zeng, Long Wang, Lei Zhang, Yunlang She, Hui Zheng, Guofang Zhao, Dong Xie, Xiumei Mo, Chang Chen
  • Journal Title: Advanced Fiber Materials Volume: 5 Pages: 327-348
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Electrospinning Inorganic Nanomaterials to Fabricate Bionanocomposites for Soft and Hard Tissue Repair (2023)
  • Author(s): Jie Cui, Xiao Yu, Yihong Shen, Binbin Sun, Wanxin Guo, Mingyue Liu, Yujie Chen, Li Wang, Xingping Zhou, Muhammad Shafiq, Xiumei Mo
  • Journal Title: Nanomaterials Volume: 13 Pages: 204-204
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Heparin/Growth Factors-Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin-Based Nerve Guidance Conduits (2022)
  • Author(s): Ikegami Yasuhiro、Shafiq Muhammad、Aishima Shinichi、Ijima Hiroyuki
  • Journal Title: Advanced Fiber Materials Volume: 5 Pages: 554～573
  • DOI: 10.1007/s42765-022-00244-6
  • Peer Reviewed / Int'l Joint Research