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

• Project/Area Number: 22KF0287
• Project/Area Number (Other): 21F21353 (2021-2022)
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Multi-year Fund (2023); Single-year Grants (2021-2022)
• Section: 外国
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• 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, 工学研究院, 外国人特別研究員
• Project Period (FY): 2023-03-08 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 2023: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2022: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2021: ¥300,000 (Direct Cost: ¥300,000)
• Keywords: Hybrid vascular graft / Decellularized ECM / Polycaprolactone / Nanofibrous membrane / Tubular scaffold / Electrospun membrane / Nanofibrous Membrane

Outline of Research at the Start

The aim of this research is to decipher the role of immunomodulation for engineering synthetic vascular grafts, which will be accomplished by exploiting decellularized extracellular matrix (dECM) and different immunomodulatory cues. Cell free vascular grafts may offer an invaluable platform for vascular tissue engineering. In this study, PLCL / dECM based hybrid vascular grafts will be developed by electrospinning. Furthermore, immobilize bioactive cues will elucidate the role of immunomodulatory for vascular tissue repair.

Outline of Annual Research Achievements

Artificial nerve guidance conduits (NGCs) consisting of core/shell type electrospun fibers using brain-derived extracellular matrix (B-ECM) have been developed and their effectiveness has been demonstrated. Their details are as follows.
Fabrication of core/shell type electrospun fibers: B-ECM was blended along with gelatin to fabricate polycaprolactone/gelatin (PCL/Gel)-based core/shell type fibers. At this time, the aligned fibers using a rotating collector were also obtained.
Evaluation by cell culture: PC12 cells were used as neural model cells. In the nonwoven fabric made of the electrospun ECM described above, the effect of promoting the elongation of neurites and the elongation of neurons on the aligned fibers was confirmed. NGF was immobilized on the fibers because neurotrophic factors and growth factors can affect cell differentiation and tissue repair. Here, nerve growth factor (NGF) was able to be immobilized on the fibers via glycosaminoglycans, which are constituents of B-ECM.
Fabrication and evaluation of nerve guidance conduits: NGCs were fabricated by amassing tubular scaffolds and core/shell type aligned electrospun fibers. Physico-chemical properties of NGCs, including tensile testing and suture strength retention were sufficient for the application. Biocompatibility of tubular scaffolds was also confirmed. The NGCs were transplanted into sciatic nerve defects, and suppression of neurite outgrowth and cell infiltration from the surrounding area was achieved.

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 Issue: 1
  • DOI: 10.1080/00219592.2023.2204899
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Insight on Oxygen-Supplying Biomaterials Used to Enhance Cell Survival, Retention, and Engraftment for Tissue Repair (2023)
  • Author(s): Rafique Muhammad、Ali Onaza、Shafiq Muhammad、Yao Minghua、Wang Kai、Ijima Hiroyuki、Kong Deling、Ikeda Masato
  • Journal Title: Biomedicines Volume: 11 Issue: 6 Pages: 1592-1592
  • DOI: 10.3390/biomedicines11061592
  • Peer Reviewed / Open Access
• [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
  • 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 Issue: 2 Pages: 554-573
  • DOI: 10.1007/s42765-022-00244-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Intelligent Multifunctional Polymeric Biomaterials for Spatio-temporal Drug/growth factor Release and in situ Tissue Regeneration (2023)
  • Author(s): Muhammad Shafiq, Yifan Wu, Ming Ma, Shinichi Aishima, Kai Wang, Xiumei Mo, Hiroyuki Ijima
  • Organizer: 12th Asian-Pacific Conference on Medical and Biological Engineering
  • Int'l Joint Research
• [Presentation] Artificial Nerve Guidance Conduits based onPolycaprolactone/Gelatin-based Core/Shell typeAligned Electrospun Fibers (2023)
  • Author(s): Muhammad Shafiq, Kazuo Koyanagi, Yasuhiro Ikegami, Shinichi Aishima, Hiroyuki Ijima
  • Organizer: 12th Asian-Pacific Conference on Medical and Biological Engineering
  • Int'l Joint Research