Adipose-derived stem cell/FGF19-loaded microfluidic hydrogel microspheres for synergistic restoration of critical ischemic limb

Ruihan Wang; Fangqian Wang; Shan Lu; Bin Gao; Yuanqing Kan; Tong Yuan; Yisheng Xu; Chen Yuan; Daqiao Guo; Weiguo Fu; Xiaohua Yu; Yi Si

Bioactive Materials (Sep 2023)

Adipose-derived stem cell/FGF19-loaded microfluidic hydrogel microspheres for synergistic restoration of critical ischemic limb

Ruihan Wang,
Fangqian Wang,
Shan Lu,
Bin Gao,
Yuanqing Kan,
Tong Yuan,
Yisheng Xu,
Chen Yuan,
Daqiao Guo,
Weiguo Fu,
Xiaohua Yu,
Yi Si

Affiliations

Ruihan Wang: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China
Fangqian Wang: Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310000, Zhejiang, PR China
Shan Lu: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China
Bin Gao: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China
Yuanqing Kan: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China
Tong Yuan: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China
Yisheng Xu: State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
Chen Yuan: State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
Daqiao Guo: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China
Weiguo Fu: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China; Corresponding author. Fenglin Road 180, Shanghai, China.
Xiaohua Yu: Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310000, Zhejiang, PR China; Corresponding author. Jiefang Road 88, Hangzhou, Zhejiang Province, China.
Yi Si: Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, PR China; Institute of Vascular Surgery, Fudan University, Shanghai, 200032, PR China; National Clinical Research Center for Interventional Medicine, Shanghai, 200032, PR China; Corresponding author. Fenglin Road 180, Shanghai, 200032, China.

Journal volume & issue: Vol. 27
pp. 394 – 408

Abstract

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The efficacy of stem cell therapy is substantially compromised due to low cell survival rate and poor local retention post-delivery. These issues drastically limit the application of stem cells for ischemic limb therapy, which requires effective blood perfusion and skeletal muscle regeneration. Herein, based on microfluidic technology, an integrated stem cell and cytokine co-delivery system designed for functional ischemic limb salvage was constructed by first incorporating the myogenic cytokine, fibroblast growth factor 19 (FGF19), into microspheres composed of methacrylate gelatin (GelMA). Then adipose-derived stem cells (ADSCs) were highly absorbed into the porous structure of the microspheres, overcoming the insufficient loading efficiency and activities by conventional encapsulation strategy. The fabricated ADSCs/FGF19@μsphere system demonstrated a uniform size of about 180 μm and a highly porous structure with pore sizes between 20 and 40 μm. The resultant system allowed high doses of ADSCs to be precisely engrafted in the lesion and to survive, and achieved sustained FGF19 release in the ischemic region to facilitate myoblast recruitment and differentiation and myofibrils growth. Furthermore, the combination of ADSCs and FGF19 exhibited a positive synergistic effect which substantially improved the therapeutic benefit of angiogenesis and myogenesis, both in vitro and in vivo. In summary, a stem cell and cytokine co-delivery system with the properties of easy preparation and minimal invasiveness was designed to ensure highly efficient cell delivery, sustained cytokine release, and ultimately realizes effective treatment of ischemic limb regeneration.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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