Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing

Stem cells have shown substantial promise for various diseases in preclinical and clinical trials. However, low cell engraftment rates significantly limit the clinical translation of stem cell therapeutics. Numerous injectable hydrogels have been developed to enhance cell retention. Yet, the design...

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Published inAdvanced functional materials Vol. 27; no. 24
Main Authors Dong, Yixiao, A, Sigen, Rodrigues, Melanie, Li, Xiaolin, Kwon, Sun H., Kosaric, Nina, Khong, Sacha, Gao, Yongsheng, Wang, Wenxin, Gurtner, Geoffrey C.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc 27.06.2017
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Abstract Stem cells have shown substantial promise for various diseases in preclinical and clinical trials. However, low cell engraftment rates significantly limit the clinical translation of stem cell therapeutics. Numerous injectable hydrogels have been developed to enhance cell retention. Yet, the design of an ideal material with tunable properties that can mimic different tissue niches and regulate stem cell behaviors remains an unfulfilled promise. Here, an injectable poly(ethylene glycol) (PEG)–gelatin hydrogel is designed with highly tunable properties, from a multifunctional PEG‐based hyperbranched polymer and a commercially available thiolated gelatin. Spontaneous gelation occurs within about 2 min under the physiological condition. Murine adipose‐derived stem cells (ASCs) can be easily encapsulated into the hydrogel, which supports ASC growth and maintains their stemness. The hydrogel mechanical properties, biodegradability, and cellular responses can be finely controlled by changing hydrogel formulation and cell seeding densities. An animal study shows that the in situ formed hydrogel significantly improves cell retention, enhances angiogenesis, and accelerates wound closure using a murine wound healing model. These data suggest that injectable PEG–gelatin hydrogel can be used for regulating stem cell behaviors in 3D culture, delivering cells for wound healing and other tissue regeneration applications. An injectable poly(ethylene glycol) (PEG)–gelatin hydrogel is designed from a multifunctional PEG‐based hyperbranched polymer and a commercially available thiolated gelatin. Spontaneous gelation occurs within 2 min under the physiological condition, with finely controlled hydrogel properties. The in situ formed hydrogel significantly improves cell retention, enhances angiogenesis, and accelerates wound closure in a murine wound model.
AbstractList Stem cells have shown substantial promise for various diseases in preclinical and clinical trials. However, low cell engraftment rates significantly limit the clinical translation of stem cell therapeutics. Numerous injectable hydrogels have been developed to enhance cell retention. Yet, the design of an ideal material with tunable properties that can mimic different tissue niches and regulate stem cell behaviors remains an unfulfilled promise. Here, an injectable poly(ethylene glycol) (PEG)–gelatin hydrogel is designed with highly tunable properties, from a multifunctional PEG‐based hyperbranched polymer and a commercially available thiolated gelatin. Spontaneous gelation occurs within about 2 min under the physiological condition. Murine adipose‐derived stem cells (ASCs) can be easily encapsulated into the hydrogel, which supports ASC growth and maintains their stemness. The hydrogel mechanical properties, biodegradability, and cellular responses can be finely controlled by changing hydrogel formulation and cell seeding densities. An animal study shows that the in situ formed hydrogel significantly improves cell retention, enhances angiogenesis, and accelerates wound closure using a murine wound healing model. These data suggest that injectable PEG–gelatin hydrogel can be used for regulating stem cell behaviors in 3D culture, delivering cells for wound healing and other tissue regeneration applications. An injectable poly(ethylene glycol) (PEG)–gelatin hydrogel is designed from a multifunctional PEG‐based hyperbranched polymer and a commercially available thiolated gelatin. Spontaneous gelation occurs within 2 min under the physiological condition, with finely controlled hydrogel properties. The in situ formed hydrogel significantly improves cell retention, enhances angiogenesis, and accelerates wound closure in a murine wound model.
Stem cells have shown substantial promise for various diseases in preclinical and clinical trials. However, low cell engraftment rates significantly limit the clinical translation of stem cell therapeutics. Numerous injectable hydrogels have been developed to enhance cell retention. Yet, the design of an ideal material with tunable properties that can mimic different tissue niches and regulate stem cell behaviors remains an unfulfilled promise. Here, an injectable poly(ethylene glycol) (PEG)-gelatin hydrogel is designed with highly tunable properties, from a multifunctional PEG-based hyperbranched polymer and a commercially available thiolated gelatin. Spontaneous gelation occurs within about 2 min under the physiological condition. Murine adipose-derived stem cells (ASCs) can be easily encapsulated into the hydrogel, which supports ASC growth and maintains their stemness. The hydrogel mechanical properties, biodegradability, and cellular responses can be finely controlled by changing hydrogel formulation and cell seeding densities. An animal study shows that the in situ formed hydrogel significantly improves cell retention, enhances angiogenesis, and accelerates wound closure using a murine wound healing model. These data suggest that injectable PEG-gelatin hydrogel can be used for regulating stem cell behaviors in 3D culture, delivering cells for wound healing and other tissue regeneration applications.
Author Kwon, Sun H.
Rodrigues, Melanie
Gurtner, Geoffrey C.
Khong, Sacha
Wang, Wenxin
Li, Xiaolin
Kosaric, Nina
A, Sigen
Dong, Yixiao
Gao, Yongsheng
Author_xml – sequence: 1
  givenname: Yixiao
  surname: Dong
  fullname: Dong, Yixiao
  email: yixiaod@stanford.edu
  organization: University College Dublin
– sequence: 2
  givenname: Sigen
  surname: A
  fullname: A, Sigen
  organization: University College Dublin
– sequence: 3
  givenname: Melanie
  surname: Rodrigues
  fullname: Rodrigues, Melanie
  organization: Stanford University School of Medicine
– sequence: 4
  givenname: Xiaolin
  surname: Li
  fullname: Li, Xiaolin
  organization: University College Dublin
– sequence: 5
  givenname: Sun H.
  surname: Kwon
  fullname: Kwon, Sun H.
  organization: Stanford University School of Medicine
– sequence: 6
  givenname: Nina
  surname: Kosaric
  fullname: Kosaric, Nina
  organization: Stanford University School of Medicine
– sequence: 7
  givenname: Sacha
  surname: Khong
  fullname: Khong, Sacha
  organization: Stanford University School of Medicine
– sequence: 8
  givenname: Yongsheng
  surname: Gao
  fullname: Gao, Yongsheng
  organization: University College Dublin
– sequence: 9
  givenname: Wenxin
  surname: Wang
  fullname: Wang, Wenxin
  organization: University College Dublin
– sequence: 10
  givenname: Geoffrey C.
  surname: Gurtner
  fullname: Gurtner, Geoffrey C.
  email: ggurtner@stanford.edu
  organization: Stanford University School of Medicine
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ContentType Journal Article
Copyright 2017 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Snippet Stem cells have shown substantial promise for various diseases in preclinical and clinical trials. However, low cell engraftment rates significantly limit the...
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SubjectTerms Biodegradability
Encapsulation
gelatin
Gelation
Hydrogels
hyperbranched polymers
injectable hydrogels
Materials science
Mechanical properties
Medical research
Polyethylene glycol
Regeneration
Stem cells
Tissue engineering
Wound healing
Title Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing
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