Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring

Li, Zhonghua; Wang, Haiqin; Yang, Bo; Sun, Yi; Huo, Ran

doi:10.1016/j.msec.2015.07.062

Cited by 92 publications

(50 citation statements)

References 34 publications

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“…In these models there was also an upregulation of VEGF and basic fibroblast growth factor (bFGF), both drivers of neovascularization. In addition, there might be an anti-scarring benefit as TGF-β1 and alpha-smooth muscle actin (α-SMA) were downregulated while TGF-β3 was unregulated [182]. …”

Section: Applications In Tissue Engineering and Regenerative Medicinementioning

confidence: 99%

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Graphene-based materials for tissue engineering

Shin

Jang

et al. 2016

Advanced Drug Delivery Reviews

574

418

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Graphene and its chemical derivatives have been a pivotal new class of nanomaterials and a model system for quantum behavior. The material's excellent electrical conductivity, biocompatibility, surface area and thermal properties are of much interest to the scientific community. Two dimensional graphene materials have been widely used in various biomedical research areas such as bioelectronics, imaging, drug delivery, and tissue engineering. In this review we will highlight the recent applications of graphene-based materials in tissue engineering and regenerative medicine. In particular, we will discuss the application of graphene-based materials in cardiac, neural, bone, cartilage, skeletal muscle, and skin/adipose tissue engineering. We also discuss the potential risk factors of graphene-based materials in tissue engineering. In addition, we will outline the opportunities in the usage of graphene-based materials for clinical applications.

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Section: Applications In Tissue Engineering and Regenerative Medicinementioning

confidence: 99%

“…Data were presented by means ± SEM. *p < 0.05 and #p < 0.01 (Reprinted with permission from [182] Copyright (2015) ELSEVIER).…”

Section: Fig1mentioning

confidence: 99%

Graphene-based materials for tissue engineering

Shin

Jang

et al. 2016

Advanced Drug Delivery Reviews

574

418

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“…The HGF‐loaded implants seemed to support neo‐vascularization, particularly during the early phases of inflammation (Figure a,b), which is likely to be attributed to the angiogenic property of HGF (Bussolino et al ., ; Morishita et al ., ). For clinical situations, both neo‐vascularization and recruitment of MSCs resulting in higher amounts of (secreted) VEGF, basic fibroblast growth factor (bFGF) and TGF‐ß3 can result in a reduced scar formation (Li et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor-loaded biomaterials

Kamp

Paefgen

Wöltje

et al. 2016

J Tissue Eng Regen Med

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Mesenchymal stem cells (MSC) are precursor cells of mesodermal tissue and, because of their trophic phenotype, they are known to play beneficial roles in wound healing. In addition, various tissue engineering strategies are based on MSC/biomaterial constructs. As the isolation and expansion of MSCs is a long-term process, a major goal is to develop an endogenous stem cell recruitment system that circumvents all ex vivo steps generally used for tissue engineering. Therefore collagen and silk fibroin were loaded with hepatocyte growth factor (HGF), a chemoattractant for MSCs. Collagen was mixed with HGF during polymerization, while silk fibroin and HGF were produced as fusion proteins by transgenic silkworms. To demonstrate release of active HGF, enzyme-linked immunosorbent assay, in vitro migration assays and animal studies were performed to demonstrate MSC migration in vivo, followed by detailed examinations of the immunological effects of the biomaterials. Hepatocyte growth factor was released burst-like, both from silk fibroin and collagen during the first 8 h and gradually for up to 168 h in vitro. Directed migration in vitro was demonstrated when MSCs were exposed to HGF. In vivo, HGF-loaded collagen and silk fibroin were tolerated as subcutaneous implants. In addition, it was proved that endogenous MSCs were recruited from the local environment. These results show for the first time recruitment of endogenous MSCs to HGF-loaded collagen (fast degradable) and silk fibroin scaffolds (long-term degradable) in vitro and in vivo. This knowledge could be applied to make off-the-shelf, readily available constructs for use in patients with chronic wound or burns. Copyright © 2016 John Wiley & Sons, Ltd.

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“…Li et al demonstrated that seeding of FGF2-producing, bone marrow-derived mesenchymal stem cells into a graphene scaffold and implantation into a dorsal excision wound model resulted in faster healing and a decrease in expression of fibrosis-associated genes encoding α-SMA and TGF-β1, and an increase in expression of the gene encoding the transforming growth factor family member TGF-β3 [88]. TGF-β3 has demonstrated antifibrotic activity in vivo [89], and elevated TGF-β3/TGF-β1 ratios have been associated with scarless healing phenotypes including those of oral mucosa [90] and those induced by tattooing [91].…”

Section: Fgf2 Antagonizes Contractile Phenotypes and Myofibroblast DImentioning

confidence: 99%

Fibroblast Growth Factor 2 as an Antifibrotic: Antagonism of Myofibroblast Differentiation and Suppression of Pro-Fibrotic Gene Expression

Dolivo

Larson

Dominko

2017

Cytokine & Growth Factor Reviews

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Fibrosis is a pathological condition that is characterized by the replacement of dead or damaged tissue with a nonfunctional, mechanically aberrant scar, and fibrotic pathologies account for nearly half of all deaths worldwide. The causes of fibrosis differ somewhat from tissue to tissue and pathology to pathology, but in general some of the cellular and molecular mechanisms remain constant regardless of the specific pathology in question. One of the common mechanisms underlying fibroses is the paradigm of the activated fibroblast, termed the “myofibroblast,” a differentiated mesenchymal cell with demonstrated contractile activity and a high rate of collagen deposition. Fibroblast growth factor 2 (FGF2), one of the members of the mammalian fibroblast growth factor family, is a cytokine with demonstrated antifibrotic activity in non-human animal, human, and in vitro models. FGF2 is highly pleiotropic and its receptors are present on many different cell types throughout the body, lending a great deal of variety to the potential mechanisms of FGF2 effects on fibrosis. However, recent reports demonstrate that a substantial contribution to the antifibrotic effects of FGF2 comes from the inhibitory effects of FGF2 on connective tissue fibroblasts, activated myofibroblasts, and myofibroblast progenitors. FGF2 demonstrates effects antagonistic towards fibroblast activation and towards mesenchymal transition of potential myofibroblast-forming cells, as well as promotes a gene expression paradigm more reminiscent of regenerative healing, such as that which occurs in the fetal wound healing response, than fibrotic resolution. With a better understanding of the mechanisms by which FGF2 alters the wound healing cascade and results in a shift away from scar formation and towards functional tissue regeneration, we may be able to further address the critical need of therapy for varied fibrotic pathologies across myriad tissue types.

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Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring

Cited by 92 publications

References 34 publications

Graphene-based materials for tissue engineering

Graphene-based materials for tissue engineering

Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor-loaded biomaterials

Fibroblast Growth Factor 2 as an Antifibrotic: Antagonism of Myofibroblast Differentiation and Suppression of Pro-Fibrotic Gene Expression

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