Reduced Graphene Oxide Incorporated Acellular Dermal Composite Scaffold Enables Efficient Local Delivery of Mesenchymal Stem Cells for Accelerating Diabetic Wound Healing

Diabetic wound ulcers and unhealed ulcerations have caused in severe difficulties of diabetic patients all around the world. The anti-microbial peptides (AMP) and nanomaterials have been demonstrated beneficial in diabetic wound healing studies. Diabetic wound healing process can be delayed significantly due to the infection issues. Hence in this report, biologically synthesized cerium oxide (CeO2) nanoparticles incorporated with reduced graphene oxide (RGO) and AMP for effective and rapid diabetic wound healing have been reported. At first, reduced graphene oxide was prepared from graphene oxide to prepare CeO2/RGO nanocomposites. Biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites were accordingly prepared to study the diabetic wound healing process. Rats, the wound healing models with the wound size of about 1.5 cm2 were tested with the as-prepared samples. Further, the prepared samples were tested in a wound healing model of rate with the wound of size 1.5 cm2. Almost complete recovery of wounds i.e., 100% closure of wound area was observed after 2 weeks of treatment by the prepared samples. Biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites enhances rapid keratinocytes proliferation by short time thereby it proves the enhanced ability of the prepared samples to act as a wound healing in-vivo drugs. HE and MTC staining protocols to illustrate histological observations elucidates the keratinocytes creation by biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites.

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Bone marrow mesenchymal stem cells preconditioned with nitric oxide releasing chitosan/PVA hydrogel attenuate diabetic wound healing in rabbits

Biomedical Materials ◽

10.1088/1748-605x/abc28b ◽

2020 ◽

Author(s):

Rashid Ahmed ◽

Afshan Afreen ◽

Muhammad Tariq ◽

Alap A Zahid ◽

Muhammad Shareef Masoud ◽

...

Keyword(s):

Nitric Oxide ◽

Stem Cells ◽

Bone Marrow ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Diabetic Wound ◽

Marrow Mesenchymal Stem Cells ◽

Diabetic Wound Healing ◽

Nitric Oxide Releasing ◽

Pva Hydrogel

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Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors

Archives of Dermatological Research ◽

10.1007/s00403-019-02016-6 ◽

2019 ◽

Vol 312 (5) ◽

pp. 325-336 ◽

Cited By ~ 6

Author(s):

Mona Saheli ◽

Mohammad Bayat ◽

Rasoul Ganji ◽

Farzane Hendudari ◽

Raziyeh Kheirjou ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Human Mesenchymal Stem Cells ◽

Diabetic Wound ◽

Diabetic Wound Healing

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Combination product of dermal matrix, human mesenchymal stem cells, and timolol promotes diabetic wound healing in mice

Stem Cells Translational Medicine ◽

10.1002/sctm.19-0380 ◽

2020 ◽

Author(s):

Hsin-ya Yang ◽

Fernando Fierro ◽

Michelle So ◽

Daniel J. Yoon ◽

Alan Vu Nguyen ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Combination Product ◽

Diabetic Wound ◽

Dermal Matrix ◽

Diabetic Wound Healing

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Reduced graphene oxide-coated hydroxyapatite composites stimulate spontaneous osteogenic differentiation of human mesenchymal stem cells

Nanoscale ◽

10.1039/c5nr01580d ◽

2015 ◽

Vol 7 (27) ◽

pp. 11642-11651 ◽

Cited By ~ 79

Author(s):

Jong Ho Lee ◽

Yong Cheol Shin ◽

Oh Seong Jin ◽

Seok Hee Kang ◽

Yu-Shik Hwang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graphene Oxide ◽

Osteogenic Differentiation ◽

Reduced Graphene Oxide ◽

Human Mesenchymal Stem Cells ◽

Reduced Graphene

Reduced graphene oxide-coated hydroxyapatite (rGO-coated HAp) composites stimulated the spontaneous osteogenesis in human mesenchymal stem cells in the absence of osteoinductive agents.

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Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis

Physiological Genomics ◽

10.1152/physiolgenomics.00090.2016 ◽

2017 ◽

Vol 49 (10) ◽

pp. 541-548 ◽

Cited By ~ 13

Author(s):

Junwang Xu ◽

Carlos Zgheib ◽

Maggie M. Hodges ◽

Robert C. Caskey ◽

Junyi Hu ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Protein Content ◽

Collagen I ◽

Extracellular Matrix Protein ◽

Diabetic Wound ◽

Diabetic Wound Healing ◽

Diabetic Wounds

Impaired diabetic wound healing is associated with a dermal extracellular matrix protein profile favoring proteolysis; within the healing diabetic wound, this is represented by an increase in activated matrix metalloproteinase (MMPs). Treatment of diabetic wounds with mesenchymal stem cells (MSCs) has been shown to improve wound healing; however, there has not yet been an assessment of their ability to correct dysregulation of MMPs in diabetic wounds. Furthermore, there has been no prior assessment of the role of microRNA29b (miR-29b), an inhibitory regulatory molecule that targets MMP-9 mRNA. Using in vitro models of fibroblast coculture with MSCs and in vivo murine wound healing models, we tested the hypothesis that MSCs correct dysregulation of MMPs in a microRNA-29b-dependent mechanism. In this study, we first demonstrated that collagen I and III protein content is significantly reduced in diabetic wounds, and treatment with MSCs significantly improves collagen I content in both nondiabetic and diabetic wounds. We then found that MMP-9 gene expression and protein content were significantly upregulated in diabetic wounds, indicating elevated proteolysis. Treatment with MSCs resulted in a decrease in MMP-9 gene expression and protein content level in diabetic wounds 3 and 7 days after wounding. Zymographic analysis indicated that MSC treatment also decreased the amount of activated MMP-9 present in diabetic wounds. Furthermore, miR-29b expression was inversely associated with MMP-9 gene expression; miR-29b expression was decreased in diabetic wounds and diabetic fibroblast. Following treatment of diabetic wounds with MSCs, as well as in diabetic fibroblasts cocultured with MSCs, miR-29b was significantly increased. These findings suggest a potential mechanism through which MSCs enhance diabetic wound healing by improving collagen I content in diabetic wounds through decreasing MMP-9 expression and increasing miR-29b expression.

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Reduced graphene oxide facilitates biocompatibility of alginate for cardiac repair

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911520933913 ◽

2020 ◽

Vol 35 (4-5) ◽

pp. 363-377

Author(s):

Negar Karimi Hajishoreh ◽

Nafiseh Baheiraei ◽

Nasim Naderi ◽

Mojdeh Salehnia

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Tissue Culture ◽

Mesenchymal Stem Cells ◽

Graphene Oxide ◽

Physicochemical Properties ◽

Reduced Graphene Oxide ◽

Cardiac Repair ◽

Reduced Graphene ◽

Tissue Culture Plate

The benefits of combined cell/material therapy appear promising for myocardial infarction treatment. The safety of alginate, along with its excellent biocompatibility and biodegradability, has been extensively investigated for cardiac tissue engineering. Among graphene-based nanomaterials, reduced graphene oxide has been considered as a promising candidate for cardiac treatment due to its unique physicochemical properties. In this study, the reduced graphene oxide incorporation effect within alginate hydrogels was investigated for cardiac repair application. Reduced graphene oxide reinforced alginate properties, resulting in an increase in gel stiffness. The cytocompatibility of the hydrogels prepared with human bone marrow–derived mesenchymal stem cells was assessed by the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay. Following reduced graphene oxide addition, alginate-reduced graphene oxide retained significantly higher cell viability compared to that of alginate and cells cultured on tissue culture plates. Acridine orange/propidium iodide staining was also used to identify both viable and necrotic human bone marrow–derived mesenchymal stem cells within the prepared hydrogels. After a 72-h culture, the percentage of viable cells was twice as much as those cultured on either alginate or tissue culture plate, reaching approximately 80%. Quantitative reverse transcription polymerase chain reaction analysis was performed to assess gene expression of neonatal rat cardiac cells encapsulated on hydrogels for TrpT-2, Conx43, and Actn4 after 7 days. The expression of all genes in alginate-reduced graphene oxide increased significantly compared to that in alginate or tissue culture plate. The results obtained confirmed that the presence of reduced graphene oxide, as an electro-active moiety within alginate, could tune the physicochemical properties of this material, providing a desirable electroactive hydrogel for stem cell therapy in patients with ischemic heart disease.

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