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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

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      Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy

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          Abstract

          Purpose

          By providing a stem cell microenvironment with particular bioactive constituents in vivo, synthetic biomaterials have been progressively successful in stem cell-based tissue regeneration by enhancing the engraftment and survival of transplanted cells. Designs with bioactive motifs to influence cell behavior and with D-form amino acids to modulate scaffold stability may be critical for the development and optimization of self-assembling biomimetic hydrogel scaffolds for stem cell therapy.

          Materials and Methods

          In this study, we linked naphthalene (Nap) covalently to a short D-form peptide (Nap- DF DFG) and the C domain of insulin-like growth factor-1 (IGF-1C) as a functional hydrogel-based scaffolds, and we hypothesized that this hydrogel could enhance the therapeutic efficiency of human placenta-derived mesenchymal stem cells (hP-MSCs) in a murine acute kidney injury (AKI) model.

          Results

          The self-assembling peptide was constrained into a classical β-sheet structure and showed hydrogel properties. Our results revealed that this hydrogel exhibited increased affinity for IGF-1 receptor. Furthermore, cotransplantation of the β-IGF-1C hydrogel and hP-MSCs contributed to endogenous regeneration post-injury and boosted angiogenesis in a murine AKI model, leading to recovery of renal function.

          Conclusion

          This hydrogel could provide a favorable niche for hP-MSCs and thereby rescue renal function in an AKI model by promoting cell survival and angiogenesis. In conclusion, by covalently linking the desired functional groups to D-form peptides to create functional hydrogels, self-assembling β-sheet peptide hydrogels may serve as a promising platform for tissue-engineering and stem cell therapy.

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          Most cited references47

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          Enhanced Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes with an Injectable Hydrogel for Hindlimb Ischemia Treatment

          Zhikun Guo, Deling Kong, Zhibo Han … (2018)
          Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for cell-free treatment of various diseases. However, maintaining the retention and stability of exosomes over time in vivo after transplantation is a major challenge in the clinical application of MSC-derived exosomes. Here, we investigated if human placenta-derived MSC-derived exosomes incorporated with chitosan hydrogel could boost the retention and stability of exosomes and further enhance their therapeutic effects. Our results demonstrated that chitosan hydrogel notably increased the stability of proteins and microRNAs in exosomes, as well as augmented the retention of exosomes in vivo as confirmed by Gaussia luciferase imaging. In addition, we assessed endothelium-protective and proangiogenesis abilities of hydrogel-incorporated exosomes in vitro. Meanwhile, we evaluated the therapeutic function of hydrogel-incorporated exosomes in a murine model of hindlimb ischemia. Our data demonstrated that chitosan hydrogel could enhance the retention and stability of exosomes and further augment the therapeutic effects for hindlimb ischemia as revealed by firefly luciferase imaging of angiogenesis. The strategy used in this study may facilitate the development of easy and effective approaches for assessing and enhancing the therapeutic effects of stem cell-derived exosomes.
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            Dynamic reassembly of peptide RADA16 nanofiber scaffold.

            SHUGUANG ZHANG, T. Kinoshita, Hidenori Yokoi (2005)
            Nanofiber structures of some peptides and proteins as biological materials have been studied extensively, but their molecular mechanism of self-assembly and reassembly still remains unclear. We report here the reassembly of an ionic self-complementary peptide RADARADARADARADA (RADA16-I) that forms a well defined nanofiber scaffold. The 16-residue peptide forms stable beta-sheet structure and undergoes molecular self-assembly into nanofibers and eventually a scaffold hydrogel consisting of >99.5% water. In this study, the nanofiber scaffold was sonicated into smaller fragments. Circular dichroism, atomic force microscopy, and rheology were used to follow the kinetics of the reassembly. These sonicated fragments not only quickly reassemble into nanofibers that were indistinguishable from the original material, but their reassembly also correlated with the rheological analyses showing an increase of scaffold rigidity as a function of nanofiber length. The disassembly and reassembly processes were repeated four times and, each time, the reassembly reached the original length. We proposed a plausible sliding diffusion model to interpret the reassembly involving complementary nanofiber cohesive ends. This reassembly process is important for fabrication of new scaffolds for 3D cell culture, tissue repair, and regenerative medicine.
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              Design and applications of man-made biomimetic fibrillar hydrogels

              Elisabeth Prince, Eugenia Kumacheva (2019)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Nanomedicine
                Journal ID (iso-abbrev): Int J Nanomedicine
                Journal ID (publisher-id): IJN
                Journal ID (pmc): intjnano
                Title: International Journal of Nanomedicine
                Publisher: Dove
                ISSN (Print): 1176-9114
                ISSN (Electronic): 1178-2013
                Publication date (Electronic): 17 June 2020
                Publication date Collection: 2020
                Volume: 15
                Pages: 4311-4324
                Affiliations
                [1 ]Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases , Beijing 100039, People’s Republic of China
                [2 ]State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University , Tianjin 300071, People’s Republic of China
                [3 ]Department of Ophthalmology, Chinese PLA General Hospital , Beijing 100039, People’s Republic of China
                [4 ]Department of Pathophysiology, Nankai University School of Medicine , Tianjin, 300071, People’s Republic of China
                Author notes
                Correspondence: Xiangmei Chen Chinese PLA General Hospital , Beijing100039, People’s Republic of China Email xmchen301@126.com
                Zhimou Yang Nankai University , Tianjin300071, People’s Republic of China Email yangzm@nankai.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-4603-3743
                http://orcid.org/0000-0001-8774-6021
                Article
                Publisher ID: 254635
                DOI: 10.2147/IJN.S254635
                PMC ID: 7306577
                SO-VID: a8094096-f3ff-495e-b654-07f6dafe6663
                Copyright © © 2020 Wang et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 30 March 2020
                Date accepted : 09 June 2020
                Page count
                Figures: 6, References: 50, Pages: 14
                Funding
                Funded by: National Key R&D Program of China
                Funded by: Key Project of the National Natural Science Foundation of China
                Funded by: National Key R&D Program of China
                Funded by: Key Projects of Tianjin Science and Technology Support Program
                This research was partially supported by National Key R&D Program of China (2017YFA0103203), Key Project of the National Natural Science Foundation of China (81830060), National Key R&D Program of China (2018YFA0108803), and Key Projects of Tianjin Science and Technology Support Program (18YFZCSY00010).
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Molecular medicine
                Keywords: self-assembly,β-sheet,hydrogel,d-form peptide,c domain of insulin-like growth factor,igf-1c,mesenchymal stem cells,mscs,acute kidney injure,aki
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: self-assembly, β-sheet, hydrogel, d-form peptide, c domain of insulin-like growth factor, igf-1c, mesenchymal stem cells, mscs, acute kidney injure, aki

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