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      Integrating zinc/silicon dual ions with 3D-printed GelMA hydrogel promotes in situ hair follicle regeneration

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          Abstract

          The regeneration of hair follicles lost from injury or disease represents a major challenge in cutaneous regenerative medicine. In this study, we investigated the synergetic effects between zinc and silicon ions on dermal cells and screened the optimal concentration of ions for medical applications. We integrated zinc/silicon dual ions into gelatin methacryloyl (GelMA) to bioprint a scaffold and determined that its mechanical properties are suitable for biological treatment. Then, the scaffold was employed to treat mouse excisional model in order to promote in situ hair follicle regeneration. Our findings showed that GelMA-zinc/silicon-printed hydrogel can significantly activate hair follicle stem cells and enhance neovascularization. The beneficial effects of the scaffold were further confirmed by the growth of hairs in the center of wounds and the improvement in perfusion recovery. Taken together, the present study is the first to combine GelMA with zinc/silicon dual ions to bioprint in situ for treating excisional wound, and this approach may regulate hair follicle regeneration not only directly by impacting stem cells but also indirectly through promoting angiogenesis.

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          Most cited references47

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          Wound repair and regeneration.

          The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of fibrotic tissue known as a scar. By contrast, early in gestation, injured fetal tissues can be completely recreated, without fibrosis, in a process resembling regeneration. Some organisms, however, retain the ability to regenerate tissue throughout adult life. Knowledge gained from studying such organisms might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.
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            Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels.

            Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of tissue engineering applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental cell research, cell signaling, drug and gene delivery, and bio-sensing.
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              Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding.

              The mammalian hair follicle is a complex 'mini-organ' thought to form only during development; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits, mice and even humans fifty years ago. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provides a window for manipulation of hair follicle neogenesis by Wnt proteins. These findings suggest treatments for wounds, hair loss and other degenerative skin disorders.
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                Author and article information

                Journal
                Int J Bioprint
                Int J Bioprint
                Whioce Publishing Pte. Ltd.
                International Journal of Bioprinting
                Whioce Publishing Pte. Ltd.
                2424-7723
                2424-8002
                2023
                8 March 2023
                : 9
                : 3
                : 703
                Affiliations
                [1 ]Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital, Beijing, 100853, China
                [2 ]Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China
                [3 ]Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China
                [4 ]State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China
                Author notes
                [* ] Corresponding authors: Sha Huang ( stellarahuang@ 123456sina.com ) Jiang Chang ( jchang@ 123456mail.sic.ac.cn )
                [†]

                These authors contributed equally to this work.

                Article
                IJB-9-3-703
                10.18063/ijb.703
                10236330
                37273992
                2801ff49-3e75-4044-a8e6-f08cec93b45a
                Copyright:© 2023, Zhang F, Zhang Z, Duan X, et al

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 November 2022
                : 13 January 2023
                Categories
                Research Article

                zinc and silicon ions,3d bioprinting,gelma,hair follicle regeneration,angiogenesis

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