10th Anniversary of Biomedicines—Advances in Wound Repair and Regeneration

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 17931

Special Issue Editor


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Guest Editor
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
Interests: wound healing; fibrosis; scarring; sclerosis; regeneration; scar free/scarless; inflammation; reprogramming; dedifferentiation; redifferentiation; transdifferentiation; epithelial mesenchymal transition; endothelial mesenchymal transition; transformation; tumorigenesis; cancer; tissue remodeling; pattern formation; functional restoration; differentiated parenchymal cells; differentiated mesenchymal cells; fibroblasts, mesenchymal stem cells; tissue stem cells; myofibroblasts; complex tissues; organs; body parts; in vivo; ex vivo; animal models
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Special Issue Information

Dear Colleagues,

The year 2023 marks the 10th anniversary of Biomedicines, a peer-reviewed open access journal in the biomedical field. So far, Biomedicines has published more than 2700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we aim to publish a Special Issue entitled 10th Anniversary of Biomedicines—Advances in Wound Repair and Regeneration. In humans, when parts of organs are destroyed due to diseases or accidents, it is difficult for them to completely repair or regenerate on their own. Wounds undergo fibrosis as a result of intense inflammatory reactions, eventually settle down, hardening or scarring. However, in many cases the normal physiological function of the organ is impaired and the risk of cancer is increased. This research field is interested in the study of the mechanisms underlying fibrosis in various organs and the research and development of fibrosis control technologies for therapeutic purposes. We are also interested in the study of animal models that can regenerate various organs without fibrosis, as well as the study of mammals, including humans, in order to find novel therapeutic concepts that can help us to avoid fibrosis.

Prof. Dr. Chikafumi Chiba
Guest Editor

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Keywords

  • fibrosis
  • regeneration
  • stem cells
  • reprogramming
  • animal models

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Published Papers (6 papers)

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Research

14 pages, 2698 KiB  
Article
Ischemia Impaired Wound Healing Model in the Rat—Demonstrating Its Ability to Test Proangiogenic Factors
by Anna T. Hofmann, Paul Slezak, Sabine Neumann, James Ferguson, Heinz Redl and Rainer Mittermayr
Biomedicines 2023, 11(4), 1043; https://doi.org/10.3390/biomedicines11041043 - 28 Mar 2023
Cited by 1 | Viewed by 1521
Abstract
Chronic wounds remain a serious clinical problem with insufficient therapeutic approaches. In this study we investigated the dose dependency of rhVEGF165 in fibrin sealant in both ischemic and non-ischemic excision wounds using our recently developed impaired-wound healing model. An abdominal flap was [...] Read more.
Chronic wounds remain a serious clinical problem with insufficient therapeutic approaches. In this study we investigated the dose dependency of rhVEGF165 in fibrin sealant in both ischemic and non-ischemic excision wounds using our recently developed impaired-wound healing model. An abdominal flap was harvested from the rat with unilateral ligation of the epigastric bundle and consequent unilateral flap ischemia. Two excisional wounds were set in the ischemic and non-ischemic area. Wounds were treated with three different rhVEGF165 doses (10, 50 and 100 ng) mixed with fibrin or fibrin alone. Control animals received no therapy. Laser Doppler imaging (LDI) and immunohistochemistry were performed to verify ischemia and angiogenesis. Wound size was monitored with computed planimetric analysis. LDI revealed insufficient tissue perfusion in all groups. Planimetric analysis showed slower wound healing in the ischemic area in all groups. Wound healing was fastest with fibrin treatment—irrespective of tissue vitality. Lower dose VEGF (10 and 50 ng) led to faster wound healing compared to high-dose VEGF. Immunohistochemistry showed the highest vessel numbers in low-dose VEGF groups. In our previously established model, different rhVEGF165 treatments led to dose-dependent differences in angiogenesis and wound healing, but the fastest wound closure was achieved with fibrin matrix alone. Full article
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20 pages, 3803 KiB  
Article
Newtic1 Is a Component of Globular Structures That Accumulate along the Marginal Band of Erythrocytes in the Limb Blastema of Adult Newt, Cynops pyrrhogaster
by Xutong Chen, Ryo Ando, Roman Martin Casco-Robles, Martin Miguel Casco-Robles, Fumiaki Maruo, Shuichi Obata and Chikafumi Chiba
Biomedicines 2022, 10(11), 2772; https://doi.org/10.3390/biomedicines10112772 - 01 Nov 2022
Viewed by 1970
Abstract
In adult newts, when a limb is amputated, a mesenchymal cell mass called the blastema is formed on the stump, where blood vessels filled with premature erythrocytes, named polychromatic normoblasts (PcNobs), elongate. We previously demonstrated that PcNobs in the blastema express an orphan [...] Read more.
In adult newts, when a limb is amputated, a mesenchymal cell mass called the blastema is formed on the stump, where blood vessels filled with premature erythrocytes, named polychromatic normoblasts (PcNobs), elongate. We previously demonstrated that PcNobs in the blastema express an orphan gene, Newtic1, and that they secrete growth factors such as BMP2 and TGFβ1 into the surrounding tissues. However, the relationship between Newtic1 expression and growth factor secretion was not clear since Newtic1 was thought to encode a membrane protein. In this study, we addressed this issue using morphological techniques and found that the Newtic1 protein is a component of globular structures that accumulate at the marginal band in the cytoplasm along the equator of PcNobs. Newtic1-positive (Newtic1(+)) globular structures along the equator were found only in PcNobs with a well-developed marginal band in the blastema. Newtic1(+) globular structures were associated with microtubules and potentially incorporated TGFβ1. Based on these observations, we propose a hypothesis that the Newtic1 protein localizes to the membrane of secretory vesicles that primarily carry TGFβ1 and binds to microtubules, thereby tethering secretory vesicles to microtubules and transporting them to the cell periphery as the marginal band develops. Full article
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14 pages, 3990 KiB  
Article
Role of Wnt Signaling in Mouse Fetal Skin Wound Healing
by Kento Takaya, Ayano Sunohara, Noriko Aramaki-Hattori, Shigeki Sakai, Keisuke Okabe, Hideko Kanazawa, Toru Asou and Kazuo Kishi
Biomedicines 2022, 10(7), 1536; https://doi.org/10.3390/biomedicines10071536 - 28 Jun 2022
Cited by 2 | Viewed by 1488
Abstract
Wnt proteins secrete glycoproteins that are involved in various cellular processes to maintain homeostasis during development and adulthood. However, the expression and role of Wnt in wound healing have not been fully documented. Our previous studies have shown that, in an early-stage mouse [...] Read more.
Wnt proteins secrete glycoproteins that are involved in various cellular processes to maintain homeostasis during development and adulthood. However, the expression and role of Wnt in wound healing have not been fully documented. Our previous studies have shown that, in an early-stage mouse fetus, no scarring occurred after cutaneous wounding, and complete regeneration was achieved. In this study, the expression and localization of Wnt proteins in a mouse fetal-wound-healing model and their associations with scar formation were analyzed. Wnt-related molecules were detected by in-situ hybridization, immunostaining, and real-time polymerase chain reaction. The results showed altered expression of Wnt-related molecules during the wound-healing process. Moreover, scar formation was suppressed by Wnt inhibitors, suggesting that Wnt signaling may be involved in wound healing and scar formation. Thus, regulation of Wnt signaling may be a possible mechanism to control scar formation. Full article
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16 pages, 4715 KiB  
Article
Human Umbilical Mesenchymal Stem Cell Xenografts Repair UV-Induced Photokeratitis in a Rat Model
by Yu-Show Fu, Po-Ru Chen, Chang-Ching Yeh, Jian-Yu Pan, Wen-Chuan Kuo and Kuang-Wen Tseng
Biomedicines 2022, 10(5), 1125; https://doi.org/10.3390/biomedicines10051125 - 12 May 2022
Cited by 4 | Viewed by 1977
Abstract
Most patients with a corneal injury are administered anti-inflammatory medications and antibiotics, but no other treatments are currently available. Thus, the corneal injury healing is unsatisfactory, affects the vision, and has a risk of blindness in severe cases. Human umbilical mesenchymal stem cells [...] Read more.
Most patients with a corneal injury are administered anti-inflammatory medications and antibiotics, but no other treatments are currently available. Thus, the corneal injury healing is unsatisfactory, affects the vision, and has a risk of blindness in severe cases. Human umbilical mesenchymal stem cells exhibit pluripotent and anti-inflammatory properties and do not cause immunological rejection in the host. Rats were irradiated with type B ultraviolet (UVB) light to generate a stable animal model of photokeratitis. After irradiation-induced photokeratitis, human umbilical mesenchymal stem cells were implanted into the subconjunctival space of the lateral sclera, and the changes in the corneal pathology were evaluated. Three weeks after implantation, many mesenchymal stem cells were visible in the subconjunctival space. These mesenchymal stem cells effectively reduced the extent of injury to the adjacent corneal tissue. They accelerated the epithelial layer repair, reduced the inflammatory response and neovascularization, and improved the disorganization of collagen and fibronectin in the corneal stroma caused by the injury. In conclusion, xenografted human umbilical mesenchymal stem cells can survive in rat eye tissues for a long time, effectively support the structural integrity of injured corneal tissues, restore corneal permeability, and reduce abnormal neovascularization. This study provides a new approach to the treatment of photokeratitis. Full article
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17 pages, 4246 KiB  
Article
Dual-Layered Approach of Ovine Collagen-Gelatin/Cellulose Hybrid Biomatrix Containing Graphene Oxide-Silver Nanoparticles for Cutaneous Wound Healing: Fabrication, Physicochemical, Cytotoxicity and Antibacterial Characterisation
by Atiqah Salleh, Norlaila Mustafa, Yeit Haan Teow, Mohd Nor Fatimah, Fauzul Azim Khairudin, Ishak Ahmad and Mh Busra Fauzi
Biomedicines 2022, 10(4), 816; https://doi.org/10.3390/biomedicines10040816 - 31 Mar 2022
Cited by 21 | Viewed by 2896
Abstract
Tissue engineering products have grown rapidly as an alternative solution available for chronic wound and burn treatment. However, some drawbacks include additional procedures and a lack of antibacterial properties that can impair wound healing, which are issues that need to be tackled effectively [...] Read more.
Tissue engineering products have grown rapidly as an alternative solution available for chronic wound and burn treatment. However, some drawbacks include additional procedures and a lack of antibacterial properties that can impair wound healing, which are issues that need to be tackled effectively for better wound recovery. This study aimed to develop a functionalized dual-layered hybrid biomatrix composed of collagen sponge (bottom layer) to facilitate cell proliferation and adhesion and gelatin/cellulose hydrogel (outer layer) incorporated with graphene oxide and silver nanoparticles (GC-GO/AgNP) to prevent possible external infections post-implantation. The bilayer hybrid scaffold was crosslinked with 0.1% (w/v) genipin for 6 h followed by advanced freeze-drying technology. Various characterisation parameters were employed to investigate the microstructure, biodegradability, surface wettability, nanoparticles antibacterial activity, mechanical strength, and biocompatibility of the bilayer bioscaffold towards human skin cells. The bilayer bioscaffold exhibited favourable results for wound healing applications as it demonstrated good water uptake (1702.12 ± 161.11%), slow rate of biodegradation (0.13 ± 0.12 mg/h), and reasonable water vapour transmission rate (800.00 ± 65.85 gm−2 h−1) due to its porosity (84.83 ± 4.48%). The biomatrix was also found to possess hydrophobic properties (48.97 ± 3.68°), ideal for cell attachment and high mechanical strength. Moreover, the hybrid GO-AgNP promoted antibacterial properties via the disk diffusion method. Finally, biomatrix unravelled good cellular compatibility with human dermal fibroblasts (>90%). Therefore, the fabricated bilayer scaffold could be a potential candidate for skin wound healing application. Full article
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33 pages, 14356 KiB  
Article
Skin Wound Healing of the Adult Newt, Cynops pyrrhogaster: A Unique Re-Epithelialization and Scarless Model
by Tatsuyuki Ishii, Ikkei Takashimizu, Martin Miguel Casco-Robles, Yuji Taya, Shunsuke Yuzuriha, Fubito Toyama, Fumiaki Maruo, Kazuo Kishi and Chikafumi Chiba
Biomedicines 2021, 9(12), 1892; https://doi.org/10.3390/biomedicines9121892 - 13 Dec 2021
Cited by 8 | Viewed by 7236
Abstract
In surgical and cosmetic studies, scarless regeneration is an ideal method to heal skin wounds. To study the technologies that enable scarless skin wound healing in medicine, animal models are useful. However, four-limbed vertebrates, including humans, generally lose their competency of scarless regeneration [...] Read more.
In surgical and cosmetic studies, scarless regeneration is an ideal method to heal skin wounds. To study the technologies that enable scarless skin wound healing in medicine, animal models are useful. However, four-limbed vertebrates, including humans, generally lose their competency of scarless regeneration as they transit to their terrestrial life-stages through metamorphosis, hatching or birth. Therefore, animals that serve as a model for postnatal humans must be an exception to this rule, such as the newt. Here, we evaluated the adult newt in detail for the first time. Using a Japanese fire-bellied newt, Cynops pyrrhogaster, we excised the full-thickness skin at various locations on the body, and surveyed their re-epithelialization, granulation or dermal fibrosis, and recovery of texture and appendages as well as color (hue, tone and pattern) for more than two years. We found that the skin of adult newts eventually regenerated exceptionally well through unique processes of re-epithelialization and the absence of fibrotic scar formation, except for the dorsal-lateral to ventral skin whose unique color patterns never recovered. Color pattern is species-specific. Consequently, the adult C. pyrrhogaster provides an ideal model system for studies aimed at perfect skin wound healing and regeneration in postnatal humans. Full article
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