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Saeedi P, Nilchiani LS, Zand B, Hajimirghasemi M, Halabian R. An overview of stem cells and cell products involved in trauma injury. Regen Ther 2025; 29:60-76. [PMID: 40143930 PMCID: PMC11938091 DOI: 10.1016/j.reth.2025.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 02/01/2025] [Accepted: 02/20/2025] [Indexed: 03/28/2025] Open
Abstract
Trauma injuries represent a significant public health burden worldwide, often leading to long-term disability and reduced quality of life. This review provides a comprehensive overview of the therapeutic potential of stem cells and cell products for traumatic injuries. The extraordinary characteristics of stem cells, such as self-renewal and transdifferentiation, make them definitive candidates for tissue regeneration. Mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs) have been tested in preclinical studies for treating distinct traumatic injuries. Stem cell mechanisms of action are addressed through paracrine signaling, immunomodulation, differentiation, and neuroprotection. Cell products such as conditioned media, exosomes, and secretomes offer cell-free resources, thereby avoiding the risks of live cell transplantation. Clinical trials have reported many effective outcomes; however, variability exists across trauma types. Some challenges include tumorigenicity, standardized protocols, and regulatory issues. Collaboration and interdisciplinary research are being conducted to harness stem cells and products for trauma treatment. This emerging field is promising for improving patient recovery and quality of life after traumatic injuries.
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Affiliation(s)
- Pardis Saeedi
- Research Center for Health Management in Mass Gathering, Red Crescent Society of the Islamic Republic of Iran, Tehran, Iran
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Leila Sadat Nilchiani
- Department of Molecular and Cell Biology, Faculty of Advanced Sciences and Technology, Islamic Azad University Tehran Medical Sciences, Tehran, Iran
| | - Bita Zand
- Department of Molecular and Cell Biology, Faculty of Advanced Sciences and Technology, Islamic Azad University Tehran Medical Sciences, Tehran, Iran
| | - Maryam Hajimirghasemi
- Department of Internal Medicine, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Raheleh Halabian
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Chen S, Hou Z, Xiao M, Wu P, Yang Y, Han S, Xia J, Hu J, Zhang K, Yang L. Quaternized chitosan-based photothermal antibacterial hydrogel with pro-vascularization and on-demand degradation properties for enhanced infected wound healing. Carbohydr Polym 2025; 355:123350. [PMID: 40037730 DOI: 10.1016/j.carbpol.2025.123350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 01/22/2025] [Accepted: 02/02/2025] [Indexed: 03/06/2025]
Abstract
Compromised skin barrier fails to prevent pathogenic bacterial invasion, leading to wound infection and potentially severe tissue damage, for which conventional wound dressings provide inadequate therapeutic outcomes. Herein, we have developed a multifunctional injectable hydrogel (QCS-APA/P@D@C) based on quaternized chitosan (QCS) and aldehyde-modified aliphatic polycarbonate (APA), incorporating Prussian Blue (PB) @Polydopamine (PDA) @Cu (P@D@C) submicron particles (SPs). This novel hydrogel exhibits photothermal antibacterial properties, on-demand removal capability, and Cu2+-facilitated wound healing enhancement. The QCS-APA/P@D@C hydrogel, crosslinked via dynamic Schiff-base bonds, exhibits remarkable antibacterial efficacy (>99 %) against various bacteria, including multidrug-resistant (MDR) bacteria, through the synergistic effects of QCS, Cu2+, and 808 nm near-infrared (NIR) photothermal effect. The hydrogel demonstrates rapid degradation (~12 min) upon exposure to N-acetylcysteine (NAC), facilitating on-demand removal and minimizing secondary trauma during dressing changes. Furthermore, the sustained release of Cu2+ within 1-10 μM significantly enhances the migration and tube formation of human umbilical vein endothelial cells (HUVECs). In a Staphylococcus aureus (S. aureus)-infected wound model of Sprague-Dawley (SD) rats, the QCS-APA/P@D@C hydrogel demonstrated effectively modulating wound inflammation, promoting collagen deposition and angiogenesis, and accelerating wound closure. These findings demonstrate that the QCS-APA/P@D@C hydrogel can effectively promote the healing of bacterially infected wounds.
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Affiliation(s)
- Siwen Chen
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang 110819, PR China; Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 11004, PR China
| | - Zhipeng Hou
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 11004, PR China
| | - Miaomiao Xiao
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 11004, PR China
| | - Peng Wu
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, PR China
| | - Yuanyuan Yang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, PR China
| | - Siyu Han
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang 110819, PR China
| | - Jiangli Xia
- School of Pharmaceutical Science, Liaoning University, Shenyang 110036, PR China
| | - Jianshe Hu
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang 110819, PR China.
| | - Kai Zhang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, PR China.
| | - Liqun Yang
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 11004, PR China.
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Khan F, Mondal B, Bairagi B, Mandal S, Mandal D, Nath D. Fabrication of Chitosan/PEO/Rosmarinic acid based nanofibrous mat for diabetic burn wound healing and its anti-bacterial efficacy in mice. Int J Biol Macromol 2025; 301:140416. [PMID: 39884624 DOI: 10.1016/j.ijbiomac.2025.140416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/30/2024] [Accepted: 01/26/2025] [Indexed: 02/01/2025]
Abstract
The pathophysiological relationship between wound healing impairment and diabetes is an intricate process. Burn injury among diabetes patients leads to neurological, vascular, and immunological abnormalities along with impaired activities of cell proliferation, collagen production, growth factors, and cytokine activities with huge bacterial infestation. In our study, we aimed to achieve a burn wound dressing material with the help of electrospun Chitosan/Polyethylene oxide/Rosmarinic acid (CS/PEO/RA) nanofibers. Chitosan is known for its biocompatibility and anti-bacterial properties; however, the electrospinning of CS requires a co-polymer such as PEO, a synthetic biodegradable polymer. With the addition of a low concentration of RA, known for its antibacterial, antioxidative nature, we enhanced the antibacterial efficacy of the electrospun nanofiber. Electrospinning CS/PEO/RA, we were able to develop a non-toxic scaffold with fibers having an average diameter of 127.035 nm, mimicking the extracellular matrix and exhibiting sustained drug release. Excellent antimicrobial activity was observed against the identified bacterial species. It showed increased wound contraction and reduced scar formation in the diabetic mice model along with rapid repair of the damaged epithelial barrier. It enhanced the production of collagen, elastin, and α-smooth muscle actin (α-SMA). Thus, it justifies itself as a diabetic burn wound dressing at low drug concentration.
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Affiliation(s)
- Farhin Khan
- Department of Zoology, University of Kalyani, Kalyani, Nadia, West Bengal 741235, India
| | - Bidya Mondal
- Quantum Materials and Devices Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali 140306, India
| | - Baishakhi Bairagi
- Department of Zoology, University of Kalyani, Kalyani, Nadia, West Bengal 741235, India
| | - Sukanta Mandal
- Department of Zoology, University of Kalyani, Kalyani, Nadia, West Bengal 741235, India
| | - Dipankar Mandal
- Quantum Materials and Devices Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali 140306, India
| | - Debjani Nath
- Department of Zoology, University of Kalyani, Kalyani, Nadia, West Bengal 741235, India.
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Lee KI, Song WS, Han SK, Moon KC, Jeong SH, Dhong ES. Comparison of Tissue-Engineered Dermis with Micronized Adipose Tissue and Artificial Dermis for Facial Reconstruction Following Skin Cancer Resection. Bioengineering (Basel) 2025; 12:145. [PMID: 40001665 PMCID: PMC11851542 DOI: 10.3390/bioengineering12020145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/31/2025] [Accepted: 02/01/2025] [Indexed: 02/27/2025] Open
Abstract
Our group has previously demonstrated that tissue-engineered dermis containing cultured fibroblasts or adipose-derived stromal vascular fraction cells is superior to artificial dermis in terms of scar quality for covering facial defects. However, using these cells for clinical applications requires Food and Drug Administration approval and involves complex procedures for cell culture or isolation. This retrospective study aimed to compare effects of tissue-engineered dermis containing micronized adipose tissue (MAT) and artificial dermis for facial reconstruction. Tissue-engineered dermis consisting of MAT seeded on artificial dermis was applied in 30 cases, while artificial dermis without MAT was grafted in 35 cases. Healing time and severities of scar contraction, color mismatch, and landmark distortion at one year after healing were evaluated. Wounds in the tissue-engineered dermis group re-epithelialized in 30.0 ± 4.3 days compared to 34.3 ± 5.4 days in the artificial dermis group (p < 0.05). The average dE2000 score in color mismatch analysis was 4.9 ± 1.7 in the tissue-engineered dermis group and 5.1 ± 1.7 in the artificial dermis group (p = 0.57). The extent of scar contraction was 16.2 ± 12.3% in the tissue-engineered dermis group and 23.2 ± 12.8% in the artificial dermis group (p < 0.05). The average severity grade of landmark distortion was 0.20 ± 0.50 in the tissue-engineered dermis group and 0.50 ± 0.71 in the artificial dermis group (p < 0.05). These findings indicate that tissue-engineered dermis grafts containing MAT are superior to artificial dermis grafts for facial reconstruction in terms of healing time, scar contraction, and landmark distortion severity. However, there was no significant difference in color mismatch between the two groups.
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Affiliation(s)
- Kyu-Il Lee
- Department of Plastic Surgery, Taean Public Health Office, Taean-gun 32148, Republic of Korea
| | - Won-Seok Song
- Department of Plastic Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Seung-Kyu Han
- Department of Plastic Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Department of Plastic Surgery, Korea University Guro Hospital, 148 Gurodong-Gil, Guro-Ku, Seoul 08308, Republic of Korea
| | - Kyung-Chul Moon
- Department of Plastic Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Seong-Ho Jeong
- Department of Plastic Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Eun-Sang Dhong
- Department of Plastic Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
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Luo Y, Guo Q, Liu C, Zheng Y, Wang Y, Wang B. Adipose mesenchymal stem cell-derived extracellular vesicles regulate PINK1/parkin-mediated mitophagy to repair high glucose-induced dermal fibroblast senescence and promote wound healing in rats with diabetic foot ulcer. Acta Diabetol 2024:10.1007/s00592-024-02422-x. [PMID: 39680129 DOI: 10.1007/s00592-024-02422-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 11/18/2024] [Indexed: 12/17/2024]
Abstract
AIMS Diabetic foot ulcers (DFUs) cause prominent morbidity and mortality. Adipose mesenchymal stem cell (ASC)-derived extracellular vesicles (EVs) show property in facilitating diabetic wound healing, and we explored their role in DFU rats. METHODS ASCs were cultured in vitro, passaged and then identified by flow cytometry and induction of osteogenic/adipogenic differentiation. ASC-EVs were extracted and identified. DFU rat model was treated with ASC-EVs. High glucose (HG)-induced rat dermal fibroblasts were treated with ASC-EVs or 3-MA and sh-PINK1 plasmid in vitro. Wound healing was observed. Histological changes, inflammatory cytokines (TNF-α, IL-1β), and α-SMA and p21 double-positive cell level were assessed by HE staining, ELISA, and immunofluorescence. Mitochondrial membrane potential (MMP), cell viability and senescence, and ROS production in cells were assessed by fluorescence dye JC-1, CCK-8, SA-β-gal staining, and ROS kit. p21, LC3II/I, p62, PINK1 and parkin protein levels were determined by Western blot. RESULTS DFU rats had slow wound healing and elevated levels of IL-1β, TNF-α, α-SMA and p21 double-positive cells, and SA-β-gal, while HG-induced cells had weakened viability, elevated ROS, SA-β-gal, p21 and p62 protein levels, and decreased LC3II/I, PINK1 and parkin protein levels and MMP, which were reversed by ASC-EVs. HG inhibited mitophagy by suppressing the PINK1/parkin pathway to accelerate dermal fibroblast senescence. The PINK1/parkin pathway inhibition partly mitigated the effect of ASC-EVs. ASC-EVs promoted mitophagy by activating the PINK1/parkin pathway in vivo. CONCLUSIONS ASC-EVs mediated mitophagy by activating the PINK1/parkin pathway, thereby impeding HG-induced rat dermal fibroblast senescence and promoting wound healing in DFU rats.
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Affiliation(s)
- Yinji Luo
- Department of Bone Surgery, The Second Affiliated Hospital, Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, 510145, Guangdong Province, China
| | - Qijie Guo
- Department of Bone Surgery, The Second Affiliated Hospital, Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, 510145, Guangdong Province, China
| | - Chang Liu
- Department of Bone Surgery, The Second Affiliated Hospital, Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, 510145, Guangdong Province, China
| | - Yuxuan Zheng
- Department of Bone Surgery, The Second Affiliated Hospital, Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, 510145, Guangdong Province, China
| | - Yichong Wang
- Department of Bone Surgery, The Second Affiliated Hospital, Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, 510145, Guangdong Province, China
| | - Bin Wang
- Department of Bone Surgery, The Second Affiliated Hospital, Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, 510145, Guangdong Province, China.
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Chen S, Li Y, Ren S, Yang Y, Hou Z, Han S, Zhang W, Guo J, Hu J, Zhang X, Yang L. Amorphous zinc phosphate nanoclusters loaded polycarbonate thermosensitive hydrogel: An innovative strategy for promoting wound healing. Mater Today Bio 2024; 29:101266. [PMID: 39381263 PMCID: PMC11460505 DOI: 10.1016/j.mtbio.2024.101266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 08/10/2024] [Accepted: 09/22/2024] [Indexed: 10/10/2024] Open
Abstract
Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.
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Affiliation(s)
- Siwen Chen
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang, 110819, PR China
- Research Center for Biomedical Materials, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, 110004, PR China
| | - Yutong Li
- Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, PR China
| | - Sihang Ren
- Department of Plastic Surgery, The Second Hospital of Dalian Medical University, Dalian, 116027, PR China
| | - Yuanyuan Yang
- Research Center for Biomedical Materials, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, 110004, PR China
| | - Zhipeng Hou
- Research Center for Biomedical Materials, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, 110004, PR China
| | - Siyu Han
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang, 110819, PR China
| | - Wanhong Zhang
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang, 110819, PR China
| | - Jing Guo
- Liaoning Research Institute for Eugenic Birth & Fertility, China Medical University, Shenyang, 110031, PR China
| | - Jianshe Hu
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang, 110819, PR China
| | - Xing Zhang
- Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, PR China
| | - Liqun Yang
- Research Center for Biomedical Materials, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, 110004, PR China
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Yang Y, Ma S, Li A, Xia G, Li M, Ding C, Sun X, Yan L, Yang M, Zhao T. Antibacterial and antioxidant phlorizin-loaded nanofiber film effectively promotes the healing of burn wounds. Front Bioeng Biotechnol 2024; 12:1428988. [PMID: 39161349 PMCID: PMC11330827 DOI: 10.3389/fbioe.2024.1428988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 07/19/2024] [Indexed: 08/21/2024] Open
Abstract
Burns usually result in damage and loss of skin forming irregular wound wounds. The lack of skin tissue protection makes the wound site highly vulnerable to bacterial infections, hindering the healing process. However, commonly used wound dressings do not readily provide complete coverage of irregular wounds compared to regular wounds. Therefore, there is an urgent need to prepare a wound dressing with high antimicrobial efficacy for the administration of drugs to irregular wounds. In this study, a chitosan (CS)/polyvinylpyrrolidone (PVP) composite nanofiber membrane (CS/PVP/Phlorizin) loaded with root bark glycosides (Phlorizin) was developed using an electrostatic spinning technique. The incorporation of phlorizin, a natural antioxidant, into the fiber membranes notably boosted their antimicrobial and antioxidant capabilities, along with demonstrating excellent hydrophilic characteristics. In vitro cellular experiments showed that CS/PVP/Phlorizin increased Hacat cell viability with the presence of better cytocompatibility. In scald wound healing experiments, Phlorizin-loaded nanofibrous membranes significantly promoted re-epithelialization and angiogenesis at the wound site, and reduced the inflammatory response at the wound site. Therefore, the above results indicate that this nanofiber membrane is expected to be an ideal dressing for burn wounds.
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Affiliation(s)
- Ying Yang
- College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology University, Jilin, China
| | - Shuang Ma
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun, China
| | - Anning Li
- Jilin Aodong Yanbian Pharmaceutical Co, Ltd., Dunhua, China
| | - Guofeng Xia
- Jilin Aodong Yanbian Pharmaceutical Co, Ltd., Dunhua, China
| | - Min Li
- College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology University, Jilin, China
| | - Chuanbo Ding
- College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology University, Jilin, China
- Jilin Aodong Yanbian Pharmaceutical Co, Ltd., Dunhua, China
| | - Xiaofei Sun
- Jilin Aodong Yanbian Pharmaceutical Co, Ltd., Dunhua, China
| | - Li Yan
- Jilin Aodong Yanbian Pharmaceutical Co, Ltd., Dunhua, China
| | - Min Yang
- College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology University, Jilin, China
- Jilin Aodong Yanbian Pharmaceutical Co, Ltd., Dunhua, China
| | - Ting Zhao
- College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology University, Jilin, China
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Rakkan T, Zhang S, Lehner S, Hufenus R, Sangkharak K, Ren Q. Bio-based modification of polyhydroxyalkanoates (PHA) towards increased antimicrobial activities and reduced cytotoxicity. Int J Biol Macromol 2024; 275:133132. [PMID: 38945725 DOI: 10.1016/j.ijbiomac.2024.133132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 06/10/2024] [Accepted: 06/11/2024] [Indexed: 07/02/2024]
Abstract
With the increased occurrence of bacteria resistance to conventional antibiotics, the development of novel antimicrobials is urgently needed. Traditional biomaterials used for delivering these agents often struggle to achieve sustained release while maintaining non-cytotoxic properties. In this study, we present an innovative approach using bacterial polyhydroxyalkanoates (PHA) as a carrier for antimicrobial delivery, specifically designed for wound healing applications. Octenidine dihydrochloride (OCT), a widely used antimicrobial agent, served as our model drug. To achieve the desired balance of OCT release and low cytotoxicity, we introduced a novel bio-derived additive, 3-hydroxy-pentadecanoic acid (3OHC15), extracted from bacteria. This additive significantly improved the hydrophilicity of PHA films, resulting in enhanced and sustained release of OCT. Importantly, the additive did not adversely affect the material's tensile strength or thermal properties. The increased OCT release led to improved antibacterial activity against both Gram-negative and -positive strains. Most notably, the incorporation of 3OHC15 in PHA mitigated the cytotoxic effects of the released drug on human fibroblasts, ensuring biocompatibility. This work represents a novel strategy in the design of biomaterials for the delivery of bioactive compounds, achieving a critical balance between efficacy and cytocompatibility, and marks a significant advancement in the field of antimicrobial delivery systems.
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Affiliation(s)
- Thanaphorn Rakkan
- Department of Biology, Faculty of Science, Thaksin University, Phatthalung, Thailand; Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, 9014 St. Gallen, Switzerland; Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Sixuan Zhang
- Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, 9014 St. Gallen, Switzerland.
| | - Sandro Lehner
- Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, 9014 St. Gallen, Switzerland.
| | - Rudolf Hufenus
- Laboratory for Advanced Fibers, Empa, Swiss Federal Laboratories for Materials Science and Technology, 9014 St. Gallen, Switzerland.
| | - Kanokphorn Sangkharak
- Department of Chemistry, Faculty of Science, Thaksin University, Phatthalung, Thailand.
| | - Qun Ren
- Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, 9014 St. Gallen, Switzerland.
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9
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Barbosa JL, de Melo MIA, da Silva Cunha P, de Miranda MC, Barrioni BR, Moreira CDF, da Fonseca Ferreira A, Arantes RME, de Sá MA, de Magalhães Pereira M, Rodrigues MA, Novikoff S, Gomes DA, de Goes AM. Development of a membrane and a bilayer of chitosan, gelatin, and polyhydroxybutyrate to be used as wound dressing for the regeneration of rat excisional wounds. J Biomed Mater Res A 2024; 112:82-98. [PMID: 37795871 DOI: 10.1002/jbm.a.37616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 08/09/2023] [Accepted: 09/07/2023] [Indexed: 10/06/2023]
Abstract
The skin is the largest organ in the human body that acts as a protective barrier from the outside environment. Certain dermatological pathologies or significant skin lesions can result in serious complications. Several studies have focused on the development of tissue-engineered skin substitutes. In this study, a new bilayer scaffold composed of a chitosan-gelatin membrane and a chitosan-polyhydroxybutyrate (PHB) porous matrix was synthesized and populated with human adipose-derived mesenchymal stem cells (hASCs) to be potentially used for wound dressing applications. By combining this membrane and porous matrix with the stem cells, we aimed to provide immunomodulation and differentiation capabilities for the wound environment, as well as mechanical strength and biocompatibility for the underlying tissue. The membrane was prepared from the mixture of chitosan and gelatin in a 2:1 ratio and the porous matrix was prepared from the mixture of chitosan and PHB, in equal proportions to form a final solution at 2.5% (m/v). Fourier transform infrared spectroscopy analysis showed the formation of blends, and micro-computed tomography, scanning electron microscopy and atomic force microscopy images demonstrated membrane roughness and matrix porosity. The MTT assay showed that the scaffolds were biocompatible with hASC. The membrane and the bilayer were used as dressing and support for cell migration in the dorsal excisional wound model in Wistar rats. Histological and gene transcriptional analyses showed that the animals that received the scaffolds regenerated the hair follicles in the deep dermis in the central region of the wound. Our results demonstrate the potential of these new biomaterials as dressings in wound healing studies, favoring tissue regeneration.
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Affiliation(s)
- Joana Lobato Barbosa
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Mariane Izabella Abreu de Melo
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Serviço de Radiofármacos, Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, Brazil
| | - Pricila da Silva Cunha
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais, Muriaé, Brazil
| | - Marcelo Coutinho de Miranda
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | | | | | - Rosa Maria Esteves Arantes
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Marcos Augusto de Sá
- Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Michele Angela Rodrigues
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Serviço de Radiofármacos, Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, Brazil
| | - Silviene Novikoff
- Transplants Immunobiology Laboratory, Department of Immunology, University of São Paulo, São Paulo, Brazil
| | - Dawidson Assis Gomes
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Alfredo Miranda de Goes
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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10
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Dehnavi S, Sadeghi M, Tavakol Afshari J, Mohammadi M. Interactions of mesenchymal stromal/stem cells and immune cells following MSC-based therapeutic approaches in rheumatoid arthritis. Cell Immunol 2023; 393-394:104771. [PMID: 37783061 DOI: 10.1016/j.cellimm.2023.104771] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/21/2023] [Accepted: 09/21/2023] [Indexed: 10/04/2023]
Abstract
Rheumatoid arthritis (RA) is considered to be a degenerative and progressive autoimmune disorder. Although several medicinal regimens are used to treat RA, potential adverse events such as metabolic disorders and increased risk of infection, as well as drug resistance in some patients, make it essential to find an effective and safe therapeutic approach. Mesenchymal stromal/stem cells (MSCs) are a group of non-hematopoietic stromal cells with immunomodulatory and inhibitory potential. These cells exert their regulatory properties through direct cell-to-cell interactions and paracrine effects on various immune and non-immune cells. As conventional therapeutic approaches for RA are limited due to their side effects, and some patients became refractory to the treatment, MSCs are considered as a promising alternative treatment for RA. In this review, we introduced various experimental and clinical studies conducted to evaluate the therapeutic effects of MSCs on animal models of arthritis and RA patients. Then, possible modulatory and suppressive effects of MSCs on different innate and adaptive immune cells, including dendritic cells, neutrophils, macrophages, natural killer cells, B lymphocytes, and various subtypes of T cells, were categorized and summarized. Finally, limitations and future considerations for the efficient application of MSCs as a therapeutic approach in RA patients were presented.
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Affiliation(s)
- Sajad Dehnavi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahvash Sadeghi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Mojgan Mohammadi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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11
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Malekzadeh H, Tirmizi Z, Arellano JA, Egro FM, Ejaz A. Application of Adipose-Tissue Derived Products for Burn Wound Healing. Pharmaceuticals (Basel) 2023; 16:1302. [PMID: 37765109 PMCID: PMC10534650 DOI: 10.3390/ph16091302] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/05/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Burn injuries are a significant global health concern, leading to high morbidity and mortality. Deep burn injuries often result in delayed healing and scar formation, necessitating effective treatment options. Regenerative medicine, particularly cell therapy using adipose-derived stem cells (ASCs), has emerged as a promising approach to improving burn wound healing and reducing scarring. Both in vitro and preclinical studies have demonstrated the efficacy of ASCs and the stromal vascular fraction (SVF) in addressing burn wounds. The application of ASCs for burn healing has been studied in various forms, including autologous or allogeneic cells delivered in suspension or within scaffolds in animal burn models. Additionally, ASC-derived non-cellular components, such as conditioned media or exosomes have shown promise. Injection of ASCs and SVF at burn sites have been demonstrated to enhance wound healing by reducing inflammation and promoting angiogenesis, epithelialization, and granulation tissue formation through their paracrine secretome. This review discusses the applications of adipose tissue derivatives in burn injury treatment, encompassing ASC transplantation, as well as the utilization of non-cellular components utilization for therapeutic benefits. The application of ASCs in burn healing in the future will require addressing donor variability, safety, and efficacy for successful clinical application.
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Affiliation(s)
| | | | | | | | - Asim Ejaz
- Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA
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12
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Liu YX, Sun JM, Ho CK, Gao Y, Wen DS, Liu YD, Huang L, Zhang YF. Advancements in adipose-derived stem cell therapy for skin fibrosis. World J Stem Cells 2023; 15:342-353. [PMID: 37342214 PMCID: PMC10277960 DOI: 10.4252/wjsc.v15.i5.342] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/30/2023] [Accepted: 04/13/2023] [Indexed: 05/26/2023] Open
Abstract
Pathological scarring and scleroderma, which are the most common conditions of skin fibrosis, pathologically manifest as fibroblast proliferation and extracellular matrix (ECM) hyperplasia. Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling, causing an exaggerated and prolonged wound-healing response. The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects. Currently, a promising and relatively low-cost treatment has emerged-adipose-derived stem cell (ASC) therapy as a branch of stem cell therapy, including ASCs and their derivatives-purified ASC, stromal vascular fraction, ASC-conditioned medium, ASC exosomes, etc., which are rich in sources and easy to obtain. ASCs have been widely used in therapeutic settings for patients, primarily for the defection of soft tissues, such as breast enhancement and facial contouring. In the field of skin regeneration, ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis. The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review, as well as their new applications in the treatment of skin fibrosis. Although the long-term effect of ASC therapy is still unclear, ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.
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Affiliation(s)
- Yu-Xin Liu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Jia-Ming Sun
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Chia-Kang Ho
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Ya Gao
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Dong-Sheng Wen
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Yang-Dan Liu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Lu Huang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Yi-Fan Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
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13
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Rybak D, Su YC, Li Y, Ding B, Lv X, Li Z, Yeh YC, Nakielski P, Rinoldi C, Pierini F, Dodda JM. Evolution of nanostructured skin patches towards multifunctional wearable platforms for biomedical applications. NANOSCALE 2023; 15:8044-8083. [PMID: 37070933 DOI: 10.1039/d3nr00807j] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
Recent advances in the field of skin patches have promoted the development of wearable and implantable bioelectronics for long-term, continuous healthcare management and targeted therapy. However, the design of electronic skin (e-skin) patches with stretchable components is still challenging and requires an in-depth understanding of the skin-attachable substrate layer, functional biomaterials and advanced self-powered electronics. In this comprehensive review, we present the evolution of skin patches from functional nanostructured materials to multi-functional and stimuli-responsive patches towards flexible substrates and emerging biomaterials for e-skin patches, including the material selection, structure design and promising applications. Stretchable sensors and self-powered e-skin patches are also discussed, ranging from electrical stimulation for clinical procedures to continuous health monitoring and integrated systems for comprehensive healthcare management. Moreover, an integrated energy harvester with bioelectronics enables the fabrication of self-powered electronic skin patches, which can effectively solve the energy supply and overcome the drawbacks induced by bulky battery-driven devices. However, to realize the full potential offered by these advancements, several challenges must be addressed for next-generation e-skin patches. Finally, future opportunities and positive outlooks are presented on the future directions of bioelectronics. It is believed that innovative material design, structure engineering, and in-depth study of fundamental principles can foster the rapid evolution of electronic skin patches, and eventually enable self-powered close-looped bioelectronic systems to benefit mankind.
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Affiliation(s)
- Daniel Rybak
- Institute of Fundamental Technological Research, Polish Academy of Science, 02-106 Warsaw, Poland.
| | - Yu-Chia Su
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan
| | - Yang Li
- College of Electronic and Optical Engineering & College of Microelectronics, Institute of Flexible Electronics (Future Technology), Nanjing University of Posts & Telecommunications (NJUPT), Nanjing, 210023, China
| | - Bin Ding
- Innovation Center for Textile Science and Technology, Donghua University, Shanghai 200051, China.
| | - Xiaoshuang Lv
- Shanghai Frontier Science Research Center for Modern Textiles, College of Textiles, Donghua University, Shanghai 201620, China
| | - Zhaoling Li
- Shanghai Frontier Science Research Center for Modern Textiles, College of Textiles, Donghua University, Shanghai 201620, China
| | - Yi-Cheun Yeh
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan
| | - Pawel Nakielski
- Institute of Fundamental Technological Research, Polish Academy of Science, 02-106 Warsaw, Poland.
| | - Chiara Rinoldi
- Institute of Fundamental Technological Research, Polish Academy of Science, 02-106 Warsaw, Poland.
| | - Filippo Pierini
- Institute of Fundamental Technological Research, Polish Academy of Science, 02-106 Warsaw, Poland.
| | - Jagan Mohan Dodda
- New Technologies - Research Centre (NTC), University of West Bohemia, Univerzitní 8, 301 00 Pilsen, Czech Republic.
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14
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Hoseinzadeh A, Rezaieyazdi Z, Afshari JT, Mahmoudi A, Heydari S, Moradi R, Esmaeili SA, Mahmoudi M. Modulation of Mesenchymal Stem Cells-Mediated Adaptive Immune Effectors' Repertoire in the Recovery of Systemic Lupus Erythematosus. Stem Cell Rev Rep 2023; 19:322-344. [PMID: 36272020 DOI: 10.1007/s12015-022-10452-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2022] [Indexed: 02/07/2023]
Abstract
The breakdown of self-tolerance of the immune response can lead to autoimmune conditions in which chronic inflammation induces tissue damage. Systemic lupus erythematosus (SLE) is a debilitating multisystemic autoimmune disorder with a high prevalence in women of childbearing age; however, SLE incidence, prevalence, and severity are strongly influenced by ethnicity. Although the mystery of autoimmune diseases remains unsolved, disturbance in the proportion and function of B cell subsets has a major role in SLE's pathogenesis. Additionally, colocalizing hyperactive T helper cell subgroups within inflammatory niches are indispensable. Despite significant advances in standard treatments, nonspecific immunosuppression, the risk of serious infections, and resistance to conventional therapies in some cases have raised the urgent need for new treatment strategies. Without the need to suppress the immune system, mesenchymal stem cells (MSCs), as ''smart" immune modulators, are able to control cellular and humoral auto-aggression responses by participating in precursor cell development. In lupus, due to autologous MSCs disorder, the ability of allogenic engrafted MSCs in tissue regeneration and resetting immune homeostasis with the provision of a new immunocyte repertoire has been considered simultaneously. In Brief The bone marrow mesenchymal stem cells (BM-MSCs) lineage plays a critical role in maintaining the hematopoietic stem-cell microstructure and modulating immunocytes. The impairment of BM-MSCs and their niche partially contribute to the pathogenesis of SLE-like diseases. Allogenic MSC transplantation can reconstruct BM microstructure, possibly contributing to the recovery of immunocyte phenotype restoration of immune homeostasis. In terms of future prospects of MSCs, artificially gained by ex vivo isolation and culture adaptation, the wide variety of potential mediators and mechanisms might be linked to the promotion of the immunomodulatory function of MSCs.
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Affiliation(s)
- Akram Hoseinzadeh
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Rezaieyazdi
- Department of Rheumatology, Ghaem Hospital, Mashhad University of Medical Science, Mashhad, Iran.,Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jalil Tavakol Afshari
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Mahmoudi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Heydari
- Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Reza Moradi
- Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed-Alireza Esmaeili
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Mahmoudi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. .,Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. .,Department of Immunology, Mashhad University of Medical Sciences, Azadi Square, Kalantari Blvd, Pardi's campusMashhad, Iran.
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15
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Saffari TM, Saffari S, Vyas KS, Mardini S, Shin AY. Role of adipose tissue grafting and adipose-derived stem cells in peripheral nerve surgery. Neural Regen Res 2022; 17:2179-2184. [PMID: 35259826 PMCID: PMC9083182 DOI: 10.4103/1673-5374.336870] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form. This review aims to provide an overview of the scientific evidence on the biology of adipose tissue, the role of adipose-derived stem cells, and the indications of adipose tissue grafting in peripheral nerve surgery. Adipose tissue is easily accessible through the lower abdomen and inner thighs. Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress, resulting in variable survival of adipocytes within the first 24 hours. Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts. Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization, and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue. In clinical studies, the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results. Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new, more studies are needed to explore safety and long-term effects on peripheral nerve regeneration. The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated, enzyme-free, and used in the same surgical procedure, e.g. adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction. Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival. Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.
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Affiliation(s)
- Tiam M Saffari
- Department of Orthopedic Surgery, Division of Microvascular and Hand Surgery, Mayo Clinic, Rochester, MN, USA; Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Plastic Surgery, Nijmegen, The Netherlands
| | - Sara Saffari
- Department of Orthopedic Surgery, Division of Microvascular and Hand Surgery, Mayo Clinic, Rochester, MN, USA; Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Plastic Surgery, Nijmegen, The Netherlands
| | - Krishna S Vyas
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Mayo Clinic, Rochester, MN, USA
| | - Samir Mardini
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Mayo Clinic, Rochester, MN, USA
| | - Alexander Y Shin
- Department of Orthopedic Surgery, Division of Microvascular and Hand Surgery, Mayo Clinic, Rochester, MN, USA
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16
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Patel PR, Singam A, Iyer AK, Gundloori RVN. Bioinspired hyaluronic acid based nanofibers immobilized with 3, 4- difluorobenzylidene curcumin for treating bacterial infections. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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17
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Mechanomodulatory Biomaterials Prospects in Scar Prevention and Treatment. Acta Biomater 2022; 150:22-33. [DOI: 10.1016/j.actbio.2022.07.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 06/25/2022] [Accepted: 07/25/2022] [Indexed: 11/18/2022]
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18
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Mendes AI, Rebelo R, Aroso I, Correlo VM, Fraga AG, Pedrosa J, Marques AP. Development of an antibiotics delivery system for topical treatment of the neglected tropical disease Buruli ulcer. Int J Pharm 2022; 623:121954. [PMID: 35760261 DOI: 10.1016/j.ijpharm.2022.121954] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/31/2022] [Accepted: 06/21/2022] [Indexed: 01/10/2023]
Abstract
Skin infection by Mycobacterium ulcerans causes Buruli ulcer (BU) disease, a serious condition that significantly impact patient' health and quality of life and can be very difficult to treat. Treatment of BU is based on daily systemic administration of antibiotics for at least 8 weeks and presents drawbacks associated with the mode and duration of drug administration and potential side effects. Thus, new therapeutic strategies are needed to improve the efficacy and modality of BU therapeutics, resulting in a more convenient and safer antibiotic regimen. Hence, we developed a dual delivery system based on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles and a gellan gum (GG) hydrogel for delivery of rifampicin (RIF) and streptomycin (STR), two antibiotics used for BU treatment. RIF was successfully loaded into PHBV microparticles, with an encapsulation efficiency of 43%, that also revealed a mean size of 10 µm, spherical form and rough topography. These microparticles were further embedded in a GG hydrogel containing STR. The resultant hydrogel showed a porous microstructure that conferred a high water retention capability (superior to 2000%) and a controlled release of both antibiotics. Also, biological studies revealed antibacterial activity against M. ulcerans, and a good cytocompatibility in a fibroblast cell line. Thus, the proposed drug delivery system can constitute a potential topical approach for treatment of skin ulcers caused by BU disease.
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Affiliation(s)
- Ana I Mendes
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rita Rebelo
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
| | - Ivo Aroso
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
| | - Vitor M Correlo
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
| | - Alexandra G Fraga
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Jorge Pedrosa
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Alexandra P Marques
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.
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de Prado EML, de Paula GA, Dutra JAP, Cipriano DF, Kitagawa RR, Siman FDM, Meira EF, de Freitas JCC, Severi JA, Carreira LG, Oréfice RL, Villanova JCO. Crude dry extract from Colocasia esculenta in association with poly(vinyl alcohol) as biomaterial to prepare bioactive wound dressing. Polym Bull (Berl) 2022. [DOI: 10.1007/s00289-022-04263-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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20
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van der Sluis N, Scheers EC, Krenning G, van der Lei B, Oonk MH, van Dongen JA. Autologous lipoaspirate as a new treatment of vulvar lichen sclerosus: A review on literature. Exp Dermatol 2022; 31:689-699. [PMID: 35276020 PMCID: PMC9314062 DOI: 10.1111/exd.14561] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/03/2022] [Accepted: 03/05/2022] [Indexed: 11/29/2022]
Abstract
Lichen sclerosus (LS) is a chronic inflammatory dermatosis that mostly affects the genital and anal skin areas. Symptoms may vary from pruritis and pain to sexual dysfunction; however, LS can also be asymptomatic. LS occurs at all ages and in both sexes. Approximately 5% of all women affected by vulvar LS will develop vulvar squamous cell carcinoma. Topical treatment is safe but less effective resulting in chronic course in most patients, who suffer from persistent itching and pain. In severe cases of therapy-resistant LS, there is no adequate treatment. Fat grafting is a novel regenerative therapy to reduce dermal fibrosis. The therapeutic effect of adipose tissue grafts for LS is already investigated in various pioneering studies. This review provides an overview of these studies and the putative mechanisms-of-action of fat grafting to treat LS.
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Affiliation(s)
- Nanouk van der Sluis
- Department of Plastic SurgeryUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
- Department of Plastic‐, Reconstructive‐ and Hand SurgeryMedisch Spectrum TwenteEnschedeThe Netherlands
| | - Esther C.A.H. Scheers
- Department of Obstetrics and GynecologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Guido Krenning
- Department of Pathology and Medical BiologyUniversity of Groningen and University Medical Center GroningenGroningenThe Netherlands
| | - Berend van der Lei
- Department of Plastic SurgeryUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Maaike H.M. Oonk
- Department of Obstetrics and GynecologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Joris A. van Dongen
- Department of Plastic‐, Reconstructive‐ and Hand Surgery, Utrecht University Medical CenterUtrecht UniversityUtrechtThe Netherlands
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22
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Vanderstichele S, Vranckx JJ. Anti-fibrotic effect of adipose-derived stem cells on fibrotic scars. World J Stem Cells 2022; 14:200-213. [PMID: 35432731 PMCID: PMC8963379 DOI: 10.4252/wjsc.v14.i2.200] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/01/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Sustained injury, through radiotherapy, burns or surgical trauma, can result in fibrosis, displaying an excessive deposition of extracellular matrix (ECM), persisting inflammatory reaction, and reduced vascularization. The increasing recognition of fibrosis as a cause for disease and mortality, and increasing use of radiotherapy causing fibrosis, stresses the importance of a decent anti-fibrotic treatment.
AIM To obtain an in-depth understanding of the complex mechanisms underlying fibrosis, and more specifically, the potential mechanisms-of-action of adipose-derived stomal cells (ADSCs) in realizing their anti-fibrotic effect.
METHODS A systematic review of the literature using PubMed, Embase and Web of Science was performed by two independent reviewers.
RESULTS The injection of fat grafts into fibrotic tissue, releases ADSC into the environment. ADSCs’ capacity to directly differentiate into key cell types (e.g., ECs, fibroblasts), as well as to secrete multiple paracrine factors (e.g., hepatocyte growth factor, basis fibroblast growth factor, IL-10), allows them to alter different mechanisms underlying fibrosis in a combined approach. ADSCs favor ECM degradation by impacting the fibroblast-to-myofibroblast differentiation, favoring matrix metalloproteinases over tissue inhibitors of metalloproteinases, positively influencing collagen organization, and inhibiting the pro-fibrotic effects of transforming growth factor-β1. Furthermore, they impact elements of both the innate and adaptive immune response system, and stimulate angiogenesis on the site of injury (through secretion of pro-angiogenic cytokines like stromal cell-derived factor-1 and vascular endothelial growth factor).
CONCLUSION This review shows that understanding the complex interactions of ECM accumulation, immune response and vascularization, is vital to fibrosis treatments’ effectiveness like fat grafting. It details how ADSCs intelligently steer this complex system in an anti-fibrotic or pro-angiogenic direction, without falling into extreme dilation or stimulation of a single aspect. Detailing this combined approach, has brought fat grafting one step closer to unlocking its full potential as a non-anecdotal treatment for fibrosis.
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Affiliation(s)
| | - Jan Jeroen Vranckx
- Department of Plastic, Reconstructive Surgery, KU-Leuven University Hospitals, Leuven 3000, Belgium
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Guo W, Yang K, Qin X, Luo R, Wang H, Huang R. Polyhydroxyalkanoates in tissue repair and regeneration. ENGINEERED REGENERATION 2022. [DOI: 10.1016/j.engreg.2022.01.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Raghav PK, Mann Z, Ahlawat S, Mohanty S. Mesenchymal stem cell-based nanoparticles and scaffolds in regenerative medicine. Eur J Pharmacol 2021; 918:174657. [PMID: 34871557 DOI: 10.1016/j.ejphar.2021.174657] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 11/05/2021] [Accepted: 11/24/2021] [Indexed: 12/20/2022]
Abstract
Mesenchymal stem cells (MSCs) are adult stem cells owing to their regenerative potential and multilineage potency. MSCs have wide-scale applications either in their native cellular form or in conjugation with specific biomaterials as nanocomposites. Majorly, these natural or synthetic biomaterials are being used in the form of metallic and non-metallic nanoparticles (NPs) to encapsulate MSCs within hydrogels like alginate or chitosan or drug cargo loading into MSCs. In contrast, nanofibers of polymer scaffolds such as polycaprolactone (PCL), poly-lactic-co-glycolic acid (PLGA), poly-L-lactic acid (PLLA), silk fibroin, collagen, chitosan, alginate, hyaluronic acid (HA), and cellulose are used to support or grow MSCs directly on it. These MSCs based nanotherapies have application in multiple domains of biomedicine including wound healing, bone and cartilage engineering, cardiac disorders, and neurological disorders. This study focused on current approaches of MSCs-based therapies and has been divided into two major sections. The first section elaborates on MSC-based nano-therapies and their plausible applications including exosome engineering and NPs encapsulation. The following section focuses on the various MSC-based scaffold approaches in tissue engineering. Conclusively, this review mainly focused on MSC-based nanocomposite's current approaches and compared their advantages and limitations for building effective regenerative medicines.
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Affiliation(s)
- Pawan Kumar Raghav
- Stem Cell Facility, DBT Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Zoya Mann
- Stem Cell Facility, DBT Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Swati Ahlawat
- Stem Cell Facility, DBT Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Sujata Mohanty
- Stem Cell Facility, DBT Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Dalgic AD, Koman E, Karatas A, Tezcaner A, Keskin D. Natural origin bilayer pullulan-PHBV scaffold for wound healing applications. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 134:112554. [DOI: 10.1016/j.msec.2021.112554] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 11/03/2021] [Accepted: 11/12/2021] [Indexed: 01/14/2023]
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Sousa RC, Viana VGF, Meneses LFC, Maia Filho ALM, Santos FEP, Azevedo MMF, Nascimento HMS, Pinto LSS, Vasconcelos DFP. In vivo evaluation of bone repair guided with biological membrane based on polyhydroxybutyrate and norbixin. J Biomed Mater Res B Appl Biomater 2021; 110:743-754. [PMID: 34632693 DOI: 10.1002/jbm.b.34953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 08/23/2021] [Accepted: 09/29/2021] [Indexed: 11/09/2022]
Abstract
The present work aimed to synthesize and verify the effectiveness of the polyhydroxybutyrate and norbixin membrane as a scaffold in bone defects induced in the tibia of rats. Twenty-four male Rattus norvegicus rats were used, divided into control and membrane groups. After anesthesia, a bone defect was induced in the right tibia, followed by the implantation of the biomaterial at the site of the lesion only in the membrane group, with euthanasia after 15 and 30 days of the experiment. The deposition of organic and inorganic matrix, the quality of newly formed bone tissue and the morphology of the bone defect were measured. After 15 days of the experiment, the biomaterial significantly influenced the deposition of hydroxyapatite crystals, the formation of collagen I matrix and mineralization content in relation to the control group, in addition to the abbreviation of the inflammatory process and superior quality of the newly formed bone tissue. After 30 days, only the membrane group had fully completed its repair process. The biomaterial acted as a scaffold in the regeneration of the guided bone defect by accelerating the synthesis of collagen matrix, mineralization content, density, and maturity when compared to the control group.
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Affiliation(s)
- Rayssilane C Sousa
- Programa de Pós-Graduação em Biotecnologia/RENORBIO, Universidade Federal do Piauí, Teresina, Brazil
| | - Vicente G F Viana
- Programa de Pós-Graduação em Engenharia de Materiais, Instituto Federal de Educação, Ciência e Tecnologia do Piauí, Teresina, Brazil
| | - Luiz F C Meneses
- Programa de Pós-Graduação em Engenharia de Materiais, Instituto Federal de Educação, Ciência e Tecnologia do Piauí, Teresina, Brazil
| | - Antônio L M Maia Filho
- Núcleo de Pesquisa em Biotecnologia e Biodiversidade, Universidade Estadual do Piauí, Teresina, Brazil
| | | | | | - Hélio M S Nascimento
- Programa de Pós-Graduação em Biotecnologia/RENORBIO, Universidade Federal do Piauí, Teresina, Brazil
| | - Lucielma S S Pinto
- Departamento de Histologia e Embriologia da Faculdade de Ciências Médicas da Universidade Estadual do Piauí (UESPI), CCS/FACIME, Teresina, Brazil
| | - Daniel F P Vasconcelos
- Programa de Pós-Graduação em Biotecnologia/RENORBIO, Universidade Federal do Piauí, Teresina, Brazil
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Abdul Kareem N, Aijaz A, Jeschke MG. Stem Cell Therapy for Burns: Story so Far. Biologics 2021; 15:379-397. [PMID: 34511880 PMCID: PMC8418374 DOI: 10.2147/btt.s259124] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 06/24/2021] [Indexed: 12/12/2022]
Abstract
Burn injuries affect approximately 11 million people annually, with fatalities amounting up to 180,000. Burn injuries constitute a global health issue associated with high morbidity and mortality. Recent years have seen advancements in regenerative medicine for burn wound healing encompassing stem cells and stem cell-derived products such as exosomes and conditioned media with promising results compared to current treatment approaches. Sources of stem cells used for treatment vary ranging from hair follicle stem cells, embryonic stem cells, umbilical cord stem cells, to mesenchymal stem cells, such as adipose-derived mesenchymal stem cells, bone marrow-derived mesenchymal stem cells, and even stem cells harvested from discarded burn tissue. Stem cells utilize various pathways for wound healing, such as PI3/AKT pathway, WNT-β catenin pathway, TGF-β pathway, Notch and Hedgehog signaling pathway. Due to the paracrine signaling mechanism of stem cells, exosomes and conditioned media derived from stem cells have also been utilized in burn wound therapy. As exosomes and conditioned media are cell-free therapy and contain various biomolecules that facilitate wound healing, they are gaining popularity as an alternative treatment strategy with significant improvement in outcomes. The treatment is provided either as direct injections or embedded in a natural/artificial scaffold. This paper reviews in detail the different sources of stem cells, stem cell-derived products, their efficacy in burn wound repair, associated signaling pathways and modes of delivery for wound healing.
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Affiliation(s)
| | - Ayesha Aijaz
- Sunnybrook Research Institute, Toronto, ON, Canada
| | - Marc G Jeschke
- Sunnybrook Research Institute, Toronto, ON, Canada.,Department of Surgery, Division of Plastic Surgery, University of Toronto, Toronto, ON, Canada.,Department of Immunology, University of Toronto, Toronto, ON, Canada.,Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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Henckes NAC, Faleiro D, Chuang LC, Cirne-Lima EO. Scaffold strategies combined with mesenchymal stem cells in vaginal construction: a review. CELL REGENERATION (LONDON, ENGLAND) 2021; 10:26. [PMID: 34337675 PMCID: PMC8326237 DOI: 10.1186/s13619-021-00088-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 06/17/2021] [Indexed: 11/10/2022]
Abstract
Tissue engineering has provided new treatment alternatives for tissue reconstruction. Advances in the tissue engineering field have resulted in mechanical support and biological substitutes to restore, maintain or improve tissue/organs structures and functions. The application of tissue engineering technology in the vaginal reconstruction treatment can not only provide mechanical requirements, but also offer tissue repairing as an alternative to traditional approaches. In this review, we discuss recent advances in cell-based therapy in combination with scaffolds strategies that can potentially be adopted for gynaecological transplantation.
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Affiliation(s)
- Nicole Andréa Corbellini Henckes
- Programa de Pós-Graduação em Ciências da Saúde-Ginecologia e Obstetrícia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
- Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
| | - Dalana Faleiro
- Programa de Pós-Graduação em Ciências da Saúde-Ginecologia e Obstetrícia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Laura Chao Chuang
- Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Elizabeth Obino Cirne-Lima
- Programa de Pós-Graduação em Ciências da Saúde-Ginecologia e Obstetrícia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Departamento de Patologia Clínica Veterinária, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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Barone N, Safran T, Vorstenbosch J, Davison PG, Cugno S, Murphy AM. Current Advances in Hypertrophic Scar and Keloid Management. Semin Plast Surg 2021; 35:145-152. [PMID: 34526861 PMCID: PMC8432993 DOI: 10.1055/s-0041-1731461] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hypertrophic scars and keloids are caused by excessive tissue response to dermal injury due to local fibroblast proliferation and collagen overproduction. This response occurs because of pathologic wound healing due to dysregulation in the inflammatory, proliferative, and/or remodeling phase. Patients with hypertrophic scars or keloids report reduced quality of life, physical status, and psychological health. Hypertrophic scars or keloids will develop in 30 to 90% of individuals, and despite their prevalence, treatment remains a challenge. Of the treatments currently available for hypertrophic scars and keloids few have been adequately supported by studies with appropriate experimental design. Here, we aim to review the available literature to provide up-to-date information on the etiology, epidemiology, histology, pathophysiology, prevention, and management options available for the treatment of hypertrophic scars and keloids and highlight areas where further research is required.
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Affiliation(s)
- Natasha Barone
- Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada
| | - Tyler Safran
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Canada
| | - Joshua Vorstenbosch
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Canada
| | - Peter G. Davison
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Canada
| | - Sabrina Cugno
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Canada
| | - Amanda M. Murphy
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Canada
- Division of Plastic and Reconstructive Surgery, Jewish General Hospital, Montreal, Canada
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Goonoo N, Gimié F, Ait-Arsa I, Cordonin C, Andries J, Jhurry D, Bhaw-Luximon A. Piezoelectric core-shell PHBV/PDX blend scaffolds for reduced superficial wound contraction and scarless tissue regeneration. Biomater Sci 2021; 9:5259-5274. [PMID: 34164641 DOI: 10.1039/d1bm00379h] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The use of non-invasive scaffold materials which can mimic the innate piezoelectric properties of biological tissues is a promising strategy to promote native tissue regeneration. Piezoelectric and cell instructive electrospun core-shell PDX/PHBV mats have been engineered to promote native tissue and skin regeneration. In depth physicochemical characterisation, in vitro and in vivo studies of a rat model showed that the 20/80 PDX/PHBV composition possessed the right balance of physicochemical and piezoelectric properties leading to enhanced fibroblast stimulation, proliferation and migration, reduced fibroblast-mediated contraction and macrophage-induced inflammation, improved keratinocyte proliferation, proper balance between endothelial cell phenotypes, decreased in vivo fibrosis and accelerated in vivo scarless wound regeneration. Overall, this study highlights the importance of exploiting cell-material interactions to match tissue biological needs to sustain the wound healing cascade.
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Affiliation(s)
- Nowsheen Goonoo
- Biomaterials, Drug Delivery and Nanotechnology Unit, Centre for Biomedical and Biomaterials Research, MSIRI Building, University of Mauritius, 80837 Réduit, Mauritius.
| | - Fanny Gimié
- Animalerie, Plateforme de recherche CYROI, 2 rue Maxime Rivière, 97490 Sainte Clotilde, Ile de La Réunion, France
| | - Imade Ait-Arsa
- Animalerie, Plateforme de recherche CYROI, 2 rue Maxime Rivière, 97490 Sainte Clotilde, Ile de La Réunion, France
| | - Colette Cordonin
- Animalerie, Plateforme de recherche CYROI, 2 rue Maxime Rivière, 97490 Sainte Clotilde, Ile de La Réunion, France
| | - Jessica Andries
- RIPA, Plateforme de recherche CYROI, 2 rue Maxime Rivière, 97490 Sainte Clotilde, Ile de La Réunion, France
| | - Dhanjay Jhurry
- Biomaterials, Drug Delivery and Nanotechnology Unit, Centre for Biomedical and Biomaterials Research, MSIRI Building, University of Mauritius, 80837 Réduit, Mauritius.
| | - Archana Bhaw-Luximon
- Biomaterials, Drug Delivery and Nanotechnology Unit, Centre for Biomedical and Biomaterials Research, MSIRI Building, University of Mauritius, 80837 Réduit, Mauritius.
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Lee MH, Kang BY, Wong CC, Li AW, Naseer N, Ibrahim SA, Keimig EL, Poon E, Alam M. A systematic review of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds. Arch Dermatol Res 2021; 314:417-425. [PMID: 34047823 DOI: 10.1007/s00403-021-02242-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 04/27/2021] [Accepted: 05/11/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Stromal vascular fraction (SVF), derived enzymatically or mechanically from adipose tissue, contains a heterogenous population of cells and stroma, including multipotent stem cells. The regenerative capacity of SVF may potentially be adapted for a broad range of clinical applications, including the healing of acute cutaneous wounds. OBJECTIVE To evaluate the available literature on the efficacy and safety of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds in humans. METHODS A systematic review of the literature utilizing MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify published clinical trials of autologous adipose-derived SVF or similar ADSC-containing derivatives for patients with acute cutaneous wounds. This was supplemented by searches for ongoing clinical trials through ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. RESULTS 872 records were initially retrieved. Application of inclusion and exclusion criteria yielded 10 relevant studies: two completed non-randomized controlled trials and eight ongoing clinical trials. Both completed studies reported a statistically significant benefit in percentage re-epithelialization and time to healing for the SVF treatment arms. Safety information for SVF was not provided. Ongoing clinical trials were assessing outcomes such as safety, patient and observer reported scar appearance, wound healing rate, and wound epithelization. CONCLUSION In the context of substantial limitations in the quantity and quality of available evidence, the existing literature suggests that SVF may be a useful treatment for acute cutaneous wounds in humans. More clinical trials with improved outcome measures and safety assessment are needed.
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Affiliation(s)
- M H Lee
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - B Y Kang
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - C C Wong
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - A W Li
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - N Naseer
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - Sarah A Ibrahim
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - E L Keimig
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - E Poon
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA
| | - M Alam
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair Street, Suite 1600, Chicago, IL, 60611, USA.
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
- Department of Otolaryngology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
- Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
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He T, Yang J, Liu P, Xu L, Lü Q, Tan Q. [Research progress of adipose-derived stem cells in skin scar prevention and treatment]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2021; 35:234-240. [PMID: 33624480 DOI: 10.7507/1002-1892.202007083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Objective To review the research progress of adipose-derived stem cells (ADSCs) in skin scar prevention and treatment. Methods The related literature was extensively reviewed and analyzed. The recent in vitroand in vivo experiments and clinical studies on the role of ADSCs in skin scar prevention and treatment, and the possible mechanisms and biomaterials to optimize the effect of ADSCs were summarized. Results As demonstrated by in vitro and in vivo experiments and clinical studies, ADSCs participate in the whole process of skin wound healing and may prevent and treat skin scars by reducing inflammation, promoting angiogenesis, or inhibiting (muscle) fibroblasts activity to reduce collagen deposition through the p38/mitogen-activated protein kinase, peroxisome proliferator activated receptor γ, transforming growth factor β 1/Smads pathways. Moreover, bioengineered materials such as hydrogel from acellular porcine adipose tissue, porcine small-intestine submucosa, and poly (3-hydroxybutyrate-co-hydroxyvalerate) scaffold may further enhance the efficacy of ADSCs in preventing and treating skin scars. Conclusion Remarkable progress has been made in the application of ADSCs in skin scar prevention and treatment. While, further studies are still needed to explore the application methods of ADSCs in the clinic.
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Affiliation(s)
- Tao He
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;Laboratory of Stem Cell and Tissue Engineering, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Jiqiao Yang
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Pengcheng Liu
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;Laboratory of Stem Cell and Tissue Engineering, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Li Xu
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;Laboratory of Stem Cell and Tissue Engineering, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Qing Lü
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Qiuwen Tan
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;Laboratory of Stem Cell and Tissue Engineering, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
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Xie F, Teng L, Xu J, Lu J, Zhang C, Yang L, Ma X, Zhao M. Adipose-derived mesenchymal stem cells inhibit cell proliferation and migration and suppress extracellular matrix synthesis in hypertrophic-scar and keloid fibroblasts. Exp Ther Med 2021; 21:139. [PMID: 33456506 PMCID: PMC7791925 DOI: 10.3892/etm.2020.9571] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 03/26/2020] [Indexed: 12/13/2022] Open
Abstract
Pathological scars occur during skin wound healing, and the use of adipose-derived stem cells (ADSCs) is one of the various treatments. The present study aimed to investigate the in vitro effects of ADSCs on the biological properties of hypertrophic scar fibroblasts (HSFs) and keloid fibroblasts (KFs), such as proliferation, migration, and the synthesis of extracellular matrix proteins. Transwell chambers were used to establish a co-culture system of ADSCs with normal skin fibroblasts (NFs), HSFs or KFs. The effect of ADSCs on the proliferation of fibroblasts was evaluated by CCK8 measurement, while the migration ability of fibroblasts was assessed using cell scratch assay. The expression of extracellular matrix proteins was measured by immunoblotting. Co-culture of NFs with ADSCs did not affect cell proliferation and migration, nor the expression of extracellular matrix proteins [collagen-I, collagen-III, fibronectin (FN) and α-smooth muscle actin (α-SMA)] in NFs. However, as with the inhibitor SB431542, ADSCs significantly inhibited cell proliferation and migration and the expression of extracellular matrix proteins (collagen-I, collagen-III, FN and α-SMA), but also suppressed the protein expression of transforming growth factor β1 (TGF-β1), phosphorylated (p-) mothers against decapentaplegic homolog (Smad) 2, p-Smad3 and Smad7 in HSFs and KFs. The results show that ADSCs inhibited cell proliferation and migration and the expression of extracellular matrix proteins in HSCs and KFs in vitro, possibly through inhibition of the TGF-β1/Smad pathway.
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Affiliation(s)
- Fang Xie
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
| | - Li Teng
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
| | - Jiajie Xu
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
| | - Jianjian Lu
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
| | - Chao Zhang
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
| | - Liya Yang
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
| | - Xiaoyang Ma
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
| | - Minghao Zhao
- Cranio-Maxillo-Facial Surgery Department 2, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
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Guo X, Liu Y, Bera H, Zhang H, Chen Y, Cun D, Foderà V, Yang M. α-Lactalbumin-Based Nanofiber Dressings Improve Burn Wound Healing and Reduce Scarring. ACS APPLIED MATERIALS & INTERFACES 2020; 12:45702-45713. [PMID: 32667794 DOI: 10.1021/acsami.0c05175] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Skin wound especially burn injury is a major threat for public health. One of the pursuits in the current wound healing research is to identify new promising biological materials, which can not only promote tissue repair but also reduce scar formation. In this current study, the potentials of α-lactalbumin (ALA), a tryptophan-rich dietary protein acting as a precursor of neurotransmitter serotonin, to promote the burn wound healing and reduce the scar formation were investigated. The ALA was initially electrospun with polycaprolactone (PCL) to accomplish electrospun nanofibrous mats (ENMs), subsequently assessed for their physicochemical attributes and wound healing efficiency on a burn rat model, and then their healing mechanisms at cellular and molecular levels were explored. The results showed that ALA and PCL were physicochemically compatible in ENMs. The average diameter of various nanofibers was within 183-344 nm. Their wettability and mechanical properties could be readily modulated by adjusting the mass ratios of ALA and PCL from 1/9 to 1/2. The selected ENMs exhibited negligible cytotoxicity and satisfactory adhesion to fibroblasts and promoting the proliferation of the fibroblasts. As compared to pristine PCL based ENMs, the composite scaffolds could accelerate the wound healing process and exhibit effects comparable to a marketed wound dressing over 16 days. Moreover, the ALA/PCL based ENMs could increase the synthesis of type I collagen and decrease the expression of α-smooth muscle actin, conferring that the novel wound dressings could reduce the formation of scars. Collectively, this study demonstrates that the ALA is a promising biological material and could promote the regeneration of burn skins with reduced scar formation, when being loaded on ultrafine fibrous scaffolds, mimicking the structure of the natural extra cellular matrix.
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Affiliation(s)
- Xiong Guo
- Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China
| | - Yunen Liu
- Department of Emergency Medicine, General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Trauma PLA, No. 83 Road, Shenhe District, 110016 Shenyang, China
| | - Hriday Bera
- Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China
| | - Haotian Zhang
- Department of Pharmacology, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China
| | - Yang Chen
- Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China
| | - Dongmei Cun
- Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China
| | - Vito Foderà
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
| | - Mingshi Yang
- Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
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Chogan F, Mirmajidi T, Rezayan AH, Sharifi AM, Ghahary A, Nourmohammadi J, Kamali A, Rahaie M. Design, fabrication, and optimization of a dual function three-layer scaffold for controlled release of metformin hydrochloride to alleviate fibrosis and accelerate wound healing. Acta Biomater 2020; 113:144-163. [PMID: 32590170 DOI: 10.1016/j.actbio.2020.06.031] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 06/17/2020] [Accepted: 06/18/2020] [Indexed: 12/12/2022]
Abstract
Abnormal wound healing caused by the over-expression of collagen and fibronectin leads to fibrosis, the major complication of all treatment modalities. A three-layer nanofiber scaffold was designed, optimized, and fabricated. This scaffold comprised two supportive polycaprolactone (PCL)-chitosan layers on the sides and a polyvinyl alcohol (PVA)-metformin hydrochloride (metformin-HCl) in the middle. The physico-chemical properties of scaffold, such as mechanical characteristics, degradation, swelling, and in-vitro drug release, were evaluated. The biological tests, including cell viability in response to metformin-HCl and Tween 80, scaffold biocompatibility, cell attachment, and antibacterial activity, were further conducted. The wound healing effect of scaffold loaded with metformin-HCl (MSc+Met) was assessed in donut-shaped silicone splints in rats. Histopathological and immunohistochemical evaluation as well as mRNA expression levels of fibrosis markers were also studied. SEM images indicated a uniform, bead-less morphology and high porosity. Surface modification of scaffold by Tween 80 improved the surface hydrophilicity and enhanced the adhesion and proliferation of fibroblasts. The scar area on day 15 in MSc+Met was significantly lower than that of other groups. Histopathological and immunohistochemical evaluation revealed that group MSc+Met was the best, having significantly lower inflammation, higher angiogenesis, the smallest scar width and depth, maximum epitheliogenesis score, and the most optimal modulation of collagen density. Local administration of metformin-HCl substantially down-regulated the expression of fibrosis-involved genes: transforming growth factor (TGF-β1), collagen type 1 (Col-I), fibronectin, collagen type 3 (Col-III), and alpha-smooth muscle actin (α-SMA). Inhibiting these genes alleviates scar formation but delays wound healing; thus, an engineered scaffold was used to prevent delay in wound healing. These results provided evidence for the first time to introduce an anti-fibrogenic slow-releasing scaffold, which acts in a dual role, both alleviating fibrosis and accelerating wound healing.
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Thyparambil NJ, Gutgesell LC, Bromet BA, Flowers LE, Greaney S, Day DE, Semon JA. Bioactive borate glass triggers phenotypic changes in adipose stem cells. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2020; 31:35. [PMID: 32206916 DOI: 10.1007/s10856-020-06366-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 02/17/2020] [Indexed: 06/10/2023]
Abstract
A bioactive borate glass, 13-93B3 (B3), has been used successfully in the clinic to treat chronic, nonhealing wounds without scarring. However, the mechanism by which B3 stimulates wound healing is poorly understood. Because adipose stem cells (ASCs) have been shown to have multiple roles in wound repair, we hypothesized that B3 triggers ASCs. In this study, we evaluate the effects of B3 on ASC survival, migration, differentiation, and protein secretion in vitro. In concentrations ≤10 mg/ml, B3 did not affect ASC viability under static conditions. B3 promoted the migration of ASCs but did not increase differentiation into bone or fat. B3 also decreased ASCs secretion of collagen I, PAI-1, MCP-1, DR6, DKK-1, angiogenin, IL-1, IGFBP-6, VEGF, and TIMP-2; increased expression of IL-1R and E-selectin; had a transient decrease in IL-6 secretion; and had a transient increase in bFGF secretion. Together, these results show that B3 alters the protein secretion of ASCs.
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Affiliation(s)
- Nathan J Thyparambil
- Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO, USA
| | - Lisa C Gutgesell
- Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO, USA
| | - Bradley A Bromet
- Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO, USA
| | - Lauren E Flowers
- Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO, USA
| | - Samantha Greaney
- Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO, USA
| | - Delbert E Day
- Department of Material Science and Engineering, Missouri University of Science and Technology, Rolla, MO, USA
- Center for Biomedical Science and Engineering, Missouri University of Science and Technology, Rolla, MO, USA
| | - Julie A Semon
- Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO, USA.
- Center for Biomedical Science and Engineering, Missouri University of Science and Technology, Rolla, MO, USA.
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Amirsadeghi A, Jafari A, Eggermont LJ, Hashemi SS, Bencherif SA, Khorram M. Vascularization strategies for skin tissue engineering. Biomater Sci 2020; 8:4073-4094. [DOI: 10.1039/d0bm00266f] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Lack of proper vascularization after skin trauma causes delayed wound healing. This has sparked the development of various tissue engineering strategies to improve vascularization.
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Affiliation(s)
- Armin Amirsadeghi
- Department of Chemical Engineering
- School of Chemical and Petroleum Engineering
- Shiraz University
- Shiraz 71348-51154
- Iran
| | - Arman Jafari
- Department of Chemical Engineering
- School of Chemical and Petroleum Engineering
- Shiraz University
- Shiraz 71348-51154
- Iran
| | | | - Seyedeh-Sara Hashemi
- Burn & Wound Healing Research Center
- Shiraz University of Medical Science
- Shiraz 71345-1978
- Iran
| | - Sidi A. Bencherif
- Department of Chemical Engineering
- Northeastern University
- Boston
- USA
- Department of Bioengineering
| | - Mohammad Khorram
- Department of Chemical Engineering
- School of Chemical and Petroleum Engineering
- Shiraz University
- Shiraz 71348-51154
- Iran
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Moon KC, Chung HY, Han SK, Jeong SH, Dhong ES. Tissue-engineered dermis grafts using stromal vascular fraction cells on the nose: A retrospective case-control study. J Plast Reconstr Aesthet Surg 2019; 73:965-974. [PMID: 31902623 DOI: 10.1016/j.bjps.2019.11.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 10/29/2019] [Accepted: 11/22/2019] [Indexed: 01/04/2023]
Abstract
BACKGROUND In a previous study, our group demonstrated that cultured autologous fibroblast-seeded artificial dermis was superior to artificial dermis for covering defects after surgical excision of basal cell carcinoma (BCC) in terms of scar quality. However, utilizing cultured cells for clinical purposes requires Food and Drug Administration-approved facilities and techniques and a lengthy culture period. The purpose of this retrospective study was to compare the effects of tissue-engineered dermis containing stromal vascular fraction (SVF) cells with artificial dermis on scar quality after surgical excision of BCC on the nose. METHODS Between April 2010 and February 2018, patients who were treated with tissue-engineered or artificial dermis grafts and those with a follow-up period of greater than a year were included in this study. The Patient and Observer Scar Assessment Scales (POSAS) were compared between two groups according to the location of the graft, which was classified based on nasal subunits: the upper two-thirds zone; the lower one-third zone, except for the ala; and the alar zone. RESULTS A tissue-engineered dermis composed of SVF cells and an artificial dermis were applied to 30 and 47 patients, respectively. In upper two-thirds and lower one-third zones, except for the ala, no statistically significant differences were found in any parameters. In the alar zone, statistically significant differences were detected in 10 of 21 POSAS parameters. CONCLUSION To cover nasal defects, the tissue-engineered dermis graft may be superior to the artificial dermis graft regarding scar quality at the ala. However, there were no significant differences in other zones.
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Affiliation(s)
- Kyung-Chul Moon
- Department of Plastic Surgery, Korea University College of Medicine, 148 Guro-Dong, Guro-Ku, 152-703 Seoul, Republic of Korea
| | - Ha-Yoon Chung
- Department of Plastic Surgery, Korea University College of Medicine, 148 Guro-Dong, Guro-Ku, 152-703 Seoul, Republic of Korea
| | - Seung-Kyu Han
- Department of Plastic Surgery, Korea University College of Medicine, 148 Guro-Dong, Guro-Ku, 152-703 Seoul, Republic of Korea.
| | - Seong-Ho Jeong
- Department of Plastic Surgery, Korea University College of Medicine, 148 Guro-Dong, Guro-Ku, 152-703 Seoul, Republic of Korea
| | - Eun-Sang Dhong
- Department of Plastic Surgery, Korea University College of Medicine, 148 Guro-Dong, Guro-Ku, 152-703 Seoul, Republic of Korea
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Łapa A, Cresswell M, Campbell I, Jackson P, Goldmann WH, Detsch R, Parsons A, Ahmed I, Boccaccini AR. Ga and Ce ion-doped phosphate glass fibres with antibacterial properties and their composite for wound healing applications. J Mater Chem B 2019; 7:6981-6993. [PMID: 31624824 DOI: 10.1039/c9tb00820a] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Novel gallium/cerium-doped phosphate glass fibres (PGF) were successfully manufactured by the melt-quenching and melt-spinning process. The amorphous character of the materials produced was confirmed using X-ray powder diffraction (XRD), and the elemental composition was investigated with X-ray fluorescence confirming the presence of 2 mol% of Ga2O3 or CeO2. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the presence of Q1 and Q2 structural phosphate species. Mechanical properties of the PGFs revealed tensile strength values of 428 ± 94 MPa and 379 ± 80 MPa, with elastic modulus values of 45 ± 4 GPa and 54 ± 9 GPa for Ce-PGF (diameter 25 μm) and Ga-PGF (diameter 18 μm), respectively. The influence of both dopants on the glass degradation properties was evaluated by tests in deionised water, which revealed a decreased dissolution rate for gallium-doped PGF in comparison to cerium-doped PGF. Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) measurements were used to explore ion release in cell culture medium, while ICP-mass spectrometry (ICP-MS) was used to measure ion release in deionised water. These techniques showed controlled release of therapeutic and antibacterial ions from the PGF. Antibacterial properties of Ce-PGF and Ga-PGF, based on turbidity measurements, were confirmed against Gram-positive bacteria. Moreover, Ce-doped phosphate glass fibres did not disturb the proliferation of human epidermal keratinocyte (HaCaT) cells or the mobility of mice embryonic fibroblasts (MEF). Applying an in vitro scratch assay showed full wound closure after 24 h of indirect incubation with Ga-PGF. Due to their superior processability as compared with Ga-PGFs, a fully degradable mesh based on Ce-PGF was designed and found to achieve high water uptake (up to 800%), suggesting its suitability for wound healing applications.
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Affiliation(s)
- Agata Łapa
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen, Germany.
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The Effects of Adipose Stem Cell-Conditioned Media on Fibrogenesis of Dermal Fibroblasts Stimulated by Transforming Growth Factor-β1. J Burn Care Res 2019; 39:129-140. [PMID: 29931303 PMCID: PMC6083853 DOI: 10.1097/bcr.0000000000000558] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 03/05/2018] [Indexed: 01/09/2023]
Abstract
Adipose-derived stem cells (ASCs) have been shown to enhance wound healing by human dermal fibroblasts; however, the interactions between ASCs and fibroblasts during injury remain unclear. Fibroblasts were treated with ASC-conditioned medium (ASC-CM) with and without transforming growth factor-β1 (TGF-β1) stimulation. Fibroblast proliferation, apoptosis, differentiation and expression of extracellular matrix genes and proteins, type I collagen, and type III collagen were measured. Also, wound-healing effect of ASC-CM was verified with in vivo animal study. ASC-CM inhibited proliferation and enhanced apoptosis of fibroblasts under TGF-β1 stimulation. Furthermore, 10% ASC-CM inhibited α-smooth muscle actin expression in fibroblasts, whereas 100% ASC-CM increased collagen, especially type III, expression in fibroblasts. ASC-CM was found to contain more basic fibroblast growth factor than hepatocyte growth factor, and 100% ASC-CM increased hepatocyte growth factor gene expression in fibroblasts. These results suggest ASCs affect fibrogenesis by dermal fibroblasts stimulated with TGF-β1 via paracrine signaling by adipocytokines present in ASC-CM. These results also suggest that higher concentrations of ASC-CM increase collagen production and inhibit fibroblast proliferation to avoid excessive fibrogenesis. We demonstrated that a lower ASC-CM concentration attenuated fibroblast differentiation. Additionally, 100% ASC-CM significantly reduced the wound size in an in vivo wound-healing model. In this study, we provided evidence that ASCs modulate fibrogenesis by fibroblasts via paracrine signaling, suggesting that application of ASCs during wound healing may improve the quality of wound repair.
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Augustine R, Hasan A, Patan NK, Dalvi YB, Varghese R, Antony A, Unni RN, Sandhyarani N, Moustafa AEA. Cerium Oxide Nanoparticle Incorporated Electrospun Poly(3-hydroxybutyrate- co-3-hydroxyvalerate) Membranes for Diabetic Wound Healing Applications. ACS Biomater Sci Eng 2019; 6:58-70. [PMID: 33463234 DOI: 10.1021/acsbiomaterials.8b01352] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Insufficient cell proliferation, cell migration, and angiogenesis are among the major causes for nonhealing of chronic diabetic wounds. Incorporation of cerium oxide nanoparticles (nCeO2) in wound dressings can be a promising approach to promote angiogenesis and healing of diabetic wounds. In this paper, we report the development of a novel nCeO2 containing electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) membrane for diabetic wound healing applications. In vitro cell adhesion studies, chicken embryo angiogenesis assay, and in vivo diabetic wound healing studies were performed to assess the cell proliferation, angiogenesis, and wound healing potential of the developed membranes. The experimental results showed that nCeO2 containing PHBV membranes can promote cell proliferation and cell adhesion when used as wound dressings. For less than 1% w/w of nCeO2 content, human mammary epithelial cells (HMEC) were adhered parallel to the individual fibers of PHBV. For higher than 1% w/w of nCeO2 content, cells started to flatten and spread over the fibers. In ovo angiogenic assay showed the ability of nCeO2 incorporated PHBV membranes to enhance blood vessel formation. In vivo wound healing study in diabetic rats confirmed the wound healing potential of nCeO2 incorporated PHBV membranes. The study suggests that nCeO2 incorporated PHBV membranes have strong potential to be used as wound dressings to enhance cell proliferation and vascularization and promote the healing of diabetic wounds.
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Affiliation(s)
- Robin Augustine
- Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha-2713, Qatar.,Biomedical Research Centre, Qatar University, Doha-2713, Qatar
| | - Anwarul Hasan
- Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha-2713, Qatar.,Biomedical Research Centre, Qatar University, Doha-2713, Qatar
| | - Noorunnisa Khanam Patan
- Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha-2713, Qatar
| | - Yogesh B Dalvi
- Pushpagiri Research Centre, Pushpagiri Institute of Medical Science & Research, Tiruvalla, Kerala-689101, India
| | - Ruby Varghese
- Pushpagiri Research Centre, Pushpagiri Institute of Medical Science & Research, Tiruvalla, Kerala-689101, India
| | - Aloy Antony
- Pushpagiri Research Centre, Pushpagiri Institute of Medical Science & Research, Tiruvalla, Kerala-689101, India
| | | | - Neelakandapillai Sandhyarani
- Nanoscience Research Laboratory, School of Materials Science & Engineering, National Institute of Technology Calicut, Kozhikode, Kerala-673601, India
| | - Ala-Eddin Al Moustafa
- Biomedical Research Centre, Qatar University, Doha-2713, Qatar.,College of Medicine, Qatar University, Doha-2713, Qatar
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Hamada T, Matsubara H, Yoshida Y, Ugaji S, Nomura I, Tsuchiya H. Autologous adipose-derived stem cell transplantation enhances healing of wound with exposed bone in a rat model. PLoS One 2019; 14:e0214106. [PMID: 31083652 PMCID: PMC6513073 DOI: 10.1371/journal.pone.0214106] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 04/30/2019] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES Soft tissue wounds with exposed bone often require extended healing times and can be associated with severe complications. We describe the ability of artificial dermis with autogenic adipose-derived stem cells (ADSCs) to promote the healing of wounds with exposed bone in a rat model. METHODS Adipose tissues harvested from the bilateral inguinal regions of Wistar rats were used as ADSCs. Rats were randomly divided into control and ADSC groups to investigate the efficacy of ADSC transplantation for wound healing (n = 20 per group). Soft tissue defects were created on the heads of the rats and were covered with artificial dermis with or without the seeded ADSCs. Specimens from these rats were evaluated using digital image analysis, histology, immunohistochemistry, cell labeling, and real-time reverse-transcription polymerase chain reaction (real-time RT-PCR). RESULTS The average global wound area was significantly smaller in the ADSC group than in the control group on days 3, 7, and 14 after surgery (p<0.05). After 14 days, the blood vessel density in the wound increased by 1.6-fold in the ADSC group compared with that in the control group (p<0.01). Real-time RT-PCR results showed higher Fgfb and Vegf expression levels at all time points, and higher Tgfb1 and Tgfb3 expression levels until 14 days after surgery in the ADSC group than in the control group (p<0.05). CONCLUSIONS In wounds with exposed bone, autogenic ADSCs can promote vascularization and wound healing. Use of this cell source has multiple benefits, including convenient clinical application and lack of ethical concerns.
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Affiliation(s)
- Tomo Hamada
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Hidenori Matsubara
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
- * E-mail:
| | - Yasuhisa Yoshida
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Shuhei Ugaji
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Issei Nomura
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Hiroyuki Tsuchiya
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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Memic A, Abudula T, Mohammed HS, Joshi Navare K, Colombani T, Bencherif SA. Latest Progress in Electrospun Nanofibers for Wound Healing Applications. ACS APPLIED BIO MATERIALS 2019; 2:952-969. [DOI: 10.1021/acsabm.8b00637] [Citation(s) in RCA: 166] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Adnan Memic
- Center of Nanotechnology, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Tuerdimaimaiti Abudula
- Center of Nanotechnology, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Chemical and Materials Engineering, Faculty of Engineering, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Halimatu S. Mohammed
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, United States
| | - Kasturi Joshi Navare
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, United States
| | - Thibault Colombani
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, United States
| | - Sidi A. Bencherif
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, United States
- Department of Bioengineering, Northeastern University, Boston, Massachusetts 02120, United States
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States
- Sorbonne University, UTC CNTS UMR 7338, Biomechanics and Bioengineering, University of Technology of Compiegne, 60203 Compiegne, Cedex, France
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Lu G, Ding Z, Wei Y, Lu X, Lu Q, Kaplan DL. Anisotropic Biomimetic Silk Scaffolds for Improved Cell Migration and Healing of Skin Wounds. ACS APPLIED MATERIALS & INTERFACES 2018; 10:44314-44323. [PMID: 30507148 DOI: 10.1021/acsami.8b18626] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Improved and more rapid healing of full-thickness skin wounds remains a major clinical need. Silk fibroin (SF) is a natural protein biomaterial that has been used in skin repair. However, there has been little effort aimed at improving skin healing through tuning the hierarchical microstructure of SF-based matrices and introducing multiple physical cues. Recently, enhanced vascularization was achieved with SF scaffolds with nanofibrous structures and tunable secondary conformation of the matrices. We hypothesized that anisotropic features in nanofibrous SF scaffolds would promote cell migration, neovascularization, and tissue regeneration in wounds. To address this hypothesis, SF nanofibers were aligned in an electric field to form anisotropic porous scaffolds after lyophilization. In vitro and in vivo studies indicated good cytocompatibility, and improved cell migration and vascularization than nanofibrous scaffolds without these anisotropic features. These improvements resulted in more rapid wound closure, tissue ingrowth, and the formation of new epidermis, as well as higher collagen deposition with a structure similar to the surrounding native tissue. The new epidermal layers and neovascularization were achieved by day 7, with wound healing complete by day 28. It was concluded that anisotropic SF scaffolds alone, without a need for growth factors and cells, promoted significant cell migration, vascularization, and skin regeneration and may have the potential to effectively treat dermal wounds.
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Affiliation(s)
- Guozhong Lu
- Department of Burns and Plastic Surgery , The Third Affiliated Hospital of Nantong University , Wuxi 214041 , People's Republic of China
| | - ZhaoZhao Ding
- National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology , Soochow University , Suzhou 215123 , People's Republic of China
| | - Yuanyuan Wei
- Department of Maternity and Child Care Hospital , Lanzhou 730050 , Gansu Province , People's Republic of China
| | - Xiaohong Lu
- National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology , Soochow University , Suzhou 215123 , People's Republic of China
| | - Qiang Lu
- National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology , Soochow University , Suzhou 215123 , People's Republic of China
| | - David L Kaplan
- Department of Biomedical Engineering , Tufts University , Medford , Massachusetts 02155 , United States
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Li P, Guo X. A review: therapeutic potential of adipose-derived stem cells in cutaneous wound healing and regeneration. Stem Cell Res Ther 2018; 9:302. [PMID: 30409218 PMCID: PMC6225584 DOI: 10.1186/s13287-018-1044-5] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
As the most important barrier for the human body, the skin often suffers from acute and chronic injuries, especially refractory wounds, which seriously affect the quality of life of patients. For these refractory wounds that cannot be cured by various surgical methods, stem cell transplantation becomes an effective research direction. As one of the adult stem cells, adipose-derived stem cells play an indispensable role in the repair of skin wounds more than other stem cells because of their advantages such as immune compatibility and freedom from ethical constraints. Here, we actively explore the role of adipose-derived stem cells in the repair of cutaneous wound and conclude that it can significantly promote cutaneous wound healing and regeneration. Based on a large number of animal and clinical trials, we believe that adipose-derived stem cells will have a greater breakthrough in the field of skin wound repair in the future, especially in chronic refractory wounds.
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Affiliation(s)
- Peng Li
- Department of Anorectal Surgery, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Xiutian Guo
- Department of Anorectal Surgery, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
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Han B, Fan J, Liu L, Tian J, Gan C, Yang Z, Jiao H, Zhang T, Liu Z, Zhang H. Adipose-derived mesenchymal stem cells treatments for fibroblasts of fibrotic scar via downregulating TGF-β1 and Notch-1 expression enhanced by photobiomodulation therapy. Lasers Med Sci 2018; 34:1-10. [DOI: 10.1007/s10103-018-2567-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 06/14/2018] [Indexed: 12/23/2022]
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47
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Mukheem A, Muthoosamy K, Manickam S, Sudesh K, Shahabuddin S, Saidur R, Akbar N, Sridewi N. Fabrication and Characterization of an Electrospun PHA/Graphene Silver Nanocomposite Scaffold for Antibacterial Applications. MATERIALS 2018; 11:ma11091673. [PMID: 30201852 PMCID: PMC6163631 DOI: 10.3390/ma11091673] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 08/21/2018] [Accepted: 08/23/2018] [Indexed: 11/16/2022]
Abstract
Many wounds are unresponsive to currently available treatment techniques and therefore there is an immense need to explore suitable materials, including biomaterials, which could be considered as the crucial factor to accelerate the healing cascade. In this study, we fabricated polyhydroxyalkanoate-based antibacterial mats via an electrospinning technique. One-pot green synthesized graphene-decorated silver nanoparticles (GAg) were incorporated into the fibres of poly-3 hydroxybutarate-co-12 mol.% hydroxyhexanoate (P3HB-co-12 mol.% HHx), a co-polymer of the polyhydroxyalkanoate (PHA) family which is highly biocompatible, biodegradable, and flexible in nature. The synthesized PHA/GAg biomaterial has been characterized by field emission scanning electron microscopy (FESEM), elemental mapping, thermogravimetric analysis (TGA), UV-visible spectroscopy (UV-vis), and Fourier transform infrared spectroscopy (FTIR). An in vitro antibacterial analysis was performed to investigate the efficacy of PHA/GAg against gram-positive Staphylococcus aureus (S. aureus) strain 12,600 ATCC and gram-negative Escherichia coli (E. coli) strain 8739 ATCC. The results indicated that the PHA/GAg demonstrated significant reduction of S. aureus and E. coli as compared to bare PHA or PHA- reduced graphene oxide (rGO) in 2 h of time. The p value (p < 0.05) was obtained by using a two-sample t-test distribution.
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Affiliation(s)
- Abdul Mukheem
- Department of Maritime Science and Technology Faculty of Science and Defence Technology, National Defence University of Malaysia, Kuala Lumpur 57000, Malaysia.
| | - Kasturi Muthoosamy
- Department of Chemical and Nano pharmaceutical Process Engineering, Faculty of Engineering, University of Nottingham Malaysia Campus, Semenyih 43500, Malaysia.
| | - Sivakumar Manickam
- Department of Chemical and Nano pharmaceutical Process Engineering, Faculty of Engineering, University of Nottingham Malaysia Campus, Semenyih 43500, Malaysia.
| | - Kumar Sudesh
- Applied Microbiology and Ecobiomaterial Research Laboratory, School of Biological Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Syed Shahabuddin
- Research Centre for Nano-Materials and Energy Technology (RCNMET), School of Science and Technology, Sunway University, Subang Jaya 47500, Malaysia.
| | - Rahman Saidur
- Research Centre for Nano-Materials and Energy Technology (RCNMET), School of Science and Technology, Sunway University, Subang Jaya 47500, Malaysia.
- School of Postgraduate Studies and Research, American University of Ras Al Khaimah, Ras Al Khaimah 31208, UAE.
| | - Noor Akbar
- Department of Biological Sciences, School of Science and Technology, Sunway University, Subang Jaya 47500, Malaysia.
| | - Nanthini Sridewi
- Department of Maritime Science and Technology Faculty of Science and Defence Technology, National Defence University of Malaysia, Kuala Lumpur 57000, Malaysia.
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Yu J, Wang MY, Tai HC, Cheng NC. Cell sheet composed of adipose-derived stem cells demonstrates enhanced skin wound healing with reduced scar formation. Acta Biomater 2018; 77:191-200. [PMID: 30017923 DOI: 10.1016/j.actbio.2018.07.022] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 06/16/2018] [Accepted: 07/10/2018] [Indexed: 12/21/2022]
Abstract
Scar formation remains a major clinical concern following tissue injuries such as skin wounds. Adipose-derived stem cell (ASC) sheets can be fabricated quickly through stimulation with l-ascorbate 2-phosphate and have valuable applications in tissue regeneration and wound healing. However, the antifibrotic capability of ASCs in cell sheet format has not been sufficiently investigated. We employed a murine model of healing-impaired cutaneous wounds and observed faster wound healing with ASC sheet treatment. Significantly more engrafted ASCs were observed in the wound tissue treated with ASC sheets at 14 days after wounding compared with dissociated cells. Moreover, no ASCs were found at day 28, which indicated a minimal risk of long-term side effects. The neoskin formed in the presence of ASC sheets exhibited a thickness comparable to normal skin and possessed a highly organized collagen structure. ASC sheets also suppressed macrophage infiltration and modulated TNF-α and TGF-β1 expression in vivo. Examination of fibroblasts cultured in ASC-conditioned medium indicated an anti-scarring effect of the ASC sheets evidenced by the downregulation of TGF-β1 and α-SMA in fibroblasts, which was likely mediated through the increased secretion of hepatocyte growth factor. Moreover, ASC sheets secreted significantly more C1q/TNF-related protein-3, which inhibited the C-C motif ligand 2 release by macrophages in vitro and subsequently reduced the chemotaxis of unstimulated macrophages. This mechanism may account for the observed decrease in recruitment of macrophages into the wound tissue. We conclude that ASC sheets possess the necessary paracrine factors to improve skin wound healing with a superior neoskin quality. STATEMENT OF SIGNIFICANCE Adipose-derived stem cell (ASC) sheets exhibit great potential for tissue regeneration. In this study, we investigated whether ASC sheets can ameliorate skin wound healing with reduced scar formation, and faster wound healing was observed when applying ASC sheets in an impaired wound healing model of mice. The neoskin formed in the presence of ASC sheets exhibited a thickness comparable to normal skin with a more organized collagen structure. In vitro experiments suggested that the anti-scarring effect of the ASC sheets was partly mediated through increased secretion of hepatocyte growth factor. Moreover, ASC sheets secreted significantly more C1q/TNF-related protein-3, which may account for the decreased recruitment of macrophages into the wound tissue. Therefore, ASC sheets possess the necessary paracrine factors to improve skin wound healing with less scarring, thus representing a desirable method of topical wound treatment.
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Deng C, Wang L, Feng J, Lu F. Treatment of human chronic wounds with autologous extracellular matrix/stromal vascular fraction gel: A STROBE-compliant study. Medicine (Baltimore) 2018; 97:e11667. [PMID: 30095623 PMCID: PMC6133447 DOI: 10.1097/md.0000000000011667] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Stem cell therapy is considered as the most promising treatment for chronic wounds. Extracellular matrix/stromal vascular fraction gel (ECM/SVF gel), an adipose-derived stem cell-based cytotherapy, has shown healing potential in experimental wounds in animal models. However, the effects of ECM/SVF gel on human chronic wounds have not been investigated. The aim of the present study is to investigate the therapeutic effect of ECM/SVF gel on human chronic wounds.Autologous ECM/SVF gel was prepared and used to treat patients with chronic wounds in clinics, with negative pressure wound therapy as the positive control. Wound healing rate per week and histological changes were performed.The average wound healing rate per week in the ECM/SVF gel group was 34.55 ± 11.18% compared with 10.16 ± 2.67% in the negative pressure wound therapy group (P < .001). Histological analysis with hematoxylin and eosin, Masson's trichrome staining, and CD31 immunohistochemistry showed less lymphocyte infiltration, more collagen accumulation, and more newly formed vessels in the ECM/SVF gel group treated skins compared to the control.ECM/SVF gel is an effective therapeutic option for chronic wound healing in clinics.
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Affiliation(s)
- Chengliang Deng
- Department of Plastic Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou
- Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Liangyue Wang
- Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Jingwei Feng
- Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Feng Lu
- Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China
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Gholipourmalekabadi M, Seifalian AM, Urbanska AM, Omrani MD, Hardy JG, Madjd Z, Hashemi SM, Ghanbarian H, Brouki Milan P, Mozafari M, Reis RL, Kundu SC, Samadikuchaksaraei A. 3D Protein-Based Bilayer Artificial Skin for the Guided Scarless Healing of Third-Degree Burn Wounds in Vivo. Biomacromolecules 2018; 19:2409-2422. [PMID: 29529861 DOI: 10.1021/acs.biomac.7b01807] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Severe burn injuries can lead to delays in healing and devastating scar formation. Attempts have been made to develop a suitable skin substitute for the scarless healing of such skin wounds. Currently, there is no effective strategy for completely scarless healing after the thermal injuries. In our recent work, we fabricated and evaluated a 3D protein-based artificial skin made from decellularized human amniotic membrane (AM) and electrospun nanofibrous silk fibroin (ESF) in vitro. We also characterized both biophysical and cell culture investigation to establish in vitro performance of the developed bilayer scaffolds. In this report, we evaluate the appropriate utility of this fabricated bilayered artificial skin in vivo with particular emphasis on healing and scar formation due to the biochemical and biomechanical complexity of the skin. For this work, AM and AM/ESF membranes alone or seeded with adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are implanted on full-thickness burn wounds in mice. The healing efficacy and scar formation are evaluated at 7, 14, and 28 days post-implantation in vivo. Our data reveal that ESF accelerates the wound-healing process through the early recruitment of inflammatory cells such as macrophages into the defective site as well as the up-regulation of angiogenic factors from the AT-MSCs and the facilitation of the remodeling phase. In vivo application of the prepared AM/ESF membrane seeded with the AT-MSCs reduces significantly the post-burn scars. The in vivo data suggest that the potential applications of the AM/ESF bilayered artificial skin may be considered a clinical translational product with stem cells to guide the scarless healing of severe burn injuries.
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Affiliation(s)
| | - Alexander M Seifalian
- Nanotechnology & Regenerative Medicine Commercialization Centre Ltd., The London BioScience Innovation Centre , London , NW1 0NH , United Kingdom
| | - Aleksandra M Urbanska
- Division of Digestive and Liver Diseases, Department of Medicine, Herbert Irving Comprehensive Cancer Center , Columbia University , New York , NY 10032 , United States
| | - Mir Davood Omrani
- Department of Medical Genetics, Faculty of Medicine , ○Cellular & Molecular Biology Research Centre , and ∥Department of Immunology, School of Medicine , and ◆Biotechnology Department, School of Advanced Technologies in Medicine , Shahid Beheshti University of Medical Sciences , Tehran , 19857-17443 Iran
| | | | | | | | | | | | - Masoud Mozafari
- Bioengineering Research Group, Department of Nanotechnology and Advanced Materials , Materials and Energy Research Center (MERC) , P.O. Box 31787-316 , Tehran , Iran
| | - Rui L Reis
- 3Bs Research Group, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , University of Minho , 4805-017 Barco, Guimaraes , Portugal
| | - Subhas C Kundu
- 3Bs Research Group, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , University of Minho , 4805-017 Barco, Guimaraes , Portugal
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