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Yang J, Zhang Z, Jing L, Ge J, Deng D. Thioredoxin-loaded nanocomposite wound dressing for the delivery of adipose derived stem cells for wound healing applications. J Biomater Appl 2025:8853282251336554. [PMID: 40293717 DOI: 10.1177/08853282251336554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
In the current research, Thioredoxin was loaded into chitosan nanoparticles and then loaded into the matrix of collagen hydrogel containing adipose-derived stem cells (ASCs). In vitro studies including Scanning electron microscopy imaging, cell viability assay, cell migration assay, swelling assay, release assay, radical scavenging assay were performed in order to characterize the dressings. Then, the wound healing activity of these scaffolds were studied in a rat model of wound healing. Our findings indicate that the scaffolds markedly accelerated wound closure, enhanced epithelial regeneration, and increased collagen deposition. The wound closure values for the developed dressings were 60.507 ± 2.287% on Day 7 and 95.270 ± 2.600% on Day 14. ELISA results demonstrated an upregulation of VEGF, b-FGF, and TGF-β expression, while TNF-α and IL-6 levels were significantly reduced. For our developed dressings, VEGF levels were 661.307 ± 80.195 pg/mL, while bFGF was detected at 524.410 ± 81.040 pg/mL. The concentration of TGF-β was 315.357 ± 54.783 pg/mL, and TNF-α was measured at 176.093 ± 43.934 pg/mL. Additionally, IL-6 levels were found to be 187.577 ± 40.860 pg/mL. Our results suggest that our developed hydrogel system has improved wound healing via improving angiogenesis and modulating inflammation. These mechanisms can be attributed to the proangiogenic and immunomodulatory activities of ASCs and the antioxidative properties of Thioredoxin.
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Affiliation(s)
- Jingyi Yang
- Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Zheng Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Lin Jing
- Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Junwen Ge
- Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Dan Deng
- Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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Iqbal MZ, Riaz M, Biedermann T, Klar AS. Breathing new life into tissue engineering: exploring cutting-edge vascularization strategies for skin substitutes. Angiogenesis 2024; 27:587-621. [PMID: 38842751 PMCID: PMC11564345 DOI: 10.1007/s10456-024-09928-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 05/02/2024] [Indexed: 06/07/2024]
Abstract
Tissue-engineered skin substitutes (TESS) emerged as a new therapeutic option to improve skin transplantation. However, establishing an adequate and rapid vascularization in TESS is a critical factor for their clinical application and successful engraftment in patients. Therefore, several methods have been applied to improve the vascularization of skin substitutes including (i) modifying the structural and physicochemical properties of dermal scaffolds; (ii) activating biological scaffolds with growth factor-releasing systems or gene vectors; and (iii) developing prevascularized skin substitutes by loading scaffolds with capillary-forming cells. This review provides a detailed overview of the most recent and important developments in the vascularization strategies for skin substitutes. On the one hand, we present cell-based approaches using stem cells, microvascular fragments, adipose tissue derived stromal vascular fraction, endothelial cells derived from blood and skin as well as other pro-angiogenic stimulation methods. On the other hand, we discuss how distinct 3D bioprinting techniques and microfluidics, miRNA manipulation, cell sheet engineering and photosynthetic scaffolds like GelMA, can enhance skin vascularization for clinical applications. Finally, we summarize and discuss the challenges and prospects of the currently available vascularization techniques that may serve as a steppingstone to a mainstream application of skin tissue engineering.
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Affiliation(s)
- M Zohaib Iqbal
- Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Wagistrasse 12, CH-8952, Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Mahrukh Riaz
- Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Wagistrasse 12, CH-8952, Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Thomas Biedermann
- Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Wagistrasse 12, CH-8952, Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Agnes S Klar
- Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Wagistrasse 12, CH-8952, Zurich, Switzerland.
- Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
- University of Zurich, Zurich, Switzerland.
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Gandolfi S, Sanouj A, Chaput B, Coste A, Sallerin B, Varin A. The role of adipose tissue-derived stromal cells, macrophages and bioscaffolds in cutaneous wound repair. Biol Direct 2024; 19:85. [PMID: 39343924 PMCID: PMC11439310 DOI: 10.1186/s13062-024-00534-6] [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: 08/28/2024] [Accepted: 09/12/2024] [Indexed: 10/01/2024] Open
Abstract
Skin healing is a complex and dynamic physiological process that follows mechanical alteration of the skin barrier. Under normal conditions, this complex process can be divided into at least three continuous and overlapping phases: an inflammatory reaction, a proliferative phase that leads to tissue reconstruction and a phase of tissue remodeling. Macrophages critically contribute to the physiological cascade for tissue repair. In fact, as the inflammatory phase progresses, macrophage gene expression gradually shifts from pro-inflammatory M1-like to pro-resolutive M2-like characteristics, which is critical for entry into the repair phase. A dysregulation in this macrophage' shift phenotype leads to the persistence of the inflammatory phase. Mesenchymal stromal cells and specifically the MSC-derived from adipose tissue (ADSCs) are more and more use to treat inflammatory diseases and several studies have demonstrated that ADSCs promote the wound healing thanks to their neoangiogenic, immunomodulant and regenerative properties. In several studies, ADSCs and macrophages have been injected directly into the wound bed, but the delivery of exogenous cells directly to the wound raise the problem of cell engraftment and preservation of pro-resolutive phenotype and viability of the cells. Complementary approaches have therefore been explored, such as the use of biomaterials enriched with therapeutic cell to improve cell survival and function. This review will present a background of the current scaffold models, using adipose derived stromal-cells and macrophage as therapeutic cells for wound healing, through a discussion on the potential impact for future applications in skin regeneration. According to the PRISMA statement, we resumed data from investigations reporting the use ADSCs and bioscaffolds and data from macrophages behavior with functional biomaterials in wound healing models. In the era of tissue engineering, functional biomaterials, that can maintain cell delivery and cellular viability, have had a profound impact on the development of dressings for the treatment of chronic wounds. Promising results have been showed in pre-clinical reports using ADSCs- and macrophages-based scaffolds to accelerate and to improve the quality of the cutaneous healing.
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Affiliation(s)
- S Gandolfi
- FLAMES Team, Restore Institute, Inserm, Toulouse III Paul Sabatier University, 4Bis Av. H. Curien, 31100, Toulouse, France.
- Department of Plastic and Reconstructive Surgery, Toulouse University Hospital, 1 Av. Pr.Jean Poulhès, 31400, Toulouse, France.
| | - A Sanouj
- FLAMES Team, Restore Institute, Inserm, Toulouse III Paul Sabatier University, 4Bis Av. H. Curien, 31100, Toulouse, France
| | - B Chaput
- Department of Plastic and Reconstructive Surgery, Toulouse University Hospital, 1 Av. Pr.Jean Poulhès, 31400, Toulouse, France
| | - A Coste
- FLAMES Team, Restore Institute, Inserm, Toulouse III Paul Sabatier University, 4Bis Av. H. Curien, 31100, Toulouse, France
| | - B Sallerin
- FLAMES Team, Restore Institute, Inserm, Toulouse III Paul Sabatier University, 4Bis Av. H. Curien, 31100, Toulouse, France
- Department of Pharmacology, Toulouse University Hospital, 1 Av Pr.Jean Poulhès, 31400, Toulouse, France
| | - A Varin
- FLAMES Team, Restore Institute, Inserm, Toulouse III Paul Sabatier University, 4Bis Av. H. Curien, 31100, Toulouse, France
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Hajihosseintehrani M, Amini A, Heidari M, Gholipourmalekabadi M, Fadaei Fathabady F, Mostafavinia A, Ahmadi H, Khodadadi M, Naser R, Zare F, Alizadeh S, Moeinian N, Chien S, Bayat M. The Application of Photobiomodulation and Stem Cells Seeded on the Scaffold Accelerates the Wound Healing Process in Mice. J Lasers Med Sci 2024; 15:e40. [PMID: 39381785 PMCID: PMC11459249 DOI: 10.34172/jlms.2024.40] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 05/08/2024] [Indexed: 10/10/2024]
Abstract
Introduction: The purpose of this research was to test the impact of seeding a hydrogel chitosan scaffold (HCS) with human adipose-derived stem cells (hADSCs) under the influence of photobiomodulation (PBM) on the remodeling step on the wound repairing process in mice. Methods: Thirty mice were randomly assigned to five groups (n=6 per group ): The control group (group 1) consisted of mice without any intervention. In group 2, an HCS was implanted into the wound. In group 3, a combination of HCS+hADSC was inserted into the wound. In group 4, an HCS was inserted into the wound and PBM was applied. In group 5, a combination of HCS+hADSCs was inserted into the wound, followed by PBM treatment. Results: Improvements in the injury closing rate (WCR) and microbial flora were observed in all groups. However, the highest WCRs were observed in group s 5, 4, 3, and 2 (all P values were 0.000). Groups 3-5 showed increased wound strength compared to group s 1 and 2, with group 2 demonstrating better results than group 1 (P values ranged from 0.000 to 0.013). Although group s 3-5 showed increases in certain stereological elements compared to group s 1 and 2, group 2 exhibited superior results in comparison with group 1 (P values ranged from 0.000 to 0.049). Conclusion: The joined use of HCS+hADSCs+PBM significantly accelerated the wound healing process during the maturation phase in healthy mice. This approach demonstrated superior wound healing compared to the use of HCS alone, hADSCs+HCS, or PBM+HCS. The findings suggest an additive effect when HCS+hADSCs+PBM are combined.
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Affiliation(s)
- Masoumeh Hajihosseintehrani
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Abdollah Amini
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Mohammadhossein Heidari
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Mazaher Gholipourmalekabadi
- Department of Tissue Engineering & Regenerative Medicine, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran
| | - Fatemeh Fadaei Fathabady
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Atarodalsadat Mostafavinia
- Department of Anatomical Sciences and Cognitive Neuroscience at the Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Houssein Ahmadi
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Maryam Khodadadi
- Xi’an jiaotong University School of Stomatology, Xi’an, Shaanxi Province, China
| | - Reza Naser
- Tissue Engineering Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fateme Zare
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Sanaz Alizadeh
- Department of Anatomical Sciences and Cognitive Neuroscience at the Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Nafiseh Moeinian
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Sufan Chien
- Price Institute of Surgical Research at the University of Louisville and Noveratech LLC of Louisville in Louisville, KY, USA
| | - Mohammad Bayat
- Department of Tissue Engineering & Regenerative Medicine, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran
- Price Institute of Surgical Research at the University of Louisville and Noveratech LLC of Louisville in Louisville, KY, USA
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Farabi B, Roster K, Hirani R, Tepper K, Atak MF, Safai B. The Efficacy of Stem Cells in Wound Healing: A Systematic Review. Int J Mol Sci 2024; 25:3006. [PMID: 38474251 PMCID: PMC10931571 DOI: 10.3390/ijms25053006] [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: 01/14/2024] [Revised: 02/18/2024] [Accepted: 02/29/2024] [Indexed: 03/14/2024] Open
Abstract
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.
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Affiliation(s)
- Banu Farabi
- Department of Dermatology, New York Medical College, Valhalla, NY 10595, USA;
- Department of Dermatology, NYC H+Health Hospitals/Metropolitan Hospital Center, New York, NY 10029, USA
- Department of Dermatology, NYC H+Health Hospitals/South Brooklyn Health, Brooklyn, NY 11235, USA
| | - Katie Roster
- School of Medicine, New York Medical College, Valhalla, NY 10595, USA; (K.R.); (R.H.)
| | - Rahim Hirani
- School of Medicine, New York Medical College, Valhalla, NY 10595, USA; (K.R.); (R.H.)
| | - Katharine Tepper
- Phillip Capozzi, M.D. Library, New York Medical College, Valhalla, NY 10595, USA;
| | - Mehmet Fatih Atak
- Department of Internal Medicine, NYC H+Health Hospitals/Metropolitan Hospital Center, New York, NY 10029, USA;
| | - Bijan Safai
- Department of Dermatology, New York Medical College, Valhalla, NY 10595, USA;
- Department of Dermatology, NYC H+Health Hospitals/Metropolitan Hospital Center, New York, NY 10029, USA
- Department of Dermatology, NYC H+Health Hospitals/South Brooklyn Health, Brooklyn, NY 11235, USA
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Amiri Z, Molavi AM, Amani A, Moqadam KH, Vatanchian M, Hashemi SA, Oroojalian F. Fabrication, Characterization and Wound-Healing Properties of Core-Shell SF@chitosan/ZnO/ Astragalus Arbusculinus Gum Nanofibers. Nanomedicine (Lond) 2024; 19:499-518. [PMID: 38293919 DOI: 10.2217/nnm-2023-0311] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 01/08/2024] [Indexed: 02/01/2024] Open
Abstract
AIM Silk fibroin/chitosan/ZnO/Astragalus arbusculinus (Ast) gum fibrous scaffolds along with adipose-derived mesenchymal stem cells (ADSCs) were investigated for accelerating diabetic wound healing. METHODS Scaffolds with a core-shell structure and different compositions were synthesized using the electrospinning method. Biological in vitro investigations included antibacterial testing, cell viability analysis and cell attachment evaluation. In vivo experiments, including the chicken chorioallantoic membrane (CAM) test, were conducted to assess wound-healing efficacy and histopathological changes. RESULTS The incorporation of Ast to the silk fibroin@ chitosan/ZnO scaffold improved wound healing in diabetic mice. In addition, seeding of ADSCs on the scaffold accelerated wound healing. CONCLUSION These findings suggest that the designed scaffold can be useful for skin regeneration applications.
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Affiliation(s)
- Zahra Amiri
- Department of Advanced Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, 74877-94149, Iran
| | - Amir Mahdi Molavi
- Department of Materials Research, Iranian Academic Center for Education, Culture & Research (ACECR), Khorasan Razavi Branch, Mashhad, 9177-948974, Iran
| | - Amir Amani
- Natural Products & Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, 74877-94149, Iran
| | | | - Mehran Vatanchian
- Department of Anatomical Sciences School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, 74877-94149, Iran
| | - Seyyed Ahmad Hashemi
- Vector-borne Diseases Research Center, North Khorasan University of Medical Sciences, Bojnurd, 74877-94149, Iran
| | - Fatemeh Oroojalian
- Department of Advanced Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, 74877-94149, Iran
- Natural Products & Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, 74877-94149, Iran
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Geng Y, Cui P, Hu M, Zhang B, Dai L, Han F, Patrick YH, Fu SC, Li B, Zhang X. Biomimetic triphasic silk fibroin scaffolds seeded with tendon-derived stem cells for tendon-bone junction regeneration. Biomater Sci 2024; 12:1239-1248. [PMID: 38231128 DOI: 10.1039/d3bm00548h] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
The regeneration of tendon and bone junctions (TBJs), a fibrocartilage transition zone between tendons and bones, is a challenge due to the special triphasic structure. In our study, a silk fibroin (SF)-based triphasic scaffold consisting of aligned type I collagen (Col I), transforming growth factor β (TGF-β), and hydroxyapatite (HA) was fabricated to mimic the compositional gradient feature of the native tendon-bone architecture. Rat tendon-derived stem cells (rTDSCs) were loaded on the triphasic SF scaffold, and the high cell viability suggested that the scaffold presents good biocompatibility. Meanwhile, increased expressions of tenogenic-, chondrogenic-, and osteogenic-related genes in the TBJs were observed. The in vivo studies of the rTDSC-seeded scaffold in a rat TBJ rupture model showed tendon tissue regeneration with a clear transition zone within 8 weeks of implantation. These results indicated that the biomimetic triphasic SF scaffolds seeded with rTDSCs have great potential to be applied in TBJ regeneration.
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Affiliation(s)
- Yiyun Geng
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
- School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, Jiangsu, China
| | - Penglei Cui
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
| | - Muli Hu
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
- Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Bingjun Zhang
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
- National Facility for Translational Medicine, Shanghai, China
| | - Liming Dai
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
| | - Fengxuan Han
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
- Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Yungshu-Hang Patrick
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China
| | - Sai-Chuen Fu
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China
| | - Bin Li
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
- Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Xiaoling Zhang
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
- National Facility for Translational Medicine, Shanghai, China
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Geropoulos G, Psarras K, Papaioannou M, Geropoulos V, Niti A, Nikolaidou C, Koimtzis G, Symeonidis N, Pavlidis ET, Koliakos G, Pavlidis TE, Galanis I. The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats. J Pers Med 2024; 14:121. [PMID: 38276243 PMCID: PMC10817310 DOI: 10.3390/jpm14010121] [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: 12/12/2023] [Revised: 12/22/2023] [Accepted: 12/25/2023] [Indexed: 01/27/2024] Open
Abstract
Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann-Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p > 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses.
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Affiliation(s)
- Georgios Geropoulos
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Kyriakos Psarras
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Maria Papaioannou
- Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Vasileios Geropoulos
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Argyri Niti
- Biohellenika Biotechnology Company, 55535 Thessaloniki, Greece; (A.N.)
| | - Christina Nikolaidou
- Department of Histopathology, Hippokration Hospital, 54642 Thessaloniki, Greece;
| | - Georgios Koimtzis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Nikolaos Symeonidis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Efstathios T. Pavlidis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Georgios Koliakos
- Biohellenika Biotechnology Company, 55535 Thessaloniki, Greece; (A.N.)
| | - Theodoros E. Pavlidis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Ioannis Galanis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
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Yu S, Shu X, Chen L, Wang C, Wang X, Jing J, Yan G, Zhang Y, Wu C. Construction of ultrasonically treated collagen/silk fibroin composite scaffolds to induce cartilage regeneration. Sci Rep 2023; 13:20168. [PMID: 37978248 PMCID: PMC10656553 DOI: 10.1038/s41598-023-43397-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 09/22/2023] [Indexed: 11/19/2023] Open
Abstract
A novel tissue-specific functional tissue engineering scaffold for cartilage repair should have a three-dimensional structure, good biosafety and biological activity, and should be able to promote cartilage tissue regeneration. This study aimed to determine the effect of ultrasound-treated collagen/silk fibroin (Col/SF) composite scaffolds with good mechanical properties and high biological activity on cartilage repair. The characteristics of the scaffolds with different Col/SF ratios (7:3, 8:2, and 9:1) were determined by scanning electron microscopy, Fourier-transform infrared spectroscopy, and porosity, water absorption, and compression tests. In vitro evaluations revealed the biocompatibility of the Col/SF scaffolds. Results suggested that the optimal ratio of Col/SF composite scaffolds was 7:3. The Col/SF scaffolds induced adipose-derived stem cells to undergo chondrogenic differentiation under chondrogenic culture conditions. The efficiency of Col/SF scaffolds for cartilage regeneration applications was further evaluated using an in vivo model of full-thickness articular cartilage defects in New Zealand rabbits. The Col/SF scaffolds effectively promoted osteochondral regeneration as evidenced by macroscopic, histological, and immunohistochemical evaluation. The study demonstrates that ultrasound-treated Col/SF scaffolds show great potential for repairing cartilage defects.
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Affiliation(s)
- Shunan Yu
- Department of Molecular Orthopedics, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Xiong Shu
- Department of Molecular Orthopedics, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Lei Chen
- Department of Molecular Orthopedics, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Chao Wang
- Department of Molecular Orthopedics, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Xinyu Wang
- Department of Molecular Orthopedics, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Jinzhu Jing
- Animal Laboratory Laboratory, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Guoqiang Yan
- Animal Laboratory Laboratory, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Yanzhuo Zhang
- Department of Molecular Orthopedics, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China
| | - Chengai Wu
- Department of Molecular Orthopedics, Beijing Research Institute of Traumatology and Orthopedics, Beijing, 100035, People's Republic of China.
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10
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Xing X, Han Y, Cheng H. Biomedical applications of chitosan/silk fibroin composites: A review. Int J Biol Macromol 2023; 240:124407. [PMID: 37060984 DOI: 10.1016/j.ijbiomac.2023.124407] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/31/2023] [Accepted: 04/06/2023] [Indexed: 04/17/2023]
Abstract
Natural polymers have been used in the biomedical fields for decades, mainly derived from animals and plants with high similarities with biomacromolecules in the human body. As an alkaline polysaccharide, chitosan (CS) attracts much attention in tissue regeneration and drug delivery with favorable biocompatibility, biodegradation, and antibacterial activity. However, to overcome its mechanical properties and degradation behavior drawbacks, a robust fibrous protein-silk fibroin (SF) was introduced to prepare the CS/SF composites. Not only can CS be combined with SF via the amide and hydrogen bond formation, but also their functions are complementary and tunable with the blending ratio. To further improve the performances of CS/SF composites, natural (e.g., hyaluronic acid and collagen) and synthetic biopolymers (e.g., polyvinyl alcohol and hexanone) were incorporated. Also, the CS/SF composites acted as slow-release carriers for inorganic non-metals (e.g., hydroxyapatite and graphene) and metal particles (e.g., silver and magnesium), which could enhance cell functions, facilitate tissue healing, and inhibit bacterial growth. This review presents the state-of-the-art and future perspectives of different biomaterials combined with CS/SF composites as sponges, hydrogels, membranes, particles, and coatings. Emphasis is devoted to the biological potentialities of these hybrid systems, which look rather promising toward a multitude of applications.
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Affiliation(s)
- Xiaojie Xing
- Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, China
| | - Yu Han
- Division of Craniofacial Development and Regeneration, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
| | - Hui Cheng
- Institute of Stomatology & Research Center of Dental Esthetics and Biomechanics, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, Fujian 350002, China.
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11
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Zhang M, Xu S, Du C, Wang R, Han C, Che Y, Feng W, Wang C, Gao S, Zhao W. Novel PLCL nanofibrous/keratin hydrogel bilayer wound dressing for skin wound repair. Colloids Surf B Biointerfaces 2023; 222:113119. [PMID: 36621177 DOI: 10.1016/j.colsurfb.2022.113119] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/13/2022] [Accepted: 12/26/2022] [Indexed: 12/29/2022]
Abstract
In this study, a novel poly(L-lactate-caprolactone) copolymer (PLCL) nanofibrous/keratin hydrogel bilayer wound dressing loaded with fibroblast growth factor (FGF-2) was prepared by the low-pressure filtration-assisted method. The ability of the keratin hydrogel in the bilayer dressing to mimic the dermis and that of the nanofibrous PLCL to mimic the epidermis were discussed. Keratin hydrogel exhibited good porosity and maximum water absorption of 874.09%. Compared with that of the dressing prepared by the coating method, the interface of the bilayer dressing manufactured by the low-pressure filtration-assisted method (filtration time: 20 min) was tightly bonded, and its bilayer dressing interface could not be easily peeled off. The elastic modulus of hydrogel was about 44 kPa, which was similar to the elastic modulus of the dermis (2-80 kPa). Additionally, PLCL nanofibers had certain toughness and flexibility suitable for simulating the epidermal structures. In vitro studies showed that the bilayer dressing was biocompatible and biodegradable. In vivo studies indicated that PLCL/keratin-FGF-2 bilayer dressing could promote re-epithelialization, collagen deposition, skin appendages (hair follicles) regeneration, microangiogenesis construction, and adipose-derived stem cells (ADSCs) recruitment. The introduction of FGF-2 resulted in a better repair effect. The bilayer dressing also solved the problems of poor interface adhesion of hydrogel/electrospinning nanofibers. This paper also explored the preliminary role and mechanism of bilayer dressing in promoting skin healing, showing that its potential applications as a biomedical wound dressing in the field of skin tissue engineering.
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Affiliation(s)
- Miaomiao Zhang
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Shixin Xu
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Chen Du
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Ruoying Wang
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Cuicui Han
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Yongan Che
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Wei Feng
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Chengwei Wang
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Shan Gao
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Wen Zhao
- Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.
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12
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Biomimetic nanofiber-enabled rapid creation of skin grafts. Nanomedicine (Lond) 2023. [DOI: 10.1016/b978-0-12-818627-5.00009-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023] Open
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13
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Nanoengineered hydrogels as 3D biomimetic extracellular matrix with injectable and sustained delivery capability for cartilage regeneration. Bioact Mater 2023; 19:487-498. [PMID: 35600973 PMCID: PMC9092603 DOI: 10.1016/j.bioactmat.2022.03.032] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 03/16/2022] [Accepted: 03/17/2022] [Indexed: 12/11/2022] Open
Abstract
The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous healing. Recently, the combination of implanted stem cells, suitable biomaterials and bioactive molecules has attracted attention for tissue regeneration. In this study, a novel injectable nanocomposite was rationally designed as a sustained release platform for enhanced cartilage regeneration through integration of a chitosan-based hydrogel, articular cartilage stem cells (ACSCs) and mesoporous SiO2 nanoparticles loaded with anhydroicaritin (AHI). The biocompatible engineered nanocomposite acting as a novel 3D biomimetic extracellular matrix exhibited a remarkable sustained release effect due to the synergistic regulation of the organic hydrogel framework and mesopore channels of inorganic mSiO2 nanoparticles (mSiO2 NPs). Histological assessment and biomechanical tests showed that the nanocomposites exhibited superior performance in inducing ACSCs proliferation and differentiation in vitro and promoting extracellular matrix (ECM) production and cartilage regeneration in vivo. Such a novel multifunctional biocompatible platform was demonstrated to significantly enhance cartilage regeneration based on the sustained release of AHI, an efficient bioactive natural small molecule for ACSCs chondrogenesis, within the hybrid matrix of hydrogel and mSiO2 NPs. Hence, the injectable nanocomposite holds great promise for use as a 3D biomimetic extracellular matrix for tissue regeneration in clinical diagnostics.
The anhydroicaritin (AHI) was identified as a bioactive factor for promoting cartilage repair. The hydrogel was designed to achieve sustained AHI release and optimize the microenvironment of cartilage defect sites. The hydrogel exhibited superior advantages for chondrogenic differentiation and cartilage regeneration. The hydrogel holds a great promise for use as functional scaffold for tissue and organ regeneration in the future.
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14
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Hu Z, Liu Y, Yao Z, Chen L, Wang G, Liu X, Tian Y, Cao G. Stages of preadipocyte differentiation: biomarkers and pathways for extracellular structural remodeling. Hereditas 2022; 159:47. [PMID: 36572937 PMCID: PMC9793557 DOI: 10.1186/s41065-022-00261-w] [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: 06/09/2022] [Accepted: 12/05/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND This study utilized bioinformatics to analyze the underlying biological mechanisms involved in adipogenic differentiation, synthesis of the extracellular matrix (ECM), and angiogenesis during preadipocyte differentiation in human Simpson-Golabi-Behmel syndrome at different time points and identify targets that can potentially improve fat graft survival. RESULTS We analyzed two expression profiles from the Gene Expression Omnibus and identified differentially expressed genes (DEGs) at six different time points after the initiation of preadipocyte differentiation. Related pathways were identified using Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis (GSEA). We further constructed a protein-protein interaction (PPI) network and its central genes. The results showed that upregulated DEGs were involved in cell differentiation, lipid metabolism, and other cellular activities, while downregulated DEGs were associated with angiogenesis and development, ECM tissue synthesis, and intercellular and intertissue adhesion. GSEA provided a more comprehensive basis, including participation in and positive regulation of key pathways of cell metabolic differentiation, such as the "peroxisome proliferator-activated receptor signaling pathway" and the "adenylate-activated protein kinase signaling pathway," a key pathway that negatively regulates pro-angiogenic development, ECM synthesis, and adhesion. CONCLUSIONS We identified the top 20 hub genes in the PPI network, including genes involved in cell differentiation, ECM synthesis, and angiogenesis development, providing potential targets to improve the long-term survival rate of fat grafts. Additionally, we identified drugs that may interact with these targets to potentially improve fat graft survival.
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Affiliation(s)
- Zhihan Hu
- grid.412194.b0000 0004 1761 9803Department of Clinical Medicine, Ningxia Medical University, Yinchuan, 750000 China
| | - Yi Liu
- grid.411294.b0000 0004 1798 9345Department of Burn Plastic Surgery and Wound Repair, Second Hospital of Lanzhou University, Lanzhou, 730030 China
| | - Zongjiang Yao
- grid.411294.b0000 0004 1798 9345Department of Burn Plastic Surgery and Wound Repair, Second Hospital of Lanzhou University, Lanzhou, 730030 China
| | - Liming Chen
- grid.411294.b0000 0004 1798 9345Department of Burn Plastic Surgery and Wound Repair, Second Hospital of Lanzhou University, Lanzhou, 730030 China
| | - Gang Wang
- grid.411294.b0000 0004 1798 9345Department of Burn Plastic Surgery and Wound Repair, Second Hospital of Lanzhou University, Lanzhou, 730030 China
| | - Xiaohui Liu
- grid.411294.b0000 0004 1798 9345Department of Burn Plastic Surgery and Wound Repair, Second Hospital of Lanzhou University, Lanzhou, 730030 China
| | - Yafei Tian
- grid.411294.b0000 0004 1798 9345Department of Burn Plastic Surgery and Wound Repair, Second Hospital of Lanzhou University, Lanzhou, 730030 China
| | - Guangtong Cao
- grid.411294.b0000 0004 1798 9345Department of Burn Plastic Surgery and Wound Repair, Second Hospital of Lanzhou University, Lanzhou, 730030 China
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15
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Zheng D, Chen T, Han L, Lv S, Yin J, Yang K, Wang Y, Xu N. Synergetic integrations of bone marrow stem cells and transforming growth factor-β1 loaded chitosan nanoparticles blended silk fibroin injectable hydrogel to enhance repair and regeneration potential in articular cartilage tissue. Int Wound J 2022; 19:1023-1038. [PMID: 35266304 PMCID: PMC9284642 DOI: 10.1111/iwj.13699] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/16/2021] [Accepted: 09/22/2021] [Indexed: 01/22/2023] Open
Abstract
The cartilage repair and regeneration show inadequate self-healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell-carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell-based cartilage-regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal-sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell-based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF-β1 and efficiently regulate cartilage-specific and inflammatory-related gene expressions. Finally, the cartilage-regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF-β1-SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration.
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Affiliation(s)
- Dong Zheng
- Department of OrthopedicsThe Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical UniversityChangzhouChina
| | - Tong Chen
- Department of Sports Medicine and Joint SurgeryNanjing First Hospital, Nanjing Medical UniversityNanjingChina
| | - Long Han
- Department of OrthopedicsThe Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical UniversityChangzhouChina
| | - Songwei Lv
- School of Pharmacy, Changzhou UniversityChangzhouChina
| | - Jianjian Yin
- Department of OrthopedicsThe Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical UniversityChangzhouChina
| | - Kaiyuan Yang
- Department of OrthopedicsThe Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical UniversityChangzhouChina
| | - Yuji Wang
- Department of OrthopedicsThe Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical UniversityChangzhouChina
| | - Nanwei Xu
- Department of OrthopedicsThe Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical UniversityChangzhouChina
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16
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Zhang S, Shah SAUM, Basharat K, Qamar SA, Raza A, Mohamed A, Bilal M, Iqbal HM. Silk-based nano-hydrogels for futuristic biomedical applications. J Drug Deliv Sci Technol 2022; 72:103385. [DOI: 10.1016/j.jddst.2022.103385] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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17
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Tuwalska A, Grabska-Zielińska S, Sionkowska A. Chitosan/Silk Fibroin Materials for Biomedical Applications-A Review. Polymers (Basel) 2022; 14:polym14071343. [PMID: 35406217 PMCID: PMC9003105 DOI: 10.3390/polym14071343] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 03/21/2022] [Accepted: 03/24/2022] [Indexed: 01/21/2023] Open
Abstract
This review provides a report on recent advances in the field of chitosan (CTS) and silk fibroin (SF) biopolymer blends as new biomaterials. Chitosan and silk fibroin are widely used to obtain biomaterials. However, the materials based on the blends of these two biopolymers have not been summarized in a review paper yet. As these materials can attract both academic and industrial attention, we propose this review paper to showcase the latest achievements in this area. In this review, the latest literature regarding the preparation and properties of chitosan and silk fibroin and their blends has been reviewed.
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Affiliation(s)
- Anna Tuwalska
- Department of Biomaterials and Cosmetics Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Toruń, Poland;
| | - Sylwia Grabska-Zielińska
- Department of Physical Chemistry and Physicochemistry of Polymers, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Toruń, Poland;
| | - Alina Sionkowska
- Department of Biomaterials and Cosmetics Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Toruń, Poland;
- Correspondence:
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18
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Silk Fibroin-Based Therapeutics for Impaired Wound Healing. Pharmaceutics 2022; 14:pharmaceutics14030651. [PMID: 35336024 PMCID: PMC8949428 DOI: 10.3390/pharmaceutics14030651] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/04/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open
Abstract
Impaired wound healing can lead to local hypoxia or tissue necrosis and ultimately result in amputation or even death. Various factors can influence the wound healing environment, including bacterial or fungal infections, different disease states, desiccation, edema, and even systemic viral infections such as COVID-19. Silk fibroin, the fibrous structural-protein component in silk, has emerged as a promising treatment for these impaired processes by promoting functional tissue regeneration. Silk fibroin’s dynamic properties allow for customizable nanoarchitectures, which can be tailored for effectively treating several wound healing impairments. Different forms of silk fibroin include nanoparticles, biosensors, tissue scaffolds, wound dressings, and novel drug-delivery systems. Silk fibroin can be combined with other biomaterials, such as chitosan or microRNA-bound cerium oxide nanoparticles (CNP), to have a synergistic effect on improving impaired wound healing. This review focuses on the different applications of silk-fibroin-based nanotechnology in improving the wound healing process; here we discuss silk fibroin as a tissue scaffold, topical solution, biosensor, and nanoparticle.
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19
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Ferroni L, De Francesco F, Pinton P, Gardin C, Zavan B. Methods to isolate adipose tissue-derived stem cells. Methods Cell Biol 2022; 171:215-228. [DOI: 10.1016/bs.mcb.2022.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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20
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Soriano L, Khalid T, Whelan D, O'Huallachain N, Redmond KC, O'Brien FJ, O'Leary C, Cryan SA. Development and clinical translation of tubular constructs for tracheal tissue engineering: a review. Eur Respir Rev 2021; 30:30/162/210154. [PMID: 34750116 DOI: 10.1183/16000617.0154-2021] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 07/26/2021] [Indexed: 02/07/2023] Open
Abstract
Effective restoration of extensive tracheal damage arising from cancer, stenosis, infection or congenital abnormalities remains an unmet clinical need in respiratory medicine. The trachea is a 10-11 cm long fibrocartilaginous tube of the lower respiratory tract, with 16-20 tracheal cartilages anterolaterally and a dynamic trachealis muscle posteriorly. Tracheal resection is commonly offered to patients suffering from short-length tracheal defects, but replacement is required when the trauma exceeds 50% of total length of the trachea in adults and 30% in children. Recently, tissue engineering (TE) has shown promise to fabricate biocompatible tissue-engineered tracheal implants for tracheal replacement and regeneration. However, its widespread use is hampered by inadequate re-epithelialisation, poor mechanical properties, insufficient revascularisation and unsatisfactory durability, leading to little success in the clinical use of tissue-engineered tracheal implants to date. Here, we describe in detail the historical attempts and the lessons learned for tracheal TE approaches by contextualising the clinical needs and essential requirements for a functional tracheal graft. TE manufacturing approaches explored to date and the clinical translation of both TE and non-TE strategies for tracheal regeneration are summarised to fully understand the big picture of tracheal TE and its impact on clinical treatment of extensive tracheal defects.
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Affiliation(s)
- Luis Soriano
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,Tissue Engineering Research Group, Dept of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Centre for Research in Medical Devices (CÚRAM), RCSI University of Medicine and Health Sciences, Dublin, Ireland.,Joint first authors
| | - Tehreem Khalid
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,Tissue Engineering Research Group, Dept of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI University of Medicine and Health Sciences and Trinity College Dublin, Dublin, Ireland.,Joint first authors
| | - Derek Whelan
- Dept of Mechanical, Biomedical and Manufacturing Engineering, Munster Technological University, Cork, Ireland
| | - Niall O'Huallachain
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Karen C Redmond
- National Cardio-thoracic Transplant Unit, Mater Misericordiae University Hospital and UCD School of Medicine, Dublin, Ireland
| | - Fergal J O'Brien
- Tissue Engineering Research Group, Dept of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Centre for Research in Medical Devices (CÚRAM), RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI University of Medicine and Health Sciences and Trinity College Dublin, Dublin, Ireland.,Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland
| | - Cian O'Leary
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,Tissue Engineering Research Group, Dept of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Centre for Research in Medical Devices (CÚRAM), RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI University of Medicine and Health Sciences and Trinity College Dublin, Dublin, Ireland.,Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland.,Both authors contributed equally
| | - Sally-Ann Cryan
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland .,Tissue Engineering Research Group, Dept of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Centre for Research in Medical Devices (CÚRAM), RCSI University of Medicine and Health Sciences, Dublin, Ireland.,SFI Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI University of Medicine and Health Sciences and Trinity College Dublin, Dublin, Ireland.,Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland.,Both authors contributed equally
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21
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Kim MJ, Lee WB, Park BY. Effect of Morphologically Transformed Acellular Dermal Matrix on Chronic Diabetic Wounds: An Experimental Study in a Calvarial Bone Exposure Diabetic Rat Model. J Surg Res 2021; 272:153-165. [PMID: 34974331 DOI: 10.1016/j.jss.2021.11.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 10/21/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The use of acellular dermal matrix on chronic diabetic wounds in clinical practice is hindered by its high cost and difficulty in application. We aimed to acquire experimental evidence on the effect of morphologically transformed acellular dermal matrix on chronic diabetic wounds and investigate how this transformation affects the wound healing mechanism. MATERIALS AND METHODS We developed a new chronic wound model that resembles a diabetic chronic wound as it involves an open wound with partial calvarial bone exposure in diabetic rats. According to treatment materials, rats were assigned into the CONTROL, ADM, and PASTE groups. The wound healing period was subdivided into T1 and T2 (postoperative days 14 and 30, respectively). Three-staged analyses were performed using 3D camera, histological analysis, and real-time quantitative polymerase chain reaction. RESULTS The morphologically transformed acellular dermal matrix showed a compatible treatment rate in the total wound and more rapidly reduced the initial bone exposure area. In the PASTE group, collagen scaffold appeared at a later period and expression levels of epidermal growth factor and epidermal growth factor receptor increased. CONCLUSIONS The transformation of acellular dermal matrix into the pulverized form is thought to contribute to its non-inferior therapeutic effect compared with normal acellular dermal matrix. With respect to the mechanism, the pulverized form reduced the bone exposure area in the early stage and provided a collagen scaffold at a later period. An increase in epithelial growth factors through mechanochemical transformations along with increased contact area contribute to the enhanced healing capacity of the morphologically transformed acellular dermal matrix.
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Affiliation(s)
- Min Ji Kim
- Department of Plastic and Reconstructive Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Woo Beom Lee
- Department of Plastic and Reconstructive Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Bo Young Park
- Department of Plastic and Reconstructive Surgery, School of Medicine, Ewha Womans University, Seoul, South Korea.
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22
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Nolan GS, Smith OJ, Jell G, Mosahebi A. Fat grafting and platelet-rich plasma in wound healing: a review of histology from animal studies. Adipocyte 2021; 10:80-90. [PMID: 33525977 PMCID: PMC7872055 DOI: 10.1080/21623945.2021.1876374] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Stem cells could form the basis of a novel, autologous treatment for chronic wounds like diabetic foot ulcers. Fat grafts contain adipose-derived stem cells (ADSC) but low survival of cells within the grafts is a major limitation. Platelet-rich plasma (PRP) may increase graft survival. This review examines the histology from animal studies on fat grafting, ADSC and PRP in wound healing. A literature review of major electronic databases was undertaken, and narrative synthesis performed. Data from 30 animal studies were included. ADSC increase angiogenesis over 14 days and often clinically accelerated wound healing. ADSC had a greater effect in animals with impaired wound healing (e.g. diabetes). Activated PRP increased viability of fat grafts. Despite the high number of studies, the quality is variable which weakens the evidence. It does suggest there is a benefit of ADSC, particularly in impaired wound healing. High-quality evidence in humans is required, to establish its clinical usefulness.
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Affiliation(s)
- Grant S. Nolan
- Division of Surgery & Interventional Science, University College London, London, UK
| | - Oliver J. Smith
- Division of Surgery & Interventional Science, University College London, London, UK
| | - Gavin Jell
- Division of Surgery & Interventional Science, University College London, London, UK
| | - Afshin Mosahebi
- Division of Surgery & Interventional Science, University College London, London, UK
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23
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Moakes RJA, Senior JJ, Robinson TE, Chipara M, Atanasov A, Naylor A, Metcalfe AD, Smith AM, Grover LM. A suspended layer additive manufacturing approach to the bioprinting of tri-layered skin equivalents. APL Bioeng 2021; 5:046103. [PMID: 34888433 PMCID: PMC8635740 DOI: 10.1063/5.0061361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 03/15/2023] [Accepted: 10/20/2021] [Indexed: 11/17/2022] Open
Abstract
Skin exhibits a complex structure consisting of three predominant layers (epidermis, dermis, and hypodermis). Extensive trauma may result in the loss of these structures and poor repair, in the longer term, forming scarred tissue and associated reduction in function. Although a number of skin replacements exist, there have been no solutions that recapitulate the chemical, mechanical, and biological roles that exist within native skin. This study reports the use of suspended layer additive manufacturing to produce a continuous tri-layered implant, which closely resembles human skin. Through careful control of the bioink composition, gradients (chemical and cellular) were formed throughout the printed construct. Culture of the model demonstrated that over 21 days, the cellular components played a key role in remodeling the supporting matrix into architectures comparable with those of healthy skin. Indeed, it has been demonstrated that even at seven days post-implantation, the integration of the implant had occurred, with mobilization of the adipose tissue from the surrounding tissue into the construct itself. As such, it is believed that these implants can facilitate healing, commencing from the fascia, up toward the skin surface-a mechanism recently shown to be key within deep wounds.
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Affiliation(s)
- Richard J. A. Moakes
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Jessica J. Senior
- Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom
| | - Thomas E. Robinson
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Miruna Chipara
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Aleksandar Atanasov
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Amy Naylor
- Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Anthony D. Metcalfe
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Alan M. Smith
- Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom
| | - Liam M. Grover
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, United Kingdom
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24
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Zhang S, Wang J, Zheng Z, Yan J, Zhang L, Li Y, Zhang J, Li G, Wang X, Kaplan D. Porous nerve guidance conduits reinforced with braided composite structures of silk/magnesium filaments for peripheral nerve repair. Acta Biomater 2021; 134:116-130. [PMID: 34289421 DOI: 10.1016/j.actbio.2021.07.028] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 07/05/2021] [Accepted: 07/13/2021] [Indexed: 02/06/2023]
Abstract
Peripheral nerve repair is a common but challenging surgical treatment. Many artificial nerve grafts have been developed, including nerve guidance conduits (NGCs) with biocompatibility, suitable mechanical properties and topography to guide axon growth. However, there remains a need to promote nerve regeneration and accelerate functional recovery using NGCs for nerve reconstruction. Here, silk fibroin (SF) and magnesium (S/Mg) filaments were braided into an inner layer of NGC and freeze-dried with a solution of SF and chitosan (CS). The mechanical stress of these S/Mg-SF/CS conduits reached 2.8 ± 0.2 N and possessed high compression strength. The conduits were evaluated with subcutaneous implantation. Sustainable mechanical function was demonstrated when used to repair 10 mm sciatic nerve gaps in rats. The hollow NGCs improved neurochemotaxis from the damaged nerves. The wet weight ratio of the gastrocnemius muscle, a target muscle for the sciatic nerve related to motor and sensory functions in the NGC group, reached 83.5% of that in the autologous group in 8 weeks; the nerve ports at both ends of the NGC grew well. When the distal end of the regenerated nerve was observed by Transmission Electron Microscopy (TEM), there was no significance difference in the diameter and thickness of the myelin sheath of the distal nerve between the autograft and S/Mg-SF/CS group, indicating that S/Mg-SF/CS NGC in this study promoted the growth of damaged nerves and provided appropriate physio mechanical guidance, thus suggesting potential utility for this approach in artificial nerve transplantation. STATEMENT OF SIGNIFICANCE: 1. Porous nerve guidance conduits (NGCs) is reinforced by a braided composite structure consisting of silk/magnesium filaments, which provides the NGC with appropriate physio-mechanical guidance as well as sufficient stability to support the biological micro-environment during early-stages of nerve regeneration and functional recovery. 2. Sufficient mechanical properties, biocompatibility with Schwan cells and good performance after sciatic nerve transplantation demonstrates that the S/Mg-SF/CS NGC in this study promotes the growth of damaged nerves and provides a suitable physio-mechanical guide for potential in artificial nerve transplantation. 3. A facile scalable manufacturing process is achieved by utilizing multidisciplinary engineering, such as textile technologies, biomaterial engineering and medical science.
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Affiliation(s)
- Shujun Zhang
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China
| | - Jing Wang
- Laboratory animal center of Soochow University, Suzhou 215123, China
| | - Zhaozhu Zheng
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China
| | - Jia Yan
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China
| | - Li Zhang
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China
| | - Yi Li
- School of Materials, The University of Manchester, Manchester M13 9PL, UK
| | - Jiaheng Zhang
- Research Centre of Printed Flexible Electronics, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen 518055, PR China
| | - Gang Li
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.
| | - Xiaoqin Wang
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.
| | - David Kaplan
- Department of Biomedical Engineering, 4 Colby Street, Tufts University, Medford, MA 02155, USA.
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25
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Linares-Gonzalez L, Rodenas-Herranz T, Campos F, Ruiz-Villaverde R, Carriel V. Basic Quality Controls Used in Skin Tissue Engineering. Life (Basel) 2021; 11:1033. [PMID: 34685402 PMCID: PMC8541591 DOI: 10.3390/life11101033] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/25/2021] [Accepted: 09/25/2021] [Indexed: 12/15/2022] Open
Abstract
Reconstruction of skin defects is often a challenging effort due to the currently limited reconstructive options. In this sense, tissue engineering has emerged as a possible alternative to replace or repair diseased or damaged tissues from the patient's own cells. A substantial number of tissue-engineered skin substitutes (TESSs) have been conceived and evaluated in vitro and in vivo showing promising results in the preclinical stage. However, only a few constructs have been used in the clinic. The lack of standardization in evaluation methods employed may in part be responsible for this discrepancy. This review covers the most well-known and up-to-date methods for evaluating the optimization of new TESSs and orientative guidelines for the evaluation of TESSs are proposed.
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Affiliation(s)
- Laura Linares-Gonzalez
- Servicio de Dermatología, Hospital Universitario San Cecilio, 18016 Granada, Spain; (L.L.-G.); (T.R.-H.)
- Ibs. GRANADA, Instituto Biosanitario de Granada, 18016 Granada, Spain; (F.C.); (V.C.)
- Department of Histology, University of Granada, 18016 Granada, Spain
| | - Teresa Rodenas-Herranz
- Servicio de Dermatología, Hospital Universitario San Cecilio, 18016 Granada, Spain; (L.L.-G.); (T.R.-H.)
- Ibs. GRANADA, Instituto Biosanitario de Granada, 18016 Granada, Spain; (F.C.); (V.C.)
- Department of Histology, University of Granada, 18016 Granada, Spain
| | - Fernando Campos
- Ibs. GRANADA, Instituto Biosanitario de Granada, 18016 Granada, Spain; (F.C.); (V.C.)
- Department of Histology, University of Granada, 18016 Granada, Spain
| | - Ricardo Ruiz-Villaverde
- Servicio de Dermatología, Hospital Universitario San Cecilio, 18016 Granada, Spain; (L.L.-G.); (T.R.-H.)
- Ibs. GRANADA, Instituto Biosanitario de Granada, 18016 Granada, Spain; (F.C.); (V.C.)
- Department of Histology, University of Granada, 18016 Granada, Spain
| | - Víctor Carriel
- Ibs. GRANADA, Instituto Biosanitario de Granada, 18016 Granada, Spain; (F.C.); (V.C.)
- Department of Histology, University of Granada, 18016 Granada, Spain
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26
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Troy E, Tilbury MA, Power AM, Wall JG. Nature-Based Biomaterials and Their Application in Biomedicine. Polymers (Basel) 2021; 13:3321. [PMID: 34641137 PMCID: PMC8513057 DOI: 10.3390/polym13193321] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/09/2021] [Accepted: 09/17/2021] [Indexed: 02/07/2023] Open
Abstract
Natural polymers, based on proteins or polysaccharides, have attracted increasing interest in recent years due to their broad potential uses in biomedicine. The chemical stability, structural versatility, biocompatibility and high availability of these materials lend them to diverse applications in areas such as tissue engineering, drug delivery and wound healing. Biomaterials purified from animal or plant sources have also been engineered to improve their structural properties or promote interactions with surrounding cells and tissues for improved in vivo performance, leading to novel applications as implantable devices, in controlled drug release and as surface coatings. This review describes biomaterials derived from and inspired by natural proteins and polysaccharides and highlights their promise across diverse biomedical fields. We outline current therapeutic applications of these nature-based materials and consider expected future developments in identifying and utilising innovative biomaterials in new biomedical applications.
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Affiliation(s)
- Eoin Troy
- Microbiology, College of Science and Engineering, National University of Ireland, NUI Galway, H91 TK33 Galway, Ireland; (E.T.); (M.A.T.)
| | - Maura A. Tilbury
- Microbiology, College of Science and Engineering, National University of Ireland, NUI Galway, H91 TK33 Galway, Ireland; (E.T.); (M.A.T.)
- SFI Centre for Medical Devices (CÚRAM), NUI Galway, H91 TK33 Galway, Ireland
| | - Anne Marie Power
- Zoology, School of Natural Sciences, NUI Galway, H91 TK33 Galway, Ireland;
| | - J. Gerard Wall
- Microbiology, College of Science and Engineering, National University of Ireland, NUI Galway, H91 TK33 Galway, Ireland; (E.T.); (M.A.T.)
- SFI Centre for Medical Devices (CÚRAM), NUI Galway, H91 TK33 Galway, Ireland
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27
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Alt EU, Schmitz C, Bai X. Perspective: Why and How Ubiquitously Distributed, Vascular-Associated, Pluripotent Stem Cells in the Adult Body (vaPS Cells) Are the Next Generation of Medicine. Cells 2021; 10:2303. [PMID: 34571951 PMCID: PMC8467324 DOI: 10.3390/cells10092303] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 08/30/2021] [Accepted: 08/31/2021] [Indexed: 12/21/2022] Open
Abstract
A certain cell type can be isolated from different organs in the adult body that can differentiate into ectoderm, mesoderm, and endoderm, providing significant support for the existence of a certain type of small, vascular-associated, pluripotent stem cell ubiquitously distributed in all organs in the adult body (vaPS cells). These vaPS cells fundamentally differ from embryonic stem cells and induced pluripotent stem cells in that the latter possess the necessary genetic guidance that makes them intrinsically pluripotent. In contrast, vaPS cells do not have this intrinsic genetic guidance, but are able to differentiate into somatic cells of all three lineages under guidance of the microenvironment they are located in, independent from the original tissue or organ where they had resided. These vaPS cells are of high relevance for clinical application because they are contained in unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs). The latter can be obtained from and re-applied to the same patient at the point of care, without the need for further processing, manipulation, and culturing. These findings as well as various clinical examples presented in this paper demonstrate the potential of UA-ADRCs for enabling an entirely new generation of medicine for the benefit of patients and healthcare systems.
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Affiliation(s)
- Eckhard U. Alt
- Heart and Vascular Institute, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA;
- Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57104, USA
- MD Anderson Cancer Center, University of Texas, Houston, TX 77054, USA
- Isar Klinikum Munich, 80331 Munich, Germany
| | - Christoph Schmitz
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians University of Munich, 80336 Munich, Germany;
| | - Xiaowen Bai
- Heart and Vascular Institute, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA;
- MD Anderson Cancer Center, University of Texas, Houston, TX 77054, USA
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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28
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Nolan GS, Smith OJ, Heavey S, Jell G, Mosahebi A. Histological analysis of fat grafting with platelet-rich plasma for diabetic foot ulcers-A randomised controlled trial. Int Wound J 2021; 19:389-398. [PMID: 34169656 PMCID: PMC8762540 DOI: 10.1111/iwj.13640] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/26/2021] [Accepted: 05/31/2021] [Indexed: 11/28/2022] Open
Abstract
Diabetic foot ulcers are often unresponsive to conventional therapy and are a leading cause of amputation. Animal studies have shown stem cells and growth factors can accelerate wound healing. Adipose‐derived stem cells are found in fat grafts and mixing them with platelet‐rich plasma (PRP) may improve graft survival. This study aimed to establish the histological changes when diabetic foot ulcers are treated with fat grafts and PRP. A three‐armed RCT was undertaken of 18 diabetic foot ulcer patients: fat grafting; fat grafting with PRP; and routine podiatry care. Biopsies were obtained at week 0, 1, and 4, and underwent quantitative histology/immunohistochemistry (H&E, CD31, and Ki67). Treatment with fat and PRP increased mean microvessel density at 1 week to 1645 (SD 96) microvessels/mm2 (+32%‐45% to other arms, P = .035). PRP appeared to increase vascularity surrounding fat grafts, and histology suggested PRP may enhance fat graft survival. There was no clinical difference between arms. This study demonstrates PRP with fat grafts increased neovascularisation and graft survival in diabetic foot ulcers. The histology was not, however, correlated with wound healing time. Future studies should consider using apoptosis markers and fluorescent labelling to ascertain if enhanced fat graft survival is due to proliferation or reduced apoptosis. Trial registration NCT03085550.
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Affiliation(s)
- Grant Switzer Nolan
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Oliver John Smith
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Susan Heavey
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Gavin Jell
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Afshin Mosahebi
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
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29
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Zeolite A enhanced chitosan films with high water absorption ability and antimicrobial activity. Chin J Chem Eng 2021. [DOI: 10.1016/j.cjche.2020.08.057] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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30
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Chen Z, Zhang B, Shu J, Wang H, Han Y, Zeng Q, Chen Y, Xi J, Tao R, Pei X, Yue W, Han Y. Human decellularized adipose matrix derived hydrogel assists mesenchymal stem cells delivery and accelerates chronic wound healing. J Biomed Mater Res A 2020; 109:1418-1428. [PMID: 33253453 DOI: 10.1002/jbm.a.37133] [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: 06/05/2020] [Revised: 10/28/2020] [Accepted: 11/28/2020] [Indexed: 12/18/2022]
Abstract
Biological scaffolds based stem cell delivery methods have emerged as a promising approach for tissue repair and regeneration. Here we developed a hydrogel biological scaffold from human decellularized adipose matrix (hDAM) for human adipose-derived stem cells (hASCs) delivery to accelerate chronic wound healing. The hDAM hydrogel was prepared by pepsin mediated digestion and pH controlled neutralization. The morphology, survival, proliferation, and angiogenic paracrine activity of hASCs cultured in the hydrogel were assessed. Moreover, the therapeutic efficacy of the hASCs-hydrogel composite for impaired wound healing was evaluated by using a full-thickness wound model on diabetic mouse. The developed hDAM hydrogel was a thermosensitive hydrogel, presented the biochemical complexity of native extracellular matrix and formed a porous nanofiber structure after gelation. The hydrogel can support hASCs adhesion, survival, and proliferation. Compared to standard culture condition, hASCs cultured in the hydrogel exhibited enhanced paracrine activity with increased secretion of hepatocyte growth factor. In the diabetic mice model with excisional full-thickness skin wounds, mice treated with the hASCs-hydrogel composite displayed accelerated wound closure and increased neovascularization. Our results suggested that the developed hDAM hydrogel can provide a favorable microenvironment for hASCs with augmented regeneration potential to accelerate chronic wound healing.
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Affiliation(s)
- Zhaoyang Chen
- Medical School of Chinese PLA, Beijing, China.,Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China
| | - Bowen Zhang
- South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, China.,Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, AMMS, Beijing, China
| | - Jun Shu
- Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China
| | - Haiyang Wang
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, AMMS, Beijing, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, China
| | - Yudi Han
- Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China
| | - Quan Zeng
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, AMMS, Beijing, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, China
| | - Youbai Chen
- Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China
| | - Jiafei Xi
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, AMMS, Beijing, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, China
| | - Ran Tao
- Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China
| | - Xuetao Pei
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, AMMS, Beijing, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, China
| | - Wen Yue
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, AMMS, Beijing, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, China
| | - Yan Han
- Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China
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31
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Silk fibroin as a natural polymeric based bio-material for tissue engineering and drug delivery systems-A review. Int J Biol Macromol 2020; 163:2145-2161. [DOI: 10.1016/j.ijbiomac.2020.09.057] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/06/2020] [Accepted: 09/09/2020] [Indexed: 12/13/2022]
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32
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Lin W, Qi X, Guo W, Liang D, Chen H, Lin B, Deng X. A barrier against reactive oxygen species: chitosan/acellular dermal matrix scaffold enhances stem cell retention and improves cutaneous wound healing. Stem Cell Res Ther 2020; 11:383. [PMID: 32894204 PMCID: PMC7487689 DOI: 10.1186/s13287-020-01901-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 08/13/2020] [Accepted: 08/24/2020] [Indexed: 12/30/2022] Open
Abstract
Background Stem cell therapies have gained great attention for providing novel solutions for treatment of various injuries and diseases due to stem cells’ self-renewal, ability to differentiate into various cell types, and favorite paracrine function. Nevertheless, the low retention of transplanted stem cell still limits their clinical applications such as in wound healing in view of an induced harsh microenvironment rich in reactive oxygen species (ROS) during inflammatory reactions. Methods Herein, a novel chitosan/acellular dermal matrix (CHS/ADM) stem cell delivery system is developed, which is of great ROS scavenging activity and significantly attenuates inflammatory response. Result Under ROS microenvironment, this stem cell delivery system acts as a barrier, effectively scavenging an amount of ROS and protecting mesenchymal stem cells (MSCs) from the oxidative stress. It notably regulates intracellular ROS level in MSCs and reduces ROS-induced cellular death. Most importantly, such MSCs delivery system significantly enhances in vivo transplanted stem cell retention, promotes the vessel growth, and accelerates wound healing. Conclusions This novel delivery system, which overcomes the limitations of conventional plain collagen-based delivery system in lacking of ROS-environmental responsive mechanisms, demonstrates a great potential use in stem cell therapies in wound healing.
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Affiliation(s)
- Wei Lin
- MOE Key Laboratory of Laser Life Science, College of Biophotonics & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.,Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Xiaoyang Qi
- The Brain Cognition and Brain Disease Institute of Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Wenjing Guo
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China
| | - Danyang Liang
- MOE Key Laboratory of Laser Life Science, College of Biophotonics & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.,Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Heting Chen
- MOE Key Laboratory of Laser Life Science, College of Biophotonics & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.,Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Baoping Lin
- MOE Key Laboratory of Laser Life Science, College of Biophotonics & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.,Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Xiaoyuan Deng
- MOE Key Laboratory of Laser Life Science, College of Biophotonics & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China. .,Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
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33
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Shahin H, Elmasry M, Steinvall I, Söberg F, El-Serafi A. Vascularization is the next challenge for skin tissue engineering as a solution for burn management. BURNS & TRAUMA 2020; 8:tkaa022. [PMID: 32766342 PMCID: PMC7396265 DOI: 10.1093/burnst/tkaa022] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/23/2020] [Indexed: 12/19/2022]
Abstract
Skin regeneration represents a promising line of management for patients with skin loss, including burn victims. The current approach of spraying single cells over the defective areas results in variable success rates in different centers. The modern approach is to synthesize a multilayer skin construct that is based on autologous stem cells. One of the main complications with different types of transplants is sloughing due to the absence of proper vascularization. Ensuring proper vascularization will be crucial for the integration of skin constructs with the surrounding tissues. Combination of the right cells with scaffolds of proper physico-chemical properties, vascularization can be markedly enhanced. The material effect, pore size and adsorption of certain proteins, as well as the application of appropriate growth factors, such as vascular endothelial growth factors, can have an additive effect. A selection of the most effective protocols is discussed in this review.
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Affiliation(s)
- Hady Shahin
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, 581 85, Linköping, Östergötland, Sweden
- The Department of Biomedical and Clinical Sciences, Linköping University, Linköping University Hospital, 581 83, Linköping, Östergötland, Sweden
- Faculty of Biotechnology, MSA University, 26 July Mehwar Road, 125 85, 6th October City. Egypt
| | - Moustafa Elmasry
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, 581 85, Linköping, Östergötland, Sweden
- The Department of Biomedical and Clinical Sciences, Linköping University, Linköping University Hospital, 581 83, Linköping, Östergötland, Sweden
| | - Ingrid Steinvall
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, 581 85, Linköping, Östergötland, Sweden
- The Department of Biomedical and Clinical Sciences, Linköping University, Linköping University Hospital, 581 83, Linköping, Östergötland, Sweden
| | - Folke Söberg
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, 581 85, Linköping, Östergötland, Sweden
- The Department of Biomedical and Clinical Sciences, Linköping University, Linköping University Hospital, 581 83, Linköping, Östergötland, Sweden
| | - Ahmed El-Serafi
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, 581 85, Linköping, Östergötland, Sweden
- The Department of Biomedical and Clinical Sciences, Linköping University, Linköping University Hospital, 581 83, Linköping, Östergötland, Sweden
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Adipose Tissue: A Source of Stem Cells with Potential for Regenerative Therapies for Wound Healing. J Clin Med 2020; 9:jcm9072161. [PMID: 32650555 PMCID: PMC7408846 DOI: 10.3390/jcm9072161] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/25/2020] [Accepted: 07/06/2020] [Indexed: 12/11/2022] Open
Abstract
Interest in adipose tissue is fast becoming a focus of research after many years of being considered as a simple connective tissue. It is becoming increasingly apparent that adipose tissue contains a number of diverse cell types, including adipose-derived stem cells (ASCs) with the potential to differentiate into a number of cell lineages, and thus has significant potential for developing therapies for regenerative medicine. Currently, there is no gold standard treatment for scars and impaired wound healing continues to be a challenge faced by clinicians worldwide. This review describes the current understanding of the origin, different types, anatomical location, and genetics of adipose tissue before discussing the properties of ASCs and their promising applications for tissue engineering, scarring, and wound healing.
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Echeverry-Rendon M, Echeverria F, Harmsen MC. Interaction of different cell types with magnesium modified by plasma electrolytic oxidation. Colloids Surf B Biointerfaces 2020; 193:111153. [PMID: 32505097 DOI: 10.1016/j.colsurfb.2020.111153] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/18/2020] [Accepted: 05/23/2020] [Indexed: 12/16/2022]
Abstract
Magnesium (Mg) is a material widely used in industrial applications due to its low weight, ductility, and excellent mechanical properties. For non-permanent implants, Mg is particularly well-suited because of its biodegradability, while its degradation products are not harmful. However, Mg is chemically reactive, and cytotoxic hydrogen gas is released as part of the degradation. This adverse degradation can be tuned using plasma electrolytic oxidation (PEO). With PEO, a surface layer of MgO/Mg(OH)2 is deposited on the surface of Mg in a controlled way. The electrolytes used during PEO influence the surface's chemistry and topography and thus expectedly the biological response of adhered cells. In this study, thin samples of commercial pure of Mg (c.p Mg) were modified by PEO guided by different electrolytes, and the biological activity was assessed on vascular cells, immune cells, and repair cells (adipose tissue-derived stromal cells, ASCs). Vascular cells were more vulnerable than ASCs for compounds released by surface-coated Mg. All surface coatings supported the proliferation of adhered ASC. Released compounds from surface-coated Mg delayed but did not block in vitro wound closure of fibroblasts monolayers. Preformed endothelial tubes were vulnerable for released compounds, while their supporting ASC was not. We conclude that PEO-based surface-coating of Mg supports adhesion and future delivery of therapeutic vascular repair cells such as ASC, but that the observed vulnerability of vascular cells for coated Mg components warrants investigations in vivo.
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Affiliation(s)
- Monica Echeverry-Rendon
- Centro de Investigación, Innovación y Desarrollo de Materiales CIDEMAT, Facultad de Ingeniería, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Hanzeplein 1, EA11, NL-9713 GZ, Groningen, The Netherlands.
| | - Felix Echeverria
- Centro de Investigación, Innovación y Desarrollo de Materiales CIDEMAT, Facultad de Ingeniería, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia
| | - Martin C Harmsen
- University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Hanzeplein 1, EA11, NL-9713 GZ, Groningen, The Netherlands
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Huang YZ, Gou M, Da LC, Zhang WQ, Xie HQ. Mesenchymal Stem Cells for Chronic Wound Healing: Current Status of Preclinical and Clinical Studies. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:555-570. [PMID: 32242479 DOI: 10.1089/ten.teb.2019.0351] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Healing skin wounds with anatomic and functional integrity, especially under chronic pathological conditions, remain an enormous challenge. Due to their outstanding regenerative potential, mesenchymal stem cells (MSCs) have been explored in many studies to determine the healing ability for difficult-to-treat diseases. In this article, we review current animal studies and clinical trials of MSC-based therapy for chronic wounds, and discuss major challenges that confront future clinical applications. We found that a wealth of animal studies have revealed the versatile roles and the benefits of MSCs for chronic wound healing. MSC treatment results in enhanced angiogenesis, facilitated reepithelialization, improved granulation, and accelerated wound closure. There are some evidences of the transdifferentiation of MSCs into skin cells. However, the healing effect of MSCs depends primarily on their paracrine actions, which alleviate the harsh microenvironment of chronic wounds and regulate local cellular responses. Consistent with the findings of preclinical studies, some clinical trials have shown improved wound healing after transplantation of MSCs in chronic wounds, mainly lower extremity ulcers, pressure sores, and radiation burns. However, there are some limitations in these clinical trials, especially a small number of patients and imperfect methodology. Therefore, to better define the safety and efficiency of MSC-based wound therapy, large-scale controlled multicenter trials are needed in the future. In addition, to build a robust pool of clinical evidence, standardized protocols, especially the cultivation and quality control of MSCs, are recommended. Altogether, based on current data, MSC-based therapy represents a promising treatment option for chronic wounds. Impact statement Chronic wounds persist as a significant health care problem, particularly with increasing number of patients and the lack of efficient treatments. The main goal of this article is to provide an overview of current status of mesenchymal stem cell (MSC)-based therapy for chronic wounds. The roles of MSCs in skin wound healing, as revealed in a large number of animal studies, are detailed. A critical view is made on the clinical application of MSCs for lower extremity ulcers, pressure sores, and radiation burns. Main challenges that confront future clinical applications are discussed, which hopefully contribute to innovations in MSC-based wound treatment.
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Affiliation(s)
- Yi-Zhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.,Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China
| | - Min Gou
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Lin-Cui Da
- Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Wen-Qian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Hui-Qi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.,Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China
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Zhou LN, Wang JC, Zilundu PLM, Wang YQ, Guo WP, Zhang SX, Luo H, Zhou JH, Deng RD, Chen DF. A comparison of the use of adipose-derived and bone marrow-derived stem cells for peripheral nerve regeneration in vitro and in vivo. Stem Cell Res Ther 2020; 11:153. [PMID: 32272974 PMCID: PMC7147018 DOI: 10.1186/s13287-020-01661-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 01/15/2020] [Accepted: 03/23/2020] [Indexed: 01/08/2023] Open
Abstract
Background To date, it has repeatedly been demonstrated that infusing bone marrow-derived stem cells (BMSCs) into acellular nerve scaffolds can promote and support axon regeneration through a peripheral nerve defect. However, harvesting BMSCs is an invasive and painful process fraught with a low cellular yield. Methods In pursuit of alternative stem cell sources, we isolated stem cells from the inguinal subcutaneous adipose tissue of adult Sprague–Dawley rats (adipose-derived stem cells, ADSCs). We used a co-culture system that allows isolated adult mesenchymal stem cells (MSCs) and Schwann cells (SCs) to grow in the same culture medium but without direct cellular contact. We verified SC phenotype in vitro by cell marker analysis and used red fluorescent protein-tagged ADSCs to detect their fate after being injected into a chemically extracted acellular nerve allograft (CEANA). To compare the regenerative effects of CEANA containing either BMSCs or ADSCs with an autograft and CEANA only on the sciatic nerve defect in vivo, we performed histological and functional assessments up to 16 weeks after grafting. Results In vitro, we observed reciprocal beneficial effects of ADSCs and SCs in the ADSC–SC co-culture system. Moreover, ADSCs were able to survive in CEANA for 5 days after in vitro implantation. Sixteen weeks after grafting, all results consistently showed that CEANA infused with BMSCs or ADSCs enhanced injured sciatic nerve repair compared to the acellular CEANA-only treatment. Furthermore, their beneficial effects on sciatic injury regeneration were comparable as histological and functional parameters evaluated showed no statistically significant differences. However, the autograft group was roundly superior to both the BMSC- or ADSC-loaded CEANA groups. Conclusion The results of the present study show that ADSCs are a viable alternative stem cell source for treating sciatic nerve injury in lieu of BMSCs.
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Affiliation(s)
- Li Na Zhou
- Department of Anatomy, School of basic medical sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, 510006, Guangdong, China.
| | - Jia Chuan Wang
- Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | | | - Ya Qiong Wang
- Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Wen Ping Guo
- Department of Anatomy, School of basic medical sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Sai Xia Zhang
- Department of Anatomy, School of basic medical sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Hui Luo
- Department of Anatomy, School of basic medical sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Jian Hong Zhou
- Department of Anatomy, School of basic medical sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Ru Dong Deng
- Department of Anatomy, School of basic medical sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Dong Feng Chen
- Department of Anatomy, School of basic medical sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, 510006, Guangdong, China.
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Integrin β1 in Adipose-Derived Stem Cells Accelerates Wound Healing via Activating PI3K/AKT Pathway. Tissue Eng Regen Med 2020; 17:183-192. [PMID: 32200515 DOI: 10.1007/s13770-019-00229-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 10/27/2019] [Accepted: 11/01/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND This study aims to investigate the effect of integrin β1 on wound healing induced by adipose-derived stem cells (ADSCs), as well as the corresponding mechanism. METHODS Integrin β1 was overexpressed in ADSCs. Thereafter, flow cytometry and transwell chambers technology were used to measure the endothelial-like differentiation (CD31 as a biomarker of endothelial cell) and cell migration, respectively. Western blot was used to detect the activation of PI3K/AKT, NF-κB and ERK signaling pathways. The effects of integrin β1 overexpression on healing time, healing rate and fibroblast number were further evaluated in the rat models of chronic refractory wound. RESULTS The overexpression of integrin β1 increased CD31+ endothelial-like cells (about 3.6-fold), promoted cell migration (about 1.9-fold) and enhanced the activation of PI3K (p-PI3K; about 2.1-fold) and AKT (p-AKT; about 2.2-fold). These effects were all weakened when PI3K/AKT pathway was inhibited by LY294002 treatment. In addition, the experiments in rat wound models showed that integrin β1 overexpression obviously shortened healing time (approximately 0.41-fold), increased healing rate (about 2.7-fold, 2.8-fold and 1.6-fold at day 7, 14 and 21) and increased the number of fibroblasts (approximately 3.1-fold at day 21). All of the above differences were statistically significant (p < 0.05). CONCLUSION Integrin β1 can promote the migration and endothelial-like differentiation of ADSCs by activating PI3K/AKT pathway and then enhance the function of ADSCs in promoting wound healing.
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The Role of Adipose-Derived Stem Cells, Dermal Regenerative Templates, and Platelet-Rich Plasma in Tissue Engineering-Based Treatments of Chronic Skin Wounds. Stem Cells Int 2020; 2020:7056261. [PMID: 32399048 PMCID: PMC7199611 DOI: 10.1155/2020/7056261] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 11/29/2019] [Indexed: 12/12/2022] Open
Abstract
The continuous improvements in the field of both regenerative medicine and tissue engineering have allowed the design of new and more efficacious strategies for the treatment of chronic or hard-to-heal skin wounds, which represent heavy burden, from a medical and economic point of view. These novel approaches are based on the usage of three key methodologies: stem cells, growth factors, and biomimetic scaffolds. These days, the adipose tissue can be considered the main source of multipotent mesenchymal stem cells, especially adipose-derived stem cells (ASCs). ASCs are easily accessible from various fat depots and show an intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. ASCs can be found in fat grafts, historically used in the treatment of chronic wounds, and have been evaluated as such in both animal models and human trials, to exploit their capability of accelerating wound closure and inducing a correct remodeling of the newly formed fibrovascular tissue. Since survival and fitness of ASCs need to be improved, they are now employed in conjunction with advanced wound dressings, together with dermal regenerative templates and platelet-rich plasma (as a source of growth and healing factors). In this work, we provide an overview of the current knowledge on the topic, based on existing studies and on our own experience.
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Silk fibroin for skin injury repair: Where do things stand? Adv Drug Deliv Rev 2020; 153:28-53. [PMID: 31678360 DOI: 10.1016/j.addr.2019.09.003] [Citation(s) in RCA: 166] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 09/12/2019] [Accepted: 09/26/2019] [Indexed: 12/29/2022]
Abstract
Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed. STATEMENT OF SIGNIFICANCE: Silk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications.
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Li L, Ngo HT, Hwang E, Wei X, Liu Y, Liu J, Yi TH. Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cell Culture Prevents UVB-Induced Skin Aging in Human Keratinocytes and Dermal Fibroblasts. Int J Mol Sci 2019; 21:ijms21010049. [PMID: 31861704 PMCID: PMC6981944 DOI: 10.3390/ijms21010049] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/09/2019] [Accepted: 11/14/2019] [Indexed: 02/04/2023] Open
Abstract
Human adipose-derived mesenchymal stem cells-conditioned medium (ADSC-CM) contains cytokines and growth factors that can facilitate the regeneration and repair of various tissues and organs. In the present study, the protective activity of ADSC-CM treatment was investigated in UVB-irradiated human keratinocyte cell line HaCaTs and normal human dermal fibroblasts (NHDFs). It was found that ADSC-CM can modulate the expression of the signaling molecules in the early UVB responsive signaling pathways, including mitogen activated protein kinases (MAPKs), activator protein 1 (AP-1), and nuclear factor kappa B (NF-κB). In addition, ADSC-CM treatment could upregulate antioxidant response element (ARE) such as phase II gene heme oxygenase-1 (HO-1) and increase the expression of collagen synthesis enhancer gene transforming growth factor-β (TGF-β). The expression of matrix metalloproteinase-1 (MMP-1) and procollagen type I synthesis inhibitors such as interleukin-6 (IL-6) was also found to be suppressed upon ADSC-CM treatment. Taken together, our study illustrates the anti-photoaging activities of ADSC-CM in cell-based models.
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Affiliation(s)
- Lu Li
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai SH021, China; (L.L.); (X.W.)
- College of Life Sciences, Kyung Hee University, 1732, Deogyeongdae-ro, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Korea (E.H.); (Y.L.)
| | - Hien T.T. Ngo
- College of Life Sciences, Kyung Hee University, 1732, Deogyeongdae-ro, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Korea (E.H.); (Y.L.)
| | - Eunson Hwang
- College of Life Sciences, Kyung Hee University, 1732, Deogyeongdae-ro, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Korea (E.H.); (Y.L.)
| | - Xuan Wei
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai SH021, China; (L.L.); (X.W.)
| | - Ying Liu
- College of Life Sciences, Kyung Hee University, 1732, Deogyeongdae-ro, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Korea (E.H.); (Y.L.)
| | - Jia Liu
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai SH021, China; (L.L.); (X.W.)
- Correspondence: (J.L.); (T.-H.Y.)
| | - Tae-Hoo Yi
- College of Life Sciences, Kyung Hee University, 1732, Deogyeongdae-ro, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Korea (E.H.); (Y.L.)
- Correspondence: (J.L.); (T.-H.Y.)
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Paganelli A, Benassi L, Pastar I, Pellegrini M, Azzoni P, Vaschieri C, Pisciotta A, Carnevale G, Pellacani G, Magnoni C. In vitro Engineering of a Skin Substitute Based on Adipose-Derived Stem Cells. Cells Tissues Organs 2019; 207:46-57. [PMID: 31261153 DOI: 10.1159/000501071] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 05/21/2019] [Indexed: 11/19/2022] Open
Abstract
In the field of wound healing, stem cell-based strategies are gaining importance for their regenerative potential. Adipose-derived stem cells (ADSCs) are a particular subset of mesenchymal stem cells present in the stromal-vascular fraction of the adipose tissue, today considered very attractive for their relative abundance and accessibility in the human body. However, ADSCs are still not routinely used in normal clinical practice. Several studies have also reported ADSC transplantation in association with biomaterials in an attempt to enhance the local retention and growth rate of the cells. The aim of our study was to evaluate the ability of ADSCs to build a dermal scaffold to be potentially used as a dermal substitute in the field of wound healing, with optimal biocompatibility and mechanical properties. ADSCs were defined as CD90-, CD73-, and CD105-positive cells. ADSCs turned out to be capable of secreting all the main components of the extracellular matrix (ECM) upon stimulation, thus efficiently producing a collagen and fibronectin-containing dermal matrix. We also checked whether the ADSC-produced dermal scaffold could be seeded with keratinocytes. The scaffolding material directly produced by ADSCs has several advantages when compared to the commercially available ones: it is easily obtained from the patients and it is 100% biocompatible and supports cell-ECM interaction. Moreover, it represents a possible powerful therapeutic tool for patients with chronic ulcers since it appears to be potentially grafted with keratinocytes layers, thus bypassing the classical two-step grafting procedure.
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Affiliation(s)
- Alessia Paganelli
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy,
| | - Luisa Benassi
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Irena Pastar
- Department of Dermatology and Cutaneous Surgery, Wound Healing and Regenerative Medicine Research Program, Miami, Florida, USA
| | - Massimo Pellegrini
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.,Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Paola Azzoni
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Cristina Vaschieri
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandra Pisciotta
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Gianluca Carnevale
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Giovanni Pellacani
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Cristina Magnoni
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
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Cohen E, Merzendorfer H. Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications. EXTRACELLULAR SUGAR-BASED BIOPOLYMERS MATRICES 2019; 12. [PMCID: PMC7115017 DOI: 10.1007/978-3-030-12919-4_14] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Chitin is a linear polysaccharide of N-acetylglucosamine, which is highly abundant in nature and mainly produced by marine crustaceans. Chitosan is obtained by hydrolytic deacetylation. Both polysaccharides are renewable resources, simply and cost-effectively extracted from waste material of fish industry, mainly crab and shrimp shells. Research over the past five decades has revealed that chitosan, in particular, possesses unique and useful characteristics such as chemical versatility, polyelectrolyte properties, gel- and film-forming ability, high adsorption capacity, antimicrobial and antioxidative properties, low toxicity, and biocompatibility and biodegradability features. A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. The number of studies in this research field has exploded particularly during the last two decades. Here, we review recent advances in utilizing chitosan and chitosan derivatives in different technical, agricultural, and biomedical fields.
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Affiliation(s)
- Ephraim Cohen
- Department of Entomology, The Robert H. Smith Faculty of Agriculture Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Hans Merzendorfer
- School of Science and Technology, Institute of Biology – Molecular Biology, University of Siegen, Siegen, Germany
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Assisting Rapid Soft-Tissue Expansion with Adipose-Derived Stem Cells: An Experimental Study in a Pig Model. Plast Reconstr Surg 2019; 142:674e-684e. [PMID: 30511978 DOI: 10.1097/prs.0000000000004884] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Rapid tissue expansion has been attempted, aiming at shortening the period of conventional expansion. However, it has scarcely been clinically applied because of its drawbacks such as low expansion efficiency and tissue destruction. Adipose-derived stem cell transplantation is a promising therapeutic method in regenerative medicine. However, its effects on rapid expansion remain poorly understood. METHODS Twenty-four expanders were implanted in the dorsum of 12 pigs. Rapid expansion persisted for 1 week with 20 ml of saline daily. The increased area of the expanded skin was measured. Histologic and ultrastructural analysis and cell tracking were performed. The expression of vascular endothelial growth factor, fibroblast growth factor-2, and epidermal growth factor was also determined. RESULTS The increased area of adipose-derived stem cell-grafted expanded skin (0.91 ± 0.06 cm) was significantly more than the non-adipose-derived stem cell-treated control (0.51 ± 0.05 cm) (p < 0.01). Enhanced tissue regeneration in the adipose-derived stem cell-grafted expanded skin was evidenced by increased skin thickness, proliferating cells, extracellular matrix, and vascularization (113 ± 19/mm versus control 59 ± 14/mm) (all p < 0.05). Higher expression of vascular endothelial growth factor and epidermal growth factor was observed in the adipose-derived stem cell-transplanted expanded skin (p < 0.01 and p < 0.05, respectively), whereas the expression of fibroblast growth factor-2 was higher in the non-adipose-derived stem cell-treated control (p < 0.05). Transmission electron microscopy showed that a high density of collagen fibers could be seen in the adipose-derived stem cell-treated expanded skin. Cell tracking showed that the positively stained cells could be seen. CONCLUSION For rapid tissue expansion, adipose-derived stem cell transplantation may limit tissue destruction and improve the expansion efficiency by promoting tissue regeneration.
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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: 63] [Impact Index Per Article: 9.0] [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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Smith OJ, Jell G, Mosahebi A. The use of fat grafting and platelet-rich plasma for wound healing: A review of the current evidence. Int Wound J 2018; 16:275-285. [PMID: 30460739 DOI: 10.1111/iwj.13029] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 10/16/2018] [Indexed: 12/17/2022] Open
Abstract
Fat grafting is becoming a common procedure in regenerative medicine because of its high content of growth factors and adipose derived stem cells (ADSCs) and the ease of harvest, safety, and low cost. The high concentration of ADSCs found in fat has the potential to differentiate into a wide range of wound-healing cells including fibroblasts and keratinocytes as well as demonstrating proangiogenic qualities. This suggests that fat could play an important role in wound healing. However retention rates of fat grafts are highly variable due in part to inconsistent vascularisation of the transplanted fat. Furthermore, conditions such as diabetes, which have a high prevalence of chronic wounds, reduce the potency and regenerative potential of ADSCs. Platelet-rich plasma (PRP) is an autologous blood product rich in growth factors, cell adhesion molecules, and cytokines. It has been hypothesised that PRP may have a positive effect on the survival and retention of fat grafts because of improved proliferation and differentiations of ADSCs, reduced inflammation, and improved vascularisation. There is also increasing interest in a possible synergistic effect that PRP may have on the healing potential of fat, although the evidence for this is very limited. In this review, we evaluate the evidence in both in vitro and animal studies on the mechanistic relationship between fat and PRP and how this translates to a benefit in wound healing. We also discuss future directions for both research and clinical practice on how to enhance the regenerative potential of the combination of PRP and fat.
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Affiliation(s)
- Oliver J Smith
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
| | - Gavin Jell
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Ash Mosahebi
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
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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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Xu Q, A S, Gao Y, Guo L, Creagh-Flynn J, Zhou D, Greiser U, Dong Y, Wang F, Tai H, Liu W, Wang W, Wang W. A hybrid injectable hydrogel from hyperbranched PEG macromer as a stem cell delivery and retention platform for diabetic wound healing. Acta Biomater 2018; 75:63-74. [PMID: 29803782 DOI: 10.1016/j.actbio.2018.05.039] [Citation(s) in RCA: 203] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 05/09/2018] [Accepted: 05/24/2018] [Indexed: 12/15/2022]
Abstract
The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system was fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform. The new HP-PEGs were synthesized via in situ reversible addition fragmentation chain transfer (RAFT) polymerization using an FDA approved anti-alcoholic drug-Disulfiram (DS) as the RAFT agent precursor. HP-PEGs can form injectable hydrogels with HA-SH rapidly via thiol-ene click reaction under physiological conditions. The hydrogels exhibited stable mechanical properties, non-swelling and anti-fouling properties. Hydrogels encapsulating adipose-derived stem cells (ADSCs) have demonstrated promising regenerative capabilities such as the maintenance of ADSCs' stemness and secretion abilities. The ADSCs embedded hydrogels were tested on the treatment of diabetic wound in a diabetic murine animal model, showing enhanced wound healing. STATEMENT OF SIGNIFICANCE Diabetic wounds, which are a severe type of diabetes, have become one of the most serious clinical problems. There is a great promise in the delivery of adipose stem cells into wound sites using injectable hydrogels that can improve diabetic wound healing. Due to the biocompatibility of poly(ethylene glycol) diacrylate (PEGDA), we developed an in situ RAFT polymerization approach using anti-alcoholic drug-Disulfiram (DS) as a RAFT agent precursor to achieve hyperbranched PEGDA (HP-PEG). HP-PEG can form an injectable hydrogel by crosslinking with thiolated hyaluronic acid (HA-SH). ADSCs can maintain their regenerative ability and be delivered into the wound sites. Hence, diabetic wound healing process was remarkably promoted, including inhibition of inflammation, enhanced angiogenesis and re-epithelialization. Taken together, the ADSCs-seeded injectable hydrogel may be a promising candidate for diabetic wound treatment.
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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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Cheng G, Davoudi Z, Xing X, Yu X, Cheng X, Li Z, Deng H, Wang Q. Advanced Silk Fibroin Biomaterials for Cartilage Regeneration. ACS Biomater Sci Eng 2018; 4:2704-2715. [DOI: 10.1021/acsbiomaterials.8b00150] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Gu Cheng
- Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan 430079, China
- Hubei International Scientific and Technological Cooperation Base of Sustainable Resource and Energy, School of Resource and Environmental Science, Wuhan University, Wuhan 430079, China
| | - Zahra Davoudi
- Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa 50014, United States
| | - Xin Xing
- Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan 430079, China
| | - Xin Yu
- Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan 430079, China
| | - Xin Cheng
- Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan 430079, China
| | - Zubing Li
- Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan 430079, China
| | - Hongbing Deng
- Hubei International Scientific and Technological Cooperation Base of Sustainable Resource and Energy, School of Resource and Environmental Science, Wuhan University, Wuhan 430079, China
| | - Qun Wang
- Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa 50014, United States
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