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Huang W, Hill JC, Patel S, Richards TD, Sultan I, Kaczorowski DJ, Phillippi JA. Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm. Am J Physiol Heart Circ Physiol 2025; 328:H1130-H1143. [PMID: 40214073 DOI: 10.1152/ajpheart.00834.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/31/2024] [Accepted: 03/20/2025] [Indexed: 05/01/2025]
Abstract
Pericytes exhibit progenitor cell-like qualities and associate with the vasa vasorum-vital microvessels nourishing larger arteries and veins. How pericytes change in human ascending thoracic aortic aneurysm (ATAA) remains unknown. Here, we used the public single-nuclei sequencing data to reveal a contractile phenotype transition of pericytes in human ATAA specimens. In addition, we found that a protective factor, fibroblast growth factor 2 (FGF2), is decreased in the aortic adventitia of both male and female patients with ATAA and impacts pericytes. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic phenotype via MAPK and PI3K-AKT signaling pathways. These findings suggested the latent engagement of pericytes in ATAA, providing insights that could guide the development of new therapies against aortic disease.NEW & NOTEWORTHY Here, we revealed that pericytes transition into a contractile phenotype in human ATAA. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic stage via MAPK and PI3K-AKT signaling pathway, whereas we found FGF2 is decreased in the aortic adventitia of patients with ATAA. Our findings suggest how growth factor deficiency in the microenvironment affects pericytes during ATAA, offering leads for potential new therapies for aortic diseases.
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Affiliation(s)
- Weijian Huang
- Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Department of Cardiac Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Jennifer C Hill
- Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Sakshi Patel
- Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Tara D Richards
- Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Ibrahim Sultan
- Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
| | - David J Kaczorowski
- Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
| | - Julie A Phillippi
- Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
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Niu H, Liu Z, Guan Y, Wen J, Dang Y, Guan J. Harnessing synergistic effects of MMP-2 Inhibition and bFGF to simultaneously preserve and vascularize cardiac extracellular matrix after myocardial infarction. Acta Biomater 2025; 191:189-204. [PMID: 39532649 DOI: 10.1016/j.actbio.2024.10.050] [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: 08/12/2024] [Revised: 10/15/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
Myocardial infarction (MI) leads to cardiac extracellular matrix (ECM) degradation and fibrosis, reducing heart function. Consequently, simultaneously addressing ECM degradation and inhibiting cardiac fibrosis is essential for preserving heart function and mitigating adverse remodeling. However, the preserved ECM becomes unstable if not vascularized, as its structure and composition undergo changes over time. ECM vascularization is crucial to improve cardiac function. Presently, there is no clinically approved therapy that can simultaneously preserve and vascularize the ECM, and inhibit cardiac fibrosis. Our study develops a drug delivery system aiming to achieve these goals. It includes the peptide CTTHWGFTLC (CTT), a specific MMP-2 inhibitor, and basic fibroblast growth factor (bFGF), a potent factor with pro-angiogenic and anti-fibrotic properties. An injectable hydrogel serves as the carrier, featuring a rapid gelation that allows for the substantial retention of drugs. Additionally, the hydrogel has the capability to scavenge upregulated reactive oxygen species (ROS), thereby reducing tissue inflammation. Our findings indicate that CTT and bFGF synergistically enhance endothelial cell migration and tube formation while inhibiting the differentiation of fibroblasts into myofibroblasts. Upon delivery into hearts, the system significantly decreases MMP-2 level, promotes angiogenesis, attenuates cardiac fibrosis, and alleviates inflammation, resulting in a noteworthy cardiac function improvement. STATEMENT OF SIGNIFICANCE: 1) This work addresses key challenges in cardiac repair after myocardial infarction (MI), including extracellular matrix (ECM) degradation, vascularization, and fibrosis. 2) We combined an MMP-2/9 inhibitor (CTT) with bFGF to prevent ECM degradation, enhance vascularization, and inhibit fibrosis, providing a comprehensive strategy to improve cardiac function. 3) An injectable hydrogel was developed with rapid gelation and mechanical properties similar to heart tissue, ensuring efficient drug retention and reducing tissue stress. 4) The hydrogel enabled controlled, spatiotemporal release of CTT to dynamically reduce MMP-2/9 activity, and gradually released bFGF to promote angiogenesis and inhibit fibrosis.
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Affiliation(s)
- Hong Niu
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, USA; Center of Regenerative Medicine, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
| | - Zhongting Liu
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, USA; Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Ya Guan
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, USA; Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Jiaxing Wen
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, USA; Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Yu Dang
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, USA; Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Jianjun Guan
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, USA; Center of Regenerative Medicine, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA.
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Doherty EL, Krohn G, Warren EC, Patton A, Whitworth CP, Rathod M, Biehl A, Aw WY, Freytes DO, Polacheck WJ. Human Cell-Derived Matrix Composite Hydrogels with Diverse Composition for Use in Vasculature-on-chip Models. Adv Healthc Mater 2024; 13:e2400192. [PMID: 38518808 PMCID: PMC11281875 DOI: 10.1002/adhm.202400192] [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: 02/16/2024] [Revised: 03/19/2024] [Indexed: 03/24/2024]
Abstract
Microphysiological and organ-on-chip platforms seek to address critical gaps in human disease models and drug development that underlie poor rates of clinical success for novel interventions. While the fabrication technology and model cells used to synthesize organs-on-chip have advanced considerably, most platforms rely on animal-derived or synthetic extracellular matrix as a cell substrate, limiting mimicry of human physiology and precluding use in modeling diseases in which matrix dynamics play a role in pathogenesis. Here, the development of human cell-derived matrix (hCDM) composite hydrogels for use in 3D microphysiologic models of the vasculature is reported. hCDM composite hydrogels are derived from human donor fibroblasts and maintain a complex milieu of basement membrane, proteoglycans, and nonfibrillar matrix components. The use of hCDM composite hydrogels as 2D and 3D cell culture substrates is demonstrated, and hCDM composite hydrogels are patterned to form engineered human microvessels. Interestingly, hCDM composite hydrogels are enriched in proteins associated with vascular morphogenesis as determined by mass spectrometry, and functional analysis demonstrates proangiogenic signatures in human endothelial cells cultured in these hydrogels. In conclusion, this study suggests that human donor-derived hCDM composite hydrogels could address technical gaps in human organs-on-chip development and serve as substrates to promote vascularization.
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Affiliation(s)
- Elizabeth L Doherty
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - Grace Krohn
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - Emily C Warren
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - Alexandra Patton
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - Chloe P Whitworth
- Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill School of Medicine, 130 Mason Farm Road, Chapel Hill, Carolina, NC 27599, USA
| | - Mitesh Rathod
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - Andreea Biehl
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - Wen Yih Aw
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - Donald O Freytes
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
| | - William J Polacheck
- The Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 10010 Mary Ellen Jones Building, 116 Manning Drive, Chapel Hill, NC 27514, USA
- Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, 111 Mason Farm Road, Chapel Hill, Carolina, NC 27599, USA
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Khodayari H, Khodayari S, Rezaee M, Rezaeiani S, Alipour Choshali M, Erfanian S, Muhammadnejad A, Nili F, Pourmehran Y, Pirjani R, Rajabi S, Aghdami N, Nebigil-Désaubry C, Wang K, Mahmoodzadeh H, Pahlavan S. Promotion of cardiac microtissue assembly within G-CSF-enriched collagen I-cardiogel hybrid hydrogel. Regen Biomater 2024; 11:rbae072. [PMID: 38974665 PMCID: PMC11226883 DOI: 10.1093/rb/rbae072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/20/2024] [Accepted: 06/10/2024] [Indexed: 07/09/2024] Open
Abstract
Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a well-cellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31+ tube-like structures as well as vimentin+ cardiac fibroblasts and cTNT+ human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico-identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis.
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Affiliation(s)
- Hamid Khodayari
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
- Department of Developmental Biology, University of Science and Culture, Tehran 13145-871, Iran
| | - Saeed Khodayari
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran
| | - Malihe Rezaee
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
| | - Siamak Rezaeiani
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
| | - Mahmoud Alipour Choshali
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
| | - Saiedeh Erfanian
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
- Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
| | - Ahad Muhammadnejad
- Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran
| | - Fatemeh Nili
- Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1419733141, Iran
| | - Yasaman Pourmehran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
- Department of Developmental Biology, University of Science and Culture, Tehran 13145-871, Iran
| | - Reihaneh Pirjani
- Obstetrics and Gynecology Department, Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran 1653915981, Iran
| | - Sarah Rajabi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
- Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
| | - Naser Aghdami
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran 19395-4644, Iran
| | - Canan Nebigil-Désaubry
- Institute National de le santé et de la recherce médicale, INSERM, University of Strasbourg, UMR 1260-Regenerative Nanomedicine, CRBS, Central of Research in biomedicine of Strasbourg, Strasbourg 90032, France
| | - Kai Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
| | - Habibollah Mahmoodzadeh
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran
| | - Sara Pahlavan
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran
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Guo W, Liu H, Zhang J, Zhang J, Wang F, Zhang P, Yang Y. Preparation and characterization of a novel composite acellular matrix/hyaluronic acid thermosensitive hydrogel for interstitial cystitis/bladder pain syndrome. J Biomed Mater Res A 2024; 112:449-462. [PMID: 37975156 DOI: 10.1002/jbm.a.37643] [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: 02/13/2023] [Revised: 10/14/2023] [Accepted: 10/25/2023] [Indexed: 11/19/2023]
Abstract
Bladder mucosa damage that causes harm to the interstitium is a recognized pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). The intravesical instillation of drugs is an important second-line therapy, but it is often necessary to use drugs repeatedly in the clinic because of their short residence time in the bladder cavity, which alters the therapeutic effect. To overcome this drawback, this study developed a novel composite acellular matrix/hyaluronic acid (HA) thermosensitive hydrogel (HA-Gel) using rabbit small intestinal submucosa extracellular matrix (ECM) as the thermosensitive material and HA as the drug component and examined its composition, microstructure, thermodynamic properties, temperature sensitivity, rheological properties, biocompatibility, drug release, hydrogel residue, and bacteriostatic properties. The study showed HA-Gel was liquid at temperatures of 15-37.5°C and solid at 37.5-50°C, its swelling rate decreased with increasing temperature, and its lower critical solution temperature occurred at approximately 37.5°C. This property made the hydrogel liquid at room temperature convenient for intravesical perfusion and turned into a solid about 1 min after entering the body and rising to body temperature to increase its residence time. Subsequent experiments also proved that the gel residue time of HA-Gel in vivo and the drug release time of HA in vivo could reach more than 5 days, which was significantly higher than that of HA alone, and it had good biocompatibility and antibacterial properties. Therefore, this hydrogel possesses the proper characteristics to possibly make it an ideal dosage form for IC/BPS intravesical instillation therapy.
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Affiliation(s)
- Wei Guo
- Department of Urology, Beijing Chao-Yang Hospital, Beijing, China
| | - Haichao Liu
- Department of Urology, Hebei Yanda Hospital, West of SiPuLan Road, Langfang, China
| | - Jiaxing Zhang
- Department of Urology, Hebei Yanda Hospital, West of SiPuLan Road, Langfang, China
| | - Jianzhong Zhang
- Department of Urology, Beijing Chao-Yang Hospital, Beijing, China
| | - Fei Wang
- Department of Urology, Beijing Chao-Yang Hospital, Beijing, China
| | - Peng Zhang
- Department of Urology, Beijing Chao-Yang Hospital, Beijing, China
| | - Yunbo Yang
- Department of Urology, Hebei Yanda Hospital, West of SiPuLan Road, Langfang, China
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Guo X, Liu B, Zhang Y, Cheong S, Xu T, Lu F, He Y. Decellularized extracellular matrix for organoid and engineered organ culture. J Tissue Eng 2024; 15:20417314241300386. [PMID: 39611117 PMCID: PMC11603474 DOI: 10.1177/20417314241300386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 11/01/2024] [Indexed: 11/30/2024] Open
Abstract
The repair and regeneration of tissues and organs using engineered biomaterials has attracted great interest in tissue engineering and regenerative medicine. Recent advances in organoids and engineered organs technologies have enabled scientists to generate 3D tissue that recapitulate the structural and functional characteristics of native organs, opening up new avenues in regenerative medicine. The matrix is one of the most important aspects for improving organoids and engineered organs construction. However, the clinical application of these techniques remained a big challenge because current commercial matrix does not represent the complexity of native microenvironment, thereby limiting the optimal regenerative capacity. Decellularized extracellular matrix (dECM) is expected to maintain key native matrix biomolecules and is believed to hold enormous potential for regenerative medicine applications. Thus, it is worth investigating whether the dECM can be used as matrix for improving organoid and engineered organs construction. In this review, the characteristics of dECM and its preparation method were summarized. In addition, the present review highlights the applications of dECM in the fabrication of organoids and engineered organs.
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Affiliation(s)
- Xiaoxu Guo
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Boxun Liu
- Research and Development Department, Huamei Biotech Co. Ltd., Shenzhen, China
| | - Yi Zhang
- Research and Development Department, Huamei Biotech Co. Ltd., Shenzhen, China
| | - Sousan Cheong
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Tao Xu
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, People’s Republic of China
- Bio-intelligent Manufacturing and Living Matter Bioprinting Center, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen, People’s Republic of China
| | - Feng Lu
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yunfan He
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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Cui L, Zhao Y, Zhong Y, Zhang L, Zhang X, Guo Z, Wang F, Chen X, Tong H, Fan J. Combining decellularized adipose tissue with decellularized adventitia extravascular matrix or small intestinal submucosa matrix for the construction of vascularized tissue-engineered adipose. Acta Biomater 2023; 170:567-579. [PMID: 37683968 DOI: 10.1016/j.actbio.2023.08.060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 08/24/2023] [Accepted: 08/31/2023] [Indexed: 09/10/2023]
Abstract
Adipose tissue is an endocrine organ. It serves many important functions, such as energy storage, hormones secretion, and providing insulation, cushioning and aesthetics to the body etc. Adipose tissue engineering offers a promising treatment for soft tissue defects. Early adipose tissue production and long-term survival are closely associated with angiogenesis. Decellularized matrix has a natural ECM (extracellular matrix) component, good biocompatibility, and low immunogenicity. Therefore, in this study, the injectable composite hydrogels were developed to construct vascularized tissue-engineered adipose by using the pro-angiogenic effects of aortic adventitia extravascular matrix (Adv) or small intestinal submucosa (SIS), and the pro-adipogenic effects of decellularized adipose tissue (DAT). The composite hydrogels were cross-linked by genipin. The adipogenic and angiogenic abilities of composite hydrogels were investigated in vitro, and in a rat dorsal subcutaneous implant model. The results showed that DAT and SIS or Adv 1:1 composite hydrogel promoted the migration and tube formation of endothelial cells. Furthermore, DAT and SIS or Adv 1:1 composite hydrogel enhanced adipogenic differentiation of adipose-derived mesenchymal stem cells (ASCs) through activation of PPARγ and C/EBPα. The in vivo studies further demonstrated that DAT with SIS or Adv in a 1:1 ratio also significantly promoted adipogenesis and angiogenesis. In addition, DAT with SIS or Adv in a 1:1 ratio hydrogel recruited macrophage population with enhanced M2-type macrophage polarization, suggesting a positive effect of inflammatory response on angiogenesis. In conclusion, these data suggest that the composite hydrogels of DAT with SIS or Adv in 1:1 ratio have apparent pro-adiogenic and angiogenic abilities, thus providing a promising cell-free tissue engineering biomaterial with broad clinical applications. STATEMENT OF SIGNIFICANCE: Decellularized adipose tissue (DAT) has emerged as an important biomaterial in adipose tissue regeneration. Early adipose tissue production and long-term survival is tightly related to the angiogenesis. The revascularization of the DAT is a key issue that needs to be solved in adipose regeneration. In this study, the injectable composite hydrogels were developed by using DAT with Adv (aortic adventitia extravascular matrix) or SIS (small intestinal submucosa) in different ratio. We demonstrated that the combination of DAT with SIS or Adv in 1:1 ratio effectively improved the proliferation of adipose stem cells and endothelial cells, and promoted greater adipose regeneration and tissue vascularization as compared to the DAT scaffold. This study provides the potential biomaterial for clinical soft tissue regeneration.
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Affiliation(s)
- Lu Cui
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Yujia Zhao
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Yuxuan Zhong
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Lanlan Zhang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Xinnan Zhang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Zhenglong Guo
- Second Clinical Medical College, Shengjing Hospital, China Medical University, No.36 Sanhao Road, Heping District, Shenyang, Liaoning Province 110004, PR China
| | - Fanglin Wang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Xin Chen
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Hao Tong
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Jun Fan
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China.
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Shirasu T, Yodsanit N, Li J, Huang Y, Xie X, Tang R, Wang Q, Zhang M, Urabe G, Webb A, Wang Y, Wang X, Xie R, Wang B, Kent KC, Gong S, Guo LW. Neointima abating and endothelium preserving - An adventitia-localized nanoformulation to inhibit the epigenetic writer DOT1L. Biomaterials 2023; 301:122245. [PMID: 37467597 PMCID: PMC10530408 DOI: 10.1016/j.biomaterials.2023.122245] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 06/05/2023] [Accepted: 07/12/2023] [Indexed: 07/21/2023]
Abstract
Open vascular reconstructions such as bypass are common treatments for cardiovascular disease. Unfortunately, neointimal hyperplasia (IH) follows, leading to treatment failure for which there is no approved therapy. Here we combined the strengths of tailoring nanoplatforms for open vascular reconstructions and targeting new epigenetic mechanisms. We produced adhesive nanoparticles (ahNP) that could be pen-brushed and immobilized on the adventitia to sustainably release pinometostat, an inhibitor drug selective to the epigenetic writer DOT1L that catalyzes histone-3 lysine-79 dimethylation (H3K79me2). This treatment not only reduced IH by 76.8% in injured arteries mimicking open reconstructions in obese Zucker rats with human-like diseases but also avoided the shortcoming of endothelial impairment in IH management. In mechanistic studies, chromatin immunoprecipitation (ChIP) sequencing revealed co-enrichment of the histone mark H3K27ac(acetyl) and its reader BRD4 at the gene of aurora kinase B (AURKB), where H3K79me2 was also enriched as indicated by ChIP-qPCR. Accordingly, DOT1L co-immunoprecipitated with H3K27ac. Furthermore, the known IH driver BRD4 governed the expression of DOT1L which controlled AURKB's protein level, revealing a BRD4- > DOT1L- > AURKB axis. Consistently, AURKB-selective inhibition reduced IH. Thus, this study presents a prototype nanoformulation suited for open vascular reconstructions, and the new insights into chromatin modulators may aid future translational advances.
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Affiliation(s)
- Takuro Shirasu
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Nisakorn Yodsanit
- Department of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA
| | - Jing Li
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Yitao Huang
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA; The Biomedical Sciences Graduate Program (BIMS), School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Xiujie Xie
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Runze Tang
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Qingwei Wang
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Mengxue Zhang
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Go Urabe
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - Amy Webb
- Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Yuyuan Wang
- Department of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA
| | - Xiuxiu Wang
- Department of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA
| | - Ruosen Xie
- Department of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA
| | - Bowen Wang
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA
| | - K Craig Kent
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
| | - Shaoqin Gong
- Department of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA.
| | - Lian-Wang Guo
- Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, 22908, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA.
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9
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Nicosia A, Salamone M, Costa S, Ragusa MA, Ghersi G. Mimicking Molecular Pathways in the Design of Smart Hydrogels for the Design of Vascularized Engineered Tissues. Int J Mol Sci 2023; 24:12314. [PMID: 37569691 PMCID: PMC10418696 DOI: 10.3390/ijms241512314] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 07/21/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
Biomaterials are pivotal in supporting and guiding vascularization for therapeutic applications. To design effective, bioactive biomaterials, understanding the cellular and molecular processes involved in angiogenesis and vasculogenesis is crucial. Biomaterial platforms can replicate the interactions between cells, the ECM, and the signaling molecules that trigger blood vessel formation. Hydrogels, with their soft and hydrated properties resembling natural tissues, are widely utilized; particularly synthetic hydrogels, known for their bio-inertness and precise control over cell-material interactions, are utilized. Naturally derived and synthetic hydrogel bases are tailored with specific mechanical properties, controlled for biodegradation, and enhanced for cell adhesion, appropriate biochemical signaling, and architectural features that facilitate the assembly and tubulogenesis of vascular cells. This comprehensive review showcases the latest advancements in hydrogel materials and innovative design modifications aimed at effectively guiding and supporting vascularization processes. Furthermore, by leveraging this knowledge, researchers can advance biomaterial design, which will enable precise support and guidance of vascularization processes and ultimately enhance tissue functionality and therapeutic outcomes.
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Affiliation(s)
- Aldo Nicosia
- Institute for Biomedical Research and Innovation-National Research Council (IRIB-CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy;
| | - Monica Salamone
- Institute for Biomedical Research and Innovation-National Research Council (IRIB-CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy;
| | - Salvatore Costa
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy; (S.C.); (M.A.R.); (G.G.)
| | - Maria Antonietta Ragusa
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy; (S.C.); (M.A.R.); (G.G.)
| | - Giulio Ghersi
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy; (S.C.); (M.A.R.); (G.G.)
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Xiao P, Zhang Y, Zeng Y, Yang D, Mo J, Zheng Z, Wang J, Zhang Y, Zhou Z, Zhong X, Yan W. Impaired angiogenesis in ageing: the central role of the extracellular matrix. J Transl Med 2023; 21:457. [PMID: 37434156 PMCID: PMC10334673 DOI: 10.1186/s12967-023-04315-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 06/30/2023] [Indexed: 07/13/2023] Open
Abstract
Each step in angiogenesis is regulated by the extracellular matrix (ECM). Accumulating evidence indicates that ageing-related changes in the ECM driven by cellular senescence lead to a reduction in neovascularisation, reduced microvascular density, and an increased risk of tissue ischaemic injury. These changes can lead to health events that have major negative impacts on quality of life and place a significant financial burden on the healthcare system. Elucidating interactions between the ECM and cells during angiogenesis in the context of ageing is neceary to clarify the mechanisms underlying reduced angiogenesis in older adults. In this review, we summarize ageing-related changes in the composition, structure, and function of the ECM and their relevance for angiogenesis. Then, we explore in detail the mechanisms of interaction between the aged ECM and cells during impaired angiogenesis in the older population for the first time, discussing diseases caused by restricted angiogenesis. We also outline several novel pro-angiogenic therapeutic strategies targeting the ECM that can provide new insights into the choice of appropriate treatments for a variety of age-related diseases. Based on the knowledge gathered from recent reports and journal articles, we provide a better understanding of the mechanisms underlying impaired angiogenesis with age and contribute to the development of effective treatments that will enhance quality of life.
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Affiliation(s)
- Ping Xiao
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yanli Zhang
- Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Yuting Zeng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Dehong Yang
- Department of Orthopedics Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jiayao Mo
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ziting Zheng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jilei Wang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yuxin Zhang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Zhiyan Zhou
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xincen Zhong
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Wenjuan Yan
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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11
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Hatlen RR, Rajagopalan P. Investigating Trans-differentiation of Glioblastoma Cells in an In Vitro 3D Model of the Perivascular Niche. ACS Biomater Sci Eng 2023. [PMID: 37129167 DOI: 10.1021/acsbiomaterials.2c01310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Glioblastoma multiforme (GBM) is the deadliest form of brain cancer, responsible for over 50% of adult brain tumors. A specific region within the GBM environment is known as the perivascular niche (PVN). This area is defined as within approximately 100 μm of vasculature and plays an important role in the interactions between endothelial cells (ECs), astrocytes, GBM cells, and stem cells. We have designed a 3D in vitro model of the PVN comprising either collagen Type 1 or HyStem-C, human umbilical vein ECs (HUVECs), and LN229 (GBM) cells. HUVECs were encapsulated within the hydrogels to form vascular networks. After 7 days, LN229 cells were co-cultured to investigate changes in both cell types. Over a 14 day culture period, we measured alterations in HUVEC networks, the contraction of the hydrogels, trans-differentiation of LN229 cells, and the concentrations of two chemokines; CXCL12 and TGF-β. Increased cellular proliferation ranging from 10- to 16-fold was exhibited in co-cultures from days 8 to 14. This was accompanied with a decrease in the height of hydrogels of up to 68%. These changes in the biomaterial scaffold indicate that LN229-HUVEC interactions promote changes to the matrix. TGF-β and CXCL12 secretion increased approximately 2-2.6-fold each from day 8 to 14 in all co-cultures. The expression of CXCL12 correlated with cell colocalization, indicating a chemotactic role in enabling the migration of LN229 cells toward HUVECs in co-cultures. von Willebrand factor (vWF) was co-expressed with glial fibrillary acidic protein (GFAP) in up to 15% of LN229 cells after 24 h in co-culture. Additionally, when LN229 cells were co-cultured with human brain microvascular ECs, the percentages of GFAP+/vWF+ cells were up to 20% higher than that in co-cultures with HUVECs in collagen (2.2 mg/mL) and HyStem-C gels on day 14. The expression of vWF indicates the early stages of trans-differentiation of LN229 cells to an EC phenotype. Designing in vitro models of trans-differentiation may provide additional insights into how vasculature and cellular phenotypes are altered in GBM.
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Affiliation(s)
- Rosalyn R Hatlen
- Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States
| | - Padmavathy Rajagopalan
- Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States
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12
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Zhao X, Amevor FK, Xue X, Wang C, Cui Z, Dai S, Peng C, Li Y. Remodeling the hepatic fibrotic microenvironment with emerging nanotherapeutics: a comprehensive review. J Nanobiotechnology 2023; 21:121. [PMID: 37029392 PMCID: PMC10081370 DOI: 10.1186/s12951-023-01876-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 03/30/2023] [Indexed: 04/09/2023] Open
Abstract
Liver fibrosis could be the last hope for treating liver cancer and remodeling of the hepatic microenvironment has emerged as a strategy to promote the ablation of liver fibrosis. In recent years, especially with the rapid development of nanomedicine, hepatic microenvironment therapy has been widely researched in studies concerning liver cancer and fibrosis. In this comprehensive review, we summarized recent advances in nano therapy-based remodeling of the hepatic microenvironment. Firstly, we discussed novel strategies for regulatory immune suppression caused by capillarization of liver sinusoidal endothelial cells (LSECs) and macrophage polarization. Furthermore, metabolic reprogramming and extracellular matrix (ECM) deposition are caused by the activation of hepatic stellate cells (HSCs). In addition, recent advances in ROS, hypoxia, and impaired vascular remodeling in the hepatic fibrotic microenvironment due to ECM deposition have also been summarized. Finally, emerging nanotherapeutic approaches based on correlated signals were discussed in this review. We have proposed novel strategies such as engineered nanotherapeutics targeting antigen-presenting cells (APCs) or direct targeting T cells in liver fibrotic immunotherapy to be used in preventing liver fibrosis. In summary, this comprehensive review illustrated the opportunities in drug targeting and nanomedicine, and the current challenges to be addressed.
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Affiliation(s)
- Xingtao Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu, 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Felix Kwame Amevor
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China
| | - Xinyan Xue
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu, 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Cheng Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu, 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Zhifu Cui
- College of Animal Science and Technology, Southwest University, Chongqing, 400715, China
| | - Shu Dai
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu, 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu, 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu, 611137, China.
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
- , No. 1166, Liu Tai Avenue, Wenjiang district, Chengdu, Sichuan, China.
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13
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Fok SW, Gresham RCH, Ryan W, Osipov B, Bahney C, Leach JK. Macromolecular crowding and decellularization method increase the growth factor binding potential of cell-secreted extracellular matrices. Front Bioeng Biotechnol 2023; 11:1091157. [PMID: 36756385 PMCID: PMC9899907 DOI: 10.3389/fbioe.2023.1091157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 01/13/2023] [Indexed: 01/25/2023] Open
Abstract
Recombinant growth factors are used in tissue engineering to stimulate cell proliferation, migration, and differentiation. Conventional methods of growth factor delivery for therapeutic applications employ large amounts of these bioactive cues. Effective, localized growth factor release is essential to reduce the required dose and potential deleterious effects. The endogenous extracellular matrix (ECM) sequesters native growth factors through its negatively charged sulfated glycosaminoglycans. Mesenchymal stromal cells secrete an instructive extracellular matrix that can be tuned by varying culture and decellularization methods. In this study, mesenchymal stromal cell-secreted extracellular matrix was modified using λ-carrageenan as a macromolecular crowding (MMC) agent and decellularized with DNase as an alternative to previous decellularized extracellular matrices (dECM) to improve growth factor retention. Macromolecular crowding decellularized extracellular matrix contained 7.7-fold more sulfated glycosaminoglycans and 11.7-fold more total protein than decellularized extracellular matrix, with no significant difference in residual DNA. Endogenous BMP-2 was retained in macromolecular crowding decellularized extracellular matrix, whereas BMP-2 was not detected in other extracellular matrices. When implanted in a murine muscle pouch, we observed increased mineralized tissue formation with BMP-2-adsorbed macromolecular crowding decellularized extracellular matrix in vivo compared to conventional decellularized extracellular matrix. This study demonstrates the importance of decellularization method to retain endogenous sulfated glycosaminoglycans in decellularized extracellular matrix and highlights the utility of macromolecular crowding to upregulate sulfated glycosaminoglycan content. This platform has the potential to aid in the delivery of lower doses of BMP-2 or other heparin-binding growth factors in a tunable manner.
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Affiliation(s)
- Shierly W. Fok
- Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, United States
| | - Robert C. H. Gresham
- Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, United States
| | - Weston Ryan
- Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, United States
| | - Benjamin Osipov
- Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, United States
| | - Chelsea Bahney
- Steadman Philippon Research Institute, Vail, CO, United States
| | - J. Kent Leach
- Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, United States,Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States,*Correspondence: J. Kent Leach,
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14
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Kort-Mascort J, Flores-Torres S, Peza-Chavez O, Jang JH, Pardo LA, Tran SD, Kinsella J. Decellularized ECM hydrogels: prior use considerations, applications, and opportunities in tissue engineering and biofabrication. Biomater Sci 2023; 11:400-431. [PMID: 36484344 DOI: 10.1039/d2bm01273a] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Tissue development, wound healing, pathogenesis, regeneration, and homeostasis rely upon coordinated and dynamic spatial and temporal remodeling of extracellular matrix (ECM) molecules. ECM reorganization and normal physiological tissue function, require the establishment and maintenance of biological, chemical, and mechanical feedback mechanisms directed by cell-matrix interactions. To replicate the physical and biological environment provided by the ECM in vivo, methods have been developed to decellularize and solubilize tissues which yield organ and tissue-specific bioactive hydrogels. While these biomaterials retain several important traits of the native ECM, the decellularizing process, and subsequent sterilization, and solubilization result in fragmented, cleaved, or partially denatured macromolecules. The final product has decreased viscosity, moduli, and yield strength, when compared to the source tissue, limiting the compatibility of isolated decellularized ECM (dECM) hydrogels with fabrication methods such as extrusion bioprinting. This review describes the physical and bioactive characteristics of dECM hydrogels and their role as biomaterials for biofabrication. In this work, critical variables when selecting the appropriate tissue source and extraction methods are identified. Common manual and automated fabrication techniques compatible with dECM hydrogels are described and compared. Fabrication and post-manufacturing challenges presented by the dECM hydrogels decreased mechanical and structural stability are discussed as well as circumvention strategies. We further highlight and provide examples of the use of dECM hydrogels in tissue engineering and their role in fabricating complex in vitro 3D microenvironments.
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Affiliation(s)
| | | | - Omar Peza-Chavez
- Department of Bioengineering, McGill University, Montreal, Quebec, Canada.
| | - Joyce H Jang
- Department of Bioengineering, McGill University, Montreal, Quebec, Canada.
| | | | - Simon D Tran
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Quebec, Canada
| | - Joseph Kinsella
- Department of Bioengineering, McGill University, Montreal, Quebec, Canada.
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15
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Tu J, Zeng Y, An R, Sun J, Wen H. Engineered nanovesicles from stromal vascular fraction promote angiogenesis and adipogenesis inside decellularized adipose tissue through encapsulating growth factors. Sci Rep 2023; 13:750. [PMID: 36639385 PMCID: PMC9839776 DOI: 10.1038/s41598-022-27176-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 12/27/2022] [Indexed: 01/15/2023] Open
Abstract
Acellular matrix is a commonly used biomaterial in the field of biomedical engineering and revascularization is the key process to affect the effect of acellular matrix on tissue regeneration. The application of bioactive factors related to angiogenesis has been popular in the regulation of revascularization, but the immune system clearance, uncontrollable systemic reactions, and other factors make this method face challenges. Recent reports showed that engineered cells into nanovesicles can reorganize cell membranes and encapsulate cellular active factors, extending the in vitro preservation of cytokines. However, the problems of exogenous biological contamination and tumorigenicity restricted the clinical transformation and wide application of this method. Here, we for the first time engineer stromal vascular fraction (SVF) which is extracted from fat into nanovesicles (SVF-EVs) for angiogenesis in the acellular matrix. SVF-EVs not only promote the migration of vascular endothelial cells in vitro, but also facilitate the lipogenic differentiation of mesenchymal stem cells. In vivo, SVF-EVs enhanced the retention of decellularized adipose tissue after transplanting to the subcutaneous area of nude mice. Immunofluorescence staining further showed that SVF-EVs promoted the formation of vascular networks with large lumen diameter in the grafted acellular matrix, accompanied by adipocyte regeneration peripherally. These findings reveal that SVF-EVs can be a viable method for accelerating revascularization in acellular matrix, and this process of squeezing tissue into nanovesicles shows the potential for rapid clinical transformation.
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Affiliation(s)
- Jun Tu
- Department of Plastic, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
| | - Yuyang Zeng
- Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ran An
- Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiaming Sun
- Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huicai Wen
- Department of Plastic, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China.
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16
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Jiménez-Gastélum G, Ramos-Payán R, López-Gutierrez J, Ayala-Ham A, Silva-Benítez E, Bermúdez M, Romero-Quintana JG, Sanchez-Schmitz G, Aguilar-Medina M. An extracellular matrix hydrogel from porcine urinary bladder for tissue engineering: In vitro and in vivo analyses. Biomed Mater Eng 2022:BME221450. [PMID: 37125540 DOI: 10.3233/bme-221450] [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: 05/02/2023]
Abstract
BACKGROUND The necessity to manufacture scaffolds with superior capabilities of biocompatibility and biodegradability has led to the production of extracellular matrix (ECM) scaffolds. Among their advantages, they allow better cell colonization, which enables its successful integration into the hosted tissue, surrounding the area to be repaired and their formulations facilitate placing it into irregular shapes. The ECM from porcine urinary bladder (pUBM) comprises proteins, proteoglycans and glycosaminoglycans which provide support and enable signals to the cells. These properties make it an excellent option to produce hydrogels that can be used in regenerative medicine. OBJECTIVE The goal of this study was to assess the biocompatibility of an ECM hydrogel derived from the porcine urinary bladder (pUBMh) in vitro using fibroblasts, macrophages, and adipose-derived mesenchymal stem cells (AD-MCSs), as well as biocompatibility in vivo using Wistar rats. METHODS Effects upon cells proliferation/viability was measured using MTT assay, cytotoxic effects were analyzed by quantifying lactate dehydrogenase release and the Live/Dead Cell Imaging assay. Macrophage activation was assessed by quantification of IL-6, IL-10, IL-12p70, MCP-1, and TNF-α using a microsphere-based cytometric bead array. For in vivo analysis, Wistar rats were inoculated into the dorsal sub-dermis with pUBMh. The specimens were sacrificed at 24 h after inoculation for histological study. RESULTS The pUBMh obtained showed good consistency and absence of cell debris. The biocompatibility tests in vitro revealed that the pUBMh promoted cell proliferation and it is not cytotoxic on the three tested cell lines and induces the production of pro-inflammatory cytokines on macrophages, mainly TNF-α and MCP-1. In vivo, pUBMh exhibited fibroblast-like cell recruitment, without tissue damage or inflammation. CONCLUSION The results show that pUBMh allows cell proliferation without cytotoxic effects and can be considered an excellent biomaterial for tissue engineering.
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Affiliation(s)
| | - Rosalío Ramos-Payán
- Faculty of Biological and Chemical Sciences, Autonomous University of Sinaloa, Culiacan, Mexico
| | | | - Alfredo Ayala-Ham
- Faculty of Biology, Autonomous University of Sinaloa, Culiacan, Mexico
- Faculty of Odontology, Autonomous University of Sinaloa, Culiacan, Mexico
| | | | - Mercedes Bermúdez
- Faculty of Odontology, Autonomous University of Chihuahua, Chihuahua, Mexico
| | | | - Guzman Sanchez-Schmitz
- Boston Children's Hospital and Harvard Medical School, Harvard University, Boston, MA, USA
| | - Maribel Aguilar-Medina
- Faculty of Biological and Chemical Sciences, Autonomous University of Sinaloa, Culiacan, Mexico
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17
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Wei S, Hu Q, Ma J, Dai X, Sun Y, Han G, Meng H, Xu W, Zhang L, Ma X, Peng J, Wang Y. Acellular nerve xenografts based on supercritical extraction technology for repairing long-distance sciatic nerve defects in rats. Bioact Mater 2022; 18:300-320. [PMID: 35387172 PMCID: PMC8961471 DOI: 10.1016/j.bioactmat.2022.03.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/20/2022] [Accepted: 03/08/2022] [Indexed: 11/18/2022] Open
Abstract
Compared to conventional artificial nerve guide conduits (NGCs) prepared using natural polymers or synthetic polymers, acellular nerve grafts (ACNGs) derived from natural nerves with eliminated immune components have natural bionic advantages in composition and structure that polymer materials do not have. To further optimize the repair effect of ACNGs, in this study, we used a composite technology based on supercritical carbon dioxide (scCO2) extraction to process the peripheral nerve of a large mammal, the Yorkshire pig, and obtained an innovative Acellular nerve xenografts (ANXs, namely, CD + scCO2 NG). After scCO2 extraction, the fat and DNA content in CD + scCO2 NG has been removed to the greatest extent, which can better supported cell adhesion and proliferation, inducing an extremely weak inflammatory response. Interestingly, the protein in the CD + scCO2 NG was primarily involved in signaling pathways related to axon guidance. Moreover, compared with the pure chemical decellularized nerve graft (CD NG), the DRG axons grew naturally on the CD + scCO2 NG membrane and extended long distances. In vivo studies further revealed that the regenerated nerve axons had basically crossed the CD + scCO2 NG 3 weeks after surgery. 12 weeks after surgery, CD + scCO2 NG was similar to autologous nerves in improving the quality of nerve regeneration, target muscle morphology and motor function recovery and was significantly better than hollow NGCs and CD NG. Therefore, we believe that the fully decellularized and fat-free porcine ACNGs may be the most promising “bridge” for repairing human nerve defects at this stage and for some time to come.
The native adipose tissue inside acellular nerve xenografts hinders regenerated nerve fibers. Environmentally friendly scCO2 extraction has natural advantages in reducing fat content. Natural three-dimensional nerve basement membrane tube structure guides regenerating axons.
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18
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Chick embryo chorioallantoic membrane: a biomaterial testing platform for tissue engineering applications. Process Biochem 2022. [DOI: 10.1016/j.procbio.2022.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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19
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Using of Single-Layer Porcine Small Intestinal Submucosa in Urethroplasty on a Beagle Model. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1755886. [PMID: 36203480 PMCID: PMC9532100 DOI: 10.1155/2022/1755886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 04/11/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022]
Abstract
Purpose To evaluate the role of porcine small intestinal submucosa (SIS) in reducing fistula during urethroplasty and to observe its degradation process in beagle models. Methods 22 male beagles were divided into the SIS group and control group. All animals received surgical operation to establish the hypospadias model. Urethroplasty was followed. In the SIS group, the urethra was covered with a single-layer SIS material while no SIS material covered in the control group. At the 2nd, 4th, and 12th weeks after the operation, there were 3, 3, and 5 animals in each group, respectively, sacrificed for surgical site histological examinations. The inflammation reaction and collagen hyperplasia levels were assessed. The fistula was identified by retrograde cystourethrography at the 4th and 12th weeks after the operation. Results the incidence of urethral fistula was 25% (2/8) in the SIS group and 75% (6/8) in the control group. The inflammation reaction of SIS and control groups had no significant difference (U = 52.50, P = 0.58). The collagen fiber increased in both groups; however, the SIS group had a much more gentle increase compared to the control group (U = −0.00, P < 0.001). In the SIS group, the SIS material was roughly complete on the specimens 2 w after surgery but became loose and discontinuous 4 w after surgery and could not be found 12 w after surgery. Conclusion The material can decrease the incidence of urethral fistula in the animal models, when used as a coverage layer. The SIS degradation process started 2 w–4 w after the operation and finished before 12 w in the animal model.
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20
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Wintruba KL, Hill JC, Richards TD, Lee YC, Kaczorowski DJ, Sultan I, Badylak SF, Billaud M, Gleason TG, Phillippi JA. Adventitia-derived extracellular matrix hydrogel enhances contractility of human vasa vasorum-derived pericytes via α 2 β 1 integrin and TGFβ receptor. J Biomed Mater Res A 2022; 110:1912-1920. [PMID: 35770946 DOI: 10.1002/jbm.a.37422] [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: 04/25/2022] [Revised: 06/07/2022] [Accepted: 06/15/2022] [Indexed: 11/11/2022]
Abstract
Pericytes are essential components of small blood vessels and are found in human aortic vasa vasorum. Prior work uncovered lower vasa vasorum density and decreased levels of pro-angiogenic growth factors in adventitial specimens of human ascending thoracic aortic aneurysm. We hypothesized that adventitial extracellular matrix (ECM) from normal aorta promotes pericyte function by increasing pericyte contractile function through mechanisms deficient in ECM derived from aneurysmal aortic adventitia. ECM biomaterials were prepared as lyophilized particulates from decellularized adventitial specimens of human and porcine aorta. Immortalized human aortic adventitia-derived pericytes were cultured within Type I collagen gels in the presence or absence of human or porcine adventitial ECMs. Cell contractility index was quantified by measuring the gel area immediately following gelation and after 48 h of culture. Normal human and porcine adventitial ECM increased contractility of pericytes when compared with pericytes cultured in absence of adventitial ECM. In contrast, aneurysm-derived human adventitial ECM failed to promote pericyte contractility. Pharmacological inhibition of TGFβR1 and antibody blockade of α2 β1 integrin independently decreased porcine adventitial ECM-induced pericyte contractility. By increasing pericyte contractility, adventitial ECM may improve microvascular function and thus represents a candidate biomaterial for less invasive and preventative treatment of human ascending aortic disease.
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Affiliation(s)
- Kaitlyn L Wintruba
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jennifer C Hill
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Tara D Richards
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Yoojin C Lee
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David J Kaczorowski
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.,McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ibrahim Sultan
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Stephen F Badylak
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Marie Billaud
- Department of Surgery, Division of Thoracic and Cardiac Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Thomas G Gleason
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Julie A Phillippi
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.,Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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21
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Xia B, Chen G. Research progress of natural tissue-derived hydrogels for tissue repair and reconstruction. Int J Biol Macromol 2022; 214:480-491. [PMID: 35753517 DOI: 10.1016/j.ijbiomac.2022.06.137] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 06/05/2022] [Accepted: 06/20/2022] [Indexed: 12/26/2022]
Abstract
There are many different grafts to repair damaged tissue. Various types of biological scaffolds, including films, fibers, microspheres, and hydrogels, can be used for tissue repair. A hydrogel, which is composed a natural or synthetic polymer network with high water absorption capacity, can provide a microenvironment closely resembling the extracellular matrix (ECM) of natural tissues to stimulate cell adhesion, proliferation, and differentiation. It has been shown to have great application potential in the field of tissue repair and regeneration. Hydrogels derived from natural tissues retain a variety of proteins and growth factors in optimal proportions, which is beneficial for the regeneration of specific tissues. This article reviews the latest research advances in the field of hydrogels from a variety of natural tissue sources, including bone tissue, blood vessels, nerve tissue, adipose tissue, skin tissue, and muscle tissue, including preparation methods, advantages, and applications in tissue engineering and regenerative medicine. Finally, it summarizes and discusses the challenges faced by natural tissue-derived hydrogels used in tissue repair, as well as future research and application directions.
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Affiliation(s)
- Bin Xia
- Engineering Research Center for Waste Oil Recovery Technology and Equipment, Ministry of Education, Chongqing Technology and Business University, Chongqing 400067, PR China
| | - Guobao Chen
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, PR China; Chongqing Key Laboratory of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, PR China.
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22
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Li Y, Yang L, Hu F, Xu J, Ye J, Liu S, Wang L, Zhuo M, Ran B, Zhang H, Ye J, Xiao J. Novel Thermosensitive Hydrogel Promotes Spinal Cord Repair by Regulating Mitochondrial Function. ACS APPLIED MATERIALS & INTERFACES 2022; 14:25155-25172. [PMID: 35618676 DOI: 10.1021/acsami.2c04341] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The repair of spinal cord injury (SCI) is still a tough clinical challenge and needs innovative therapies. Mitochondrial function is significantly compromised after SCI and has emerged as an important factor causing neuronal apoptosis and hindering functional recovery. In this study, umbilical cord mesenchymal stem cells (UCMSC), which are promising seed cells for nerve regeneration, and basic fibroblast growth factor (bFGF) that have been demonstrated to have a variety of effects on neural regeneration were jointly immobilized in extracellular matrix (ECM) and heparin-poloxamer (HP) to create a polymer bioactive system that brings more hope and possibility for the treatment of SCI. Our results in vitro and in vivo showed that the UCMSC-bFGF-ECM-HP thermosensitive hydrogel has good therapeutic effects, mainly in reducing apoptosis and improving the mitochondrial function. It showed promising utility for the functional recovery of impaired mitochondrial function by promoting mitochondrial fusion, reducing pathological mitochondrial fragmentation, increasing mitochondrial energy supply, and improving the metabolism of MDA, LDH, and ROS. In addition, we uncovered a distinct molecular mechanism underlying the protective effects associated with activating p21-activated kinase 1 (PAK1) and mitochondrial sirtuin 4 (SIRT4) by the UCMSC-bFGF-ECM-HP hydrogel. The expansion of new insights into the molecular relationships between PAK1 and SIRT4, which links the mitochondrial function in SCI, can lay the foundation for future applications and help to provide promising interventions of stem-cell-based biological scaffold therapies and potential therapeutic targets for the clinical formulation of SCI treatment strategies.
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Affiliation(s)
- Yi Li
- Medical College of Soochow University, Suzhou, Jiangsu 215123, China
- Department of Anesthesiology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China
| | - Liangliang Yang
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Fei Hu
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Ji Xu
- Department of Emergency, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Junsong Ye
- Subcenter for Stem Cell Clinical Translation, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, China
- Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province, Gannan Medical University, Ganzhou, Jiangxi 341000, China
| | - Shuhua Liu
- Department of Anesthesiology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China
| | - Lifeng Wang
- Medical College of Soochow University, Suzhou, Jiangsu 215123, China
- Department of Anesthesiology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China
| | - Ming Zhuo
- Medical College of Soochow University, Suzhou, Jiangsu 215123, China
- Department of Anesthesiology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China
| | - Bing Ran
- Medical College of Soochow University, Suzhou, Jiangsu 215123, China
- Department of Pain, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China
| | - Hongyu Zhang
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Junming Ye
- Medical College of Soochow University, Suzhou, Jiangsu 215123, China
- Department of Anesthesiology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China
| | - Jian Xiao
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
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23
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Phillippi JA. On vasa vasorum: A history of advances in understanding the vessels of vessels. SCIENCE ADVANCES 2022; 8:eabl6364. [PMID: 35442731 PMCID: PMC9020663 DOI: 10.1126/sciadv.abl6364] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 03/01/2022] [Indexed: 05/09/2023]
Abstract
The vasa vasorum are a vital microvascular network supporting the outer wall of larger blood vessels. Although these dynamic microvessels have been studied for centuries, the importance and impact of their functions in vascular health and disease are not yet fully realized. There is now rich knowledge regarding what local progenitor cell populations comprise and cohabitate with the vasa vasorum and how they might contribute to physiological and pathological changes in the network or its expansion via angiogenesis or vasculogenesis. Evidence of whether vasa vasorum remodeling incites or governs disease progression or is a consequence of cardiovascular pathologies remains limited. Recent advances in vasa vasorum imaging for understanding cardiovascular disease severity and pathophysiology open the door for theranostic opportunities. Approaches that strive to control angiogenesis and vasculogenesis potentiate mitigation of vasa vasorum-mediated contributions to cardiovascular diseases and emerging diseases involving the microcirculation.
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Affiliation(s)
- Julie A. Phillippi
- Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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24
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Zhao P, Fang Q, Gao D, Wang Q, Cheng Y, Ao Q, Wang X, Tian X, Zhang Y, Tong H, Yan N, Hu X, Fan J. Klotho functionalization on vascular graft for improved patency and endothelialization. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2022; 133:112630. [DOI: 10.1016/j.msec.2021.112630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 12/13/2021] [Accepted: 12/19/2021] [Indexed: 10/19/2022]
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25
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Liu K, Zhao M, Li Y, Luo L, Hu D. VEGF loaded porcine decellularized adipose tissue derived hydrogel could enhance angiogenesis in vitro and in vivo. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2021; 33:569-589. [PMID: 34779715 DOI: 10.1080/09205063.2021.2002235] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Decellularized adipose tissue (DAT) has been widely applied in soft tissue regeneration, however, DAT may play a promising role in accelerating wound healing because of suitable physical characteristics and biological properties. In this research, we fabricated the DAT hydrogel and the VEGF loaded heparinized-DAT hydrogel (VEGF hydrogel) and evaluated their efficiency in full-thickness skin wound model. We designed one method to encapsulate VEGF to hep-DAT hydrogel in order to control VEGF release rate. Result showed that the VEGF release could last up to 3 day, and 1 ml hep-DAT hydrogel (5 mg/ml) could bind up to (64.521 ± 11.550) ng VEGF which was 4.2 times to that of DAT hydrogels. Moreover, the VEGF released in 3 days still preserved biological activities that the released VEGF could enhance tube formation of HUVECs in vitro. Otherwise, the VEGF hydrogel could significantly accelerate wound healing compared with DAT hydrogel and VEGF injection, collagen deposition and newly formed vessels in the VEGF hydrogel groups were also higher than those of other groups. We believed that the VEGF hydrogel could be one attractive biomaterial for potential clinical applications.
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Affiliation(s)
- Kaituo Liu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, China.,Department of Burns and Plastic Surgery, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
| | - Ming Zhao
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, China
| | - Yan Li
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, China
| | - Liang Luo
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, China
| | - Dahai Hu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, China
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26
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Xiao ST, Kuang CY. Endothelial progenitor cells and coronary artery disease: Current concepts and future research directions. World J Clin Cases 2021; 9:8953-8966. [PMID: 34786379 PMCID: PMC8567528 DOI: 10.12998/wjcc.v9.i30.8953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/12/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Vascular injury is a frequent pathology in coronary artery disease. To repair the vasculature, scientists have found that endothelial progenitor cells (EPCs) have excellent properties associated with angiogenesis. Over time, research on EPCs has made encouraging progress regardless of pathology or clinical technology. This review focuses on the origins and cell markers of EPCs, and the connection between EPCs and coronary artery disease. In addition, we summarized various studies of EPC-capturing stents and EPC infusion therapy, and aim to learn from past technology to predict the future.
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Affiliation(s)
- Sen-Tong Xiao
- Department of Cardiovascular Diseases, People’s Hospital Affiliated to Guizhou Medical University, Guiyang 550003, Guizhou Province, China
| | - Chun-Yan Kuang
- Department of Cardiovascular Diseases, Guizhou Provincial People's Hospital, Guiyang 550003, Guizhou Province, China
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27
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Zhao Z, Wang M, Shao F, Liu G, Li J, Wei X, Zhang X, Yang J, Cao F, Wang Q, Wang H, Zhao D. Porous tantalum-composited gelatin nanoparticles hydrogel integrated with mesenchymal stem cell-derived endothelial cells to construct vascularized tissue in vivo. Regen Biomater 2021; 8:rbab051. [PMID: 34603743 PMCID: PMC8481010 DOI: 10.1093/rb/rbab051] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 08/08/2021] [Accepted: 08/30/2021] [Indexed: 12/12/2022] Open
Abstract
The ideal scaffold material of angiogenesis should have mechanical strength and provide appropriate physiological microporous structures to mimic the extracellular matrix environment. In this study, we constructed an integrated three-dimensional scaffold material using porous tantalum (pTa), gelatin nanoparticles (GNPs) hydrogel, and seeded with bone marrow mesenchymal stem cells (BMSCs)-derived endothelial cells (ECs) for vascular tissue engineering. The characteristics and biocompatibility of pTa and GNPs hydrogel were evaluated by mechanical testing, scanning electron microscopy, cell counting kit, and live-cell assay. The BMSCs-derived ECs were identified by flow cytometry and angiogenesis assay. BMSCs-derived ECs were seeded on the pTa-GNPs hydrogel scaffold and implanted subcutaneously in nude mice. Four weeks after the operation, the scaffold material was evaluated by histomorphology. The superior biocompatible ability of pTa-GNPs hydrogel scaffold was observed. Our in vivo results suggested that 28 days after implantation, the formation of the stable capillary-like network in scaffold material could be promoted significantly. The novel, integrated pTa-GNPs hydrogel scaffold is biocompatible with the host, and exhibits biomechanical and angiogenic properties. Moreover, combined with BMSCs-derived ECs, it could construct vascular engineered tissue in vivo. This study may provide a basis for applying pTa in bone regeneration and autologous BMSCs in tissue-engineered vascular grafts.
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Affiliation(s)
- Zhenhua Zhao
- Orthopaedic Department, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
- National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
| | - Mang Wang
- Orthopaedic Department, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
| | - Fei Shao
- Key State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, No. 2, Linggong Road, High-Tech District, Dalian 116024, P. R. China
| | - Ge Liu
- National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
- School of Mechanical Engineering, Dalian Jiaotong University, Dalian 116028, P. R. China
| | - Junlei Li
- National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
| | - Xiaowei Wei
- National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
| | - Xiuzhi Zhang
- National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
- Reproductive Medicine Centre, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
| | - Jiahui Yang
- National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
| | - Fang Cao
- Department of Biomedical Engineering, Faculty of Electronic Information and Electronical Engineering, Dalian University of Technology, Dalian 116024, P. R. China
| | - Qiushi Wang
- Laboratory Animal Center, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
| | - Huanan Wang
- Key State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, No. 2, Linggong Road, High-Tech District, Dalian 116024, P. R. China
| | - Dewei Zhao
- Orthopaedic Department, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
- National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated ZhongShan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, Liaoning 116001, P. R. China
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28
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Boso D, Carraro E, Maghin E, Todros S, Dedja A, Giomo M, Elvassore N, De Coppi P, Pavan PG, Piccoli M. Porcine Decellularized Diaphragm Hydrogel: A New Option for Skeletal Muscle Malformations. Biomedicines 2021; 9:biomedicines9070709. [PMID: 34206569 PMCID: PMC8301461 DOI: 10.3390/biomedicines9070709] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/17/2021] [Accepted: 06/18/2021] [Indexed: 12/14/2022] Open
Abstract
Hydrogels are biomaterials that, thanks to their unique hydrophilic and biomimetic characteristics, are used to support cell growth and attachment and promote tissue regeneration. The use of decellularized extracellular matrix (dECM) from different tissues or organs significantly demonstrated to be far superior to other types of hydrogel since it recapitulates the native tissue’s ECM composition and bioactivity. Different muscle injuries and malformations require the application of patches or fillers to replenish the defect and boost tissue regeneration. Herein, we develop, produce, and characterize a porcine diaphragmatic dECM-derived hydrogel for diaphragmatic applications. We obtain a tissue-specific biomaterial able to mimic the complex structure of skeletal muscle ECM; we characterize hydrogel properties in terms of biomechanical properties, biocompatibility, and adaptability for in vivo applications. Lastly, we demonstrate that dECM-derived hydrogel obtained from porcine diaphragms can represent a useful biological product for diaphragmatic muscle defect repair when used as relevant acellular stand-alone patch.
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Affiliation(s)
- Daniele Boso
- Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy; (D.B.); (E.C.); (E.M.); (P.G.P.)
- Department of Industrial Engineering, University of Padova, Via Venezia 1, 35131 Padova, Italy;
| | - Eugenia Carraro
- Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy; (D.B.); (E.C.); (E.M.); (P.G.P.)
- Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy
| | - Edoardo Maghin
- Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy; (D.B.); (E.C.); (E.M.); (P.G.P.)
- Department of Industrial Engineering, University of Padova, Via Venezia 1, 35131 Padova, Italy;
| | - Silvia Todros
- Department of Industrial Engineering, University of Padova, Via Venezia 1, 35131 Padova, Italy;
| | - Arben Dedja
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy;
| | - Monica Giomo
- Department of Industrial Engineering, University of Padova, Via Marzolo 9, 35131 Padova, Italy; (M.G.); (N.E.)
| | - Nicola Elvassore
- Department of Industrial Engineering, University of Padova, Via Marzolo 9, 35131 Padova, Italy; (M.G.); (N.E.)
- Veneto Institute of Molecular Medicine, Via G. Orus 2, 35127 Padova, Italy
- Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Y Building, No. 393 Middle Huaxia Road, Pudong, Shanghai 201210, China
- NIHR Biomedical Research Center, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK;
| | - Paolo De Coppi
- NIHR Biomedical Research Center, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK;
- Specialist Neonatal and Pediatric Surgery, Great Ormond Street Hospital, London WC1N 3JH, UK
| | - Piero Giovanni Pavan
- Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy; (D.B.); (E.C.); (E.M.); (P.G.P.)
- Department of Industrial Engineering, University of Padova, Via Venezia 1, 35131 Padova, Italy;
| | - Martina Piccoli
- Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy; (D.B.); (E.C.); (E.M.); (P.G.P.)
- Correspondence:
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29
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Sun F, Lu Y, Wang Z, Shi H. Vascularization strategies for tissue engineering for tracheal reconstruction. Regen Med 2021; 16:549-566. [PMID: 34114475 DOI: 10.2217/rme-2020-0091] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Tissue engineering technology provides effective alternative treatments for tracheal reconstruction. The formation of a functional microvascular network is essential to support cell metabolism and ensure the long-term survival of grafts. Although several tracheal replacement therapy strategies have been developed in the past, the critical significance of the formation of microvascular networks in 3D scaffolds has not attracted sufficient attention. Here, we review key technologies and related factors of microvascular network construction in tissue-engineered trachea and explore optimized preparation processes of vascularized functional tissues for clinical applications.
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Affiliation(s)
- Fei Sun
- Clinical Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Jiangsu Key Laboratory of Integrated Traditional Chinese & Western Medicine for Prevention & Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, PR China
| | - Yi Lu
- Clinical Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Jiangsu Key Laboratory of Integrated Traditional Chinese & Western Medicine for Prevention & Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, PR China
| | - Zhihao Wang
- Clinical Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Jiangsu Key Laboratory of Integrated Traditional Chinese & Western Medicine for Prevention & Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, PR China
| | - Hongcan Shi
- Clinical Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China.,Jiangsu Key Laboratory of Integrated Traditional Chinese & Western Medicine for Prevention & Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, PR China
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30
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López-Martínez S, Campo H, de Miguel-Gómez L, Faus A, Navarro AT, Díaz A, Pellicer A, Ferrero H, Cervelló I. A Natural Xenogeneic Endometrial Extracellular Matrix Hydrogel Toward Improving Current Human in vitro Models and Future in vivo Applications. Front Bioeng Biotechnol 2021; 9:639688. [PMID: 33748086 PMCID: PMC7973233 DOI: 10.3389/fbioe.2021.639688] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 02/12/2021] [Indexed: 12/25/2022] Open
Abstract
Decellularization techniques support the creation of biocompatible extracellular matrix hydrogels, providing tissue-specific environments for both in vitro cell culture and in vivo tissue regeneration. We obtained endometrium derived from porcine decellularized uteri to create endometrial extracellular matrix (EndoECM) hydrogels. After decellularization and detergent removal, we investigated the physicochemical features of the EndoECM, including gelation kinetics, ultrastructure, and proteomic profile. The matrisome showed conservation of structural and tissue-specific components with low amounts of immunoreactive molecules. EndoECM supported in vitro culture of human endometrial cells in two- and three-dimensional conditions and improved proliferation of endometrial stem cells with respect to collagen and Matrigel. Further, we developed a three-dimensional endometrium-like co-culture system of epithelial and stromal cells from different origins. Endometrial co-cultures remained viable and showed significant remodeling. Finally, EndoECM was injected subcutaneously in immunocompetent mice in a preliminary study to test a possible hypoimmunogenic reaction. Biomimetic endometrial milieus offer new strategies in reproductive techniques and endometrial repair and our findings demonstrate that EndoECM has potential for in vitro endometrial culture and as treatment for endometrial pathologies.
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Affiliation(s)
- Sara López-Martínez
- Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Hannes Campo
- Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Lucía de Miguel-Gómez
- Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.,University of Valencia, Valencia, Spain
| | - Amparo Faus
- Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Alfredo T Navarro
- Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Ana Díaz
- University of Valencia, Valencia, Spain
| | - Antonio Pellicer
- University of Valencia, Valencia, Spain.,IVIRMA Roma, Rome, Italy
| | - Hortensia Ferrero
- Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.,IVIRMA Valencia, Valencia, Spain
| | - Irene Cervelló
- Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
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31
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Tao M, Ao T, Mao X, Yan X, Javed R, Hou W, Wang Y, Sun C, Lin S, Yu T, Ao Q. Sterilization and disinfection methods for decellularized matrix materials: Review, consideration and proposal. Bioact Mater 2021; 6:2927-2945. [PMID: 33732964 PMCID: PMC7930362 DOI: 10.1016/j.bioactmat.2021.02.010] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 02/08/2023] Open
Abstract
Sterilization is the process of killing all microorganisms, while disinfection is the process of killing or removing all kinds of pathogenic microorganisms except bacterial spores. Biomaterials involved in cell experiments, animal experiments, and clinical applications need to be in the aseptic state, but their physical and chemical properties as well as biological activities can be affected by sterilization or disinfection. Decellularized matrix (dECM) is the low immunogenicity material obtained by removing cells from tissues, which retains many inherent components in tissues such as proteins and proteoglycans. But there are few studies concerning the effects of sterilization or disinfection on dECM, and the systematic introduction of sterilization or disinfection for dECM is even less. Therefore, this review systematically introduces and analyzes the mechanism, advantages, disadvantages, and applications of various sterilization and disinfection methods, discusses the factors influencing the selection of sterilization and disinfection methods, summarizes the sterilization and disinfection methods for various common dECM, and finally proposes a graphical route for selecting an appropriate sterilization or disinfection method for dECM and a technical route for validating the selected method, so as to provide the reference and basis for choosing more appropriate sterilization or disinfection methods of various dECM.
Asepsis is the prerequisite for the experiment and application of biomaterials. Sterilization or disinfection affects physic-chemical properties of biomaterials. Mechanism, advantages and disadvantages of sterilization or disinfection methods. Factors influencing the selection of sterilization or disinfection methods. Selection of sterilization or disinfection methods for decellularized matrix.
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Affiliation(s)
- Meihan Tao
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Tianrang Ao
- Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyan Mao
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Xinzhu Yan
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Rabia Javed
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Weijian Hou
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Yang Wang
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Cong Sun
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Shuang Lin
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Tianhao Yu
- The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China
| | - Qiang Ao
- Department of Tissue Engineering, China Medical University, Shenyang, China.,Department of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.,Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
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32
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Characterization of Properties, In Vitro and In Vivo Evaluation of Calcium Phosphate/Amino Acid Cements for Treatment of Osteochondral Defects. MATERIALS 2021; 14:ma14020436. [PMID: 33477289 PMCID: PMC7830446 DOI: 10.3390/ma14020436] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 01/08/2021] [Accepted: 01/12/2021] [Indexed: 12/13/2022]
Abstract
Novel calcium phosphate cements containing a mixture of four amino acids, glycine, proline, hydroxyproline and either lysine or arginine (CAL, CAK) were characterized and used for treatment of artificial osteochondral defects in knee. It was hypothesized that an enhanced concentration of extracellular collagen amino acids (in complex mixture), in connection with bone cement in defect sites, would support the healing of osteochondral defects with successful formation of hyaline cartilage and subchondral bone. Calcium phosphate cement mixtures were prepared by in situ reaction in a planetary ball mill at aseptic conditions and characterized. It was verified that about 30–60% of amino acids remained adsorbed on hydroxyapatite particles in cements and the addition of amino acids caused around 60% reduction in compressive strength and refinement of hydroxyapatite particles in their microstructure. The significant over-expression of osteogenic genes after the culture of osteoblasts was demonstrated in the cement extracts containing lysine and compared with other cements. The cement pastes were inserted into artificial osteochondral defects in the medial femoral condyle of pigs and, after 3 months post-surgery, tissues were analyzed macroscopically, histologically, immunohistochemically using MRI and X-ray methods. Analysis clearly showed the excellent healing process of artificial osteochondral defects in pigs after treatment with CAL and CAK cements without any inflammation, as well as formation of subchondral bone and hyaline cartilage morphologically and structurally identical to the original tissues. Good integration of the hyaline neocartilage with the surrounding tissue, as well as perfect interconnection between the neocartilage and new subchondral bone tissue, was demonstrated. Tissues were stable after 12 months’ healing.
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Kao CY, Nguyen HQD, Weng YC. Characterization of Porcine Urinary Bladder Matrix Hydrogels from Sodium Dodecyl Sulfate Decellularization Method. Polymers (Basel) 2020; 12:polym12123007. [PMID: 33339345 PMCID: PMC7766358 DOI: 10.3390/polym12123007] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/15/2020] [Accepted: 12/15/2020] [Indexed: 01/05/2023] Open
Abstract
Urinary bladder matrix (UBM) is one of the most studied extracellular matrixes (ECM) in the tissue engineering field. Although almost all of the UBM hydrogels were prepared by using peracetic acid (PAA), recent studies indicated that PAA was not a trustworthy way to decellularize UBM. A stronger detergent, such as sodium dodecyl sulfate (SDS), may help tackle this issue; however, its effects on the hydrogels’ characteristics remain unknown. Therefore, the objective of this study was to develop a more reliable protocol to decellularize UBM, using SDS, and to compare the characteristics of hydrogels obtained from this method to the widely employed technique, using PAA. The results indicated that SDS was superior to PAA in decellularization efficacy. Different decellularization methods led to dissimilar gelation kinetics; however, the methods did not affect other hydrogel characteristics in terms of biochemical composition, surface morphology and rheological properties. The SDS-treated hydrogels possessed excellent cytocompatibility in vitro. These results showed that the SDS decellularization method could offer a more stable and safer way to obtain acellular UBM, due to reducing immunogenicity. The hydrogels prepared from this technique had comparable characteristics as those from PAA and could be a potential candidate as a scaffold for tissue remodeling.
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Affiliation(s)
- Chen-Yu Kao
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan;
- Biomedical Engineering Research Center, National Defense Medical Center, Taipei 11490, Taiwan
- Correspondence: ; Tel.: +886-2-2730-3676; Fax: +886-2-2730-3733
| | - Huynh-Quang-Dieu Nguyen
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan;
- Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
| | - Yu-Chuan Weng
- School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan;
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Effect of bFGF on fibroblasts derived from the golden snub-nosed monkey. Primates 2020; 62:369-378. [PMID: 33211213 DOI: 10.1007/s10329-020-00875-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 10/31/2020] [Indexed: 10/22/2022]
Abstract
Golden snub-nosed monkeys are endangered animals in China, and their cells have been demonstrated to be important as genetic resources and in applications for advancing biological research. Moreover, in primary research, basic fibroblast growth factor (bFGF) is used to promote the proliferation of fibroblasts to create abundant cells for cryopreservation. To further investigate the effect of bFGF on the efficiency of preservation of fibroblasts obtained from an endangered species, a fibroblast cell line was isolated from a dead golden snub-nosed monkey. Cell viability and mitochondrial membrane potential were assessed using CCK8 and JC-1 assay kits. The karyotype was analyzed by chromosomal microarray analysis, while RNA sequencing and gene expression analyses were performed to assess molecular changes in response to bFGF. Flow cytometry was used to characterize changes in cell surface markers in response to bFGF treatment. The results showed that cells maintained typical fibroblast morphology, while cell viability and mitochondrial membrane potential were not significantly affected between three and eight passages (p > 0.05). We also observed that the addition of bFGF promoted fibroblast proliferation and increased mitochondrial membrane potential. In addition, the bFGF treatment did not alter the normal karyotype of cells, downregulating fibroblast-associated genes and upregulating those associated with cell regulation, including those of the WNT, PI3K and MAPK pathways. The addition of bFGF also increased CD29, CD90, CD105, CD34 and CD44 expression while decreasing that of CD14 and HLA-DR at the protein level. Taken together, these results demonstrate that bFGF may upregulate the WNT, PI3K and MAPK pathways to promote cell proliferation while also increasing the expression of genes and surface markers associated with mesenchymal and hematopoietic cell linages.
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Nour S, Imani R, Chaudhry GR, Sharifi AM. Skin wound healing assisted by angiogenic targeted tissue engineering: A comprehensive review of bioengineered approaches. J Biomed Mater Res A 2020; 109:453-478. [PMID: 32985051 DOI: 10.1002/jbm.a.37105] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 09/23/2020] [Accepted: 09/26/2020] [Indexed: 12/16/2022]
Abstract
Skin injuries and in particular, chronic wounds, are one of the major prevalent medical problems, worldwide. Due to the pivotal role of angiogenesis in tissue regeneration, impaired angiogenesis can cause several complications during the wound healing process and skin regeneration. Therefore, induction or promotion of angiogenesis can be considered as a promising approach to accelerate wound healing. This article presents a comprehensive overview of current and emerging angiogenesis induction methods applied in several studies for skin regeneration, which are classified into the cell, growth factor, scaffold, and biological/chemical compound-based strategies. In addition, the advantages and disadvantages of these angiogenic strategies along with related research examples are discussed in order to demonstrate their potential in the treatment of wounds.
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Affiliation(s)
- Shirin Nour
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - Rana Imani
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - G Rasul Chaudhry
- OU-WB Institute for Stem Cell and Regenerative Medicine, Department of Biological Sciences, Oakland University, Rochester, Michigan, USA
| | - Ali Mohammad Sharifi
- Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran.,Tissue Engineering Group (NOCERAL), Department of Orthopedics Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.,Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Decellularized porcine cornea-derived hydrogels for the regeneration of epithelium and stroma in focal corneal defects. Ocul Surf 2020; 18:748-760. [PMID: 32841745 DOI: 10.1016/j.jtos.2020.07.020] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 07/21/2020] [Accepted: 07/26/2020] [Indexed: 01/15/2023]
Abstract
PURPOSE Hydrogels derived from decellularized tissues provide superior biocompatibility, tenability and tissue-specific extracellular matrix (ECM) components. Based on the preparation of decellularized porcine cornea (DPC), here we developed an injectable and transparent hydrogel for the regeneration of epithelium and stroma in focal corneal defects. METHODS The DPC-derived hydrogel was prepared with N-cyclohexyl-N'-(2-morpholinethyl) carbodiimide metho-p-toluenesulfonate/N-hydroxysuccinimide (CMC/NHS) as cross-linkers. The characteristics of the hydrogel were analyzed and its cytocompatibility was assessed by Live/Dead and Cell Counting Kit (CCK)-8 assays. Immunofluorescence staining, quantitative PCR and Western blot analyses were performed to assess the relative protein and gene expression in corneal fibroblasts on hydrogel. The safety and efficiency of the hydrogel for repairing focal corneal defects in rabbit were measured by slit-lamp, anterior segment optical coherence tomography (AS-OCT), confocal microscopy and histological analyses. RESULTS The DPC-derived hydrogel cross-linked with CMC/NHS assumed favorable transparency, exhibited distinct mechanical properties and preserved the ECM components of native porcine cornea (NPC). In vitro experiments showed that the hydrogel maintained the phenotype, supported the proliferation and promoted the ECM synthesis of corneal fibroblasts. When injected onto rabbit corneas, the hydrogel rapidly covered, solidified and formed a smooth surface on the focal defect. Corneal epithelium was fully regenerated within 3 days. The thickness of the corneal epithelium and stroma was restored at 12 weeks after surgery without significant inflammation or scar formation. Notably, the hydrogel showed no harmful effects on the resident stroma and endothelium. CONCLUSIONS The DPC-derived hydrogel may represent a promising biomaterial for corneal epithelial and stromal regeneration.
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Hussein KH, Park KM, Yu L, Kwak HH, Woo HM. Decellularized hepatic extracellular matrix hydrogel attenuates hepatic stellate cell activation and liver fibrosis. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 116:111160. [PMID: 32806289 DOI: 10.1016/j.msec.2020.111160] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 05/31/2020] [Accepted: 06/03/2020] [Indexed: 12/21/2022]
Abstract
Liver fibrosis results from excessive accumulation of extracellular matrix (ECM) proteins that distort the hepatic architecture. Progression of liver fibrosis results in cirrhosis and liver failure, and often, liver transplantation is required. The decellularized liver tissue contains different components that mimic the natural hepatic environment. We hypothesized that a decellularized liver hydrogel can be used to replace the necrotic hepatocytes and damaged ECM. Therefore, our aim in this study is to develop a therapy for treating liver fibrosis. Mice livers were decellularized and processed to form a hepatic hydrogel. We evaluated the biocompatibility and bioactivity of the hydrogel. The ability of the hydrogel to enhance the migration of hepatocytes and endothelial cells was investigated. Human hepatic stellate cell line (LX-2) activated by transforming growth factor-β1 (TGF-β1) was used as in vitro model for fibrogenesis. Then, the hydrogel was injected into the liver parenchyma of mice after the induction of liver fibrosis using thioacetamide. The resulting hydrogel maintained a complex composition, which included glycosaminoglycans, collagen, elastin, and growth factors. Hepatocytes and endothelial cells were shown to migrate toward the hydrogel in vitro. Liver hydrogel improved TGF-β1-induced LX-2 cells activation via blocking the TGF-β1/Smad pathway. The matrix was delivered successfully in vivo and enhanced the reduction of fibrosis and recovery to a nearly normal structure. In conclusion, we have demonstrated that the liver hydrogel can be utilized as an injectable biomaterial for liver tissue engineering in order to reduce the degree of fibrosis.
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Affiliation(s)
- Kamal H Hussein
- Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Department of Animal Surgery, College of Veterinary Medicine, Assiut University, Assiut 71515, Egypt
| | - Kyung-Mee Park
- College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Lina Yu
- Stem Cell institute, College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
| | - Ho-Hyun Kwak
- Stem Cell institute, College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
| | - Heung-Myong Woo
- Stem Cell institute, College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
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The use of the chick embryo CAM assay in the study of angiogenic activiy of biomaterials. Microvasc Res 2020; 131:104026. [PMID: 32505611 DOI: 10.1016/j.mvr.2020.104026] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 04/30/2020] [Accepted: 06/03/2020] [Indexed: 02/08/2023]
Abstract
The chick embryo chorioallantoic membrane (CAM) is a highly vascularized extraembryonic membrane, which carries out several functions during embryonic development, including exchange of respiratory gases, calcium transport from the eggshell, acid-base homeostasis in the embryo, and ion and water reabsorption from the allantoic fluid. Due to its easy accessibility, affordability and given that it constitutes an immunodeficient environment, CAM has been used as an experimental model for >50 years and in particular it has been broadly used to study angiogenesis and anti-angiogenesis. This review article describes the use of the CAM assay as a valuable assay to test angiogenic activity of biomaterials in vivo before they are further investigated in animal models. In this context, the use of CAM has become an integral part of the biocompatibility testing process for developing potential biomaterials.
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39
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Liguori GR, Liguori TTA, de Moraes SR, Sinkunas V, Terlizzi V, van Dongen JA, Sharma PK, Moreira LFP, Harmsen MC. Molecular and Biomechanical Clues From Cardiac Tissue Decellularized Extracellular Matrix Drive Stromal Cell Plasticity. Front Bioeng Biotechnol 2020; 8:520. [PMID: 32548106 PMCID: PMC7273975 DOI: 10.3389/fbioe.2020.00520] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 05/01/2020] [Indexed: 01/09/2023] Open
Abstract
Decellularized-organ-derived extracellular matrix (dECM) has been used for many years in tissue engineering and regenerative medicine. The manufacturing of hydrogels from dECM allows to make use of the pro-regenerative properties of the ECM and, simultaneously, to shape the material in any necessary way. The objective of the present project was to investigate differences between cardiovascular tissues (left ventricle, mitral valve, and aorta) with respect to generating dECM hydrogels and their interaction with cells in 2D and 3D. The left ventricle, mitral valve, and aorta of porcine hearts were decellularized using a series of detergent treatments (SDS, Triton-X 100 and deoxycholate). Mass spectrometry-based proteomics yielded the ECM proteins composition of the dECM. The dECM was digested with pepsin and resuspended in PBS (pH 7.4). Upon warming to 37°C, the suspension turns into a gel. Hydrogel stiffness was determined for samples with a dECM concentration of 20 mg/mL. Adipose tissue-derived stromal cells (ASC) and a combination of ASC with human pulmonary microvascular endothelial cells (HPMVEC) were cultured, respectively, on and in hydrogels to analyze cellular plasticity in 2D and vascular network formation in 3D. Differentiation of ASC was induced with 10 ng/mL of TGF-β1 and SM22α used as differentiation marker. 3D vascular network formation was evaluated with confocal microscopy after immunofluorescent staining of PECAM-1. In dECM, the most abundant protein was collagen VI for the left ventricle and mitral valve and elastin for the aorta. The stiffness of the hydrogel derived from the aorta (6,998 ± 895 Pa) was significantly higher than those derived from the left ventricle (3,384 ± 698 Pa) and the mitral valve (3,233 ± 323 Pa) (One-way ANOVA, p = 0.0008). Aorta-derived dECM hydrogel drove non-induced (without TGF-β1) differentiation, while hydrogels derived from the left ventricle and mitral valve inhibited TGF-β1-induced differentiation. All hydrogels supported vascular network formation within 7 days of culture, but ventricular dECM hydrogel demonstrated more robust vascular networks, with thicker and longer vascular structures. All the three main cardiovascular tissues, myocardium, valves, and large arteries, could be used to fabricate hydrogels from dECM, and these showed an origin-dependent influence on ASC differentiation and vascular network formation.
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Affiliation(s)
- Gabriel Romero Liguori
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.,Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Tácia Tavares Aquinas Liguori
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.,Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Sérgio Rodrigues de Moraes
- Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Viktor Sinkunas
- Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Vincenzo Terlizzi
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Joris A van Dongen
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Prashant K Sharma
- Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Luiz Felipe Pinho Moreira
- Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Martin Conrad Harmsen
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Xu H, Yang W, Chen P, Chen R, Xue P, Wang L, Yuan J, Yao Q, Chen B, Zhao Y. Bone‐Inspired Tube Filling Decellularized Matrix of Toad Cartilage Provided an Osteoinductive Microenvironment for Mesenchymal Stem Cells to Facilitate the Radius Defect Repair of Rabbit. Biotechnol J 2020; 15:e2000004. [DOI: 10.1002/biot.202000004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 04/18/2020] [Indexed: 12/13/2022]
Affiliation(s)
- He‐Lin Xu
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
| | - Wai‐Geng Yang
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
| | - Pian‐Pian Chen
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
| | - Rui Chen
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
| | - Peng‐Peng Xue
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
| | - Li‐Fen Wang
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
| | - Jian‐Dong Yuan
- Department of OrthopedicsThe First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang 325000 P. R. China
| | - Qing Yao
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
| | - Bin Chen
- Department of UltrasonographyThe First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang Province 325000 China
| | - Ying‐Zheng Zhao
- Department of Pharmaceutics, School of Pharmaceutical SciencesWenzhou Medical University Wenzhou Zhejiang Province 325035 China
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Feng M, Liu X, Hou X, Chen J, Zhang H, Song S, Han X, Shi C. Specific angiogenic peptide binding with injectable cardiac ECM collagen gel promotes the recovery of myocardial infarction in rat. J Biomed Mater Res A 2020; 108:1881-1889. [PMID: 32314537 DOI: 10.1002/jbm.a.36951] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 03/16/2020] [Accepted: 03/28/2020] [Indexed: 12/19/2022]
Abstract
Restoring blood supply is an effective way for the therapy of myocardial infarction (MI). It was reported a specific angiogenic peptide (VMP) derived from vascular endothelial growth factor (VEGF) could activate its receptor to mimic the biological activity of VEGF. In this study, in order to improve the local concentration in infarction region, a collagen-binding domain was synthesized with VMP to construct collagen binding domain (CBD)-VMP peptides. The fused CBD-VMP could bind specifically to collagen which was rich in cardiac extracellular matrix (c-ECM), without impacting the biological activity of VMP peptides. When the CBD-VMP peptides loaded on collagen scaffold and implanted into the rats subcutaneously, significant vascularization was observed. Then, CBD-VMP peptides binding with injectable c-ECM injected into the MI rat by intramuscular administration, significant blood vessels regeneration, and decrease of cell apoptosis were observed, that corelated with the recovery of cardiac function. It might be an alternative promising strategy for the clinical application of MI.
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Affiliation(s)
- Manman Feng
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Xinyu Liu
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Xianglin Hou
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
| | - Jixuan Chen
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Hong Zhang
- Department of Cardiac Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Siqi Song
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Xiaohua Han
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Chunying Shi
- School of Basic Medicine, Qingdao University, Qingdao, China
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Mu Z, Chen K, Yuan S, Li Y, Huang Y, Wang C, Zhang Y, Liu W, Luo W, Liang P, Li X, Song J, Ji P, Cheng F, Wang H, Chen T. Gelatin Nanoparticle-Injectable Platelet-Rich Fibrin Double Network Hydrogels with Local Adaptability and Bioactivity for Enhanced Osteogenesis. Adv Healthc Mater 2020; 9:e1901469. [PMID: 31994326 DOI: 10.1002/adhm.201901469] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 12/19/2019] [Indexed: 12/11/2022]
Abstract
Bone healing is a dynamic process regulated by biochemical signals such as chemokines and growth factors, and biophysical signals such as topographical and mechanical features of extracellular matrix or mechanical stimuli. Hereby, a mechanically tough and bioactive hydrogel based on autologous injectable platelet-rich fibrin (iPRF) modified with gelatin nanoparticles (GNPs) is developed. This composite hydrogel demonstrates a double network (DN) mechanism, wherein covalent network of fibrin serves to maintain material integrity, and self-assembled colloidal network of GNPs dissipates force upon loading. A rabbit sinus augmentation model is used to investigate the bioactivity and osteogenesis capacity of the DN hydrogels. The DN hydrogels adapt to the local environmental complexity of bone defects, i.e., accommodate the irregular shape of the defects and withstand the pressure formed in the maxillary sinus during animal's respiration process. The DN hydrogel is also demonstrated to absorb and prolong the release of the bioactive growth factors stemming from iPRF, which could have contributed to the early angiogenesis and osteogenesis observed inside the sinus. This adaptable and bioactive DN hydrogel can achieve enhanced bone regeneration in treating complex bone defects by maintaining long-term bone mass and withstanding the functional mechanical stimuli.
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Affiliation(s)
- Zhixiang Mu
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Kaiwen Chen
- Key State Laboratory of Fine ChemicalsSchool of BioengineeringDalian University of Technology No. 2 Linggong Road, High‐tech District Dalian 116024 P. R. China
| | - Shuai Yuan
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Yihan Li
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Yuanding Huang
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Chao Wang
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Yang Zhang
- Laboratory of Regenerative BiomaterialsDepartment of Biomedical EngineeringHealth Science CenterShenzhen University Shenzhen Guangdong Province 518037 P. R. China
| | - Wenzhao Liu
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Wenping Luo
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Panpan Liang
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Xiaodong Li
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Jinlin Song
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Ping Ji
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
| | - Fang Cheng
- Key State Laboratory of Fine ChemicalsSchool of Chemical EngineeringDalian University of Technology No. 2 Linggong Road, High‐tech District Dalian 116024 P. R. China
| | - Huanan Wang
- Key State Laboratory of Fine ChemicalsSchool of BioengineeringDalian University of Technology No. 2 Linggong Road, High‐tech District Dalian 116024 P. R. China
| | - Tao Chen
- Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing Medical University Chongqing 401147 P. R. China
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43
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Yang G, Mahadik B, Choi JY, Fisher JP. Vascularization in tissue engineering: fundamentals and state-of-art. ACTA ACUST UNITED AC 2020; 2. [PMID: 34308105 DOI: 10.1088/2516-1091/ab5637] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Vascularization is among the top challenges that impede the clinical application of engineered tissues. This challenge has spurred tremendous research endeavor, defined as vascular tissue engineering (VTE) in this article, to establish a pre-existing vascular network inside the tissue engineered graft prior to implantation. Ideally, the engineered vasculature can be integrated into the host vasculature via anastomosis to supply nutrient to all cells instantaneously after surgery. Moreover, sufficient vascularization is of great significance in regenerative medicine from many other perspectives. Due to the critical role of vascularization in successful tissue engineering, we aim to provide an up-to-date overview of the fundamentals and VTE strategies in this article, including angiogenic cells, biomaterial/bio-scaffold design and bio-fabrication approaches, along with the reported utility of vascularized tissue complex in regenerative medicine. We will also share our opinion on the future perspective of this field.
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Affiliation(s)
- Guang Yang
- Tissue Engineering and Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD, United States of America.,Center for Engineering Complex Tissues, University of Maryland, College Park, MD, United States of America
| | - Bhushan Mahadik
- Tissue Engineering and Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD, United States of America.,Center for Engineering Complex Tissues, University of Maryland, College Park, MD, United States of America
| | - Ji Young Choi
- Tissue Engineering and Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD, United States of America
| | - John P Fisher
- Tissue Engineering and Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD, United States of America.,Center for Engineering Complex Tissues, University of Maryland, College Park, MD, United States of America
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44
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Costa A, Adamo S, Gossetti F, D'Amore L, Ceci F, Negro P, Bruzzone P. Biological Scaffolds for Abdominal Wall Repair: Future in Clinical Application? MATERIALS 2019; 12:ma12152375. [PMID: 31349716 PMCID: PMC6695954 DOI: 10.3390/ma12152375] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 07/22/2019] [Accepted: 07/24/2019] [Indexed: 12/11/2022]
Abstract
Millions of abdominal wall repair procedures are performed each year for primary and incisional hernias both in the European Union and in the United States with extremely high costs. Synthetic meshes approved for augmenting abdominal wall repair provide adequate mechanical support but have significant drawbacks (seroma formation, adhesion to viscera, stiffness of abdominal wall, and infection). Biologic scaffolds (i.e., derived from naturally occurring materials) represent an alternative to synthetic surgical meshes and are less sensitive to infection. Among biologic scaffolds, extracellular matrix scaffolds promote stem/progenitor cell recruitment in models of tissue remodeling and, in the specific application of abdominal wall repair, have enough mechanical strength to support the repair. However, many concerns remain about the use of these scaffolds in the clinic due to their higher cost of production compared with synthetic meshes, despite having the same recurrence rate. The present review aims to highlight the pros and cons of using biologic scaffolds as surgical devices for abdominal wall repair and present possible improvements to widen their use in clinical practice.
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Affiliation(s)
- Alessandra Costa
- Sezione di Istologia ed Embriologia Medica, Dipartimento SAIMLAL, Sapienza Università di Roma, Via A. Scarpa 16, 00161 Rome, Italy
| | - Sergio Adamo
- Sezione di Istologia ed Embriologia Medica, Dipartimento SAIMLAL, Sapienza Università di Roma, Via A. Scarpa 16, 00161 Rome, Italy
| | - Francesco Gossetti
- Dipartimento Assistenziale Integrato Cardio Toraco-Vascolare, Chirurgia e Trapianti d'Organo, Azienda Ospedaliera Universitaria Policlinico Umberto I. Dipartimento Universitario Chirurgia Generale e Specialistica "Paride Stefanini", Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy
| | - Linda D'Amore
- Dipartimento Assistenziale Integrato Cardio Toraco-Vascolare, Chirurgia e Trapianti d'Organo, Azienda Ospedaliera Universitaria Policlinico Umberto I. Dipartimento Universitario Chirurgia Generale e Specialistica "Paride Stefanini", Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy
| | - Francesca Ceci
- Dipartimento Assistenziale Integrato Cardio Toraco-Vascolare, Chirurgia e Trapianti d'Organo, Azienda Ospedaliera Universitaria Policlinico Umberto I. Dipartimento Universitario Chirurgia Generale e Specialistica "Paride Stefanini", Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy
| | - Paolo Negro
- Dipartimento Assistenziale Integrato Cardio Toraco-Vascolare, Chirurgia e Trapianti d'Organo, Azienda Ospedaliera Universitaria Policlinico Umberto I. Dipartimento Universitario Chirurgia Generale e Specialistica "Paride Stefanini", Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy
| | - Paolo Bruzzone
- Dipartimento Assistenziale Integrato Cardio Toraco-Vascolare, Chirurgia e Trapianti d'Organo, Azienda Ospedaliera Universitaria Policlinico Umberto I. Dipartimento Universitario Chirurgia Generale e Specialistica "Paride Stefanini", Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy.
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45
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Phillippi JA, Aikawa E, Hutcheson J. Editorial: Exploring the Frontiers of Regenerative Cardiovascular Medicine. Front Cardiovasc Med 2019; 6:13. [PMID: 30873414 PMCID: PMC6401650 DOI: 10.3389/fcvm.2019.00013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 02/06/2019] [Indexed: 11/13/2022] Open
Affiliation(s)
- Julie A Phillippi
- Departments of Cardiothoracic Surgery and Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States
| | - Elena Aikawa
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Josh Hutcheson
- Florida International University, Miami, FL, United States
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46
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Dzobo K, Rowe A, Senthebane DA, AlMazyadi MAM, Patten V, Parker MI. Three-Dimensional Organoids in Cancer Research: The Search for the Holy Grail of Preclinical Cancer Modeling. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2019; 22:733-748. [PMID: 30571609 DOI: 10.1089/omi.2018.0172] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Most solid tumors become therapy resistant and will relapse, with no durable treatment option available. One major impediment to our understanding of cancer biology and finding innovative approaches to cancer treatment stems from the lack of better preclinical tumor models that address and explain tumor heterogeneity and person-to-person differences in therapeutic and toxic responses. Past cancer research has been driven by inadequate in vitro assays utilizing two-dimensional monolayers of cancer cells and animal models. Additionally, animal models do not truly mimic the original human tumor, are time consuming, and usually costly. New preclinical models are needed for innovation in cancer translational research. Hence, it is time to welcome the three-dimensional (3D) organoids: self-organizing cells grown in 3D culture systems mimicking the parent tissues from which the primary cells originate. The 3D organoids offer deeper insights into the crucial cellular processes in tissue and organ formation and pathological processes. Generation of near-perfect physiological microenvironments allow 3D organoids to couple with gene editing tools, such as the clustered regularly interspersed short palindromic repeat (CRISPR)/CRISPR-associated 9 and the transcription activator-like effector nucleases to model human diseases, offering distinct advantages over current models. We explain in this expert review that through recapitulating patients' normal and tumor tissues, organoid technology can markedly advance personalized medicine and help reveal once hidden aspects of cancers. The use of defined tissue- or organ-specific matrices, among other factors, will likely allow organoid technology to realize its potential in innovating many fields of life sciences.
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Affiliation(s)
- Kevin Dzobo
- 1 International Center for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Cape Town, South Africa .,2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Arielle Rowe
- 1 International Center for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Cape Town, South Africa
| | - Dimakatso A Senthebane
- 1 International Center for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Cape Town, South Africa .,2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Mousa A M AlMazyadi
- 3 Al-Ahsa College of Medicine, King Faisal University , Al-Ahsa, Kingdom of Saudi Arabia
| | - Victoria Patten
- 2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - M Iqbal Parker
- 2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
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47
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Ji Y, Zhou J, Sun T, Tang K, Xiong Z, Ren Z, Yao S, Chen K, Yang F, Zhu F, Guo X. Diverse preparation methods for small intestinal submucosa (SIS): Decellularization, components, and structure. J Biomed Mater Res A 2018; 107:689-697. [PMID: 30468308 DOI: 10.1002/jbm.a.36582] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Revised: 10/16/2018] [Accepted: 11/15/2018] [Indexed: 11/10/2022]
Abstract
The native extracellular matrix (ECM) biomaterial derived from small intestinal submucosa (SIS) is widely applied in tissue engineering for tissue repair and regeneration. SIS ECM is obtained through physical and chemical methods to remove the intrinsic cells, which would otherwise cause adverse immune reactions when the SIS ECM is implanted into the host body. Several research teams have reported diverse SIS decellularization methods. However, there was no consensus on the criteria to be used for the decellularization methods for SIS and further research on the mechanism action of SIS is needed for comprehensive detection of the biological composition. In this present study, we used three reported methods to prepare SIS and compared their effects on decellularization and the remaining biological components, microstructure and cytocompatibility. SIS prepared by the three kinds of decellularization methods all achieved the recommended criteria, had good biocompatibility and retained most active components. Nevertheless, regardless of which decellularization method was used, the microstructure and bioactive components of the prepared SIS were damaged in varying degrees. We recommend that researchers need to select a decellularization method that would be appropriate to use according to their research purposes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 689-697, 2019.
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Affiliation(s)
- Yanhui Ji
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.,Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jinge Zhou
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tingfang Sun
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kai Tang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zekang Xiong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhengwei Ren
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Sheng Yao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kaifang Chen
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fan Yang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fengzhao Zhu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaodong Guo
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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48
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Wu J, Brazile B, McMahan SR, Liao J, Hong Y. Heart valve tissue-derived hydrogels: Preparation and characterization of mitral valve chordae, aortic valve, and mitral valve gels. J Biomed Mater Res B Appl Biomater 2018; 107:1732-1740. [PMID: 30419146 DOI: 10.1002/jbm.b.34266] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 08/30/2018] [Accepted: 09/30/2018] [Indexed: 12/21/2022]
Abstract
Heart valve (HV) diseases are among the leading causes of death and continue to threaten public health worldwide. The current clinical options for HV replacement include mechanical and biological prostheses. However, an ongoing problem with current HV prostheses is their failure to integrate with the host tissue and their inability grow and remodel within the body. Tissue engineered heart valves (TEHVs) are a promising solution to these problems, as they are able to grow and remodel somatically with the rest of the body. Recently, decellularized HVs have demonstrated great potential as valve replacements because they are tissue specific, but recellularization is still a challenge due to the dense HV extracellular matrix (ECM) network. In this proof-of-concept work, we decellularized porcine mitral valve chordae, aortic valve leaflets, and mitral valve leaflets and processed them into injectable hydrogels that could accommodate any geometry. While the three valvular ECMs contained various amounts of collagen, they displayed similar glycosaminoglycan contents. The hydrogels had similar nanofibrous structures and gelation kinetics with various compressive strengths. When encapsulated with NIH 3 T3 fibroblasts, all the hydrogels supported cell survivals up to 7 days. Decellularized HV ECM hydrogels may show promising potential HV tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1732-1740, 2019.
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Affiliation(s)
- Jinglei Wu
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, 76019.,Joint Graduate Biomedical Engineering Program, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
| | - Bryn Brazile
- Department of Biological Engineering, Mississippi State University, Starkville, Mississippi, 39762
| | - Sara R McMahan
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, 76019.,Joint Graduate Biomedical Engineering Program, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
| | - Jun Liao
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, 76019.,Joint Graduate Biomedical Engineering Program, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.,Department of Biological Engineering, Mississippi State University, Starkville, Mississippi, 39762
| | - Yi Hong
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, 76019.,Joint Graduate Biomedical Engineering Program, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
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49
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Rangel-Argote M, Claudio-Rizo JA, Mata-Mata JL, Mendoza-Novelo B. Characteristics of Collagen-Rich Extracellular Matrix Hydrogels and Their Functionalization with Poly(ethylene glycol) Derivatives for Enhanced Biomedical Applications: A Review. ACS APPLIED BIO MATERIALS 2018; 1:1215-1228. [DOI: 10.1021/acsabm.8b00282] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Magdalena Rangel-Argote
- Departamento de Ingenierías Química, Electrónica y Biomédica, DCI, Universidad de Guanajuato, Loma del Bosque 103, 37150 León, Guanajuato, México
- Departamento de Química, DCNE, Universidad de Guanajuato, Noria alta s/n, 36050 Guanajuato, Guanajuato, México
| | - Jesús A. Claudio-Rizo
- Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Venustiano Carranza s/n, 25280 Saltillo, Coahuila, México
| | - José L. Mata-Mata
- Departamento de Química, DCNE, Universidad de Guanajuato, Noria alta s/n, 36050 Guanajuato, Guanajuato, México
| | - Birzabith Mendoza-Novelo
- Departamento de Ingenierías Química, Electrónica y Biomédica, DCI, Universidad de Guanajuato, Loma del Bosque 103, 37150 León, Guanajuato, México
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50
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Billaud M, Hill JC, Richards TD, Gleason TG, Phillippi JA. Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm. Front Cardiovasc Med 2018; 5:124. [PMID: 30276199 PMCID: PMC6151311 DOI: 10.3389/fcvm.2018.00124] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 08/20/2018] [Indexed: 11/29/2022] Open
Abstract
Human ascending aortic aneurysms characteristically exhibit cystic medial degeneration of the aortic wall encompassing elastin degeneration, proteoglycan accumulation and smooth muscle cell loss. Most studies have focused on the aortic media and there is a limited understanding of the importance of the adventitial layer in the setting of human aneurysmal disease. We recently demonstrated that the adventitial ECM contains key angiogenic factors that are downregulated in aneurysmal aortic specimens. In this study, we investigated the adventitial microvascular network (vasa vasorum) of aneurysmal aortic specimens of different etiology and hypothesized that the vasa vasorum is disrupted in patients with ascending aortic aneurysm. Morphometric analyses of hematoxylin and eosin-stained human aortic cross-sections revealed evidence of vasa vasorum remodeling in aneurysmal specimens, including reduced density of vessels, increased lumen area and thickening of smooth muscle actin-positive layers. These alterations were inconsistently observed in specimens of bicuspid aortic valve (BAV)-associated aortopathy, while vasa vasorum remodeling was typically observed in aneurysms arising in patients with the morphologically normal tricuspid aortic valve (TAV). Gene expression of hypoxia-inducible factor 1α and its downstream targets, metallothionein 1A and the pro-angiogenic factor vascular endothelial growth factor, were down-regulated in the adventitia of aneurysmal specimens when compared with non-aneurysmal specimens, while the level of the anti-angiogenic factor thrombospondin-1 was elevated. Immunodetection of glucose transporter 1 (GLUT1), a marker of chronic tissue hypoxia, was minimal in non-aneurysmal medial specimens, and locally accumulated within regions of elastin degeneration, particularly in TAV-associated aneurysms. Quantification of GLUT1 revealed elevated levels in the aortic media of TAV-associated aneurysms when compared to non-aneurysmal counterparts. We detected evidence of chronic inflammation as infiltration of lymphoplasmacytic cells in aneurysmal specimens, with a higher prevalence of lymphoplasmacytic infiltrates in aneurysmal specimens from patients with TAV compared to that of patients with BAV. These data highlight differences in vasa vasorum remodeling and associated medial chronic hypoxia markers between aneurysms of different etiology. These aberrations could contribute to malnourishment of the aortic media and could conceivably participate in the pathogenesis of thoracic aortic aneurysm.
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Affiliation(s)
- Marie Billaud
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, United States.,McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States.,Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States
| | - Jennifer C Hill
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, United States
| | - Tara D Richards
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, United States
| | - Thomas G Gleason
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, United States.,McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States.,Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.,Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, PA, United States
| | - Julie A Phillippi
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, United States.,McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States.,Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.,Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, PA, United States
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