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Soltanmohammadi F, Mahmoudi Gharehbaba A, Javadzadeh Y. Synergistic strategies in tissue engineering: The role of exosomes and decellularized extracellular matrix hydrogels. Biomed Pharmacother 2025; 188:118200. [PMID: 40414001 DOI: 10.1016/j.biopha.2025.118200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 05/07/2025] [Accepted: 05/21/2025] [Indexed: 05/27/2025] Open
Abstract
Tissue engineering aims to mimic the natural microenvironment of biological structures by utilizing the distinctive characteristics of extracellular matrix (ECM) scaffolds. The combination of decellularized extracellular matrix hydrogels (dECMHs) with exosomes (EXs) represents an innovative therapeutic approach for tissue regeneration. These dECMHs, sourced from diverse tissues, provide biocompatible scaffolds that conform to irregular defect geometries, thereby addressing the limitations of conventional ECM scaffolds. EXs, which are nanovesicles secreted by virtually all cells, play crucial role in cell communication and tissue regeneration. However, their short half-life presents challenges for systemic administration. The incorporation of EXs into dECMHs enables localized and prolonged release, thereby enhancing their therapeutic merits. This review thoroughly explains the techniques for decellularization, the characteristics of dECM, as well as the preparation and applications of dECMHs in tissue engineering. It also explores the synergistic effects of EX-dECMH systems on cellular activities essential for tissue repair, including proliferation, differentiation, and neovascularization. The mechanisms of EX release from dECMHs and their applications in the regeneration of skin, intervertebral disc, cartilage, and nerve tissues are elucidated, highlighting the considerable potential of this integrated strategy to improve tissue engineering techniques. Furthermore, the synergistic effect of EX-dECMH systems in tissue healing is investigated. Finally, the limitations associated with the clinical application of EX, dECM, and dECMH as well as the future prospect are included.
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Affiliation(s)
- Fatemeh Soltanmohammadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Adel Mahmoudi Gharehbaba
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Yousef Javadzadeh
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Soltanmohammadi F, Mahmoudi Gharehbaba A, Alizadeh E, Javadzadeh Y. Innovative approaches to tissue engineering: Utilizing decellularized extracellular matrix hydrogels for mesenchymal stem cell transport. Int J Biol Macromol 2025; 290:138893. [PMID: 39706433 DOI: 10.1016/j.ijbiomac.2024.138893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/07/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024]
Abstract
In recent years, the realm of tissue regeneration experienced significant advancements, leading to the development of innovative therapeutic agents. The systemic delivery of mesenchymal stem cells (MSCs) emerged as a promising strategy for promoting tissue regeneration. However, this approach is hindered by hurdles such as poor cell survival, limited cell propagation, and inadequate cell integration. Decellularized extracellular matrix (dECM) hydrogel serves as an innovative carrier that protects MSCs from the detrimental effects of the hostile microenvironment, facilitates their localization and retention at the injection site, and preserves their viability. Regarding its low immunogenicity, low cytotoxicity, high biocompatibility, and its ability to mimic natural extracellular matrix (ECM), this natural hydrogel offers a new avenue for systemic delivery of MSCs. This review digs into the properties of dECM hydrogels (dECMHs), the methods employed for decellularization and the utilization of dECMH as carriers for various types of MSCs for tissue regeneration purposes. This review also sheds light on the benefits of hybrid hydrogels composed of dECMH and other components such as proteins and polysaccharides. By addressing the limitations of conventional hydrogels and enhancing efficacy of cell therapy, dECMH opens new pathways for the future of tissue regeneration.
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Affiliation(s)
- Fatemeh Soltanmohammadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Adel Mahmoudi Gharehbaba
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Effat Alizadeh
- Endocrin Research Center and Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Yousef Javadzadeh
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Liu J, Song Q, Yin W, Li C, An N, Le Y, Wang Q, Feng Y, Hu Y, Wang Y. Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations. EXPLORATION (BEIJING, CHINA) 2025; 5:20230078. [PMID: 40040827 PMCID: PMC11875452 DOI: 10.1002/exp.20230078] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 03/12/2024] [Indexed: 03/06/2025]
Abstract
Decellularized extracellular matrix (dECM) offers a three-dimensional, non-immunogenic scaffold, enriched with bioactive components, making it a suitable candidate for tissue regeneration. Although dECM-based scaffolds have been successfully implemented in preclinical and clinical settings within tissue engineering and regenerative medicine, the mechanisms of tissue remodeling and functional restoration are not fully understood. This review critically assesses the state-of-the-art in dECM scaffolds, including decellularization techniques for various tissues, quality control and cross-linking. It highlights the functional properties of dECM components and their latest applications in multiorgan tissue engineering and biomedicine. Additionally, the review addresses current challenges and limitations of decellularized scaffolds and offers perspectives on future directions in the field.
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Affiliation(s)
- Juan Liu
- Hepato‐Pancreato‐Biliary CenterBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijingChina
- Key Laboratory of Digital Intelligence HepatologyMinistry of EducationSchool of Clinical MedicineTsinghua UniversityBeijingChina
| | - Qingru Song
- Clinical Translational Science CenterBeijing Tsinghua Changgung HospitalTsinghua UniversityBeijingChina
| | - Wenzhen Yin
- Clinical Translational Science CenterBeijing Tsinghua Changgung HospitalTsinghua UniversityBeijingChina
| | - Chen Li
- Hepato‐Pancreato‐Biliary CenterBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijingChina
- College of Chemistry and Life SciencesBeijing University of TechnologyBeijingChina
| | - Ni An
- Clinical Translational Science CenterBeijing Tsinghua Changgung HospitalTsinghua UniversityBeijingChina
| | - Yinpeng Le
- Hepato‐Pancreato‐Biliary CenterBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijingChina
- Institute of Smart Biomedical MaterialsSchool of Materials Science and EngineeringZhejiang Sci‐Tech UniversityHangzhouPeople's Republic of China
| | - Qi Wang
- Hepato‐Pancreato‐Biliary CenterBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijingChina
- Department of Hepatobiliary and Pancreatic SurgeryThe First Hospital of Jilin UniversityJilin UniversityChangchunChina
| | - Yutian Feng
- Hepato‐Pancreato‐Biliary CenterBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijingChina
| | - Yuelei Hu
- Hepato‐Pancreato‐Biliary CenterBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijingChina
- Department of Hepatobiliary and Pancreatic SurgeryThe First Hospital of Jilin UniversityJilin UniversityChangchunChina
| | - Yunfang Wang
- Hepato‐Pancreato‐Biliary CenterBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijingChina
- Key Laboratory of Digital Intelligence HepatologyMinistry of EducationSchool of Clinical MedicineTsinghua UniversityBeijingChina
- Clinical Translational Science CenterBeijing Tsinghua Changgung HospitalTsinghua UniversityBeijingChina
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Su S, Wang R, Bai J, Chen Z, Zhou F. Novel Decellularization Scheme for Preparing Acellular Fish Scale Scaffolds for Bone Tissue Engineering. ACS OMEGA 2025; 10:230-238. [PMID: 39829519 PMCID: PMC11740628 DOI: 10.1021/acsomega.4c05096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 01/22/2025]
Abstract
In bone tissue engineering, a suitable scaffold is the key. Due to their similar composition to bone tissue, special structure, good mechanical properties, and osteogenic properties, acellular fish scale scaffolds are potential scaffolds for bone tissue engineering. At present, the fish scale decellularization scheme mostly uses a combination of sodium dodecyl sulfate and ethylenediamine tetraacetic acid (EDTA), but this method has problems. We optimized this method using a combined method of Triton X-100, EDTA, and nuclease. In this study, the optimal scheme was screened with respect to the decellularization effect, extracellular matrix composition and structure retention, mechanical properties, cell biocompatibility, and osteogenic differentiation ability. The results showed that the optimal scheme was as follows: the native fish scales were incubated in 0.1% EDTA for 24 h, and then the cellular components were removed with 1% Triton X-100 for 4 days, followed by nuclease digestion for 24 h. On that basis, we proposed a novel and more suitable fish scale decellularization scheme, and the acellular fish scale scaffold prepared by this decellularization scheme may have great potential in bone tissue engineering.
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Affiliation(s)
- Shilong Su
- Department
of Orthopedics, Peking University Third
Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
- Engineering
Research Center of Bone and Joint Precision Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
| | - Ruideng Wang
- Department
of Orthopedics, Peking University Third
Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
- Engineering
Research Center of Bone and Joint Precision Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
| | - Jinwu Bai
- Department
of Orthopedics, Peking University Third
Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
- Engineering
Research Center of Bone and Joint Precision Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
| | - Zhengyang Chen
- Department
of Orthopedics, Peking University Third
Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
- Engineering
Research Center of Bone and Joint Precision Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
| | - Fang Zhou
- Department
of Orthopedics, Peking University Third
Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
- Engineering
Research Center of Bone and Joint Precision Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian, 100191 Beijing, China
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Morawski M, Krasnodębski M, Rochoń J, Kubiszewski H, Marzęcki M, Topyła D, Murat K, Staszewski M, Szczytko J, Maleszewski M, Grąt M. Decellularized Liver Matrices for Expanding the Donor Pool-An Evaluation of Existing Protocols and Future Trends. Biomolecules 2025; 15:98. [PMID: 39858491 PMCID: PMC11762870 DOI: 10.3390/biom15010098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/07/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Liver transplantation is the only curative option for end-stage liver disease and is necessary for an increasing number of patients with advanced primary or secondary liver cancer. Many patient groups can benefit from this treatment, however the shortage of liver grafts remains an unsolved problem. Liver bioengineering offers a promising method for expanding the donor pool through the production of acellular scaffolds that can be seeded with recipient cells. Decellularization protocols involve the removal of cells using various chemical, physical, and enzymatic steps to create a collagenous network that provides support for introduced cells and future vascular and biliary beds. However, the removal of the cells causes varying degrees of matrix damage, that can affect cell seeding and future organ performance. The main objective of this review is to present the existing techniques of producing decellularized livers, with an emphasis on the assessment and definition of acellularity. Decellularization agents are discussed, and the standard process of acellular matrix production is evaluated. We also introduce the concept of the stepwise assessment of the matrix during decellularization through decellularization cycles. This method may lead to shorter detergent exposure times and less scaffold damage. The introduction of apoptosis induction in the field of organ engineering may provide a valuable alternative to existing long perfusion protocols, which lead to significant matrix damage. A thorough understanding of the decellularization process and the action of the various factors influencing the final composition of the scaffold is essential to produce a biocompatible matrix, which can be the basis for further studies regarding recellularization and retransplantation.
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Affiliation(s)
- Marcin Morawski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.K.); (J.R.); (H.K.); (M.S.); (M.G.)
| | - Maciej Krasnodębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.K.); (J.R.); (H.K.); (M.S.); (M.G.)
| | - Jakub Rochoń
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.K.); (J.R.); (H.K.); (M.S.); (M.G.)
| | - Hubert Kubiszewski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.K.); (J.R.); (H.K.); (M.S.); (M.G.)
| | - Michał Marzęcki
- Institute of Telecommunications, Warsaw University of Technology, 00-665 Warsaw, Poland; (M.M.); (D.T.); (K.M.)
| | - Dominik Topyła
- Institute of Telecommunications, Warsaw University of Technology, 00-665 Warsaw, Poland; (M.M.); (D.T.); (K.M.)
| | - Kacper Murat
- Institute of Telecommunications, Warsaw University of Technology, 00-665 Warsaw, Poland; (M.M.); (D.T.); (K.M.)
| | - Mikołaj Staszewski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.K.); (J.R.); (H.K.); (M.S.); (M.G.)
| | - Jacek Szczytko
- Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 02-093 Warsaw, Poland;
| | - Marek Maleszewski
- Department of Embryology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland;
| | - Michał Grąt
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.K.); (J.R.); (H.K.); (M.S.); (M.G.)
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Fazel Anvari Yazdi A, Tahermanesh K, Ejlali M, Babaei-Ghazvini A, Acharya B, Badea I, MacPhee DJ, Chen X. Comparative analysis of porcine-uterine decellularization for bioactive-molecule preservation and DNA removal. Front Bioeng Biotechnol 2024; 12:1418034. [PMID: 39416283 PMCID: PMC11480021 DOI: 10.3389/fbioe.2024.1418034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/27/2024] [Indexed: 10/19/2024] Open
Abstract
Introduction Decellularized uterine extracellular matrix has emerged as a pivotal focus in the realm of biomaterials, offering a promising source in uterine tissue regeneration, research on disease diagnosis and treatments, and ultimately uterine transplantation. In this study, we examined various protocols for decellularizing porcine uterine tissues, aimed to unravel the intricate dynamics of DNA removal, bioactive molecules preservation, and microstructural alterations. Methods Porcine uterine tissues were treated with 6 different, yet rigorously selected and designed, protocols with sodium dodecyl sulfate (SDS), Triton® X-100, peracetic acid + ethanol, and DNase I. After decellularization, we examined DNA quantification, histological staining (H&E and DAPI), glycosaminoglycans (GAG) assay, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and Thermogravimetric Analysis (TGA). Results A comparative analysis among all 6 protocols was conducted with the results demonstrating that all protocols achieved decellularization; while 0.1% SDS + 1% Triton® X-100, coupled with agitation, demonstrated the highest efficiency in DNA removal. Also, it was found that DNase I played a key role in enhancing the efficiency of the decellularization process by underscoring its significance in digesting cellular contents and eliminating cell debris by 99.79% (19.63 ± 3.92 ng/mg dry weight). Conclusions Our findings enhance the nuanced understanding of DNA removal, GAG preservation, microstructural alteration, and protein decomposition in decellularized uterine extracellular matrix, while highlighting the importance of decellularization protocols designed for intended applications. This study along with our findings represents meaningful progress for advancing the field of uterine transplantation and related tissue engineering/regenerative medicine.
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Affiliation(s)
| | - Kobra Tahermanesh
- Department of Obstetrics and Gynecology, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Maryam Ejlali
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Amin Babaei-Ghazvini
- Department of Chemical and Biological Engineering, University of Saskatchewan, Saskatoon, SK, Canada
| | - Bishnu Acharya
- Department of Chemical and Biological Engineering, University of Saskatchewan, Saskatoon, SK, Canada
| | - Ildiko Badea
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Daniel J. MacPhee
- Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Xiongbiao Chen
- Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Canada
- Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, Canada
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Hashimoto Y, Negishi J, Funamoto S, Kimura T, Kobayashi H, Oshika T, Kishida A. Preparation, physico-biochemical characterization, and proteomic analysis of highly transparent corneal extracellular matrices for lamellar keratoplasty and tissue-engineered cornea construction. Mater Today Bio 2024; 28:101241. [PMID: 39328788 PMCID: PMC11426139 DOI: 10.1016/j.mtbio.2024.101241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 08/26/2024] [Accepted: 09/10/2024] [Indexed: 09/28/2024] Open
Abstract
Corneal opacity and deformation, which often require corneal transplantation for treatment, are among the leading causes of monocular blindness. To restore corneal clarity and integrity, there is a need for an artificial stroma that not only matches the transparency of donated human cornea but also effectively integrates to the corneal tissue. In this study, a transparent decellularized cornea was successfully developed using the high hydrostatic pressure method with processing conditions optimized for corneal decellularization. Biochemical analyses demonstrated the effective removal of cellular components from the transparent decellularized corneas, while preserving collagen and glycosaminoglycans. Proteome analysis also revealed that core matrisome and matrisome-associated proteins remained following decellularization, similar to the composition observed in untreated corneas. The light transmittance of the transparent decellularized corneas was 86.4 ± 1.5 % in the visible region, comparable to that of donated human corneas. No complications, such as angiogenesis, were observed following interlamellar corneal transplantation in rabbits. The grafts were almost imperceptible immediately following surgery and achieved complete transparency within a few days, becoming indistinguishable even under a microscope. The transparent decellularized cornea presented here has promising potential as a material for application in lamellar keratoplasty.
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Affiliation(s)
- Yoshihide Hashimoto
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan
| | - Jun Negishi
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan
- Department of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, 3-15-1 Tokida, Ueda, Nagano, 386-8567, Japan
| | - Seiichi Funamoto
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan
| | - Tsuyoshi Kimura
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan
- Department of Biomedical Engineering, Faculty of Life Science, Toyo University, 48-1 Oka, Asaka-shi, Saitama, 351-8510, Japan
| | - Hisatoshi Kobayashi
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan
| | - Tetsuro Oshika
- Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Akio Kishida
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan
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Hussein KH, Ahmadzada B, Correa JC, Sultan A, Wilken S, Amiot B, Nyberg SL. Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities. Bioact Mater 2024; 40:280-305. [PMID: 38973992 PMCID: PMC11226731 DOI: 10.1016/j.bioactmat.2024.06.001] [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: 04/03/2024] [Revised: 05/30/2024] [Accepted: 06/01/2024] [Indexed: 07/09/2024] Open
Abstract
Liver transplantation represents the only definitive treatment for patients with end-stage liver disease. However, the shortage of liver donors provokes a dramatic gap between available grafts and patients on the waiting list. Whole liver bioengineering, an emerging field of tissue engineering, holds great potential to overcome this gap. This approach involves two main steps; the first is liver decellularization and the second is recellularization. Liver decellularization aims to remove cellular and nuclear materials from the organ, leaving behind extracellular matrices containing different structural proteins and growth factors while retaining both the vascular and biliary networks. Recellularization involves repopulating the decellularized liver with appropriate cells, theoretically from the recipient patient, to reconstruct the parenchyma, vascular tree, and biliary network. The aim of this review is to identify the major advances in decellularization and recellularization strategies and investigate obstacles for the clinical application of bioengineered liver, including immunogenicity of the designed liver extracellular matrices, the need for standardization of scaffold fabrication techniques, selection of suitable cell sources for parenchymal repopulation, vascular, and biliary tree reconstruction. In vivo transplantation models are also summarized for evaluating the functionality of bioengineered livers. Finally, the regulatory measures and future directions for confirming the safety and efficacy of bioengineered liver are also discussed. Addressing these challenges in whole liver bioengineering may offer new solutions to meet the demand for liver transplantation and improve patient outcomes.
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Affiliation(s)
- Kamal H. Hussein
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
- Department of Surgery, Anesthesiology, and Radiology, College of Veterinary Medicine, Assiut University, Assiut, Egypt
| | - Boyukkhanim Ahmadzada
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Julio Cisneros Correa
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Ahmer Sultan
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Silvana Wilken
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Bruce Amiot
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Scott L. Nyberg
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
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Duong VT, Nguyen HD, Luong NH, Chang CY, Lin CC. Photo-responsive decellularized small intestine submucosa hydrogels. ADVANCED FUNCTIONAL MATERIALS 2024; 34:2401952. [PMID: 39525288 PMCID: PMC11546089 DOI: 10.1002/adfm.202401952] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Indexed: 11/16/2024]
Abstract
Decellularized small intestine submucosa (dSIS) is a promising biomaterial for promoting tissue regeneration. Isolated from the submucosal layer of animal jejunum, SIS is rich in extracellular matrix (ECM) proteins, including collagen, laminin, and fibronectin. Following mild decellularization, dSIS becomes an acellular matrix that supports cell adhesion, proliferation, and differentiation. Conventional dSIS matrix is usually obtained by thermal crosslinking, which yields a soft scaffold with low stability. To address these challenges, dSIS has been modified with methacrylate groups for photocrosslinking into stable hydrogels. However, dSIS has not been modified with clickable handles for orthogonal crosslinking. Here, we report the development of norbornene-modified dSIS, named dSIS-NB, via reacting amine groups of dSIS with carbic anhydride in acidic aqueous reaction conditions. Using triethylamine (TEA) as a mild base catalyst, we obtained high degrees of NB substitution on dSIS. In addition to describing the synthesis of dSIS-NB, we explored its adaptability in orthogonal hydrogel crosslinking and used dSIS-NB hydrogels for cancer and vascular tissue engineering. Impressively, compared with physically crosslinked dSIS and collagen matrices, orthogonally crosslinked dSIS-NB hydrogels supported rapid dissemination of cancer cells and superior vasculogenic and angiogenic properties. dSIS-NB was also exploited as a versatile bioink for 3D bioprinting applications.
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Affiliation(s)
- Van Thuy Duong
- Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
| | - Han Dang Nguyen
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
| | - Ngoc Ha Luong
- Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
| | - Chun-Yi Chang
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
| | - Chien-Chi Lin
- Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
- Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA
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10
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Guo XX, Pu Q, Chang XJ, Li AL, Hu JJ, Li XY. Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction. Exp Eye Res 2024; 245:109953. [PMID: 38838974 DOI: 10.1016/j.exer.2024.109953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 03/10/2024] [Accepted: 06/02/2024] [Indexed: 06/07/2024]
Abstract
The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.
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Affiliation(s)
- Xiao-Xiao Guo
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China
| | - Qi Pu
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China
| | - Xue-Jiao Chang
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China
| | - Ao-Ling Li
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China
| | - Jing-Jie Hu
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China
| | - Xin-Yu Li
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China.
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11
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Sarma SAVM, Pathak D, Singh O, Uppal V, Mohindroo J, Choudhary RK. Gross morphology and morphometry of native and decellularized heart valves of caprine: A comparative study. Anat Histol Embryol 2024; 53:e13075. [PMID: 38881030 DOI: 10.1111/ahe.13075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 05/30/2024] [Accepted: 06/01/2024] [Indexed: 06/18/2024]
Abstract
The gross morphological examination of native caprine heart valves revealed distinctive structural characteristics of the caprine's cardiac anatomy. Four primary orifices were identified, each protected by thin, valve-like structures. Atrioventricular orifices featured tricuspid and bicuspid valves, while the aorta and pulmonary arteries were guarded by semilunar valves. Within the atrioventricular apparatus, distinct features were observed including the tricuspid valve's three leaflets and the bicuspid valve's anterior and posterior leaflets. Ultrasonography provided insights into valve thickness and chordae tendineae lengths. Morphometric studies compared leaflets/cusps within individual native valves, showcasing significant variations in dimensions. Comparative analysis between native and decellularized valves highlighted the effects of decellularization on leaflet thickness and chordae tendineae lengths. Decellularized valves exhibited reduced dimensions compared to native valves, indicating successful removal of cellular components. While some dimensions remained unchanged post-decellularization, significant reductions were observed in leaflet thicknesses and chordae tendineae lengths. Notably, semilunar valve cusps displayed varying responses to decellularization, with significant reductions in cusp lengths observed in the aortic valve, while the pulmonary valve exhibited more subtle changes. These findings underscore the importance of understanding structural alterations in heart valves post-decellularization, providing valuable insights for tissue engineering applications and regenerative medicine.
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Affiliation(s)
- S A V Manikanta Sarma
- Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India
| | - Devendra Pathak
- Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India
| | - Opinder Singh
- Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India
| | - Varinder Uppal
- Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India
| | - Jitender Mohindroo
- Department of Veterinary Surgery and Radiology, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India
| | - Ratan Kumar Choudhary
- College of Animal Biotechnology, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India
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12
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Rahmati S, Khazaei M, Abpeikar Z, Soleimanizadeh A, Rezakhani L. Exosome-loaded decellularized tissue: Opening a new window for regenerative medicine. J Tissue Viability 2024; 33:332-344. [PMID: 38594147 DOI: 10.1016/j.jtv.2024.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 03/29/2024] [Accepted: 04/04/2024] [Indexed: 04/11/2024]
Abstract
Mesenchymal stem cell-derived exosomes (MSCs-EXO) have received a lot of interest recently as a potential therapeutic tool in regenerative medicine. Extracellular vesicles (EVs) known as exosomes (EXOs) are crucial for cell-cell communication throughout a variety of activities including stress response, aging, angiogenesis, and cell differentiation. Exploration of the potential use of EXOs as essential therapeutic effectors of MSCs to encourage tissue regeneration was motivated by success in the field of regenerative medicine. EXOs have been administered to target tissues using a variety of methods, including direct, intravenous, intraperitoneal injection, oral delivery, and hydrogel-based encapsulation, in various disease models. Despite the significant advances in EXO therapy, various methods are still being researched to optimize the therapeutic applications of these nanoparticles, and it is not completely clear which approach to EXO administration will have the greatest effects. Here, we will review emerging developments in the applications of EXOs loaded into decellularized tissues as therapeutic agents for use in regenerative medicine in various tissues.
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Affiliation(s)
- Shima Rahmati
- Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mozafar Khazaei
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zahra Abpeikar
- Department of Tissue Engineering, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Arghavan Soleimanizadeh
- Faculty of Medicine, Graduate School 'Molecular Medicine, University of Ulm, 89081, Ulm, Germany
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Cecuda-Adamczewska V, Romanik-Chruścielewska A, Kosowska K, Łukasiewicz N, Sokołowska I, Korycka P, Florys-Jankowska K, Zakrzewska A, Wszoła M, Klak M. Characterization of a Chimeric Resilin-Elastin Structural Protein Dedicated to 3D Bioprinting as a Bioink Component. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:749. [PMID: 38727343 PMCID: PMC11085090 DOI: 10.3390/nano14090749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/16/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024]
Abstract
In this study we propose to use for bioprinting a bioink enriched with a recombinant RE15mR protein with a molecular weight of 26 kDa, containing functional sequences derived from resilin and elastin. The resulting protein also contains RGD sequences in its structure, as well as a metalloproteinase cleavage site, allowing positive interaction with the cells seeded on the construct and remodeling the structure of this protein in situ. The described protein is produced in a prokaryotic expression system using an E. coli bacterial strain and purified by a process using a unique combination of known methods not previously used for recombinant elastin-like proteins. The positive effect of RE15mR on the mechanical, physico-chemical, and biological properties of the print is shown in the attached results. The addition of RE15mR to the bioink resulted in improved mechanical and physicochemical properties and promoted the habitation of the prints by cells of the L-929 line.
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Affiliation(s)
- Violetta Cecuda-Adamczewska
- Foundation of Research and Science Development, 01-424 Warsaw, Poland; (A.R.-C.); (K.K.); (N.Ł.); (I.S.); (P.K.); (K.F.-J.)
| | | | - Katarzyna Kosowska
- Foundation of Research and Science Development, 01-424 Warsaw, Poland; (A.R.-C.); (K.K.); (N.Ł.); (I.S.); (P.K.); (K.F.-J.)
| | - Natalia Łukasiewicz
- Foundation of Research and Science Development, 01-424 Warsaw, Poland; (A.R.-C.); (K.K.); (N.Ł.); (I.S.); (P.K.); (K.F.-J.)
| | - Iwona Sokołowska
- Foundation of Research and Science Development, 01-424 Warsaw, Poland; (A.R.-C.); (K.K.); (N.Ł.); (I.S.); (P.K.); (K.F.-J.)
| | - Paulina Korycka
- Foundation of Research and Science Development, 01-424 Warsaw, Poland; (A.R.-C.); (K.K.); (N.Ł.); (I.S.); (P.K.); (K.F.-J.)
| | - Katarzyna Florys-Jankowska
- Foundation of Research and Science Development, 01-424 Warsaw, Poland; (A.R.-C.); (K.K.); (N.Ł.); (I.S.); (P.K.); (K.F.-J.)
| | | | - Michał Wszoła
- Polbionica Ltd., 01-424 Warsaw, Poland; (A.Z.); (M.W.)
| | - Marta Klak
- Polbionica Ltd., 01-424 Warsaw, Poland; (A.Z.); (M.W.)
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Ulldemolins A, Narciso M, Sanz-Fraile H, Otero J, Farré R, Gavara N, Almendros I. Effects of aging on the biomechanical properties of the lung extracellular matrix: dependence on tissular stretch. Front Cell Dev Biol 2024; 12:1381470. [PMID: 38645411 PMCID: PMC11026642 DOI: 10.3389/fcell.2024.1381470] [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: 02/03/2024] [Accepted: 03/25/2024] [Indexed: 04/23/2024] Open
Abstract
Introduction: Aging induces functional and structural changes in the lung, characterized by a decline in elasticity and diminished pulmonary remodeling and regenerative capacity. Emerging evidence suggests that most biomechanical alterations in the lung result from changes in the composition of the lung extracellular matrix (ECM), potentially modulating the behavior of pulmonary cells and increasing the susceptibility to chronic lung diseases. Therefore, it is crucial to investigate the mechanical properties of the aged lung. This study aims to assess the mechanical alterations in the lung ECM due to aging at both residual (RV) and functional (FV) lung volumes and to evaluate their effects on the survival and proliferation of mesenchymal stromal cells (MSCs). Methods: The lungs from young (4-6-month-old) and aged (20-24-month-old) mice were inflated with optimal cutting temperature compound to reach FV or non-inflated (RV). ECM proteins laminin, collagen I and fibronectin were quantified by immunofluorescence and the mechanical properties of the decellularized lung sections were assessed using atomic force microscopy. To investigate whether changes in ECM composition by aging and/or mechanical properties at RV and FV volumes affects MSCs, their viability and proliferation were evaluated after 72 h. Results: Laminin presence was significantly reduced in aged mice compared to young mice, while fibronectin and collagen I were significantly increased in aged mice. In RV conditions, the acellular lungs from aged mice were significantly softer than from young mice. By contrast, in FV conditions, the aged lung ECM becomes stiffer than that of in young mice, revealing that strain hardening significantly depends on aging. Results after MSCs recellularization showed similar viability and proliferation rate in all conditions. Discussion: This data strongly suggests that biomechanical measurements, especially in aging models, should be carried out in physiomimetic conditions rather than following the conventional non-inflated lung (RV) approach. The use of decellularized lung scaffolds from aged and/or other lung disease murine/human models at physiomimetic conditions will help to better understand the potential role of mechanotransduction on the susceptibility and progression of chronic lung diseases, lung regeneration and cancer.
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Affiliation(s)
- Anna Ulldemolins
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Maria Narciso
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Héctor Sanz-Fraile
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Jorge Otero
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, Madrid, Spain
| | - Ramon Farré
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Núria Gavara
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Isaac Almendros
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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15
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Noro J, Vilaça-Faria H, Reis RL, Pirraco RP. Extracellular matrix-derived materials for tissue engineering and regenerative medicine: A journey from isolation to characterization and application. Bioact Mater 2024; 34:494-519. [PMID: 38298755 PMCID: PMC10827697 DOI: 10.1016/j.bioactmat.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 12/19/2023] [Accepted: 01/03/2024] [Indexed: 02/02/2024] Open
Abstract
Biomaterial choice is an essential step during the development tissue engineering and regenerative medicine (TERM) applications. The selected biomaterial must present properties allowing the physiological-like recapitulation of several processes that lead to the reestablishment of homeostatic tissue or organ function. Biomaterials derived from the extracellular matrix (ECM) present many such properties and their use in the field has been steadily increasing. Considering this growing importance, it becomes imperative to provide a comprehensive overview of ECM biomaterials, encompassing their sourcing, processing, and integration into TERM applications. This review compiles the main strategies used to isolate and process ECM-derived biomaterials as well as different techniques used for its characterization, namely biochemical and chemical, physical, morphological, and biological. Lastly, some of their applications in the TERM field are explored and discussed.
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Affiliation(s)
- Jennifer Noro
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's – PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - Helena Vilaça-Faria
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's – PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - Rui L. Reis
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's – PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - Rogério P. Pirraco
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's – PT Government Associate Laboratory, Braga, Guimarães, Portugal
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16
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Dehghani S, Aghaee Z, Soleymani S, Tafazoli M, Ghabool Y, Tavassoli A. An overview of the production of tissue extracellular matrix and decellularization process. Cell Tissue Bank 2024; 25:369-387. [PMID: 37812368 DOI: 10.1007/s10561-023-10112-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 09/09/2023] [Indexed: 10/10/2023]
Abstract
Thousands of patients need an organ transplant yearly, while only a tiny percentage have this chance to receive a tissue/organ transplant. Nowadays, decellularized animal tissue is one of the most widely used methods to produce engineered scaffolds for transplantation. Decellularization is defined as physically or chemically removing cellular components from tissues while retaining structural and functional extracellular matrix (ECM) components and creating an ECM-derived scaffold. Then, decellularized scaffolds could be reseeded with different cells to fabricate an autologous graft. Effective decellularization methods preserve ECM structure and bioactivity through the application of the agents and techniques used throughout the process. The most valuable agents for the decellularization process depend on biological properties, cellular density, and the thickness of the desired tissue. ECM-derived scaffolds from various mammalian tissues have been recently used in research and preclinical applications in tissue engineering. Many studies have shown that decellularized ECM-derived scaffolds could be obtained from tissues and organs such as the liver, cartilage, bone, kidney, lung, and skin. This review addresses the significance of ECM in organisms and various decellularization agents utilized to prepare the ECM. Also, we describe the current knowledge of the decellularization of different tissues and their applications.
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Affiliation(s)
- Shima Dehghani
- Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran
| | - Zahra Aghaee
- Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran
| | - Safoura Soleymani
- Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Azadi Square, Mashhad, 9177948974, Iran
| | - Maryam Tafazoli
- Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Azadi Square, Mashhad, 9177948974, Iran
| | - Yasin Ghabool
- Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Amin Tavassoli
- Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Azadi Square, Mashhad, 9177948974, Iran.
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Li Y, Liu S, Zhang J, Wang Y, Lu H, Zhang Y, Song G, Niu F, Shen Y, Midgley AC, Li W, Kong D, Zhu M. Elastic porous microspheres/extracellular matrix hydrogel injectable composites releasing dual bio-factors enable tissue regeneration. Nat Commun 2024; 15:1377. [PMID: 38355941 PMCID: PMC10866888 DOI: 10.1038/s41467-024-45764-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 02/02/2024] [Indexed: 02/16/2024] Open
Abstract
Injectable biomaterials have garnered increasing attention for their potential and beneficial applications in minimally invasive surgical procedures and tissue regeneration. Extracellular matrix (ECM) hydrogels and porous synthetic polymer microspheres can be prepared for injectable administration to achieve in situ tissue regeneration. However, the rapid degradation of ECM hydrogels and the poor injectability and biological inertness of most polymeric microspheres limit their pro-regenerative capabilities. Here, we develop a biomaterial system consisting of elastic porous poly(l-lactide-co-ε-caprolactone) (PLCL) microspheres mixed with ECM hydrogels as injectable composites with interleukin-4 (IL-4) and insulin-like growth factor-1 (IGF-1) dual-release functionality. The developed multifunctional composites have favorable injectability and biocompatibility, and regulate the behavior of macrophages and myogenic cells following injection into muscle tissue. The elicited promotive effects on tissue regeneration are evidenced by enhanced neomusle formation, vascularization, and neuralization at 2-months post-implantation in a male rat model of volumetric muscle loss. Our developed system provides a promising strategy for engineering bioactive injectable composites that demonstrates desirable properties for clinical use and holds translational potential for application as a minimally invasive and pro-regenerative implant material in multiple types of surgical procedures.
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Affiliation(s)
- Yi Li
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Siyang Liu
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Jingjing Zhang
- Chifeng Municipal Hospital, Chifeng, 024000, Inner Mongolia, China
| | - Yumeng Wang
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Hongjiang Lu
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Yuexi Zhang
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325200, Zhejiang, China
| | - Guangzhou Song
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Fanhua Niu
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Yufan Shen
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Adam C Midgley
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Wen Li
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Deling Kong
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Meifeng Zhu
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
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18
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Zhang F, Gao H, Jiang X, Yang F, Zhang J, Song S, Shen J. Biomedical Application of Decellularized Scaffolds. ACS APPLIED BIO MATERIALS 2023; 6:5145-5168. [PMID: 38032114 DOI: 10.1021/acsabm.3c00778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2023]
Abstract
Tissue loss and end-stage organ failure are serious health problems across the world. Natural and synthetic polymer scaffold material based artificial organs play an important role in the field of tissue engineering and organ regeneration, but they are not from the body and may cause side effects such as rejection. In recent years, the biomimetic decellularized scaffold based materials have drawn great attention in the tissue engineering field for their good biocompatibility, easy modification, and excellent organism adaptability. Therefore, in this review, we comprehensively summarize the application of decellularized scaffolds in tissue engineering and biomedicine in recent years. The preparation methods, modification strategies, construction of artificial tissues, and application in biomedical applications are discussed. We hope that this review will provide a useful reference for research on decellularized scaffolds and promote their application tissue engineering.
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Affiliation(s)
- Fang Zhang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Huimin Gao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Xuefeng Jiang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Fang Yang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Jun Zhang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Saijie Song
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Jian Shen
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
- Jiangsu Engineering Research Center of Interfacial Chemistry, Nanjing University, Nanjing 210023, China
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19
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Esmaeili A, Rahimi A, Abbasi A, Hasannejad-Asl B, Bagheri-Mohammadi S, Farjami M, Keshel SH. Processing and post-processing of fish skin as a novel material in tissue engineering. Tissue Cell 2023; 85:102238. [PMID: 37832248 DOI: 10.1016/j.tice.2023.102238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/05/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023]
Abstract
As a natural material, fish skin contains significant amounts of collagen I and III, and due to its biocompatible nature, it can be used to regenerate various tissues and organs. To use fish skin, it is necessary to perform the decellularization process to avoid the immunological response of the host body. In the process of decellularization, it is crucial to conserve the extracellular matrix (ECM) three-dimensional (3D) structure. However, it is known that decellularization methods may also damage ECM strands arrangement and structure. Moreover, after decellularization, the post-processing of fish skin improves its mechanical and biological properties and preserves its 3D design and strength. Also, sterilization, which is one of the post-processing steps, is mandatory in pre-clinical and clinical settings. In this review paper, the fish skin decellularization methods performed and the various post-processes used to increase the performance of the skin have been studied. Moreover, multiple applications of acellular fish skin (AFS) and its extracted collagen have been reviewed.
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Affiliation(s)
- Ali Esmaeili
- Student Research Committee, Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Rahimi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amin Abbasi
- Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behnam Hasannejad-Asl
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti, University of Medical Sciences, Tehran, Iran
| | - Saeid Bagheri-Mohammadi
- Department of Physiology and Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Farjami
- Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Heidari Keshel
- Student Research Committee, Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Dhandapani V, Vermette P. Decellularized bladder as scaffold to support proliferation and functionality of insulin-secreting pancreatic cells. J Biomed Mater Res B Appl Biomater 2023; 111:1890-1902. [PMID: 37306142 DOI: 10.1002/jbm.b.35292] [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: 02/02/2023] [Revised: 05/07/2023] [Accepted: 05/31/2023] [Indexed: 06/13/2023]
Abstract
Loss in the number or function of insulin-producing β-cells in pancreatic islets has been associated with diabetes mellitus. Although islet transplantation can be an alternative treatment, complications such as apoptosis, ischaemia and loss of viability have been reported. The use of decellularized organs as scaffolds in tissue engineering is of interest owing to the unique ultrastructure and composition of the extracellular matrix (ECM) believed to act on tissue regeneration. In this study, a cell culture system has been designed to study the effect of decellularized porcine bladder pieces on INS-1 cells, a cell line secreting insulin in response to glucose stimulation. Porcine bladders were decellularized using two techniques: a detergent-containing and a detergent-free methods. The resulting ECMs were characterized for the removal of both cells and dsDNA. INS-1 cells were not viable on ECM produced using detergent (i.e., sodium dodecyl sulfate). INS-1 cells were visualized following 7 days of culture on detergent-free decellularized bladders using a cell viability and metabolism assay (MTT) and cell proliferation quantified (CyQUANT™ NF Cell Proliferation Assay). Further, glucose-stimulated insulin secretion and immunostaining confirmed that cells were functional in response to glucose stimulation, as well as they expressed insulin and interacted with the detergent-free produced ECM, respectively.
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Affiliation(s)
- Vignesh Dhandapani
- Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, Canada
- Centre de recherche du CHUS, Faculté de médecine et des sciences de la santé, Sherbrooke, Canada
| | - Patrick Vermette
- Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, Canada
- Centre de recherche du CHUS, Faculté de médecine et des sciences de la santé, Sherbrooke, Canada
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21
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Jiang P, Li Q, Luo Y, Luo F, Che Q, Lu Z, Yang S, Yang Y, Chen X, Cai Y. Current status and progress in research on dressing management for diabetic foot ulcer. Front Endocrinol (Lausanne) 2023; 14:1221705. [PMID: 37664860 PMCID: PMC10470649 DOI: 10.3389/fendo.2023.1221705] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%-34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%-68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain.
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Affiliation(s)
- Pingnan Jiang
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Qianhang Li
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yanhong Luo
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Feng Luo
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Qingya Che
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Zhaoyu Lu
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shuxiang Yang
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yan Yang
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Endocrinology and Metabolism, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Xia Chen
- Department of Endocrinology, Kweichow Moutai Hospital, Renhuai, Guizhou, China
| | - Yulan Cai
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Endocrinology and Metabolism, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
- Department of Endocrinology, Kweichow Moutai Hospital, Renhuai, Guizhou, China
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Kuniakova M, Klein M, Galfiova P, Csobonyeiova M, Feitscherova C, Polak S, Novakova ZV, Topoliova K, Trebaticky B, Varga I, Danisovic L, Ziaran S. Decellularization of the human urethra for tissue engineering applications. Exp Biol Med (Maywood) 2023; 248:1034-1042. [PMID: 37073134 PMCID: PMC10581165 DOI: 10.1177/15353702231162092] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 01/24/2023] [Indexed: 04/20/2023] Open
Abstract
Recently, several scaffolds have been introduced for urethral tissue engineering. However, acellular human urethral scaffold harvested from deceased donors may provide significant advantages compared to synthetic, composite, or other biological scaffolds. This study aims to develop the protocol for decellularization of the human urethra that preserves substantial extracellular matrix (ECM) components, which are essential for subsequent recellularization mimicking the natural environment of the native ECM. A total of 12 human urethras were harvested from deceased donors. An equal part of every harvested urethra was used as a control sample for analyses. The protocol design was based on the enzyme-detergent-enzyme method. Trypsin and Triton X-100 were used to remove cells, followed by DNase treatment to remove DNA residues. Subsequently, the specimens were continually rinsed in deionized water for seven days. The efficiency of decellularization was determined by histochemistry, immunohistochemical staining, scanning electron microscopy (SEM), and DNA quantification. Histological analysis confirmed cell removal and preservation of urethral structure after decellularization. The preservation of collagen IV and fibronectin was confirmed by histologic examination and immunohistochemical staining. SEM confirmed the maintenance of the ultrastructural architecture of ECM and fibers. DNA content in decellularized urethra was significantly lower compared to the native sample (P < 0.001), and so the criteria for decellularized tissue were met. Cytotoxicity analysis data showed that the matrix-conditioned medium did not contain soluble toxins and had no significant inhibitory effect on cell proliferation, providing evidence that the decellularized samples are not toxic. This study demonstrates the feasibility of the enzyme-detergent-enzyme-based decellularization protocol for removing cellular components and maintaining urethral ECM and its ultrastructure. Moreover, obtained results provide solid ground for recellularization and urethral tissue engineering, which will follow.
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Affiliation(s)
- Marcela Kuniakova
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava 811 08, Slovakia
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
| | - Martin Klein
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Bratislava 811 08, Slovakia
| | - Paulina Galfiova
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Bratislava 811 08, Slovakia
| | - Maria Csobonyeiova
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Bratislava 811 08, Slovakia
| | - Claudia Feitscherova
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Bratislava 811 08, Slovakia
| | - Stefan Polak
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Bratislava 811 08, Slovakia
| | - Zuzana Varchulova Novakova
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava 811 08, Slovakia
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
| | - Katarina Topoliova
- Department of Urology, Faculty of Medicine, Comenius University Bratislava, Bratislava 833 05, Slovakia
| | - Branislav Trebaticky
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
- Department of Urology, Faculty of Medicine, Comenius University Bratislava, Bratislava 833 05, Slovakia
| | - Ivan Varga
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Bratislava 811 08, Slovakia
| | - Lubos Danisovic
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava 811 08, Slovakia
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
| | - Stanislav Ziaran
- National Institute of Rheumatic Diseases, Piestany 921 12, Slovakia
- Department of Urology, Faculty of Medicine, Comenius University Bratislava, Bratislava 833 05, Slovakia
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23
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Kanda H, Oya K, Goto M. Surfactant-Free Decellularization of Porcine Auricular Cartilage Using Liquefied Dimethyl Ether and DNase. MATERIALS (BASEL, SWITZERLAND) 2023; 16:3172. [PMID: 37110010 PMCID: PMC10146022 DOI: 10.3390/ma16083172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/13/2023] [Accepted: 04/16/2023] [Indexed: 06/19/2023]
Abstract
The most common decellularization method involves lipid removal using surfactant sodium dodecyl sulfate (SDS) and DNA fragmentation using DNase, and is associated with residual SDS. We previously proposed a decellularization method for the porcine aorta and ostrich carotid artery using liquefied dimethyl ether (DME), which is free from the concerns associated with SDS residues, instead of SDS. In this study, the DME + DNase method was tested on crushed porcine auricular cartilage tissues. Unlike with the porcine aorta and the ostrich carotid artery, it is important to degas the porcine auricular cartilage using an aspirator before DNA fragmentation. Although approximately 90% of the lipids were removed using this method, approximately 2/3 of the water was removed, resulting in a temporary Schiff base reaction. The amount of residual DNA in the tissue was approximately 27 ng/mg dry weight, which is lower than the regulatory value of 50 ng/mg dry weight. Hematoxylin and eosin staining confirmed that cell nuclei were removed from the tissue. Residual DNA fragment length assessment by electrophoresis confirmed that the residual DNA was fragmented to less than 100 bp, which was lower than the regulatory limit of 200 bp. By contrast, in the uncrushed sample, only the surface was decellularized. Thus, although limited to a sample size of approximately 1 mm, liquefied DME can be used to decellularize porcine auricular cartilage. Thus, liquefied DME, with its low persistence and high lipid removal capacity, is an effective alternative to SDS.
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Al Qabbani A, Rani KGA, Syarif J, AlKawas S, Sheikh Abdul Hamid S, Samsudin AR, Azlina A. Evaluation of decellularization process for developing osteogenic bovine cancellous bone scaffolds in-vitro. PLoS One 2023; 18:e0283922. [PMID: 37018321 PMCID: PMC10075422 DOI: 10.1371/journal.pone.0283922] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 03/21/2023] [Indexed: 04/06/2023] Open
Abstract
Current immunological issues in bone grafting regarding the transfer of xenogeneic donor bone cells into the recipient are challenging the industry to produce safer acellular natural matrices for bone regeneration. The aim of this study was to investigate the efficacy of a novel decellularization technique for producing bovine cancellous bone scaffold and compare its physicochemical, mechanical, and biological characteristics with demineralized cancellous bone scaffold in an in-vitro study. Cancellous bone blocks were harvested from a bovine femoral head (18-24 months old) subjected to physical cleansing and chemical defatting, and further processed in two ways. Group I was subjected to demineralization, while Group II underwent decellularization through physical, chemical, and enzymatic treatments. Both were then freeze-dried, and gamma radiated, finally producing a demineralized bovine cancellous bone (DMB) scaffold and decellularized bovine cancellous bone (DCC) scaffold. Both DMB and DCC scaffolds were subjected to histological evaluation, scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS), fourier-transform infrared spectroscopy (FTIR), quantification of lipid, collagen, and residual nucleic acid content, and mechanical testing. The osteogenic potential was investigated through the recellularization of scaffolds with human osteoblast cell seeding and examined for cell attachment, proliferation, and mineralization by Alizarin staining and gene expression. DCC produced a complete acellular extracellular matrix (ECM) with the absence of nucleic acid content, wider pores with extensive interconnectivity and partially retaining collagen fibrils. DCC demonstrated a higher cell proliferation rate, upregulation of osteogenic differentiation markers, and substantial mineralized nodules production. Our findings suggest that the decellularization technique produced an acellular DCC scaffold with minimal damage to ECM and possesses osteogenic potential through the mechanisms of osteoconduction, osteoinduction, and osteogenesis in-vitro.
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Affiliation(s)
- Ali Al Qabbani
- Department of Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Basic Science and Oral Biology Unit, School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - K. G. Aghila Rani
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
| | - Junaidi Syarif
- Department of Nuclear and Mechanical Engineering, College of Engineering, University of Sharjah, Sharjah, United Arab Emirates
| | - Sausan AlKawas
- Department of Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Suzina Sheikh Abdul Hamid
- Tissue Bank, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - A. R. Samsudin
- Department of Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Tissue Bank, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Ahmad Azlina
- Basic Science and Oral Biology Unit, School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
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25
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Afzal Z, Huguet EL. Bioengineering liver tissue by repopulation of decellularised scaffolds. World J Hepatol 2023; 15:151-179. [PMID: 36926238 PMCID: PMC10011915 DOI: 10.4254/wjh.v15.i2.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/22/2022] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Liver transplantation is the only curative therapy for end stage liver disease, but is limited by the organ shortage, and is associated with the adverse consequences of immunosuppression. Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact, as well as retaining the instructive cell fate determining biochemicals contained therein. Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models, using a wide range of cell types including primary cells, cell lines, foetal stem cells, and induced pluripotent stem cells. Within these models, a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo. Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes, though advances in organoid culture may help address this. Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo, but with cell types that would limit clinical applications, and which have not been shown to have the specific functions of liver sinusoidal endothelial cells. Minority cell groups such as Kupffer cells and stellate cells have not been repopulated. Bioengineering by repopulation of decellularised scaffolds has significantly progressed, but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.
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Affiliation(s)
- Zeeshan Afzal
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Laurent Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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26
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Wei Z, Zhang J, Guo Z, Wu Z, Sun Y, Wang K, Duan R. Study on the preparation and properties of acellular matrix from the skin of silver carp (Hypophthalmichthys molitrix). J Biomed Mater Res B Appl Biomater 2023; 111:1328-1335. [PMID: 36811266 DOI: 10.1002/jbm.b.35236] [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: 09/28/2022] [Revised: 12/29/2022] [Accepted: 01/30/2023] [Indexed: 02/24/2023]
Abstract
Acellular matrices are mainly composed of mammalian tissues, and aquatic tissues with lower biological risks and less religious restrictions are considered alternatives to mammalian tissues. The acellular fish skin matrix (AFSM) has been commercially available. Silver carp has the advantages of farmability, high yield and low price, but there are few studies on the silver carp acellular fish skin matrix (SC-AFSM). In this study, an acellular matrix with low DNA and endotoxin was prepared from the skin of silver carp. After treatment with trypsin/sodium dodecyl sulfate and Triton X-100 solutions, the DNA content in SC-AFSM reached 11.03 ± 0.85 ng/mg, and the endotoxin removal rate was 96.8%. The porosity of SC-AFSM was 79.64% ± 0.17%, which is favorable for cell infiltration and proliferation. The relative cell proliferation rate of SC-AFSM extract was 117.79% ± 15.26%. The wound healing experiment showed that SC-AFSM had no adverse acute pro-inflammatory response, which had a similar effect as commercial products in promoting tissue repair. Therefore, SC-AFSM has great application potential in biomaterials.
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Affiliation(s)
- Zeyu Wei
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University, Lianyungang, China.,School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang, China
| | - Junjie Zhang
- School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang, China.,Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang, China.,Jiangsu Institute of Marine Resources Development, Jiangsu Ocean University, Lianyungang, China
| | - Zhiwen Guo
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University, Lianyungang, China.,Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang, China.,College of Marine Science and Fisheries, Jiangsu Ocean University, Lianyungang, China
| | - Zhiming Wu
- School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang, China
| | - Yaru Sun
- School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang, China
| | - Ke Wang
- School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang, China
| | - Rui Duan
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University, Lianyungang, China.,Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang, China.,College of Marine Science and Fisheries, Jiangsu Ocean University, Lianyungang, China
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27
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Han Y, Zhang B, Li J, Cen L, Zhao L, Xi Z. Preparation of extracellular matrix of fish swim bladders by decellularization with supercritical carbon dioxide. BIORESOUR BIOPROCESS 2023; 10:14. [PMID: 38647890 PMCID: PMC10991867 DOI: 10.1186/s40643-022-00621-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 12/15/2022] [Indexed: 02/23/2023] Open
Abstract
Fish swim bladders used to be considered as byproducts or waste in fishery; however, they are potential materials for biological medicine with abundant collagen. In this work, an efficient noncytotoxic decellularization process using sodium dodecyl sulfate (SDS) ternary system assisted with supercritical carbon dioxide (scCO2) as the green extraction fluid and ethanol (ET) as the cosolvent has been developed to harvest acellular fish swim bladders (AFSBs). The experimental results show that the tissue treated by SDS assisted with scCO2 and ethanol at 37 °C and 25 MPa can be decellularized thoroughly and maintains intact fibers and uniform pore distribution, which resulting in a tensile strength of 5.61 MPa and satisfactory biocompatibility. Meanwhile, the residual SDS content in scCO2/SDS/ET ternary system is 0.0122% which is significantly lower than it in scCO2/SDS system due to the enhanced mass transfer rate of SDS in tissues by scCO2 with ethanol. The synergy between SDS and ethanol can enhance the diffusion coefficient and the solubility of SDS in scCO2, which reduced the contact time between SDS and tissues. Meaningfully, the results obtained in this work can not only provide a novel strategy to produce acellular matrix with superior properties, but also offer a further understanding of the decellularization through scCO2 extraction processing with the synergy of suitable detergent/cosolvent.
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Affiliation(s)
- Yuqing Han
- State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Bingyan Zhang
- State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Jinjin Li
- State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Lian Cen
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Ling Zhao
- State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Zhenhao Xi
- State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.
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28
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Socci MC, Rodríguez G, Oliva E, Fushimi S, Takabatake K, Nagatsuka H, Felice CJ, Rodríguez AP. Polymeric Materials, Advances and Applications in Tissue Engineering: A Review. Bioengineering (Basel) 2023; 10:bioengineering10020218. [PMID: 36829712 PMCID: PMC9952269 DOI: 10.3390/bioengineering10020218] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/28/2023] [Accepted: 01/29/2023] [Indexed: 02/10/2023] Open
Abstract
Tissue Engineering (TE) is an interdisciplinary field that encompasses materials science in combination with biological and engineering sciences. In recent years, an increase in the demand for therapeutic strategies for improving quality of life has necessitated innovative approaches to designing intelligent biomaterials aimed at the regeneration of tissues and organs. Polymeric porous scaffolds play a critical role in TE strategies for providing a favorable environment for tissue restoration and establishing the interaction of the biomaterial with cells and inducing substances. This article reviewed the various polymeric scaffold materials and their production techniques, as well as the basic elements and principles of TE. Several interesting strategies in eight main TE application areas of epithelial, bone, uterine, vascular, nerve, cartilaginous, cardiac, and urinary tissue were included with the aim of learning about current approaches in TE. Different polymer-based medical devices approved for use in clinical trials and a wide variety of polymeric biomaterials are currently available as commercial products. However, there still are obstacles that limit the clinical translation of TE implants for use wide in humans, and much research work is still needed in the field of regenerative medicine.
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Affiliation(s)
- María Cecilia Socci
- Laboratorio de Medios e Interfases (LAMEIN), Departamento de Bioingeniería, FACET-UNT, Tucumán 4000, Argentina
- Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET, Tucumán 4000, Argentina
- Correspondence: (M.C.S.); (A.P.R.)
| | - Gabriela Rodríguez
- Laboratorio de Medios e Interfases (LAMEIN), Departamento de Bioingeniería, FACET-UNT, Tucumán 4000, Argentina
- Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET, Tucumán 4000, Argentina
| | - Emilia Oliva
- Laboratorio de Medios e Interfases (LAMEIN), Departamento de Bioingeniería, FACET-UNT, Tucumán 4000, Argentina
- Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET, Tucumán 4000, Argentina
| | - Shigeko Fushimi
- Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan
- Department of Oral Pathology and Medicine, Okayama University Dental School, Okayama 700-8525, Japan
| | - Kiyofumi Takabatake
- Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan
| | - Hitoshi Nagatsuka
- Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan
| | - Carmelo José Felice
- Laboratorio de Medios e Interfases (LAMEIN), Departamento de Bioingeniería, FACET-UNT, Tucumán 4000, Argentina
- Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET, Tucumán 4000, Argentina
| | - Andrea Paola Rodríguez
- Laboratorio de Medios e Interfases (LAMEIN), Departamento de Bioingeniería, FACET-UNT, Tucumán 4000, Argentina
- Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET, Tucumán 4000, Argentina
- Correspondence: (M.C.S.); (A.P.R.)
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Khan RL, Khraibi AA, Dumée LF, Corridon PR. From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation. Front Bioeng Biotechnol 2023; 11:1091554. [PMID: 36815880 PMCID: PMC9935833 DOI: 10.3389/fbioe.2023.1091554] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
Slaughterhouses produce large quantities of biological waste, and most of these materials are underutilized. In many published reports, the possibility of repurposing this form of waste to create biomaterials, fertilizers, biogas, and feeds has been discussed. However, the employment of particular offal wastes in xenotransplantation has yet to be extensively uncovered. Overall, viable transplantable tissues and organs are scarce, and developing bioartificial components using such discarded materials may help increase their supply. This perspective manuscript explores the viability and sustainability of readily available and easily sourced slaughterhouse waste, such as blood vessels, eyes, kidneys, and tracheas, as starting materials in xenotransplantation derived from decellularization technologies. The manuscript also examines the innovative use of animal stem cells derived from the excreta to create a bioartificial tissue/organ platform that can be translated to humans. Institutional and governmental regulatory approaches will also be outlined to support this endeavor.
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Affiliation(s)
- Raheema L. Khan
- Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Ali A. Khraibi
- Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Ludovic F. Dumée
- Department of Chemical Engineering, College of Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Research and Innovation Center on CO2 and Hydrogen (RICH), Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Peter R. Corridon
- Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Healthcare Engineering Innovation Center, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
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Kellaway SC, Roberton V, Jones JN, Loczenski R, Phillips JB, White LJ. Engineered neural tissue made using hydrogels derived from decellularised tissues for the regeneration of peripheral nerves. Acta Biomater 2023; 157:124-136. [PMID: 36494008 DOI: 10.1016/j.actbio.2022.12.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/10/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022]
Abstract
Engineered neural tissue (EngNT) promotes in vivo axonal regeneration. Decellularised materials (dECM) are complex biologic scaffolds that can improve the cellular environment and also encourage positive tissue remodelling in vivo. We hypothesised that we could incorporate a hydrogel derived from a decellularised tissue (dECMh) into EngNT, thereby providing an alternative to the currently used purified collagen I hydrogel for the first time. Decellularisation was carried out on bone (B-ECM), liver (LIV-ECM), and small intestinal (SIS-ECM) tissues and the resultant dECM was biochemically and mechanically characterised. dECMh differed in mechanical and biochemical properties that likely had an effect on Schwann cell behaviour observed in metabolic activity and contraction profiles. Cellular alignment was observed in tethered moulds within the B-ECM and SIS-ECM derived hydrogels only. No difference was observed in dorsal root ganglia (DRG) neurite extension between the dECMh groups and collagen I groups when applied as a coverslip coating, however, when DRG were seeded atop EngNT constructs, only the B-ECM derived EngNT performed similarly to collagen I derived EngNT. B-ECM EngNT further exhibited similar axonal regeneration to collagen I EngNT in a 10 mm gap rat sciatic nerve injury model after 4 weeks. Our results have shown that various dECMh can be utilised to produce EngNT that can promote neurite extension in vitro and axonal regeneration in vivo. STATEMENT OF SIGNIFICANCE: Nerve autografts are undesirable due to the sacrifice of a patient's own nerve tissue to repair injuries. Engineered neural tissue (EngNT) is a type of living artificial tissue that has been developed to overcome this. To date, only a collagen hydrogel has been shown to be effective in the production and utilisation of EngNT in animal models. Hydrogels may be made from decellularised extracellular matrix derived from many tissues. In this study we showed that hydrogels from various tissues may be used to create EngNT and one was shown to comparable to the currently used collagen based EngNT in a rat sciatic nerve injry model.
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Affiliation(s)
- Simon C Kellaway
- Centre for Nerve Engineering, University College London, UK; Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute, University of Nottingham, University Park, Nottingham, NG7 2RD, UK; Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; Biodiscovery Institute, University of Nottingham, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
| | - Victoria Roberton
- Centre for Nerve Engineering, University College London, UK; Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
| | - Joshua N Jones
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute, University of Nottingham, University Park, Nottingham, NG7 2RD, UK; Biodiscovery Institute, University of Nottingham, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
| | - Rabea Loczenski
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute, University of Nottingham, University Park, Nottingham, NG7 2RD, UK; Biodiscovery Institute, University of Nottingham, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
| | - James B Phillips
- Centre for Nerve Engineering, University College London, UK; Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
| | - Lisa J White
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute, University of Nottingham, University Park, Nottingham, NG7 2RD, UK; Biodiscovery Institute, University of Nottingham, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
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Kanda H, Oya K, Irisawa T, Wahyudiono, Goto M. Tensile strength of ostrich carotid artery decellularized with liquefied dimethyl ether and DNase: An effort in addressing religious and cultural concerns. ARAB J CHEM 2023. [DOI: 10.1016/j.arabjc.2023.104578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
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Braga GCD, Camargo CP, Harmsen MC, Correia AT, Souza S, Seelaender M, Nunes VA, dos Santos JF, Neri EA, Valadão IC, Moreira LFP, Gemperli R. A modified hydrogel production protocol to decrease cellular content. Acta Cir Bras 2022; 37:e371005. [PMID: 36542042 PMCID: PMC9762429 DOI: 10.1590/acb371005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 09/17/2022] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To analyze the cytotoxicity and cell in porcine-derived decellularized skin matrix. METHODS We analyzed the effect of multiple decellularization processes by histological analysis, DNA quantification, and flow cytometry. Subsequently, we analyzed the most appropriate hydrogel concentration to minimize cytotoxicity on fibroblast culture and to maximize cell proliferation. RESULTS After the fourth decellularization, the DNA quantification showed the lowest DNA concentration (< 50 ng/mg). Histological analysis showed no cell components in the hydrogel. Moreover, hematoxylin and eosin showed a heterogeneous structure of collagen fibers. The best hydrogel concentration ranged from 3 to 25%, and there was no significant difference between the 24 hours and seven days. CONCLUSIONS The process of hydrogel production was effective for removing cells and DNA elements. The best hydrogel concentration ranged from 3 to 25%.
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Affiliation(s)
- Gabriela Catão Diniz Braga
- Bachelor. Universidade de São Paulo – Discipline of Plastic Surgery, Microsurgery and Plastic Surgery Laboratory – School of Medicine – São Paulo (SP), Brazil
| | - Cristina Pires Camargo
- PhD. Universidade de São Paulo – Discipline of Plastic Surgery, Microsurgery and Plastic Surgery Laboratory – School of Medicine – São Paulo (SP), Brazil.,Corresponding author:
- (55 11) 30620415
| | - Martin Conrad Harmsen
- PhD. Associate professor. University Medical Center Groningen – Laboratory for Cardiovascular Regenerative Medicine – Department of Pathology and Medical Biology – Hanzeplein 1, Netherlands
| | - Aristides Tadeu Correia
- PhD. Universidade de São Paulo – Department of Cardiopneumology – Thoracic Surgery Research Laboratory – Heart Institute of School of Medicine – São Paulo (SP), Brazil
| | - Sonia Souza
- Bachelor. Universidade de São Paulo – Department of Cardiopneumology – Cardiovascular Surgery and Circulatory Physiopathology Laboratory – School of Medicine – São Paulo (SP), Brazil
| | - Marilia Seelaender
- PhD. Associate professor. Universidade de São Paulo – Department of Clinical Surgery – School of Medicine – São Paulo (SP), Brazil
| | - Viviane Araujo Nunes
- PhD. Associate professor. Universidade de São Paulo – Department of Biotechnology – School of Arts, Sciences and Humanities – São Paulo (SP), Brazil
| | - Jeniffer Farias dos Santos
- PhD. Universidade de São Paulo – Department of Biotechnology – School of Arts, Sciences and Humanities – São Paulo (SP), Brazil
| | - Elida Adalgisa Neri
- PhD. Universidade de São Paulo – Laboratory of Genetics and Molecular Cardiology – Heart Institute – School of Medicine – São Paulo (SP), Brazil
| | - Iuri Cordeiro Valadão
- PhD. Universidade de São Paulo – Laboratory of Genetics and Molecular Cardiology – Heart Institute – School of Medicine – São Paulo (SP), Brazil
| | - Luiz Felipe Pinho Moreira
- PhD. Associate professor. Universidade de São Paulo – Department of Cardiopneumology, Cardiovascular Surgery and Circulatory Physiopathology Laboratory – School of Medicine – São Paulo (SP), Brazil
| | - Rolf Gemperli
- PhD. Full professor. Universidade de São Paulo – Discipline of Plastic Surgery, Microsurgery and Plastic Surgery Laboratory – School of Medicine – São Paulo (SP) Brazil
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Palmosi T, Tolomeo AM, Cirillo C, Sandrin D, Sciro M, Negrisolo S, Todesco M, Caicci F, Santoro M, Dal Lago E, Marchesan M, Modesti M, Bagno A, Romanato F, Grumati P, Fabozzo A, Gerosa G. Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications. Front Bioeng Biotechnol 2022; 10:1042434. [PMID: 36578513 PMCID: PMC9792098 DOI: 10.3389/fbioe.2022.1042434] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/22/2022] [Indexed: 12/14/2022] Open
Abstract
Structural cardiac lesions are often surgically repaired using prosthetic patches, which can be biological or synthetic. In the current clinical scenario, biological patches derived from the decellularization of a xenogeneic scaffold are gaining more interest as they maintain the natural architecture of the extracellular matrix (ECM) after the removal of the native cells and remnants. Once implanted in the host, these patches can induce tissue regeneration and repair, encouraging angiogenesis, migration, proliferation, and host cell differentiation. Lastly, decellularized xenogeneic patches undergo cell repopulation, thus reducing host immuno-mediated response against the graft and preventing device failure. Porcine small intestinal submucosa (pSIS) showed such properties in alternative clinical scenarios. Specifically, the US FDA approved its use in humans for urogenital procedures such as hernia repair, cystoplasties, ureteral reconstructions, stress incontinence, Peyronie's disease, penile chordee, and even urethral reconstruction for hypospadias and strictures. In addition, it has also been successfully used for skeletal muscle tissue reconstruction in young patients. However, for cardiovascular applications, the results are controversial. In this study, we aimed to validate our decellularization protocol for SIS, which is based on the use of Tergitol 15 S 9, by comparing it to our previous and efficient method (Triton X 100), which is not more available in the market. For both treatments, we evaluated the preservation of the ECM ultrastructure, biomechanical features, biocompatibility, and final bioinductive capabilities. The overall analysis shows that the SIS tissue is macroscopically distinguishable into two regions, one smooth and one wrinkle, equivalent to the ultrastructure and biochemical and proteomic profile. Furthermore, Tergitol 15 S 9 treatment does not modify tissue biomechanics, resulting in comparable to the native one and confirming the superior preservation of the collagen fibers. In summary, the present study showed that the SIS decellularized with Tergitol 15 S 9 guarantees higher performances, compared to the Triton X 100 method, in all the explored fields and for both SIS regions: smooth and wrinkle.
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Affiliation(s)
- Tiziana Palmosi
- Laboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, Italy,L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy
| | - Anna Maria Tolomeo
- Laboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, Italy,L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy
| | - Carmine Cirillo
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
| | - Debora Sandrin
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Optics and Bioimaging Lab, Department of Physics and Astronomy, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, University of Padova, Padua, Italy
| | | | - Susanna Negrisolo
- Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women’s and Children’s Health, University of Padova, Padua, Italy
| | - Martina Todesco
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Department of Industrial Engineering, University of Padova, Padua, Italy
| | | | - Michele Santoro
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
| | - Eleonora Dal Lago
- Department of Industrial Engineering, University of Padova, Padua, Italy
| | | | - Michele Modesti
- Department of Industrial Engineering, University of Padova, Padua, Italy
| | - Andrea Bagno
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Department of Industrial Engineering, University of Padova, Padua, Italy
| | - Filippo Romanato
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Department of Physics and Astronomy “G. Galilei”, University of Padova, Padua, Italy
| | - Paolo Grumati
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy,Department of Clinical Medicine and Surgery, University of Napoli Federico II, Naples, Italy
| | - Assunta Fabozzo
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Cardiac Surgery Unit, Hospital University of Padova, Padua, Italy,*Correspondence: Assunta Fabozzo,
| | - Gino Gerosa
- Laboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, Italy,L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Cardiac Surgery Unit, Hospital University of Padova, Padua, Italy
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Sachan AK, Gangwar AK, Khangembam SD, Kumar N. Characterization of Glutaraldehyde Crosslinked Decellularized Caprine Gall Bladder Scaffolds Prepared Using Sapindus mukorossi Fruit Pericarp Extract. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2022. [DOI: 10.1007/s40883-022-00276-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Wang X, Chan V, Corridon PR. Decellularized blood vessel development: Current state-of-the-art and future directions. Front Bioeng Biotechnol 2022; 10:951644. [PMID: 36003539 PMCID: PMC9394443 DOI: 10.3389/fbioe.2022.951644] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 07/14/2022] [Indexed: 12/31/2022] Open
Abstract
Vascular diseases contribute to intensive and irreversible damage, and current treatments include medications, rehabilitation, and surgical interventions. Often, these diseases require some form of vascular replacement therapy (VRT) to help patients overcome life-threatening conditions and traumatic injuries annually. Current VRTs rely on harvesting blood vessels from various regions of the body like the arms, legs, chest, and abdomen. However, these procedures also produce further complications like donor site morbidity. Such common comorbidities may lead to substantial pain, infections, decreased function, and additional reconstructive or cosmetic surgeries. Vascular tissue engineering technology promises to reduce or eliminate these issues, and the existing state-of-the-art approach is based on synthetic or natural polymer tubes aiming to mimic various types of blood vessel. Burgeoning decellularization techniques are considered as the most viable tissue engineering strategy to fill these gaps. This review discusses various approaches and the mechanisms behind decellularization techniques and outlines a simplified model for a replacement vascular unit. The current state-of-the-art method used to create decellularized vessel segments is identified. Also, perspectives on future directions to engineer small- (inner diameter >1 mm and <6 mm) to large-caliber (inner diameter >6 mm) vessel substitutes are presented.
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Affiliation(s)
- Xinyu Wang
- Biomedical Engineering and Healthcare Engineering Innovation Center, Khalifa University, Abu Dhabi, United Arab Emirates
- Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
| | - Vincent Chan
- Biomedical Engineering and Healthcare Engineering Innovation Center, Khalifa University, Abu Dhabi, United Arab Emirates
| | - Peter R Corridon
- Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates
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Sembiring YE, Ledyastatin RA, Nurrahmah A, Sulistyaningsih NK, Sinatra JAR, Puruhito I, Suroto H. Comparative Assessment of Various Concentration and Exposure Time of Sodium Dodecyl Sulfate as Decellularization Agents for Small-Vessels Vascular Tissue Engineering. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Finding the optimum vascular grafts (VG) to replace damaged blood arteries in cardiac surgery is still a work in progress. To be employed, a tissue-engineered VG (TEVG) must have the appropriate biological and mechanical qualities. Decellularized arteries may be a better TEVG than synthetic grafts because of their natural three-dimensional architecture.
AIM: The goal of this study was to compare different concentrations and times of sodium dodecyl sulfate (SDS) to decellularize tissue to find the best decellularized VG.
METHODS: In all decellularized scaffolds, which are 1% SDS-2 weeks group, hematoxylin and eosin and Masson’s trichrome staining exhibited looser collagen networks and fewer nuclei.
RESULTS: The orientation of collagen fibers was identical to native vascular scaffolds. Collagen I deposition was seen in the immunohistochemistry assay. A tensile strength test revealed that the decellularized scaffold (0.5% SDS for 4 weeks and 0.5% SDS for 2 weeks) had exceeded the native arteries’ maximal strength. In comparison to 1% SDS in 4 weeks treated groups, scanning electron microscopy following decellularization revealed no endothelial cells on the inner side of 1% SDS in 2 weeks group with minimum extracellular matrix damage. The endothelial cells remained marginally visible on the inner side of all 0.5% SDS treated groups. The 3-(4,5-dimethylthiazol-2yl)2,5-diphenyltetrazolium bromide test was used to determine the cytotoxicity of the decellularized scaffolds.
CONCLUSION: This study reveals that exposing a bovine mesenteric artery to 1% SDS for 2 weeks is an excellent procedure for extracting the most acellular VG, potentially serving as a biological scaffold for TEVGs.
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Decellularization of Full Heart—Optimizing the Classical Sodium-Dodecyl-Sulfate-Based Decellularization Protocol. Bioengineering (Basel) 2022; 9:bioengineering9040147. [PMID: 35447709 PMCID: PMC9032179 DOI: 10.3390/bioengineering9040147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/04/2022] [Accepted: 03/22/2022] [Indexed: 12/05/2022] Open
Abstract
Compared to cell therapy, where cells are injected into a defect region, the treatment of heart infarction with cells seeded in a vascularized scaffold bears advantages, such as an immediate nutrient supply or a controllable and persistent localization of cells. For this purpose, decellularized native tissues are a preferable choice as they provide an in vivo-like microenvironment. However, the quality of such scaffolds strongly depends on the decellularization process. Therefore, two protocols based on sodium dodecyl sulfate or sodium deoxycholate were tailored and optimized for the decellularization of a porcine heart. The obtained scaffolds were tested for their applicability to generate vascularized cardiac patches. Decellularization with sodium dodecyl sulfate was found to be more suitable and resulted in scaffolds with a low amount of DNA, a highly preserved extracellular matrix composition, and structure shown by GAG quantification and immunohistochemistry. After seeding human endothelial cells into the vasculature, a coagulation assay demonstrated the functionality of the endothelial cells to minimize the clotting of blood. Human-induced pluripotent-stem-cell-derived cardiomyocytes in co-culture with fibroblasts and mesenchymal stem cells transferred the scaffold into a vascularized cardiac patch spontaneously contracting with a frequency of 25.61 ± 5.99 beats/min for over 16 weeks. The customized decellularization protocol based on sodium dodecyl sulfate renders a step towards a preclinical evaluation of the scaffolds.
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Narciso M, Ulldemolins A, Júnior C, Otero J, Navajas D, Farré R, Gavara N, Almendros I. Novel Decellularization Method for Tissue Slices. Front Bioeng Biotechnol 2022; 10:832178. [PMID: 35356779 PMCID: PMC8959585 DOI: 10.3389/fbioe.2022.832178] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/09/2022] [Indexed: 11/13/2022] Open
Abstract
Decellularization procedures have been developed and optimized for the entire organ or tissue blocks, by either perfusion of decellularizing agents through the tissue’s vasculature or submerging large sections in decellularizing solutions. However, some research aims require the analysis of native as well as decellularized tissue slices side by side, but an optimal protocol has not yet been established to address this need. Thus, the main goal of this work was to develop a fast and efficient decellularization method for tissue slices—with an emphasis on lung—while attached to a glass slide. To this end, different decellularizing agents were compared for their effectiveness in cellular removal while preserving the extracellular matrix. The intensity of DNA staining was taken as an indicator of remaining cells and compared to untreated sections. The presence of collagen, elastin and laminin were quantified using immunostaining and signal quantification. Scaffolds resulting from the optimized protocol were mechanically characterized using atomic force microscopy. Lung scaffolds were recellularized with mesenchymal stromal cells to assess their biocompatibility. Some decellularization agents (CHAPS, triton, and ammonia hydroxide) did not achieve sufficient cell removal. Sodium dodecyl sulfate (SDS) was effective in cell removal (1% remaining DNA signal), but its sharp reduction of elastin signal (only 6% remained) plus lower attachment ratio (32%) singled out sodium deoxycholate (SD) as the optimal treatment for this application (6.5% remaining DNA signal), due to its higher elastin retention (34%) and higher attachment ratio (60%). Laminin and collagen were fully preserved in all treatments. The SD decellularization protocol was also successful for porcine and murine (mice and rat) lungs as well as for other tissues such as the heart, kidney, and bladder. No significant mechanical differences were found before and after sample decellularization. The resulting acellular lung scaffolds were shown to be biocompatible (98% cell survival after 72 h of culture). This novel method to decellularize tissue slices opens up new methodological possibilities to better understand the role of the extracellular matrix in the context of several diseases as well as tissue engineering research and can be easily adapted for scarce samples like clinical biopsies.
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Affiliation(s)
- Maria Narciso
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Anna Ulldemolins
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Constança Júnior
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Jorge Otero
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, Madrid, Spain
| | - Daniel Navajas
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, Madrid, Spain
| | - Ramon Farré
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Núria Gavara
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Isaac Almendros
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- *Correspondence: Isaac Almendros,
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Singh H, Purohit SD, Bhaskar R, Yadav I, Gupta MK, Mishra NC. Development of decellularization protocol for caprine small intestine submucosa as a biomaterial. BIOMATERIALS AND BIOSYSTEMS 2022; 5:100035. [PMID: 36825113 PMCID: PMC9934478 DOI: 10.1016/j.bbiosy.2021.100035] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/10/2021] [Accepted: 12/22/2021] [Indexed: 12/14/2022] Open
Abstract
Decellularized animal tissues have been proven to be promising biomaterials for various tissue engineering (TE) applications. Among various animal tissues, small intestine submucosa (SIS) has gained attention of many researchers due to its easy availability from the abattoir waste, excellent physicochemical and biological characteristics of a good biomaterial. In this study, Caprine SIS was decellularized to get decellularized caprine SIS (DG-SIS). For decellularization, several physical, chemical and enzymatic protocols have been described in the literature. To optimize the decellularization of caprine SIS, several decellularization protocol (DP), including an in-house developed by us, had been attempted, and effect of the different DPs on the obtained DG-SIS were assessed in terms of decellularization, physiochemical and biological properties. All the DPs differ in terms of decellularization, but three DPs where ionic detergent like sodium dodecyl sulphate (SDS) has been used, largely affect the native composition (e.g. glycosaminoglycans (GAGs)), biological properties and other physiochemical properties of the G-SIS as compared to the DP that uses hypertonic solution of potassium iodide (KI) and non-ionic detergent (TritonX-100). The obtained DG-SISs were fibrous, hemocompatible, biocompatible, hydrophilic, biodegradable and exhibited significant antibacterial activity. Therefore, the DG-SIS will be a prospective biomaterial for TE applications.
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Affiliation(s)
- Hemant Singh
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
| | - Shiv Dutt Purohit
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
| | - Rakesh Bhaskar
- Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, Odisha, India
| | - Indu Yadav
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
| | - Mukesh Kumar Gupta
- Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, Odisha, India
| | - Narayan Chandra Mishra
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
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Naso F, Gandaglia A. Can Heart Valve Decellularization Be Standardized? A Review of the Parameters Used for the Quality Control of Decellularization Processes. Front Bioeng Biotechnol 2022; 10:830899. [PMID: 35252139 PMCID: PMC8891751 DOI: 10.3389/fbioe.2022.830899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/31/2022] [Indexed: 11/13/2022] Open
Abstract
When a tissue or an organ is considered, the attention inevitably falls on the complex and delicate mechanisms regulating the correct interaction of billions of cells that populate it. However, the most critical component for the functionality of specific tissue or organ is not the cell, but the cell-secreted three-dimensional structure known as the extracellular matrix (ECM). Without the presence of an adequate ECM, there would be no optimal support and stimuli for the cellular component to replicate, communicate and interact properly, thus compromising cell dynamics and behaviour and contributing to the loss of tissue-specific cellular phenotype and functions. The limitations of the current bioprosthetic implantable medical devices have led researchers to explore tissue engineering constructs, predominantly using animal tissues as a potentially unlimited source of materials. The high homology of the protein sequences that compose the mammalian ECM, can be exploited to convert a soft animal tissue into a human autologous functional and long-lasting prosthesis ensuring the viability of the cells and maintaining the proper biomechanical function. Decellularization has been shown to be a highly promising technique to generate tissue-specific ECM-derived products for multiple applications, although it might comprise very complex processes that involve the simultaneous use of chemical, biochemical, physical and enzymatic protocols. Several different approaches have been reported in the literature for the treatment of bone, cartilage, adipose, dermal, neural and cardiovascular tissues, as well as skeletal muscle, tendons and gastrointestinal tract matrices. However, most of these reports refer to experimental data. This paper reviews the most common and latest decellularization approaches that have been adopted in cardiovascular tissue engineering. The efficacy of cells removal was specifically reviewed and discussed, together with the parameters that could be used as quality control markers for the evaluation of the effectiveness of decellularization and tissue biocompatibility. The purpose was to provide a panel of parameters that can be shared and taken into consideration by the scientific community to achieve more efficient, comparable, and reliable experimental research results and a faster technology transfer to the market.
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Solarte David VA, Güiza-Argüello VR, Arango-Rodríguez ML, Sossa CL, Becerra-Bayona SM. Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Matrix Remodeling. Front Bioeng Biotechnol 2022; 10:821852. [PMID: 35252131 PMCID: PMC8896438 DOI: 10.3389/fbioe.2022.821852] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 01/28/2022] [Indexed: 12/27/2022] Open
Abstract
The absence or damage of a tissue is the main cause of most acute or chronic diseases and are one of the appealing challenges that novel therapeutic alternatives have, in order to recover lost functions through tissue regeneration. Chronic cutaneous lesions are the most frequent cause of wounds, being a massive area of regenerative medicine and tissue engineering to have efforts to develop new bioactive medical products that not only allow an appropriate and rapid healing, but also avoid severe complications such as bacterial infections. In tissue repair and regeneration processes, there are several overlapping stages that involve the synergy of cells, the extracellular matrix (ECM) and biomolecules, which coordinate processes of ECM remodeling as well as cell proliferation and differentiation. Although these three components play a crucial role in the wound healing process, the ECM has the function of acting as a biological platform to permit the correct interaction between them. In particular, ECM is a mixture of crosslinked proteins that contain bioactive domains that cells recognize in order to promote migration, proliferation and differentiation. Currently, tissue engineering has employed several synthetic polymers to design bioactive scaffolds to mimic the native ECM, by combining biopolymers with growth factors including collagen and fibrinogen. Among these, decellularized tissues have been proposed as an alternative for reconstructing cutaneous lesions since they maintain the complex protein conformation, providing the required functional domains for cell differentiation. In this review, we present an in-depth discussion of different natural matrixes recently employed for designing novel therapeutic alternatives for treating cutaneous injuries, and overview some future perspectives in this area.
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Affiliation(s)
- Víctor Alfonso Solarte David
- Program of Medicine, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
- Program of Biomedical Engineering, Faculty of Engineering, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
| | - Viviana Raquel Güiza-Argüello
- Metallurgical Engineering and Materials Science Department, Faculty of Physicochemical Engineering, Universidad Industrial de Santander, Bucaramanga, Colombia
| | - Martha L. Arango-Rodríguez
- Multi-tissue Bank and Advanced Therapy Center, Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle, Floridablanca, Colombia
| | - Claudia L. Sossa
- Program of Medicine, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
- Multi-tissue Bank and Advanced Therapy Center, Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle, Floridablanca, Colombia
| | - Silvia M. Becerra-Bayona
- Program of Medicine, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
- *Correspondence: Silvia M. Becerra-Bayona,
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Dai Q, Jiang W, Huang F, Song F, Zhang J, Zhao H. Recent Advances in Liver Engineering With Decellularized Scaffold. Front Bioeng Biotechnol 2022; 10:831477. [PMID: 35223793 PMCID: PMC8866951 DOI: 10.3389/fbioe.2022.831477] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 01/24/2022] [Indexed: 12/02/2022] Open
Abstract
Liver transplantation is currently the only effective treatment for patients with end-stage liver disease; however, donor liver scarcity is a notable concern. As a result, extensive endeavors have been made to diversify the source of donor livers. For example, the use of a decellularized scaffold in liver engineering has gained considerable attention in recent years. The decellularized scaffold preserves the original orchestral structure and bioactive chemicals of the liver, and has the potential to create a de novo liver that is fit for transplantation after recellularization. The structure of the liver and hepatic extracellular matrix, decellularization, recellularization, and recent developments are discussed in this review. Additionally, the criteria for assessment and major obstacles in using a decellularized scaffold are covered in detail.
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Affiliation(s)
- Qingqing Dai
- Department of Hepatopancreatobiliary Surgery and Organ Transplantation Center, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
| | - Wei Jiang
- Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Fan Huang
- Department of Hepatopancreatobiliary Surgery and Organ Transplantation Center, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Fei Song
- Department of Urology, Jena University Hospital, Jena, Germany
| | - Jiqian Zhang
- Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Jiqian Zhang, ; Hongchuan Zhao,
| | - Hongchuan Zhao
- Department of Hepatopancreatobiliary Surgery and Organ Transplantation Center, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Jiqian Zhang, ; Hongchuan Zhao,
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Liu C, Pei M, Li Q, Zhang Y. Decellularized extracellular matrix mediates tissue construction and regeneration. Front Med 2022; 16:56-82. [PMID: 34962624 PMCID: PMC8976706 DOI: 10.1007/s11684-021-0900-3] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 09/23/2021] [Indexed: 02/05/2023]
Abstract
Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell-matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.
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Affiliation(s)
- Chuanqi Liu
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Ming Pei
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, 26506, USA
| | - Qingfeng Li
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
| | - Yuanyuan Zhang
- Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, 27109, USA.
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Moffat D, Ye K, Jin S. Decellularization for the retention of tissue niches. J Tissue Eng 2022; 13:20417314221101151. [PMID: 35620656 PMCID: PMC9128068 DOI: 10.1177/20417314221101151] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/01/2022] [Indexed: 12/25/2022] Open
Abstract
Decellularization of natural tissues to produce extracellular matrix is a promising method for three-dimensional scaffolding and for understanding microenvironment of the tissue of interest. Due to the lack of a universal standard protocol for tissue decellularization, recent investigations seek to develop novel methods for whole or partial organ decellularization capable of supporting cell differentiation and implantation towards appropriate tissue regeneration. This review provides a comprehensive and updated perspective on the most recent advances in decellularization strategies for a variety of organs and tissues, highlighting techniques of chemical, physical, biological, enzymatic, or combinative-based methods to remove cellular contents from tissues. In addition, the review presents modernized approaches for improving standard decellularization protocols for numerous organ types.
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Affiliation(s)
- Deana Moffat
- Department of Biomedical Engineering, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
| | - Kaiming Ye
- Department of Biomedical Engineering, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
- Center of Biomanufacturing for Regenerative Medicine, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
| | - Sha Jin
- Department of Biomedical Engineering, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
- Center of Biomanufacturing for Regenerative Medicine, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
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Wu J, Xu J, Huang Y, Tang L, Hong Y. Regional-specific meniscal extracellular matrix hydrogels and their effects on cell-matrix interactions of fibrochondrocytes. Biomed Mater 2021; 17. [PMID: 34883474 DOI: 10.1088/1748-605x/ac4178] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 12/09/2021] [Indexed: 02/07/2023]
Abstract
Decellularized meniscal extracellular matrix (ECM) material holds great potential for meniscus repair and regeneration. Particularly, injectable ECM hydrogel is highly desirable for the minimally invasive treatment of irregularly shaped defects. Although regional-specific variations of the meniscus are well documented, no ECM hydrogel has been reported to simulate zonally specific microenvironments of the native meniscus. To fill the gap, different (outer, middle, and inner) zones of porcine menisci were separately decellularized. Then the regionally decellularized meniscal ECMs were solubilized by pepsin digestion, neutralized, and then form injectable hydrogels. The hydrogels were characterized in gelation behaviors and mechanical properties and seeded with bovine fibrochondrocytes to evaluate the regionally biochemical effects on the cell-matrix interactions. Our results showed that the decellularized inner meniscal ECM (IM) contained the greatest glycosaminoglycan (GAG) content and the least collagen content compared with the decellularized outer meniscal ECM (OM) and middle meniscal ECM (MM). The IM hydrogel showed lower compressive strength than the OM hydrogel. When encapsulated with fibrochondrocytes, the IM hydrogel accumulated more GAG, contracted to a greater extent and reached higher compressive strength than that of the OM hydrogel at 28 days. Our findings demonstrate that the regionally specific meniscal ECMs present biochemical variation and show various effects on the cell behaviors, thus providing information on how meniscal ECM hydrogels may be utilized to reconstruct the microenvironments of the native meniscus.
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Affiliation(s)
- Jinglei Wu
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX 76019, United States of America
| | - Jiazhu Xu
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX 76019, United States of America
| | - Yihui Huang
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX 76019, United States of America
| | - Liping Tang
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX 76019, United States of America
| | - Yi Hong
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX 76019, United States of America
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Holl J, Pawlukianiec C, Corton Ruiz J, Groth D, Grubczak K, Hady HR, Dadan J, Reszec J, Czaban S, Kowalewski C, Moniuszko M, Eljaszewicz A. Skin Substitute Preparation Method Induces Immunomodulatory Changes in Co-Incubated Cells through Collagen Modification. Pharmaceutics 2021; 13:2164. [PMID: 34959443 PMCID: PMC8705760 DOI: 10.3390/pharmaceutics13122164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/07/2021] [Accepted: 12/09/2021] [Indexed: 12/02/2022] Open
Abstract
Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin. Here we propose a novel strategy for ADM preparation from human abdominoplasty-derived skin. Skin was processed using three different methods of decellularization involving the use of ionic detergent (sodium dodecyl sulfate; SDS, in hADM 1), non-ionic detergent (Triton X-100 in hADM 2), and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We next evaluated the immunogenicity and immunomodulatory properties of this novel hADM by using an in vitro model of peripheral blood mononuclear cell culture, flow cytometry, and cytokine assays. We found that similarly sourced but differentially processed hADMs possess distinct immunogenicity. hADM 1 showed no immunogenic effects as evidenced by low T cell proliferation and no significant change in cytokine profile. In contrast, hADMs 2 and 3 showed relatively higher immunogenicity. Moreover, our novel hADMs exerted no effect on T cell composition after three-day of coincubation. However, we observed significant changes in the composition of monocytes, indicating their maturation toward a phenotype possessing anti-inflammatory and pro-angiogenic properties. Taken together, we showed here that abdominoplasty skin is suitable for hADM manufacturing. More importantly, the use of SDS-based protocols for the purposes of dermal matrix decellularization allows for the preparation of non-immunogenic scaffolds with high therapeutic potential. Despite these encouraging results, further studies are needed to evaluate the beneficial effects of our hADM 1 on deep and hard-healing wounds.
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Affiliation(s)
- Jordan Holl
- Department of Regenerative Medicine and Immune Regulation, Faculty of Medicine, Medical University of Bialystok, 15-269 Białystok, Poland; (J.H.); (C.P.); (J.C.R.); (D.G.); (K.G.)
| | - Cezary Pawlukianiec
- Department of Regenerative Medicine and Immune Regulation, Faculty of Medicine, Medical University of Bialystok, 15-269 Białystok, Poland; (J.H.); (C.P.); (J.C.R.); (D.G.); (K.G.)
| | - Javier Corton Ruiz
- Department of Regenerative Medicine and Immune Regulation, Faculty of Medicine, Medical University of Bialystok, 15-269 Białystok, Poland; (J.H.); (C.P.); (J.C.R.); (D.G.); (K.G.)
| | - Dawid Groth
- Department of Regenerative Medicine and Immune Regulation, Faculty of Medicine, Medical University of Bialystok, 15-269 Białystok, Poland; (J.H.); (C.P.); (J.C.R.); (D.G.); (K.G.)
| | - Kamil Grubczak
- Department of Regenerative Medicine and Immune Regulation, Faculty of Medicine, Medical University of Bialystok, 15-269 Białystok, Poland; (J.H.); (C.P.); (J.C.R.); (D.G.); (K.G.)
| | - Hady Razak Hady
- 1st Clinical Department of General and Endocrine Surgery, Faculty of Medicine, Medical University of Białystok, 15-276 Białystok, Poland; (H.R.H.); (J.D.)
| | - Jacek Dadan
- 1st Clinical Department of General and Endocrine Surgery, Faculty of Medicine, Medical University of Białystok, 15-276 Białystok, Poland; (H.R.H.); (J.D.)
| | - Joanna Reszec
- Department of Medical Pathomorphology, Faculty of Medicine, Medical University of Białystok, 15-269 Białystok, Poland;
| | - Slawomir Czaban
- Department of Anesthesiology & Intensive Therapy, Faculty of Medicine, Medical University of Białystok, 15-276 Białystok, Poland;
| | - Cezary Kowalewski
- Department of Dermatology and Immunodermatology, Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Marcin Moniuszko
- Department of Regenerative Medicine and Immune Regulation, Faculty of Medicine, Medical University of Bialystok, 15-269 Białystok, Poland; (J.H.); (C.P.); (J.C.R.); (D.G.); (K.G.)
- Department of Allergology and Internal Medicine, Faculty of Health Sciences, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Andrzej Eljaszewicz
- Department of Regenerative Medicine and Immune Regulation, Faculty of Medicine, Medical University of Bialystok, 15-269 Białystok, Poland; (J.H.); (C.P.); (J.C.R.); (D.G.); (K.G.)
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Abdominoplasty Skin-Based Dressing for Deep Wound Treatment-Evaluation of Different Methods of Preparation on Therapeutic Potential. Pharmaceutics 2021; 13:pharmaceutics13122118. [PMID: 34959399 PMCID: PMC8708629 DOI: 10.3390/pharmaceutics13122118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/24/2021] [Accepted: 12/03/2021] [Indexed: 11/17/2022] Open
Abstract
The management of hard-to-heal wounds is a significant clinical challenge. Acellular dermal matrices (ADMs) have been successfully introduced to enhance the healing process. Here, we aimed to develop protocol for the preparation of novel ADMs from abdominoplasty skin. We used three different decellularization protocols for skin processing, namely, 1M NaCl and sodium dodecyl sulfate (SDS, in ADM1); 2M NaCl and sodium dodecyl sulfate (SDS, in ADM1); and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We assessed the effectiveness of decellularization and ADM's structure by using histochemical and immunochemical staining. In addition, we evaluated the therapeutic potential of novel ADMs in a murine model of wound healing. Furthermore, targeted transcriptomic profiling of genes associated with wound healing was performed. First, we found that all three proposed methods of decellularization effectively removed cellular components from abdominoplasty skin. We showed, however, significant differences in the presence of class I human leukocyte antigen (HLA class I ABC), Talin 1/2, and chondroitin sulfate proteoglycan (NG2). In addition, we found that protocols, when utilized differentially, influenced the preservation of types I, III, IV, and VII collagens. Finally, we showed that abdominoplasty skin-derived ADMs might serve as an effective and safe option for deep wound treatment. More importantly, our novel dressing (ADM1) improves the kinetics of wound closure and scar maturation in the proliferative and remodeling phases of wound healing. In conclusion, we developed a protocol for abdominoplasty skin decellularization suitable for the preparation of biological dressings. We showed that different decellularization methods affect the purity, structure, and therapeutic properties of ADMs.
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Rodrigues LDS, Bovolato ALDC, Silva BE, Chizzolini LV, Cruz BLD, Moraes MPDT, Lourenção PLTDA, Bertanha M. Quantification of adhesion of mesenchymal stem cells spread on decellularized vein scaffold. Acta Cir Bras 2021; 36:e361001. [PMID: 34755757 PMCID: PMC8598214 DOI: 10.1590/acb361001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 09/09/2021] [Indexed: 01/23/2023] Open
Abstract
Purpose: To evaluate methods that improve adipose-derived stem cells (ASCs) population
in decellularized biological venous scaffold for tissue engineering in blood
vessels, a model in rabbits. Methods: The ASC was expanded until the third passage. Inferior vena cava (IVC) was
submitted to the decellularization process using 1% sodium dodecyl sulfate
(SDS) or 2% sodium deoxycholate (SD) to compose 12 study groups (G): pure SD
or SDS, exposed or not to 1% TritonX-100 (TX-100) and exposed or not to
poly-l’lysine and laminin (PL). Scaffolds were covered with 1 ×
105 or 1 × 106 ASCs diluted in 10 μL Puramatrix™.
The histological analysis was done by cell counting in hematoxylin and eosin
(HE) and nuclei count in immunofluorescence (IF) with
4’,6-Diamidine-2’-phenylindole dihydrochloride (DAPI). Results: The study of groups in HE and IF showed similar results. For both
analyses,IVC-SD-1 × 106 ASC and IVC-SD-PL-1 × 106 ASC
provided the best results. The IF technique showed better sensitivity than
HE, with a weak agreement between them. Conclusions: Decellularizing agent and the number of ASC influence scaffolds
cellularization response and the best protocols as those ones using SD with
or without the addition of PL.
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Dikici S, Aldemir Dikici B, MacNeil S, Claeyssens F. Decellularised extracellular matrix decorated PCL PolyHIPE scaffolds for enhanced cellular activity, integration and angiogenesis. Biomater Sci 2021; 9:7297-7310. [PMID: 34617526 PMCID: PMC8547328 DOI: 10.1039/d1bm01262b] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Wound healing involves a complex series of events where cell–cell and cell-extracellular matrix (ECM) interactions play a key role. Wounding can be simple, such as the loss of the epithelial integrity, or deeper and more complex, reaching to subcutaneous tissues, including blood vessels, muscles and nerves. Rapid neovascularisation of the wounded area is crucial for wound healing as it has a key role in supplying oxygen and nutrients during the highly demanding proliferative phase and transmigration of inflammatory cells to the wound area. One approach to circumvent delayed neovascularisation is the exogenous use of pro-angiogenic factors, which is expensive, highly dose-dependent, and the delivery of them requires a very well-controlled system to avoid leaky, highly permeable and haemorrhagic blood vessel formation. In this study, we decorated polycaprolactone (PCL)-based polymerised high internal phase emulsion (PolyHIPE) scaffolds with fibroblast-derived ECM to assess fibroblast, endothelial cell and keratinocyte activity in vitro and angiogenesis in ex ovo chick chorioallantoic membrane (CAM) assays. Our results showed that the inclusion of ECM in the scaffolds increased the metabolic activity of three types of cells that play a key role in wound healing and stimulated angiogenesis in ex ovo CAM assays over 7 days. Herein, we demonstrated that fibroblast-ECM functionalised PCL PolyHIPE scaffolds appear to have great potential to be used as an active wound dressing to promote angiogenesis and wound healing. Decellularisation of in vitro generated extracellular matrix (ECM) provides an effective way to stimulate angiogenesis and wound healing.![]()
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Affiliation(s)
- Serkan Dikici
- Department of Bioengineering, Izmir Institute of Technology, Izmir, 35430, Turkey. .,Department of Materials Science and Engineering, University of Sheffield, Kroto Research Institute, Sheffield, S3 7HQ, UK.
| | - Betül Aldemir Dikici
- Department of Bioengineering, Izmir Institute of Technology, Izmir, 35430, Turkey. .,Department of Materials Science and Engineering, University of Sheffield, Kroto Research Institute, Sheffield, S3 7HQ, UK.
| | - Sheila MacNeil
- Department of Materials Science and Engineering, University of Sheffield, Kroto Research Institute, Sheffield, S3 7HQ, UK.
| | - Frederik Claeyssens
- Department of Materials Science and Engineering, University of Sheffield, Kroto Research Institute, Sheffield, S3 7HQ, UK.
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Jelodari S, Sadroddiny E. Decellularization of Small Intestinal Submucosa. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1345:71-84. [PMID: 34582015 DOI: 10.1007/978-3-030-82735-9_7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Small intestinal submucosa (SIS) is the most studied extracellular matrix (ECM) for repair and regeneration of different organs and tissues. Promising results of SIS-ECM as a vascular graft, led scientists to examine its applicability for repairing other tissues. Overall results indicated that SIS grafts induce tissue regeneration and remodeling to almost native condition. Investigating immunomodulatory effects of SIS is another interesting field of research. SIS can be utilized in different forms for multiple clinical and experimental studies. The aim of this chapter is to investigate the decellularization process of SIS and its common clinical application.
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Affiliation(s)
- Sahar Jelodari
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Esmaeil Sadroddiny
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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