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Huang D, Li Z, Li G, Zhou F, Wang G, Ren X, Su J. Biomimetic structural design in 3D-printed scaffolds for bone tissue engineering. Mater Today Bio 2025; 32:101664. [PMID: 40206144 PMCID: PMC11979411 DOI: 10.1016/j.mtbio.2025.101664] [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: 02/04/2025] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 04/11/2025] Open
Abstract
The rising prevalence of bone diseases in an aging population underscores the urgent need for innovative and clinically translatable solutions in bone tissue engineering. While significant progress has been made in refining the chemical properties of biomaterials, the structural design of scaffolds-a critical determinant of repair success-remains comparatively underexplored. Structural parameters such as porosity, pore size, and interconnectivity are not only essential for achieving mechanical stability but also pivotal in regulating biological processes, including vascularization, osteogenesis, and immune modulation. This review systematically categorizes scaffold architectures documented in the literature and highlights how these design parameters can be optimized to enhance bone regeneration. Advanced fabrication technologies, particularly 3D printing, are emphasized for their transformative potential in creating precise, biomimetic scaffolds that align with the complex functional demands of native bone. Furthermore, this work synthesizes diverse findings to provide a comprehensive framework for designing next-generation scaffolds. By bridging the gap between structural innovation and clinical application, this review delivers actionable strategies and a strategic roadmap for advancing the field toward improved clinical outcomes and transformative breakthroughs in regenerative medicine.
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Affiliation(s)
- Dan Huang
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- School of Medicine, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Zuhao Li
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Guangfeng Li
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- School of Medicine, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
- Department of Trauma Orthopedics, Zhongye Hospital, Shanghai, 200941, China
| | - Fengjin Zhou
- Honghui Hospital, Xi'an Jiao Tong University, Xi'an, 710000, China
| | - Guangchao Wang
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Xiaoxiang Ren
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Jiacan Su
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
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Chi KY, Kim G, Son JS, Han J, Kim JH. Recent Advances in Three-Dimensional In Vitro Models for Studies of Liver Fibrosis. Tissue Eng Regen Med 2025:10.1007/s13770-025-00719-8. [PMID: 40358834 DOI: 10.1007/s13770-025-00719-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 02/02/2025] [Accepted: 03/11/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Liver fibrosis is a reversible but complex pathological condition associated with chronic liver diseases, affecting over 1.5 billion people worldwide. It is characterized by excessive extracellular matrix deposition resulting from sustained liver injury, often advancing to cirrhosis and cancer. As its progression involves various cell types and pathogenic factors, understanding the intricate mechanisms is essential for the development of effective therapies. In this context, extensive efforts have been made to establish three-dimensional (3D) in vitro platforms that mimic the progression of liver fibrosis. METHODS This review outlines the pathophysiology of liver fibrosis and highlights recent advancements in 3D in vitro liver models, including spheroids, organoids, assembloids, bioprinted constructs, and microfluidic systems. It further assesses their biological relevance, with particular focus on their capacity to reproduce fibrosis-related characteristics. RESULTS 3D in vitro liver models offer significant advantages over conventional two-dimensional cultures. Although each model exhibits unique strengths, they collectively recapitulate key fibrotic features, such as extracellular matrix remodeling, hepatic stellate cell activation, and collagen deposition, in a physiologically relevant 3D setting. In particular, multilineage liver organoids and assembloids integrate architectural complexity with scalability, enabling deeper mechanistic insights and supporting therapeutic evaluation with improved translational relevance. CONCLUSION 3D in vitro liver models represent a promising strategy to bridge the gap between in vitro studies and in vivo realities by faithfully replicating liver-specific architecture and microenvironments. With enhanced reproducibility through standardized protocols, these models hold great potential for advancing drug discovery and facilitating the development of personalized therapies for liver fibrosis.
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Affiliation(s)
- Kyun Yoo Chi
- Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea
| | - Gyeongmin Kim
- Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea
| | - Jeong Sang Son
- User Convenience Technology R&D Department, Korea Institute of Industrial Technology (KITECH), Ansan, 15588, South Korea
| | - Jiyou Han
- Department of Biomedical and Chemical Sciences, Hyupsung University, Hwasung-Si, 18330, South Korea
| | - Jong-Hoon Kim
- Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea.
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Vo‐An Q, Nguyen CT, Pham UT, Nguyen TA, Nguyen DT, Hoang DT, Le LT, Ngo QTC, Thai H. Antibacterial and Anti-Inflammatory Activity of Chitosan Film with Rhodomyrtus Tomentosa Leaf Extract Prepared Via 3D-Printing Method. ChemistryOpen 2025; 14:e202400302. [PMID: 39578248 PMCID: PMC12075101 DOI: 10.1002/open.202400302] [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: 08/15/2024] [Revised: 10/27/2024] [Indexed: 11/24/2024] Open
Abstract
The combination of natural polymers and plant extract attracted much attention thanks to its valuable biological activities. This study presents the preparation and characterization of chitosan (CS) film containing Rhodomyrtus tomentosa leaf extract. In which, the Rhodomyrtus tomentosa leaf extract (SLE) with polyphenol-rich fractions was extracted by an ultrasonic-assisted extraction method. The prepared chitosan/polyphenol-rich fractions film (CSPPF) was characterized using infrared (IR) spectroscopy, mechanical testing, scanning electron microscopy (SEM), and water absorption analysis. Antibacterial and anti-inflammatory activities of the CSPPF were assessed using the agar well diffusion method and nitric oxide (NO) inhibition assays, respectively. Besides, the release of the extract from the CSPPF as well as the drug release kinetics was also tested. The Rhodomyrtus tomentosa leaf extract enhanced the antibacterial efficacy against Escherichia coli and enhanced the anti-inflammatory activity as well as the swelling ability of the CSPPF. The CSPPF containing 1 wt.% of SLE can inhibit 77.70 % NO with an IC50 value of 19.40 μg/mL.
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Affiliation(s)
- Quan Vo‐An
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
| | - Chinh Thuy Nguyen
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
- Graduate University of Science and TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
| | - Uyen Thu Pham
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
| | - Tuan Anh Nguyen
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
| | - Duong Thanh Nguyen
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
- University Science and Technology HanoiVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
| | - Dung Tran Hoang
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
| | - Lu Trong Le
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
| | - Quyen Thi Cam Ngo
- Institute of Environmental SciencesNguyen Tat Thanh University300A Nguyen Tat Thanh, Ward 13, District 4Ho Chi Minh City700000Vietnam
| | - Hoang Thai
- Institute for Tropical TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
- Graduate University of Science and TechnologyVietnam Academy of Science and Technology18 Hoang Quoc Viet, Nghia Do, Cau GiayHanoi100000Vietnam
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Chen S, Wang T, Chen J, Sui M, Wang L, Zhao X, Sun J, Lu Y. 3D bioprinting technology innovation in female reproductive system. Mater Today Bio 2025; 31:101551. [PMID: 40026632 PMCID: PMC11870202 DOI: 10.1016/j.mtbio.2025.101551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 01/15/2025] [Accepted: 02/03/2025] [Indexed: 03/05/2025] Open
Abstract
Several diseases affect the female reproductive system, and both disease factors and treatments impact its integrity and function. Consequently, understanding the mechanisms of disease occurrence and exploring treatment methods are key research focuses in obstetrics and gynecology. However, constructing accurate disease models requires a microenvironment closely resembling the human body, and current animal models and 2D in vitro cell models fall short in this regard. Thus, innovative in vitro female reproductive system models are urgently needed. Additionally, female reproductive system diseases often cause tissue loss, yet effective tissue repair and regeneration have long been a bottleneck in the medical field. 3D bioprinting offers a solution by enabling the construction of implants with tissue repair and regeneration capabilities, promoting cell adhesion, extension, and proliferation. This helps maintain the long-term efficacy of bioactive implants and achieves both structural and functional repair of the reproductive system. By combining live cells with biomaterials, 3D bioprinting can create in vitro 3D biomimetic cellular models, facilitating in-depth studies of cell-cell and cell-extracellular microenvironment interactions, which enhances our understanding of reproductive system diseases and supports disease-specific drug screening. This article reviews 3D bioprinting methods and materials applicable to the female reproductive system, discussing their advantages and limitations to aid in selecting optimal 3D bioprinting strategies. We also summarize and critically evaluate recent advancements in 3D bioprinting applications for tissue regeneration and in vitro disease models and address the prospects and challenges for translating 3D bioprinting technology into clinical applications within the female reproductive system.
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Affiliation(s)
- Siyao Chen
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, PR China
| | | | - Jiaqi Chen
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, PR China
| | - Mingxing Sui
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, PR China
| | - Luyao Wang
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, PR China
| | - Xueyu Zhao
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, PR China
| | - Jianqiao Sun
- Reproductive Clinical Science, Macon & Joan Brock Virginia Health Sciences, Old Dominion University, Norfolk, VA, 23507, USA
| | - Yingli Lu
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, PR China
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Usseglio N, Andrés JLD, Marchal JA, Moroni L, Nieto D. Photochemical corneal cross-linking: Evaluating the potential of a hand-held biopen. Mater Today Bio 2025; 31:101512. [PMID: 39935895 PMCID: PMC11810839 DOI: 10.1016/j.mtbio.2025.101512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 11/24/2024] [Accepted: 01/20/2025] [Indexed: 02/13/2025] Open
Abstract
The generation of organized 3D tissue constructs that combines cells and photo-crosslinkable biomaterials has been demonstrated using a variety of 3D bioprinting technologies. These technologies have inspired the application for "in situ" bioprinting, resulting on hand-held tools called "Biopens" that can transfer bioprinting capabilities directly into the hands of the surgeons. Here, we have developed and validated a biopen for ophthalmological applications, specifically for corneal stromal regeneration using photochemical corneal crosslinking (CXL), as well as for cell bioprinting and, potentially, for corneal wound healing. We used the biopen to CXL, but also for fast crosslinking processes. Cytotoxicity, cell viability and immunofluorescence experiments were performed with human corneal stroma keratocytes (HCK) loaded inside the proposed bioink compositions. Photochemical cross-linking was performed to evaluate the biopen bioprinting functionality for corneal wound closure in porcine eyes. A full-thickness penetrating incision, 5 mm in length parallel to the limbus and perpendicular to the corneal surface, was made in the enucleated porcine cornea. The mechanical properties of cornea are imitated by tuning the proposed (GelMA/PEGDA/PI) bioink composition and crosslinking parameters, which envisage the potential for being translated to a clinical environment to corneal wound closure.
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Affiliation(s)
- Nadina Usseglio
- Advanced Biofabrication Laboratory - DNIETO LAB, Center for Interdisciplinary Chemical and Biology, CICA, University of La Coruña, Spain
| | - Julia López de Andrés
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, E-18100, Spain
| | - Juan Antonio Marchal
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, E-18100, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada- University of Granada, 18100, Granada, Spain
| | - Lorenzo Moroni
- Complex Tissue Regeneration Department, MERLN Institute for Technology-Inspired Regenerative Medicine, Universiteitssingel 40, 6229ER, Maastricht, the Netherlands
| | - Daniel Nieto
- Advanced Biofabrication Laboratory - DNIETO LAB, Center for Interdisciplinary Chemical and Biology, CICA, University of La Coruña, Spain
- Opportunius. Axencia Galega de Innovación, 15702, Santiago de Compostela, Spain
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Kim JE, Jeong GJ, Yoo YM, Bhang SH, Kim JH, Shin YM, Yoo KH, Lee BC, Baek W, Heo DN, Mongrain R, Lee JB, Yoon JK. 3D bioprinting technology for modeling vascular diseases and its application. Biofabrication 2025; 17:022014. [PMID: 40081017 DOI: 10.1088/1758-5090/adc03a] [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: 08/25/2024] [Accepted: 03/13/2025] [Indexed: 03/15/2025]
Abstract
In vitromodeling of vascular diseases provides a useful platform for drug screening and mechanistic studies, by recapitulating the essential structures and physiological characteristics of the native tissue. Bioprinting is an emerging technique that offers high-resolution 3D capabilities, which have recently been employed in the modeling of various tissues and associated diseases. Blood vessels are composed of multiple layers of distinct cell types, and experience different mechanical conditions depending on the vessel type. The intimal layer, in particular, is directly exposed to such hemodynamic conditions inducing shear stress, which in turn influence vascular physiology. 3D bioprinting techniques have addressed the structural limitations of the previous vascular models, by incorporating supporting cells such as smooth muscle cells, geometrical properties such as dilation, curvature, or branching, or mechanical stimulation such as shear stress and pulsatile pressure. This paper presents a review of the physiology of blood vessels along with the pathophysiology of the target diseases including atherosclerosis, thrombosis, aneurysms, and tumor angiogenesis. Additionally, it discusses recent advances in fabricatingin vitro3D vascular disease models utilizing bioprinting techniques, while addressing the current challenges and future perspectives for the potential clinical translation into therapeutic interventions.
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Affiliation(s)
- Ju-El Kim
- Department of Systems Biotechnology, Chung-Ang University, Anseong-Si, Gyeonggi-Do 17546, Republic of Korea
| | - Gun-Jae Jeong
- Institute of Cell and Tissue Engineering, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Young Min Yoo
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul 04310, Republic of Korea
| | - Suk Ho Bhang
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jae Hoon Kim
- Department of Systems Biotechnology, Chung-Ang University, Anseong-Si, Gyeonggi-Do 17546, Republic of Korea
| | - Young Min Shin
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul 04310, Republic of Korea
| | - Kyung Hyun Yoo
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul 04310, Republic of Korea
| | - Byung-Chul Lee
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul 04310, Republic of Korea
| | - Wooyeol Baek
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Dong Nyoung Heo
- Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea
- Biofriends Inc., Seoul 02447, Republic of Korea
| | - Rosaire Mongrain
- Mechanical Engineering Department, McGill University, H3A 0C3 Montréal, Canada
| | - Jung Bok Lee
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul 04310, Republic of Korea
| | - Jeong-Kee Yoon
- Department of Systems Biotechnology, Chung-Ang University, Anseong-Si, Gyeonggi-Do 17546, Republic of Korea
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Akter MZ, Tufail F, Ahmad A, Oh YW, Kim JM, Kim S, Hasan MM, Li L, Lee DW, Kim YS, Lee SJ, Kim HS, Ahn Y, Choi YJ, Yi HG. Harnessing native blueprints for designing bioinks to bioprint functional cardiac tissue. iScience 2025; 28:111882. [PMID: 40177403 PMCID: PMC11964760 DOI: 10.1016/j.isci.2025.111882] [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] [Indexed: 04/05/2025] Open
Abstract
Cardiac tissue lacks regenerative capacity, making heart transplantation the primary treatment for end-stage heart failure. Engineered cardiac tissues developed through three-dimensional bioprinting (3DBP) offer a promising alternative. However, reproducing the native structure, cellular diversity, and functionality of cardiac tissue requires advanced cardiac bioinks. Major obstacles in CTE (cardiac tissue engineering) include accurately characterizing bioink properties, replicating the cardiac microenvironment, and achieving precise spatial organization. Optimizing bioink properties to closely mimic the extracellular matrix (ECM) is essential, as deviations may result in pathological effects. This review encompasses the rheological and electromechanical properties of bioinks and the function of the cardiac microenvironment in the design of functional cardiac constructs. Furthermore, it focuses on improving the rheological characteristics, printability, and functionality of bioinks, offering valuable perspectives for developing new bioinks especially designed for CTE.
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Affiliation(s)
- Mst Zobaida Akter
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
- Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju 61186, Republic of Korea
- Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Fatima Tufail
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
- Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju 61186, Republic of Korea
- Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Ashfaq Ahmad
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
- Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju 61186, Republic of Korea
- Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Yoon Wha Oh
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Jung Min Kim
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Seoyeon Kim
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
- Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Md Mehedee Hasan
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Longlong Li
- Department of Mechanical Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Dong-Weon Lee
- Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju 61186, Republic of Korea
- Department of Mechanical Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
- Center for Next-Generation Sensor Research and Development, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Yong Sook Kim
- Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea
| | - Su-jin Lee
- Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea
- Department of Forensic Medicine, Chonnam National University Medical School, Gwangju 61469, Republic of Korea
| | - Hyung-Seok Kim
- Department of Forensic Medicine, Chonnam National University Medical School, Gwangju 61469, Republic of Korea
| | - Youngkeun Ahn
- Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea
| | - Yeong-Jin Choi
- Advanced Bio and Healthcare Materials Research Division, Korea Institute of Materials Science (KIMS), Changwon 51508, Republic of Korea
- Advanced Materials Engineering, Korea National University of Science and Technology (UST), Changwon, Republic of Korea
| | - Hee-Gyeong Yi
- Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju 61186, Republic of Korea
- Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju 61186, Republic of Korea
- Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju 61186, Republic of Korea
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Demir E, Metli SN, Tutum BE, Gokyer S, Oto C, Yilgor P. Hand-held bioprinters assisting in situbioprinting. Biomed Mater 2025; 20:022012. [PMID: 40043360 DOI: 10.1088/1748-605x/adbcee] [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: 09/04/2024] [Accepted: 03/05/2025] [Indexed: 03/14/2025]
Abstract
Bioprinting, an advanced additive manufacturing technology, enables the fabrication of complex, viable three-dimensional (3D) tissues using bioinks composed of biomaterials and cells. This technology has transformative applications in regenerative medicine, drug screening, disease modeling, and biohybrid robotics. In particular,in situbioprinting has emerged as a promising approach for directly repairing damaged tissues or organs at the defect site. Unlike traditional 3D bioprinting, which is confined to flat surfaces and require complex equipment,in situtechniques accommodate irregular geometries, dynamic environments and simple apparatus, offering greater versatility for clinical applications.In situbioprinting via hand-held devices prioritize flexibility, portability, and real-time adaptability while allowing clinicians to directly deposit bioinks in anatomically complex areas, making them cost-effective, accessible, and suitable for diverse environments, including field surgeries. This review explores the principles, advancements, and comparative advantages of robotic and hand-heldin situbioprinting, emphasizing their clinical relevance. While robotic systems excel in precision and scalability, hand-held bioprinters offer unparalleled flexibility, affordability, and ease of use, making them a valuable tool for personalized and minimally invasive tissue engineering. Future research should focus on improving biosafety, aseptic properties, and bioink formulations to optimize these technologies for widespread clinical adoption.
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Affiliation(s)
- Ezgi Demir
- Ankara University Department of Biomedical Engineering, Ankara, Turkey
| | - Seda Nur Metli
- Ankara University Department of Biomedical Engineering, Ankara, Turkey
| | - Burcu Ekin Tutum
- Ankara University Department of Biomedical Engineering, Ankara, Turkey
| | - Seyda Gokyer
- Ankara University Department of Biomedical Engineering, Ankara, Turkey
| | - Cagdas Oto
- Ankara University Faculty of Veterinary Medicine Department of Anatomy, Ankara, Turkey
- Ankara University Medical Design Research and Application Center MEDITAM, Ankara, Turkey
| | - Pinar Yilgor
- Ankara University Department of Biomedical Engineering, Ankara, Turkey
- Ankara University Medical Design Research and Application Center MEDITAM, Ankara, Turkey
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Wang Y, Chen S, Liang H, Bai J. A review of graded scaffolds made by additive manufacturing for tissue engineering: design, fabrication and properties. Biofabrication 2025; 17:022009. [PMID: 40009881 DOI: 10.1088/1758-5090/adba8e] [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: 09/14/2024] [Accepted: 02/26/2025] [Indexed: 02/28/2025]
Abstract
The emergence of tissue engineering (TE) has provided new vital means for human body tissue/organ repair. TE scaffolds can provide temporary structural support for cell attachment, growth, and proliferation, until the body restores the mechanical and biological properties of the host tissues. Since native tissues are inhomogeneous and in many situations are graded structures for performing their unique functions, graded scaffolds have become increasingly attractive for regenerating particular types of tissues, which aim to offer a more accurate replication of native interactions and functions. Importantly, the advances introduced by additive manufacturing (AM) have now enabled more design freedom and are capable of tailoring both structural and compositional gradients within a single scaffold. In this context, graded TE scaffolds fabricated by AM technologies have been attracting increasing attention. In this review, we start with an introduction of common graded structures in the human body and analyse the advantages and strengths of AM-formed graded scaffolds. Various AM technologies that can be leveraged to produce graded scaffolds are then reviewed based on non-cellular 3D printing and cell-laden 3D bioprinting. The comparisons among various AM technologies for fabricating graded scaffolds are presented. Subsequently, we propose several types of gradients, structural, material, biomolecular and multi-gradients for scaffolds, and highlight the design methods, resulting mechanical properties and biological responses. Finally, current status, challenges and perspectives for AM in developing graded scaffolds are exhibited and discussed.
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Affiliation(s)
- Yue Wang
- Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China
- Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Shangsi Chen
- Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Haowen Liang
- Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China
| | - Jiaming Bai
- Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China
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10
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Granelli R, Kovács-Vajna ZM, Torricelli F. Additive Manufacturing of Organic Electrochemical Transistors: Methods, Device Architectures, and Emerging Applications. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2410499. [PMID: 39945058 PMCID: PMC11922034 DOI: 10.1002/smll.202410499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 01/14/2025] [Indexed: 03/20/2025]
Abstract
Organic electrochemical transistors (OECTs) are key devices in a large set of application fields including bioelectronics, neuromorphics, sensing, and flexible electronics. This review explores the advancements in additive manufacturing techniques accounting for printing technologies, device architectures, and emerging applications. The promising applications of printed OECTs, ranging from biochemical sensors to neuromorphic computing are examined, showcasing their versatility. Despite significant advancements, ongoing challenges persist, such as material-related issues, inconsistencies in film homogeneity, and the scalability of integration processes. This review identifies these critical obstacles and offers targeted solutions and future research directions aimed at enhancing the performance and reliability of fully-printed OECTs. By addressing these challenges, the aim of this study is to facilitate the development of next-generation OECTs that can meet the demands of emerging applications in sustainable and intelligent electronic and bioelectronic systems.
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Affiliation(s)
- Roberto Granelli
- Department of Information Engineering, University of Brescia, via Branze 38, Brescia, 25123, Italy
| | - Zsolt M Kovács-Vajna
- Department of Information Engineering, University of Brescia, via Branze 38, Brescia, 25123, Italy
| | - Fabrizio Torricelli
- Department of Information Engineering, University of Brescia, via Branze 38, Brescia, 25123, Italy
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11
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Jahani Kadousaraei M, Yamada S, Aydin MS, Rashad A, Cabeza NM, Mohamed-Ahmed S, Gjerde CG, Malkoch M, Mustafa K. Bioprinting of mesenchymal stem cells in low concentration gelatin methacryloyl/alginate blends without ionic crosslinking of alginate. Sci Rep 2025; 15:6609. [PMID: 39994282 PMCID: PMC11850620 DOI: 10.1038/s41598-025-90389-2] [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: 10/21/2024] [Accepted: 02/11/2025] [Indexed: 02/26/2025] Open
Abstract
Bioprinting allows for the fabrication of tissue-like constructs by precise architecture and positioning of the bioactive hydrogels with living cells. This study was performed to determine the effect of very low concentrations of alginate (0.1, 0.3, and 0.5% w/v) on bioprinting of bone marrow mesenchymal stem cells (BMSC) in gelatin methacryloyl (GelMA; 5% w/v)/alginate blend. Furthermore, while GelMA was photocrosslinked in all bioprinted constructs, the effect of crosslinking alginate with calcium chloride on the physical and biological characteristics of the constructs was investigated. The inclusion of low-concentration alginate improved the viscosity and printability of the formulation as well as the compressive modulus of the hydrogels, particularly when ionically crosslinked with calcium chloride, compared with the group in that alginate was not crosslinked. However, the stability and degradability of 3D printed scaffolds that were only photocrosslinked were comparable to those that were additionally crosslinked with calcium chloride. Noteworthily, ionic crosslinking of alginate deteriorated the viability of BMSC. Morphology and growth of BMSC were improved by adding a low alginate concentration; however, ionic crosslinking of alginate affected these factors adversely. The findings of this study underscore the significance of carefully evaluating the crosslinking strategy used in conjunction with cell-laden GelMA/alginate hydrogel to achieve balanced physical and biological properties as well as less complicated post-bioprinting processing.
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Affiliation(s)
- Masoumeh Jahani Kadousaraei
- Tissue Engineering Group, Center of Translational Oral Research, Department of Clinical Dentistry, University of Bergen, Bergen, Norway
| | - Shuntaro Yamada
- Tissue Engineering Group, Center of Translational Oral Research, Department of Clinical Dentistry, University of Bergen, Bergen, Norway
| | - Mehmet Serhat Aydin
- Tissue Engineering Group, Center of Translational Oral Research, Department of Clinical Dentistry, University of Bergen, Bergen, Norway
| | - Ahmad Rashad
- Tissue Engineering Group, Center of Translational Oral Research, Department of Clinical Dentistry, University of Bergen, Bergen, Norway
- Bioengineering Graduate Program, Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, 46556, USA
| | - Noemi Molina Cabeza
- Division of Coating Technology and Division of Biocomposites, Department of Fiber and Polymer Technology, School of Chemical Science and Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Samih Mohamed-Ahmed
- Tissue Engineering Group, Center of Translational Oral Research, Department of Clinical Dentistry, University of Bergen, Bergen, Norway
| | - Cecilie G Gjerde
- Tissue Engineering Group, Center of Translational Oral Research, Department of Clinical Dentistry, University of Bergen, Bergen, Norway
| | - Michael Malkoch
- Division of Coating Technology and Division of Biocomposites, Department of Fiber and Polymer Technology, School of Chemical Science and Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Kamal Mustafa
- Tissue Engineering Group, Center of Translational Oral Research, Department of Clinical Dentistry, University of Bergen, Bergen, Norway.
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12
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Zheng Z, Yu D, Wang H, Wu H, Tang Z, Wu Q, Cao P, Chen Z, Huang H, Li X, Liu C, Guo Z. Advancement of 3D biofabrication in repairing and regeneration of cartilage defects. Biofabrication 2025; 17:022003. [PMID: 39793203 DOI: 10.1088/1758-5090/ada8e1] [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: 08/13/2024] [Accepted: 01/10/2025] [Indexed: 01/13/2025]
Abstract
Three-dimensional (3D) bioprinting, an additive manufacturing technology, fabricates biomimetic tissues that possess natural structure and function. It involves precise deposition of bioinks, including cells, and bioactive factors, on basis of computer-aided 3D models. Articular cartilage injuries, a common orthopedic issue. Current repair methods, for instance microfracture procedure (MF), autologous chondrocyte implantation (ACI), and osteochondral autologous transfer surgery have been applied in clinical practice. However, each procedure has inherent limitation. For instance, MF surgery associates with increased subchondral cyst formation and brittle subchondral bone. ACI procedure involves two surgeries, and associate with potential risks infection and delamination of the regenerated cartilage. In addition, chondrocyte implantation's efficacy depends on the patient's weight, joint pathology, gender-related histological changes of cartilage, and hormonal influences that affect treatment and prognosis. So far, it is a still a grand challenge for achieving a clinical satisfactory in repairing and regeneration of cartilage defects using conditional strategies. 3D biofabrication provide a potential to fabricate biomimetic articular cartilage construct that has shown promise in specific cartilage repair and regeneration of patients. This review reported the techniques of 3D bioprinting applied for cartilage repair, and analyzed their respective merits and demerits, and limitations in clinical application. A summary of commonly used bioinks has been provided, along with an outlook on the challenges and prospects faced by 3D bioprinting in the application of cartilage tissue repair. It provided an overall review of current development and promising application of 3D biofabrication technology in articular cartilage repair.
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Affiliation(s)
- Zenghui Zheng
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
- School of Clinical Medicine, Xi'an Medical University, Xi 'an 710021, People's Republic of China
| | - Dongmei Yu
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
- Institute of Orthopaedics and Musculoskeletal Science, University College London, The Royal National Orthopaedic Hospital, Stanmore HA7 4LP, United Kingdom
| | - Haoyu Wang
- Institute of Orthopaedics and Musculoskeletal Science, University College London, The Royal National Orthopaedic Hospital, Stanmore HA7 4LP, United Kingdom
| | - Hao Wu
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
| | - Zhen Tang
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
| | - Qi Wu
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
| | - Pengfei Cao
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
- School of Clinical Medicine, Xi'an Medical University, Xi 'an 710021, People's Republic of China
| | - Zhiyuan Chen
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
- School of Clinical Medicine, Xi'an Medical University, Xi 'an 710021, People's Republic of China
| | - Hai Huang
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
| | - Xiaokang Li
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
| | - Chaozong Liu
- Institute of Orthopaedics and Musculoskeletal Science, University College London, The Royal National Orthopaedic Hospital, Stanmore HA7 4LP, United Kingdom
| | - Zheng Guo
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China
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13
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Derman ID, Rivera T, Garriga Cerda L, Singh YP, Saini S, Abaci HE, Ozbolat IT. Advancements in 3D skin bioprinting: processes, bioinks, applications and sensor integration. INTERNATIONAL JOURNAL OF EXTREME MANUFACTURING 2025; 7:012009. [PMID: 39569402 PMCID: PMC11574952 DOI: 10.1088/2631-7990/ad878c] [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: 02/27/2024] [Revised: 06/23/2024] [Accepted: 10/16/2024] [Indexed: 11/22/2024]
Abstract
This comprehensive review explores the multifaceted landscape of skin bioprinting, revolutionizing dermatological research. The applications of skin bioprinting utilizing techniques like extrusion-, droplet-, laser- and light-based methods, with specialized bioinks for skin biofabrication have been critically reviewed along with the intricate aspects of bioprinting hair follicles, sweat glands, and achieving skin pigmentation. Challenges remain with the need for vascularization, safety concerns, and the integration of automated processes for effective clinical translation. The review further investigates the incorporation of biosensor technologies, emphasizing their role in monitoring and enhancing the wound healing process. While highlighting the remarkable progress in the field, critical limitations and concerns are critically examined to provide a balanced perspective. This synthesis aims to guide scientists, engineers, and healthcare providers, fostering a deeper understanding of the current state, challenges, and future directions in skin bioprinting for transformative applications in tissue engineering and regenerative medicine.
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Affiliation(s)
- I Deniz Derman
- Engineering Science and Mechanics Department, Penn State University, University Park, PA, United States of America
- The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, United States of America
| | - Taino Rivera
- Biomedical Engineering Department, Penn State University, University Park, PA, United States of America
| | - Laura Garriga Cerda
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, United States of America
| | - Yogendra Pratap Singh
- Engineering Science and Mechanics Department, Penn State University, University Park, PA, United States of America
- The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, United States of America
| | - Shweta Saini
- The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, United States of America
| | - Hasan Erbil Abaci
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, United States of America
- Department of Biomedical Engineering, Columbia University, New York, NY, United States of America
| | - Ibrahim T Ozbolat
- Engineering Science and Mechanics Department, Penn State University, University Park, PA, United States of America
- The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, United States of America
- Biomedical Engineering Department, Penn State University, University Park, PA, United States of America
- Materials Research Institute, Penn State University, University Park, PA, United States of America
- Cancer Institute, Penn State University, University Park, PA, United States of America
- Neurosurgery Department, Penn State University, University Park, PA, United States of America
- Department of Medical Oncology, Cukurova University, Adana, Turkey
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14
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Agarwal S, Mistry LN, Kamath S, Thorat R, Gupta B, Kondkari S. Pioneering the Future of Oral Healthcare: Bioprinting and Its Transformative Clinical Potential in Dentistry. Cureus 2025; 17:e79030. [PMID: 40104473 PMCID: PMC11914852 DOI: 10.7759/cureus.79030] [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: 01/06/2025] [Accepted: 02/11/2025] [Indexed: 03/20/2025] Open
Abstract
Bioprinting is revolutionizing the field of dentistry by enabling the fabrication of complex dental tissues using advanced techniques like inkjet, extrusion-based, and laser-assisted bioprinting. These methods allow for the precise placement of cells and materials to regenerate dental pulp, periodontal tissues, alveolar bone, and temporomandibular joint structures. Hydrogels, composite bioinks, and cell-laden bioinks play a crucial role in scaffold formation and improving cell viability. Preclinical models have demonstrated the potential of bioprinting for tissue regeneration and dental implants, with early clinical trials showing promising results. However, challenges remain, including scalability, material selection, immune response, and regulatory approval. Future advancements in multi-material bioprinting, real-time monitoring, and personalized treatment approaches will expand clinical applications of bioprinting, driving innovation in oral healthcare and improving patient outcomes.
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Affiliation(s)
- Sumeet Agarwal
- Prosthodontics, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Navi Mumbai, IND
| | - Laresh N Mistry
- Pediatric and Preventive Dentistry, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Navi Mumbai, IND
| | - Shamika Kamath
- Dentistry, NAMO Medical Education and Research Institute (MERI), Silvassa, IND
| | - Rohit Thorat
- Prosthodontics and Crown & Bridge and Implantology, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Pune, IND
| | - Bharat Gupta
- Periodontology, MGM Dental College and Hospital, Navi Mumbai, IND
| | - Saba Kondkari
- Dentistry, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Navi Mumbai, IND
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15
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Hu Y, Zhu T, Cui H, Cui H. Integrating 3D Bioprinting and Organoids to Better Recapitulate the Complexity of Cellular Microenvironments for Tissue Engineering. Adv Healthc Mater 2025; 14:e2403762. [PMID: 39648636 DOI: 10.1002/adhm.202403762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/16/2024] [Indexed: 12/10/2024]
Abstract
Organoids, with their capacity to mimic the structures and functions of human organs, have gained significant attention for simulating human pathophysiology and have been extensively investigated in the recent past. Additionally, 3D bioprinting, as an emerging bio-additive manufacturing technology, offers the potential for constructing heterogeneous cellular microenvironments, thereby promoting advancements in organoid research. In this review, the latest developments in 3D bioprinting technologies aimed at enhancing organoid engineering are introduced. The commonly used bioprinting methods and materials for organoids, with a particular emphasis on the potential advantages of combining 3D bioprinting with organoids are summarized. These advantages include achieving high cell concentrations to form large cellular aggregates, precise deposition of building blocks to create organoids with complex structures and functions, and automation and high throughput to ensure reproducibility and standardization in organoid culture. Furthermore, this review provides an overview of relevant studies from recent years and discusses the current limitations and prospects for future development.
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Affiliation(s)
- Yan Hu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Tong Zhu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Haitao Cui
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Haijun Cui
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
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16
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Pradal P, Kim JB, Nam SK, Kim SH, Amstad E. Direct Ink Writing of Rigid Microparticles. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2405675. [PMID: 39568272 DOI: 10.1002/smll.202405675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/29/2024] [Indexed: 11/22/2024]
Abstract
Direct ink writing (DIW) enables 3D printing of macroscopic objects with well-defined structures and compositions that controllably change over length scales of order 100 µm. Unfortunately, only a limited number of materials can be processed through DIW because it imparts stringent rheological requirements on inks. This limitation can be overcome for soft materials, if they are formulated as microparticles that, if jammed, fulfill the rheological requirements to be printed. By contrast, densely packed rigid microparticles with stiffnesses exceeding 2 MPa do not exhibit appropriate rheological properties that enable DIW. Here, an ink composed of up to 60 vol% rigid microparticles with core stiffnesses up to 50 MPa is introduced. To achieve this goal, rigid microparticles possessing soft hydrogel shells are produced. The 3D printed fragile granular structure is transformed into a load-bearing granular material through the formation of a 2nd network within the soft shells and in the interstitial spaces. The potential of these particles is demonstrated to be printed into intricate 3D structures, such as a trophy cup, or cast into flexible macroscopic photonic films.
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Affiliation(s)
- Pauline Pradal
- Soft Materials Laboratory - Institute of Materials in École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland
| | - Jong Bin Kim
- Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, 19104, USA
| | - Seong Kyeong Nam
- Department of Chemical and Biomolecular Engineering - Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea
| | - Shin-Hyun Kim
- Department of Chemical and Biomolecular Engineering - Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea
| | - Esther Amstad
- Soft Materials Laboratory - Institute of Materials in École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland
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17
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Wang Z, Xu J, Zhu J, Fang H, Lei W, Qu X, Cheng YY, Li X, Guan Y, Wang H, Song K. Osteochondral Tissue Engineering: Scaffold Materials, Fabrication Techniques and Applications. Biotechnol J 2025; 20:e202400699. [PMID: 39865414 DOI: 10.1002/biot.202400699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/24/2024] [Accepted: 01/06/2025] [Indexed: 01/28/2025]
Abstract
Osteochondral damage, caused by trauma, tumors, or degenerative diseases, presents a major challenge due to the limited self-repair capacity of the tissue. Traditional treatments often result in significant trauma and unpredictable outcomes. Recent advances in bone/cartilage tissue engineering, particularly in scaffold materials and fabrication technologies, offer promising solutions for osteochondral regeneration. This review highlights the selection and design of scaffolds using natural and synthetic materials such as collagen, chitosan (Cs), and polylactic acid (PLA), alongside inorganic components like bioactive glass and nano-hydroxyapatite (nHAp). Key fabrication techniques-freeze-drying, electrospinning, and 3D printing-have improved scaffold porosity and mechanical properties. Special focus is placed on the design of multiphasic scaffolds that mimic natural tissue structures, promoting cell adhesion and differentiation and supporting the regeneration of cartilage and subchondral bone. In addition, the current obstacles and future directions for regenerating damaged osteochondral tissues will be discussed.
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Affiliation(s)
- Zhenyu Wang
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
| | - Jie Xu
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
| | - Jingjing Zhu
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
| | - Huan Fang
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
| | - Wanyu Lei
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
| | - Xinrui Qu
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
| | - Yuen Yee Cheng
- Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Broadway, Australia
| | - Xiangqin Li
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
| | - Yanchun Guan
- Department of Rheumatology, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Hongfei Wang
- Department of Orthopedics, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Kedong Song
- Cancer Hospital of Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, China
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18
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Honkamäki L, Kulta O, Puistola P, Hopia K, Emeh P, Isosaari L, Mörö A, Narkilahti S. Hyaluronic Acid-Based 3D Bioprinted Hydrogel Structure for Directed Axonal Guidance and Modeling Innervation In Vitro. Adv Healthc Mater 2025; 14:e2402504. [PMID: 39502022 DOI: 10.1002/adhm.202402504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 09/25/2024] [Indexed: 01/03/2025]
Abstract
Neurons form predefined connections and innervate target tissues through elongating axons, which are crucial for the development, maturation, and function of these tissues. However, innervation is often overlooked in tissue engineering (TE) applications. Here, multimaterial 3D bioprinting is used to develop a novel 3D axonal guidance structure in vitro. The approach uses the stiffness difference of acellular hyaluronic acid-based bioink printed as two alternating, parallel-aligned filaments. The structure has soft passages incorporated with guidance cues for axonal elongation while the stiff bioink acts as a structural support and contact guidance. The mechanical properties and viscosity differences of the bioinks are confirmed. Additionally, human pluripotent stem cell (hPSC) -derived neurons form a 3D neuronal network in the softer bioink supplemented with guidance cues whereas the stiffer restricts the network formation. Successful 3D multimaterial bioprinting of the axonal structure enables complete innervation by peripheral neurons via soft passages within 14 days of culture. This model provides a novel, stable, and long-term platform for studies of 3D innervation and axonal dynamics in health and disease.
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Affiliation(s)
- Laura Honkamäki
- Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
| | - Oskari Kulta
- Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
| | - Paula Puistola
- Eye Regeneration Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
| | - Karoliina Hopia
- Eye Regeneration Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
| | - Promise Emeh
- Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
| | - Lotta Isosaari
- Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
| | - Anni Mörö
- Eye Regeneration Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
| | - Susanna Narkilahti
- Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland
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19
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Zhang Y, Li L, Dong L, Cheng Y, Huang X, Xue B, Jiang C, Cao Y, Yang J. Hydrogel-Based Strategies for Liver Tissue Engineering. CHEM & BIO ENGINEERING 2024; 1:887-915. [PMID: 39975572 PMCID: PMC11835278 DOI: 10.1021/cbe.4c00079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/15/2024] [Accepted: 09/15/2024] [Indexed: 02/21/2025]
Abstract
The liver's role in metabolism, detoxification, and immune regulation underscores the urgency of addressing liver diseases, which claim millions of lives annually. Due to donor shortages in liver transplantation, liver tissue engineering (LTE) offers a promising alternative. Hydrogels, with their biocompatibility and ability to mimic the liver's extracellular matrix (ECM), support cell survival and function in LTE. This review analyzes recent advances in hydrogel-based strategies for LTE, including decellularized liver tissue hydrogels, natural polymer-based hydrogels, and synthetic polymer-based hydrogels. These materials are ideal for in vitro cell culture and obtaining functional hepatocytes. Hydrogels' tunable properties facilitate creating artificial liver models, such as organoids, 3D bioprinting, and liver-on-a-chip technologies. These developments demonstrate hydrogels' versatility in advancing LTE's applications, including hepatotoxicity testing, liver tissue regeneration, and treating acute liver failure. This review highlights the transformative potential of hydrogels in LTE and their implications for future research and clinical practice.
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Affiliation(s)
- Yu Zhang
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
- Jinan
Microecological Biomedicine Shandong Laboratory, Jinan 250021, China
| | - Luofei Li
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
| | - Liang Dong
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
| | - Yuanqi Cheng
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
| | - Xiaoyu Huang
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
| | - Bin Xue
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
| | - Chunping Jiang
- Jinan
Microecological Biomedicine Shandong Laboratory, Jinan 250021, China
| | - Yi Cao
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
- Jinan
Microecological Biomedicine Shandong Laboratory, Jinan 250021, China
| | - Jiapeng Yang
- National
Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
- Jinan
Microecological Biomedicine Shandong Laboratory, Jinan 250021, China
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20
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Safavi AS, Karbasi S. A new path in bone tissue engineering: polymer-based 3D-printed magnetic scaffolds (a comprehensive review of in vitro and in vivo studies). JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2024:1-21. [PMID: 39715733 DOI: 10.1080/09205063.2024.2444077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 12/13/2024] [Indexed: 12/25/2024]
Abstract
Bone tissue engineering is a promising approach to address the increasing need for bone repair. Scaffolds play a crucial role in providing the structural framework for cell growth and differentiation. 3D printing offers precise control over scaffold design and fabrication. Polymers and inorganic compounds such as magnetic nanoparticles (MNPs) are used to create biocompatible and functional scaffolds. MNPs enhance mechanical properties, facilitate drug delivery, and enable the real-time monitoring of bone regeneration. This review highlights the potential of polymer-based 3D-printed magnetic scaffolds in advancing bone regenerative medicine.
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Affiliation(s)
- Atiyeh Sadat Safavi
- Department of Biomaterials and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Saeed Karbasi
- Department of Biomaterials and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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21
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Beque J, Poerio A, Leroux M, Jehl JP, Cleymand F. 3D Printing of a Chitosan and Tamarind Gum Ink: a Two-Step Approach. ACS APPLIED BIO MATERIALS 2024; 7:8203-8211. [PMID: 39560098 DOI: 10.1021/acsabm.4c00497] [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: 11/20/2024]
Abstract
3D bioprinting stands out as one of the most promising innovations in the field of high technologies for personalized biomedicine, enabling the fabrication of biomaterial-based scaffolds designed to repair, restore, or regenerate tissues and organs in the body. Among the various materials used as inks, hydrogels play a critical role due to their unique characteristics, including excellent biocompatibility, adjustable mechanical properties, and high solvent retention. This versatility makes them ideal for various applications such as biomedical devices, drug delivery, or flexible electronics. Although chitosan is a promising material for such applications, when used alone, it does not possess the necessary strength and stiffness for creating high-resolution 3D bioprinted structures. In this study, we propose a combined method for the fabrication of self-supporting 3D printed objects with an ink made of chitosan and tamarind gum. Our approach involves two key techniques. The first one is a controlled evaporation of the solvent, aiming to increase the concentration of the components of the ink. The second one relies on printing in a gelling bath composed of sodium hydroxide and ethanol, allowing for improved printability and long-term stability of the scaffolds. The results obtained revealed the possibility of modulating the concentration of the components based on the heating time. The latter positively influences not only the ink printability but also the properties of the resulting scaffolds such as their biodegradability and mechanical properties.
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Affiliation(s)
- Jeanne Beque
- Institut Jean Lamour, UMR 7198 CNRS, Université de Lorraine, Nancy 54000, France
| | - Aurelia Poerio
- Institut Jean Lamour, UMR 7198 CNRS, Université de Lorraine, Nancy 54000, France
| | - Mélanie Leroux
- Institut Jean Lamour, UMR 7198 CNRS, Université de Lorraine, Nancy 54000, France
| | - Jean-Philippe Jehl
- Institut Jean Lamour, UMR 7198 CNRS, Université de Lorraine, Nancy 54000, France
| | - Franck Cleymand
- Institut Jean Lamour, UMR 7198 CNRS, Université de Lorraine, Nancy 54000, France
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22
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Zhou X, Yu X, You T, Zhao B, Dong L, Huang C, Zhou X, Xing M, Qian W, Luo G. 3D Printing-Based Hydrogel Dressings for Wound Healing. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2404580. [PMID: 39552255 DOI: 10.1002/advs.202404580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 10/21/2024] [Indexed: 11/19/2024]
Abstract
Skin wounds have become an important issue that affects human health and burdens global medical care. Hydrogel materials similar to the natural extracellular matrix (ECM) are one of the best candidates for ideal wound dressings and the most feasible choices for printing inks. Distinct from hydrogels made by traditional technologies, which lack bionic and mechanical properties, 3D printing can promptly and accurately create hydrogels with complex bioactive structures and the potential to promote tissue regeneration and wound healing. Herein, a comprehensive review of multi-functional 3D printing-based hydrogel dressings for wound healing is presented. The review first summarizes the 3D printing techniques for wound hydrogel dressings, including photo-curing, extrusion, inkjet, and laser-assisted 3D printing. Then, the properties and design approaches of a series of bioinks composed of natural, synthetic, and composite polymers for 3D printing wound hydrogel dressings are described. Thereafter, the application of multi-functional 3D printing-based hydrogel dressings in a variety of wound environments is discussed in depth, including hemostasis, anti-inflammation, antibacterial, skin appendage regeneration, intelligent monitoring, and machine learning-assisted therapy. Finally, the challenges and prospects of 3D printing-based hydrogel dressings for wound healing are presented.
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Affiliation(s)
- Xuan Zhou
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Xunzhou Yu
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Tingting You
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Baohua Zhao
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Lanlan Dong
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Can Huang
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Xiaoqing Zhou
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Malcolm Xing
- Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada
| | - Wei Qian
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
| | - Gaoxing Luo
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory for Disease Proteomics, Chongqing, 400038, China
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23
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Kang R, Wu J, Cheng R, Li M, Sang L, Zhang H, Sang S. 3D bioprinting technology and equipment based on microvalve control. Biotechnol Bioeng 2024; 121:3768-3781. [PMID: 39289816 DOI: 10.1002/bit.28850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 06/26/2024] [Accepted: 09/05/2024] [Indexed: 09/19/2024]
Abstract
3D bioprinting technology is widely used in biomedical fields such as tissue regeneration and constructing pathological model. The prevailing printing technique is extrusion-based bioprinting. In this printing method, the bioink needs to meet both printability and functionality, which are often conflicting requirements. Therefore, this study has developed an innovative microvalve-based equipment, incorporating components such as pressure control, a three-dimensional motion platform, and microvalve. Here, we present a droplet-based method for constructing complex three-dimensional structures. By leveraging the rapid switching characteristics of the microvalve, this equipment can achieve precise printing of bio-materials with viscosities as low as 10mPa·s, significantly expanding the biofabrication window for bioinks. This technology is of great significance for 3D bioprinting in tissue engineering and lays a solid foundation for the construction of complex artificial organ tissues.
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Affiliation(s)
- Rihui Kang
- Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
- Shanxi Research Institute of 6D Artificial Intelligence Biomedical Science, Taiyuan, China
| | - Jiaxing Wu
- Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
- Shanxi Research Institute of 6D Artificial Intelligence Biomedical Science, Taiyuan, China
| | - Rong Cheng
- Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
- Shanxi Research Institute of 6D Artificial Intelligence Biomedical Science, Taiyuan, China
| | - Meng Li
- Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
- Shanxi Research Institute of 6D Artificial Intelligence Biomedical Science, Taiyuan, China
| | - Luxiao Sang
- Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Hulin Zhang
- Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Shengbo Sang
- Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
- Key Lab of Advanced Transducers and Intelligent Control System of the Ministry of Education, Taiyuan University of Technology, Taiyuan, China
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24
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Mikaeeli Kangarshahi B, Naghib SM, Rabiee N. 3D printing and computer-aided design techniques for drug delivery scaffolds in tissue engineering. Expert Opin Drug Deliv 2024; 21:1615-1636. [PMID: 39323396 DOI: 10.1080/17425247.2024.2409913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 09/19/2024] [Accepted: 09/24/2024] [Indexed: 09/27/2024]
Abstract
INTRODUCTION The challenge in tissue engineering lies in replicating the intricate structure of the native extracellular matrix. Recent advancements in AM, notably 3D printing, offer unprecedented capabilities to tailor scaffolds precisely, controlling properties like structure and bioactivity. CAD tools complement this by facilitating design using patient-specific data. AREA’S COVERED This review introduces additive manufacturing (AM) and computer-aided design (CAD) as pivotal tools in advancing tissue engineering, particularly cartilage regeneration. This article explores various materials utilized in AM, focusing on polymers and hydrogels for their advantageous properties in tissue engineering applications. Integrating bioactive molecules, including growth factors, into scaffolds to promote tissue regeneration is discussed alongside strategies involving different cell sources, such as stem cells, to enhance tissue development within scaffold matrices. EXPERT OPINION Applications of AM and CAD in addressing specific challenges like osteochondral defects and osteoarthritis in cartilage tissue engineering are highlighted. This review consolidates current research findings, offering expert insights into the evolving landscape of AM and CAD technologies in advancing tissue engineering, particularly in cartilage regeneration.
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Affiliation(s)
- Babak Mikaeeli Kangarshahi
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology, Tehran, Iran
| | - Seyed Morteza Naghib
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology, Tehran, Iran
| | - Navid Rabiee
- Department of Biomaterials, Saveetha Dental College and Hospitals, SIMATS, Saveetha University, Chennai, India
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25
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Perry AC, Adesida AB. Tissue Engineering Nasal Cartilage Grafts with Three-Dimensional Printing: A Comprehensive Review. TISSUE ENGINEERING. PART B, REVIEWS 2024. [PMID: 39311456 DOI: 10.1089/ten.teb.2024.0187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2024]
Abstract
Nasal cartilage serves a crucial structural function for the nose, where rebuilding the cartilaginous framework is an essential aspect of nasal reconstruction. Conventional methods of nasal reconstruction rely on autologous cartilage harvested from patients, which contributes to donor site pain and the potential for site-specific complications. Some patients are not ideal candidates for this procedure due to a lack of adequate substitute cartilage due to age-related calcification, differences in tissue quality, or due to prior surgeries. Tissue engineering, combined with three-dimensional printing technologies, has emerged as a promising method of generating biomimetic tissues to circumvent these issues to restore normal function and aesthetics. We conducted a comprehensive literature review to examine the applications of three-dimensional printing in conjunction with tissue engineering for the generation of nasal cartilage grafts. This review aims to compare various approaches and discuss critical considerations in the design of these grafts.
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Affiliation(s)
- Alexander C Perry
- Department of Surgery, Division of Plastic Surgery, University of Alberta, Edmonton, Canada
- Department of Surgery, Divisions of Orthopaedic Surgery and Surgical Research, University of Alberta, Edmonton, Canada
| | - Adetola B Adesida
- Department of Surgery, Divisions of Orthopaedic Surgery and Surgical Research, University of Alberta, Edmonton, Canada
- Department of Surgery, Division of Otolaryngology, University of Alberta, Edmonton, Canada
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26
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Zhang X, Gao X, Zhang X, Yao X, Kang X. Revolutionizing Intervertebral Disc Regeneration: Advances and Future Directions in Three-Dimensional Bioprinting of Hydrogel Scaffolds. Int J Nanomedicine 2024; 19:10661-10684. [PMID: 39464675 PMCID: PMC11505483 DOI: 10.2147/ijn.s469302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 08/10/2024] [Indexed: 10/29/2024] Open
Abstract
Hydrogels are multifunctional platforms. Through reasonable structure and function design, they use material engineering to adjust their physical and chemical properties, such as pore size, microstructure, degradability, stimulus-response characteristics, etc. and have a variety of biomedical applications. Hydrogel three-dimensional (3D) printing has emerged as a promising technique for the precise deposition of cell-laden biomaterials, enabling the fabrication of intricate 3D structures such as artificial vertebrae and intervertebral discs (IVDs). Despite being in the early stages, 3D printing techniques have shown great potential in the field of regenerative medicine for the fabrication of various transplantable tissues within the human body. Currently, the utilization of engineered hydrogels as carriers or scaffolds for treating intervertebral disc degeneration (IVDD) presents numerous challenges. However, it remains an indispensable multifunctional manufacturing technology that is imperative in addressing the escalating issue of IVDD. Moreover, it holds the potential to serve as a micron-scale platform for a diverse range of applications. This review primarily concentrates on emerging treatment strategies for IVDD, providing an in-depth analysis of their merits and drawbacks, as well as the challenges that need to be addressed. Furthermore, it extensively explores the biological properties of hydrogels and various nanoscale biomaterial inks, compares different prevalent manufacturing processes utilized in 3D printing, and thoroughly examines the potential clinical applications and prospects of integrating 3D printing technology with hydrogels.
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Affiliation(s)
- Xiaobo Zhang
- Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’An, Shaanxi, P.R. China
| | - Xidan Gao
- Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’An, Shaanxi, P.R. China
| | - Xuefang Zhang
- Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’An, Shaanxi, P.R. China
| | - Xin Yao
- Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’An, Shaanxi, P.R. China
| | - Xin Kang
- Department of Sports Medicine, Honghui Hospital, Xi’an Jiao Tong University, Xi’An, Shaanxi, P.R. China
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27
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Zoghi S. Advancements in Tissue Engineering: A Review of Bioprinting Techniques, Scaffolds, and Bioinks. Biomed Eng Comput Biol 2024; 15:11795972241288099. [PMID: 39364141 PMCID: PMC11447703 DOI: 10.1177/11795972241288099] [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: 08/01/2024] [Accepted: 09/13/2024] [Indexed: 10/05/2024] Open
Abstract
Tissue engineering is a multidisciplinary field that uses biomaterials to restore tissue function and assist with drug development. Over the last decade, the fabrication of three-dimensional (3D) multifunctional scaffolds has become commonplace in tissue engineering and regenerative medicine. Thanks to the development of 3D bioprinting technologies, these scaffolds more accurately recapitulate in vivo conditions and provide the support structure necessary for microenvironments conducive to cell growth and function. The purpose of this review is to provide a background on the leading 3D bioprinting methods and bioink selections for tissue engineering applications, with a specific focus on the growing field of developing multifunctional bioinks and possible future applications.
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Affiliation(s)
- Shervin Zoghi
- School of Medicine, University of California, Davis, Sacramento, CA, USA
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28
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Mierke CT. Bioprinting of Cells, Organoids and Organs-on-a-Chip Together with Hydrogels Improves Structural and Mechanical Cues. Cells 2024; 13:1638. [PMID: 39404401 PMCID: PMC11476109 DOI: 10.3390/cells13191638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/25/2024] [Accepted: 10/01/2024] [Indexed: 10/19/2024] Open
Abstract
The 3D bioprinting technique has made enormous progress in tissue engineering, regenerative medicine and research into diseases such as cancer. Apart from individual cells, a collection of cells, such as organoids, can be printed in combination with various hydrogels. It can be hypothesized that 3D bioprinting will even become a promising tool for mechanobiological analyses of cells, organoids and their matrix environments in highly defined and precisely structured 3D environments, in which the mechanical properties of the cell environment can be individually adjusted. Mechanical obstacles or bead markers can be integrated into bioprinted samples to analyze mechanical deformations and forces within these bioprinted constructs, such as 3D organoids, and to perform biophysical analysis in complex 3D systems, which are still not standard techniques. The review highlights the advances of 3D and 4D printing technologies in integrating mechanobiological cues so that the next step will be a detailed analysis of key future biophysical research directions in organoid generation for the development of disease model systems, tissue regeneration and drug testing from a biophysical perspective. Finally, the review highlights the combination of bioprinted hydrogels, such as pure natural or synthetic hydrogels and mixtures, with organoids, organoid-cell co-cultures, organ-on-a-chip systems and organoid-organ-on-a chip combinations and introduces the use of assembloids to determine the mutual interactions of different cell types and cell-matrix interferences in specific biological and mechanical environments.
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Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth System Science, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, Leipzig University, 04103 Leipzig, Germany
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29
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Ganguly S, Wulff D, Phan CM, Jones LW, Tang XS. Injectable and 3D Extrusion Printable Hydrophilic Silicone-Based Hydrogels for Controlled Ocular Delivery of Ophthalmic Drugs. ACS APPLIED BIO MATERIALS 2024; 7:6286-6296. [PMID: 39227342 DOI: 10.1021/acsabm.4c00901] [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: 09/05/2024]
Abstract
While silicone elastomers have found widespread use in the biomedical industry, 3D printing them has proven to be difficult due to the material's slow drying time, low viscosity, and hydrophobicity. Herein, we arrested the hydrophilic silicone (HS) macrochains into a semi-interpenetrating polymer network (semi-IPN) via an in situ photogelation-assisted 3D microextrusion printing technique. The flow behavior of the pregel solutions and the mechanical properties of the printed HS hydrogels were tested, showing a high elastic modulus (approximately 15 kPa), a low tan δ, high elasticity, and delayed network rupturing. The uniaxial compression tests demonstrated a nearly negligible permanent deformation, suggesting that the printed hybrid hydrogel maintained its elastic properties. Drug loading and diffusion in the microporous hydrogel are shown via the non-Fickian anomalous transport mechanism, leading to highly tunable loading/releasing profiles (approximately 20% cumulative release) depending on the HS concentration. The drug encapsulation exhibits exceptional stability, remaining intact without any degradation even after a storage period of 1 month. As far as we know, this is the first soft biomaterial based on HS that functions as an exceptional controlled drug delivery device.
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Affiliation(s)
- Sayan Ganguly
- Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, Ontario N2L 3G1, Canada
- Centre for Eye and Vision Research Limited, 17W, Hong Kong Science Park, Hong Kong
| | - David Wulff
- Centre for Eye and Vision Research Limited, 17W, Hong Kong Science Park, Hong Kong
- School of Optometry and Vision Science, Faculty of Science, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
| | - Chau-Minh Phan
- Centre for Eye and Vision Research Limited, 17W, Hong Kong Science Park, Hong Kong
- School of Optometry and Vision Science, Faculty of Science, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
| | - Lyndon William Jones
- Centre for Eye and Vision Research Limited, 17W, Hong Kong Science Park, Hong Kong
- School of Optometry and Vision Science, Faculty of Science, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
| | - Xiaowu Shirley Tang
- Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, Ontario N2L 3G1, Canada
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30
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Chen H, Zhang B, Huang J. Recent advances and applications of artificial intelligence in 3D bioprinting. BIOPHYSICS REVIEWS 2024; 5:031301. [PMID: 39036708 PMCID: PMC11260195 DOI: 10.1063/5.0190208] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 06/11/2024] [Indexed: 07/23/2024]
Abstract
3D bioprinting techniques enable the precise deposition of living cells, biomaterials, and biomolecules, emerging as a promising approach for engineering functional tissues and organs. Meanwhile, recent advances in 3D bioprinting enable researchers to build in vitro models with finely controlled and complex micro-architecture for drug screening and disease modeling. Recently, artificial intelligence (AI) has been applied to different stages of 3D bioprinting, including medical image reconstruction, bioink selection, and printing process, with both classical AI and machine learning approaches. The ability of AI to handle complex datasets, make complex computations, learn from past experiences, and optimize processes dynamically makes it an invaluable tool in advancing 3D bioprinting. The review highlights the current integration of AI in 3D bioprinting and discusses future approaches to harness the synergistic capabilities of 3D bioprinting and AI for developing personalized tissues and organs.
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Affiliation(s)
| | - Bin Zhang
- Department of Mechanical and Aerospace Engineering, Brunel University London, London, United Kingdom
| | - Jie Huang
- Department of Mechanical Engineering, University College London, London, United Kingdom
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31
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Yang C, Yang H, Kim H, Chung N, Shin J, Min H, Lee K, Lee JR. Injectable Biomimetic Hydrogel Constructs for Cell-Based Menopausal Hormone Therapy with Reduced Breast Cancer Potential. Biomater Res 2024; 28:0054. [PMID: 39135549 PMCID: PMC11310713 DOI: 10.34133/bmr.0054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 06/20/2024] [Indexed: 08/15/2024] Open
Abstract
Hormone replacement therapy (HRT) has been a primary method in menopausal women and patients with ablated ovaries, but safety has been a concern. Cell-based HRT has emerged as an alternative approach without side effects causing pharmaceutical HRT via 3-dimensionally engineered constructs layering ovarian hormone-producing cells. In this study, we applied micro-sized ovarian cell-laden hydrogel beads as an approach to cell-based HRT using a minimally invasive method in the menopausal rat model. Here, we constructed GC/TC-laden microbeads (GTBs; GC, granulosa cell; TC, theca cell) that allow crosstalk between endocrine cells, encapsulating multiple beads for the figuration of the original ovary. We assessed the ovarian hormone production function of GTB through in vitro culture for 90 days. We applied it to a menopausal rat model and confirmed that GTB-injected rats restored their endocrine function, leading to the regeneration of the thinned endometrium and the maintenance of regular estrous cycles in some individuals. Additionally, it was observed to alleviate menopausal symptoms, including body weight gain and osteoporosis. Notably, the GTB-injected rats did not show mammary gland hyperplasia observed in the pharmaceutical HRT groups and exhibited fewer p53- and KI67-positive and an increase in phosphatase and tensin homolog-positive mammary gland epithelial cells compared to pharmaceutical hormone-treated rats. These results suggest that GTB-based HRT could present a lower risk of breast cancer compared to conventional pharmaceutical-HRT use. Our study highlights the potential of cell-based HRT using an injectable artificial ovary, offering a safer alternative for women requiring HRT.
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Affiliation(s)
- Chungmo Yang
- Department of Obstetrics and Gynecology,
Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
- Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology,
Seoul National University, Seoul 08826, Republic of Korea
| | - Heeseon Yang
- Department of Obstetrics and Gynecology,
Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
- Department of Translational Medicine, College of Medicine,
Seoul National University, Seoul 03080, Republic of Korea
| | - Hyerim Kim
- Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology,
Seoul National University, Seoul 08826, Republic of Korea
| | - Nanum Chung
- Department of Obstetrics and Gynecology,
Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
- Department of Translational Medicine, College of Medicine,
Seoul National University, Seoul 03080, Republic of Korea
| | - Jungwoo Shin
- Department of Obstetrics and Gynecology,
Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
- Department of Translational Medicine, College of Medicine,
Seoul National University, Seoul 03080, Republic of Korea
| | - Hyewon Min
- Department of Obstetrics and Gynecology,
Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
- Department of Translational Medicine, College of Medicine,
Seoul National University, Seoul 03080, Republic of Korea
| | - Kangwon Lee
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology,
Seoul National University, Seoul 08826, Republic of Korea
- Research Institute for Convergence Science,
Seoul National University, Seoul 08826, Republic of Korea
| | - Jung Ryeol Lee
- Department of Obstetrics and Gynecology,
Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
- Department of Translational Medicine, College of Medicine,
Seoul National University, Seoul 03080, Republic of Korea
- Department of Obstetrics and Gynecology,
Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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32
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Fang W, Yu Z, Gao G, Yang M, Du X, Wang Y, Fu Q. Light-based 3D bioprinting technology applied to repair and regeneration of different tissues: A rational proposal for biomedical applications. Mater Today Bio 2024; 27:101135. [PMID: 39040222 PMCID: PMC11262185 DOI: 10.1016/j.mtbio.2024.101135] [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: 02/02/2024] [Revised: 06/10/2024] [Accepted: 06/21/2024] [Indexed: 07/24/2024] Open
Abstract
3D bioprinting technology, a subset of 3D printing technology, is currently witnessing widespread utilization in tissue repair and regeneration endeavors. In particular, light-based 3D bioprinting technology has garnered significant interest and favor. Central to its successful implementation lies the judicious selection of photosensitive polymers. Moreover, by fine-tuning parameters such as light irradiation time, choice of photoinitiators and crosslinkers, and their concentrations, the properties of the scaffolds can be tailored to suit the specific requirements of the targeted tissue repair sites. In this comprehensive review, we provide an overview of commonly utilized bio-inks suitable for light-based 3D bioprinting, delving into the distinctive characteristics of each material. Furthermore, we delineate strategies for bio-ink selection tailored to diverse repair locations, alongside methods for optimizing printing parameters. Ultimately, we present a coherent synthesis aimed at enhancing the practical application of light-based 3D bioprinting technology in tissue engineering, while also addressing current challenges and future prospects.
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Affiliation(s)
- Wenzhuo Fang
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai, 200233, China
| | - Zhenwei Yu
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai, 200233, China
| | - Guo Gao
- Key Laboratory for Thin Film and Micro Fabrication of the Ministry of Education, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Ming Yang
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai, 200233, China
| | - Xuan Du
- Key Laboratory for Thin Film and Micro Fabrication of the Ministry of Education, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Ying Wang
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai, 200233, China
| | - Qiang Fu
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai, 200233, China
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Lee W, Xu C, Fu H, Ploch M, D’Souza S, Lustig S, Long X, Hong Y, Dai G. 3D Bioprinting Highly Elastic PEG-PCL-DA Hydrogel for Soft Tissue Fabrication and Biomechanical Stimulation. ADVANCED FUNCTIONAL MATERIALS 2024; 34:2313942. [PMID: 39380942 PMCID: PMC11458153 DOI: 10.1002/adfm.202313942] [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: 11/07/2023] [Indexed: 10/10/2024]
Abstract
3-D bioprinting is a promising technology to fabricate custom geometries for tissue engineering. However, most bioprintable hydrogels are weak and fragile, difficult to handle and cannot mimetic the mechanical behaviors of the native soft elastic tissues. We have developed a visible light crosslinked, single-network, elastic and biocompatible hydrogel system based on an acrylated triblock copolymer of poly(ethylene glycol) PEG and polycaprolactone (PCL) (PEG-PCL-DA). To enable its application in bioprinting of soft tissues, we have modified the hydrogel system on its printability and biodegradability. Furthermore, we hypothesize that this elastic material can better transmit pulsatile forces to cells, leading to enhanced cellular response under mechanical stimulation. This central hypothesis was tested using vascular conduits with smooth muscle cells (SMCs) cultured under pulsatile forces in a custom-made bioreactor. The results showed that vascular conduits made of PEG-PCL-DA hydrogel faithfully recapitulate the rapid stretch and recoil under the pulsatile pressure from 1 to 3 Hz frequency, which induced a contractile SMC phenotype, consistently upregulated the core contractile transcription factors. In summary, our work demonstrates the potential of elastic hydrogel for 3D bioprinting of soft tissues by fine tuning the printability, biodegradability, while possess robust elastic property suitable for manual handling and biomechanical stimulation.
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Affiliation(s)
- Wenhan Lee
- Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
| | - Cancan Xu
- Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA
| | - Huikang Fu
- Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA
| | - Michael Ploch
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
| | - Sean D’Souza
- Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
| | - Steve Lustig
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
| | - Xiaochun Long
- Augusta University, Medical College of Georgia, Augusta, GA 30912, USA
| | - Yi Hong
- Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA
| | - Guohao Dai
- Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
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Khaledian S, Mohammadi G, Abdoli M, Fatahian A, Fatahian A, Fatahian R. Recent Advances in Implantable 3D-Printed Scaffolds for Repair of Spinal Cord Injury. Adv Pharm Bull 2024; 14:331-345. [PMID: 39206398 PMCID: PMC11347741 DOI: 10.34172/apb.2024.032] [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: 07/12/2023] [Revised: 01/27/2024] [Accepted: 03/03/2024] [Indexed: 09/04/2024] Open
Abstract
Spinal cord injury (SCI) is an important factor in sensory and motor disorders that affects thousands of people every year. Currently, despite successes in basic science and clinical research, there are few effective methods in the treatment of chronic and acute spinal cord injuries. In the last decade, the use of 3D printed scaffolds in the treatment of SCI had satisfactory and promising results. By providing a microenvironment around the injury site and in combination with growth factors or cells, 3D printed scaffolds help in axon regeneration as well as neural recovery after SCI. Here, we provide an overview of tissue engineering, 3D printing scaffolds, the different polymers used and their characterization methods. This review highlights the recent encouraging applications of 3D printing scaffolds in developing the novel SCI therapy.
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Affiliation(s)
- Salar Khaledian
- Infectious Diseases Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Clinical Research Development Center, Taleghani and Imam Ali Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ghobad Mohammadi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohadese Abdoli
- Department of Nanobiotechnology, Faculty of Innovative Science and Technology, Razi University, Kermanshah, Iran
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Arad Fatahian
- School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Arya Fatahian
- School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Reza Fatahian
- Clinical Research Development Center, Taleghani and Imam Ali Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Neurosurgery, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Randhawa A, Dutta SD, Ganguly K, Patil TV, Lim KT. Manufacturing 3D Biomimetic Tissue: A Strategy Involving the Integration of Electrospun Nanofibers with a 3D-Printed Framework for Enhanced Tissue Regeneration. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2309269. [PMID: 38308170 DOI: 10.1002/smll.202309269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 01/11/2024] [Indexed: 02/04/2024]
Abstract
3D printing and electrospinning are versatile techniques employed to produce 3D structures, such as scaffolds and ultrathin fibers, facilitating the creation of a cellular microenvironment in vitro. These two approaches operate on distinct working principles and utilize different polymeric materials to generate the desired structure. This review provides an extensive overview of these techniques and their potential roles in biomedical applications. Despite their potential role in fabricating complex structures, each technique has its own limitations. Electrospun fibers may have ambiguous geometry, while 3D-printed constructs may exhibit poor resolution with limited mechanical complexity. Consequently, the integration of electrospinning and 3D-printing methods may be explored to maximize the benefits and overcome the individual limitations of these techniques. This review highlights recent advancements in combined techniques for generating structures with controlled porosities on the micro-nano scale, leading to improved mechanical structural integrity. Collectively, these techniques also allow the fabrication of nature-inspired structures, contributing to a paradigm shift in research and technology. Finally, the review concludes by examining the advantages, disadvantages, and future outlooks of existing technologies in addressing challenges and exploring potential opportunities.
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Affiliation(s)
- Aayushi Randhawa
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea
- Interdisciplinary Program in Smart Agriculture, Kangwon National University, Chuncheon, 24341, Republic of Korea
| | - Sayan Deb Dutta
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea
- Institute of Forest Science, Kangwon National University, Chuncheon, Gangwon-do, 24341, Republic of Korea
| | - Keya Ganguly
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea
| | - Tejal V Patil
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea
- Interdisciplinary Program in Smart Agriculture, Kangwon National University, Chuncheon, 24341, Republic of Korea
| | - Ki-Taek Lim
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea
- Interdisciplinary Program in Smart Agriculture, Kangwon National University, Chuncheon, 24341, Republic of Korea
- Institute of Forest Science, Kangwon National University, Chuncheon, Gangwon-do, 24341, Republic of Korea
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Paoletti L, Baschieri F, Migliorini C, Di Meo C, Monasson O, Peroni E, Matricardi P. 3D printing of gellan-dextran methacrylate IPNs in glycerol and their bioadhesion by RGD derivatives. J Biomed Mater Res A 2024; 112:1107-1123. [PMID: 38433552 DOI: 10.1002/jbm.a.37698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 02/14/2024] [Accepted: 02/22/2024] [Indexed: 03/05/2024]
Abstract
The ever-growing need for new tissue and organ replacement approaches paved the way for tissue engineering. Successful tissue regeneration requires an appropriate scaffold, which allows cell adhesion and provides mechanical support during tissue repair. In this light, an interpenetrating polymer network (IPN) system based on biocompatible polysaccharides, dextran (Dex) and gellan (Ge), was designed and proposed as a surface that facilitates cell adhesion in tissue engineering applications. The new matrix was developed in glycerol, an unconventional solvent, before the chemical functionalization of the polymer backbone, which provides the system with enhanced properties, such as increased stiffness and bioadhesiveness. Dex was modified introducing methacrylic groups, which are known to be sensitive to UV light. At the same time, Ge was functionalized with RGD moieties, known as promoters for cell adhesion. The printability of the systems was evaluated by exploiting the ability of glycerol to act as a co-initiator in the process, speeding up the kinetics of crosslinking. Following semi-IPNs formation, the solvent was removed by extensive solvent exchange with HEPES and CaCl2, leading to conversion into IPNs due to the ionic gelation of Ge chains. Mechanical properties were investigated and IPNs ability to promote osteoblasts adhesion was evaluated on thin-layer, 3D-printed disk films. Our results show a significant increase in adhesion on hydrogels decorated with RGD moieties, where osteoblasts adopted the spindle-shaped morphology typical of adherent mesenchymal cells. Our findings support the use of RGD-decorated Ge/Dex IPNs as new matrices able to support and facilitate cell adhesion in the perspective of bone tissue regeneration.
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Affiliation(s)
- Luca Paoletti
- Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy
| | - Francesco Baschieri
- Institute of Pathophysiology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
| | - Claudia Migliorini
- Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy
| | - Chiara Di Meo
- Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy
| | - Olivier Monasson
- CY Cergy Paris Université, CNRS, BioCIS, Cergy-Pontoise, France
- Université Paris-Saclay, CNRS, BioCIS, Châtenay-Malabry, France
| | - Elisa Peroni
- CY Cergy Paris Université, CNRS, BioCIS, Cergy-Pontoise, France
- Université Paris-Saclay, CNRS, BioCIS, Châtenay-Malabry, France
| | - Pietro Matricardi
- Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy
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Lan X, Boluk Y, Adesida AB. 3D Bioprinting of Hyaline Cartilage Using Nasal Chondrocytes. Ann Biomed Eng 2024; 52:1816-1834. [PMID: 36952145 DOI: 10.1007/s10439-023-03176-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 02/22/2023] [Indexed: 03/24/2023]
Abstract
Due to the limited self-repair capacity of the hyaline cartilage, the repair of cartilage remains an unsolved clinical problem. Tissue engineering strategy with 3D bioprinting technique has emerged a new insight by providing patient's personalized cartilage grafts using autologous cells for hyaline cartilage repair and regeneration. In this review, we first summarized the intrinsic property of hyaline cartilage in both maxillofacial and orthopedic regions to establish the requirement for 3D bioprinting cartilage tissue. We then reviewed the literature and provided opinion pieces on the selection of bioprinters, bioink materials, and cell sources. This review aims to identify the current challenges for hyaline cartilage bioprinting and the directions for future clinical development in bioprinted hyaline cartilage.
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Affiliation(s)
- Xiaoyi Lan
- Department of Civil and Environmental Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada
| | - Yaman Boluk
- Department of Civil and Environmental Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.
| | - Adetola B Adesida
- Department of Surgery, Divisions of Orthopedic Surgery & Surgical Research, Faculty of Medicine & Dentistry, Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, Canada.
- Department of Surgery, Division of Otolaryngology, Faculty of Medicine & Dentistry, Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, Canada.
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38
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Qin S, Niu Y, Zhang Y, Wang W, Zhou J, Bai Y, Ma G. Metal Ion-Containing Hydrogels: Synthesis, Properties, and Applications in Bone Tissue Engineering. Biomacromolecules 2024; 25:3217-3248. [PMID: 38237033 DOI: 10.1021/acs.biomac.3c01072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2024]
Abstract
Hydrogel, as a unique scaffold material, features a three-dimensional network system that provides conducive conditions for the growth of cells and tissues in bone tissue engineering (BTE). In recent years, it has been discovered that metal ion-containing hybridized hydrogels, synthesized with metal particles as the foundation, exhibit excellent physicochemical properties, osteoinductivity, and osteogenic potential. They offer a wide range of research prospects in the field of BTE. This review provides an overview of the current state and recent advancements in research concerning metal ion-containing hydrogels in the field of BTE. Within materials science, it covers topics such as the binding mechanisms of metal ions within hydrogel networks, the types and fabrication methods of various metal ion-containing hydrogels, and the influence of metal ions on the properties of hydrogels. In the context of BTE, the review delves into the osteogenic mechanisms of various metal ions, the applications of metal ion-containing hydrogels in BTE, and relevant experimental studies in vitro and in vivo. Furthermore, future improvements in bone repair can be anticipated through advancements in bone bionics, exploring interactions between metal ions and the development of a wider range of metal ions and hydrogel types.
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Affiliation(s)
- Shengao Qin
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, P. R. China
- Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Lvshun South Road, Dalian 116044, P. R. China
| | - Yimeng Niu
- School of Stomatology, Dalian Medical University, No. 9 West Section, Lvshunnan Road, Dalian 116044, P. R. China
- Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Lvshun South Road, Dalian 116044, P. R. China
| | - Yihan Zhang
- School of Stomatology, Harbin Medical University, Harbin 150020, P. R. China
| | - Weiyi Wang
- School of Stomatology, Dalian Medical University, No. 9 West Section, Lvshunnan Road, Dalian 116044, P. R. China
- Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Lvshun South Road, Dalian 116044, P. R. China
| | - Jian Zhou
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, P. R. China
- Department of VIP Dental Service, School of Stomatology, Capital Medical University, Beijing 100050, P. R. China
- Laboratory for Oral and General Health Integration and Translation, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P. R. China
| | - Yingjie Bai
- School of Stomatology, Dalian Medical University, No. 9 West Section, Lvshunnan Road, Dalian 116044, P. R. China
- Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Lvshun South Road, Dalian 116044, P. R. China
| | - Guowu Ma
- School of Stomatology, Dalian Medical University, No. 9 West Section, Lvshunnan Road, Dalian 116044, P. R. China
- Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Lvshun South Road, Dalian 116044, P. R. China
- Department of Stomatology, Stomatological Hospital Affiliated School of Stomatology of Dalian Medical University, No. 397 Huangpu Road, Shahekou District, Dalian 116086, P. R. China
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Messaoudi O, Henrionnet C, Courtial EJ, Grossin L, Mainard D, Galois L, Loeuille D, Marquette C, Gillet P, Pinzano A. Increasing Collagen to Bioink Drives Mesenchymal Stromal Cells-Chondrogenesis from Hyaline to Calcified Layers. Tissue Eng Part A 2024; 30:322-332. [PMID: 37885209 DOI: 10.1089/ten.tea.2023.0178] [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: 10/28/2023] Open
Abstract
The bioextrusion of mesenchymal stromal cells (MSCs) directly seeded in a bioink enables the production of three-dimensional (3D) constructs, promoting their chondrogenic differentiation. Our study aimed to evaluate the effect of different type I collagen concentrations in the bioink on MSCs' chondrogenic differentiation. We printed 3D constructs using an alginate, gelatin, and fibrinogen-based bioink cellularized with MSCs, with four different quantities of type I collagen addition (0.0, 0.5, 1.0, and 5.0 mg per bioink syringe). We assessed the influence of the bioprinting process, the bioink composition, and the growth factor (TGF-ꞵ1) on the MSCs' survival rate. We confirmed the biocompatibility of the process and the bioinks' cytocompatibility. We evaluated the chondrogenic effects of TGF-ꞵ1 and collagen addition on the MSCs' chondrogenic properties through macroscopic observation, shrinking ratio, reverse transcription polymerase chain reaction, glycosaminoglycan synthesis, histology, and type II collagen immunohistochemistry. The bioink containing 0.5 mg of collagen produces the richest hyaline-like extracellular matrix, presenting itself as a promising tool to recreate the superficial layer of hyaline cartilage. The bioink containing 5.0 mg of collagen enhances the synthesis of a calcified matrix, making it a good candidate for mimicking the calcified cartilaginous layer. Type I collagen thus allows the dose-dependent design of specific hyaline cartilage layers.
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Affiliation(s)
| | | | - Edwin-Joffrey Courtial
- Plateforme 3D Fab, UMR 5246 CNRS Université de Lyon, INSA, CPE-Lyon, ICBMS, Villeurbanne, France
| | | | - Didier Mainard
- Université de Lorraine, CNRS, IMoPA, Nancy, France
- Department of Orthopedic Surgery, University Hospital of Nancy, Nancy, France
| | - Laurent Galois
- Université de Lorraine, CNRS, IMoPA, Nancy, France
- Department of Orthopedic Surgery, University Hospital of Nancy, Nancy, France
| | - Damien Loeuille
- Université de Lorraine, CNRS, IMoPA, Nancy, France
- Department of Rheumatology and Toxicology & Pharmacovigilance, University Hospital of Nancy, Vandœuvre-Lès-Nancy, France
| | - Christophe Marquette
- Plateforme 3D Fab, UMR 5246 CNRS Université de Lyon, INSA, CPE-Lyon, ICBMS, Villeurbanne, France
| | - Pierre Gillet
- Université de Lorraine, CNRS, IMoPA, Nancy, France
- Department of Pharmacology, Toxicology & Pharmacovigilance, University Hospital of Nancy, Vandœuvre-Lès-Nancy, France
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Wu Y, Yang X, Gupta D, Alioglu MA, Qin M, Ozbolat V, Li Y, Ozbolat IT. Dissecting the Interplay Mechanism among Process Parameters toward the Biofabrication of High-Quality Shapes in Embedded Bioprinting. ADVANCED FUNCTIONAL MATERIALS 2024; 34:2313088. [PMID: 38952568 PMCID: PMC11216718 DOI: 10.1002/adfm.202313088] [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: 10/23/2023] [Indexed: 07/03/2024]
Abstract
Embedded bioprinting overcomes the barriers associated with the conventional extrusion-based bioprinting process as it enables the direct deposition of bioinks in 3D inside a support bath by providing in situ self-support for deposited bioinks during bioprinting to prevent their collapse and deformation. Embedded bioprinting improves the shape quality of bioprinted constructs made up of soft materials and low-viscosity bioinks, leading to a promising strategy for better anatomical mimicry of tissues or organs. Herein, the interplay mechanism among the printing process parameters toward improved shape quality is critically reviewed. The impact of material properties of the support bath and bioink, printing conditions, cross-linking mechanisms, and post-printing treatment methods, on the printing fidelity, stability, and resolution of the structures is meticulously dissected and thoroughly discussed. Further, the potential scope and applications of this technology in the fields of bioprinting and regenerative medicine are presented. Finally, outstanding challenges and opportunities of embedded bioprinting as well as its promise for fabricating functional solid organs in the future are discussed.
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Affiliation(s)
- Yang Wu
- School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518055, China
| | - Xue Yang
- School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518055, China
| | - Deepak Gupta
- The Huck Institutes of the Life Sciences, Penn State University University Park, PA 16802, USA
- Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA
| | - Mecit Altan Alioglu
- The Huck Institutes of the Life Sciences, Penn State University University Park, PA 16802, USA
- Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA
| | - Minghao Qin
- School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518055, China
| | - Veli Ozbolat
- Biotechnology Research and Application Center, Cukurova University, Adana 01130, Turkey
- Ceyhan Engineering Faculty, Mechanical Engineering Department, Cukurova University, Adana 01330, Turkey
- Institute of Natural and Applied Sciences, Tissue Engineering Department, Cukurova University, Adana 01130, Turkey
| | - Yao Li
- School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518055, China
| | - Ibrahim T Ozbolat
- The Huck Institutes of the Life Sciences, Penn State University University Park, PA 16802, USA
- Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA
- Department of Biomedical Engineering, Penn State University, University Park, PA 16802, USA
- Materials Research Institute, Penn State University, University Park, PA 16802, USA
- Department of Neurosurgery, Penn State College of Medicine, Hershey, PA 17033, USA
- Penn State Cancer Institute, Penn State University, Hershey, PA 17033, USA
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41
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Wei Q, An Y, Zhao X, Li M, Zhang J. Three-dimensional bioprinting of tissue-engineered skin: Biomaterials, fabrication techniques, challenging difficulties, and future directions: A review. Int J Biol Macromol 2024; 266:131281. [PMID: 38641503 DOI: 10.1016/j.ijbiomac.2024.131281] [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: 12/31/2023] [Revised: 03/17/2024] [Accepted: 03/29/2024] [Indexed: 04/21/2024]
Abstract
As an emerging new manufacturing technology, Three-dimensional (3D) bioprinting provides the potential for the biomimetic construction of multifaceted and intricate architectures of functional integument, particularly functional biomimetic dermal structures inclusive of cutaneous appendages. Although the tissue-engineered skin with complete biological activity and physiological functions is still cannot be manufactured, it is believed that with the advances in matrix materials, molding process, and biotechnology, a new generation of physiologically active skin will be born in the future. In pursuit of furnishing readers and researchers involved in relevant research to have a systematic and comprehensive understanding of 3D printed tissue-engineered skin, this paper furnishes an exegesis on the prevailing research landscape, formidable obstacles, and forthcoming trajectories within the sphere of tissue-engineered skin, including: (1) the prevalent biomaterials (collagen, chitosan, agarose, alginate, etc.) routinely employed in tissue-engineered skin, and a discerning analysis and comparison of their respective merits, demerits, and inherent characteristics; (2) the underlying principles and distinguishing attributes of various current printing methodologies utilized in tissue-engineered skin fabrication; (3) the present research status and progression in the realm of tissue-engineered biomimetic skin; (4) meticulous scrutiny and summation of the extant research underpinning tissue-engineered skin inform the identification of prevailing challenges and issues.
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Affiliation(s)
- Qinghua Wei
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China; Innovation Center NPU Chongqing, Northwestern Polytechnical University, Chongqing 400000, China.
| | - Yalong An
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| | - Xudong Zhao
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| | - Mingyang Li
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| | - Juan Zhang
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
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42
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Kosowska K, Korycka P, Jankowska-Snopkiewicz K, Gierałtowska J, Czajka M, Florys-Jankowska K, Dec M, Romanik-Chruścielewska A, Małecki M, Westphal K, Wszoła M, Klak M. Graphene Oxide (GO)-Based Bioink with Enhanced 3D Printability and Mechanical Properties for Tissue Engineering Applications. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:760. [PMID: 38727354 PMCID: PMC11085087 DOI: 10.3390/nano14090760] [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: 04/24/2024] [Indexed: 05/13/2024]
Abstract
Currently, a major challenge in material engineering is to develop a cell-safe biomaterial with significant utility in processing technology such as 3D bioprinting. The main goal of this work was to optimize the composition of a new graphene oxide (GO)-based bioink containing additional extracellular matrix (ECM) with unique properties that may find application in 3D bioprinting of biomimetic scaffolds. The experimental work evaluated functional properties such as viscosity and complex modulus, printability, mechanical strength, elasticity, degradation and absorbability, as well as biological properties such as cytotoxicity and cell response after exposure to a biomaterial. The findings demonstrated that the inclusion of GO had no substantial impact on the rheological properties and printability, but it did enhance the mechanical properties. This enhancement is crucial for the advancement of 3D scaffolds that are resilient to deformation and promote their utilization in tissue engineering investigations. Furthermore, GO-based hydrogels exhibited much greater swelling, absorbability and degradation compared to non-GO-based bioink. Additionally, these biomaterials showed lower cytotoxicity. Due to its properties, it is recommended to use bioink containing GO for bioprinting functional tissue models with the vascular system, e.g., for testing drugs or hard tissue models.
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Affiliation(s)
- Katarzyna Kosowska
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
- Polbionica Sp. z o.o., 01-793 Warsaw, Poland
| | - Paulina Korycka
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
| | - Kamila Jankowska-Snopkiewicz
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
| | - Joanna Gierałtowska
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
| | - Milena Czajka
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
- Polbionica Sp. z o.o., 01-793 Warsaw, Poland
| | - Katarzyna Florys-Jankowska
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
| | - Magdalena Dec
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
- Polbionica Sp. z o.o., 01-793 Warsaw, Poland
| | - Agnieszka Romanik-Chruścielewska
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
| | - Maciej Małecki
- Department of Applied Pharmacy, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland;
- Laboratory of Gene Therapy, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland
| | - Kinga Westphal
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
- Center for Alzheimer’s and Neurodegenerative Diseases, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, 6124 Harry Hines Blvd., Dallas, TX 75390, USA
| | - Michał Wszoła
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
- Polbionica Sp. z o.o., 01-793 Warsaw, Poland
- Medispace Medical Centre, 01-044 Warsaw, Poland
| | - Marta Klak
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (P.K.); (K.J.-S.); (J.G.); (M.C.); (K.F.-J.); (M.D.); (A.R.-C.); (K.W.); (M.W.)
- Polbionica Sp. z o.o., 01-793 Warsaw, Poland
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Ahmad N, Bukhari SNA, Hussain MA, Ejaz H, Munir MU, Amjad MW. Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends. RSC Adv 2024; 14:13535-13564. [PMID: 38665493 PMCID: PMC11043667 DOI: 10.1039/d4ra00631c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 04/01/2024] [Indexed: 04/28/2024] Open
Abstract
The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed.
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Affiliation(s)
- Naveed Ahmad
- Department of Pharmaceutics, College of Pharmacy, Jouf University Sakaka 72388 Aljouf Saudi Arabia
| | - Syed Nasir Abbas Bukhari
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University Sakaka 72388 Aljouf Saudi Arabia
| | - Muhammad Ajaz Hussain
- Centre for Organic Chemistry, School of Chemistry, University of the Punjab Lahore 54590 Pakistan
| | - Hasan Ejaz
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University Sakaka 72388 Aljouf Saudi Arabia
| | - Muhammad Usman Munir
- Australian Institute for Bioengineering & Nanotechnology, The University of Queensland Brisbane Queens-land 4072 Australia
| | - Muhammad Wahab Amjad
- 6 Center for Ultrasound Molecular Imaging and Therapeutics, School of Medicine, University of Pittsburgh 15213 Pittsburgh Pennsylvania USA
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Mamidi N, Ijadi F, Norahan MH. Leveraging the Recent Advancements in GelMA Scaffolds for Bone Tissue Engineering: An Assessment of Challenges and Opportunities. Biomacromolecules 2024; 25:2075-2113. [PMID: 37406611 DOI: 10.1021/acs.biomac.3c00279] [Citation(s) in RCA: 29] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2023]
Abstract
The field of bone tissue engineering has seen significant advancements in recent years. Each year, over two million bone transplants are performed globally, and conventional treatments, such as bone grafts and metallic implants, have their limitations. Tissue engineering offers a new level of treatment, allowing for the creation of living tissue within a biomaterial framework. Recent advances in biomaterials have provided innovative approaches to rebuilding bone tissue function after damage. Among them, gelatin methacryloyl (GelMA) hydrogel is emerging as a promising biomaterial for supporting cell proliferation and tissue regeneration, and GelMA has exhibited exceptional physicochemical and biological properties, making it a viable option for clinical translation. Various methods and classes of additives have been used in the application of GelMA for bone regeneration, with the incorporation of nanofillers or other polymers enhancing its resilience and functional performance. Despite promising results, the fabrication of complex structures that mimic the bone architecture and the provision of balanced physical properties for both cell and vasculature growth and proper stiffness for load bearing remain as challenges. In terms of utilizing osteogenic additives, the priority should be on versatile components that promote angiogenesis and osteogenesis while reinforcing the structure for bone tissue engineering applications. This review focuses on recent efforts and advantages of GelMA-based composite biomaterials for bone tissue engineering, covering the literature from the last five years.
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Affiliation(s)
- Narsimha Mamidi
- Department of Chemistry and Nanotechnology, School of Engineering and Science, Tecnológico de Monterrey, Monterrey, Nuevo León 64849, México
- Wisconsin Center for NanoBioSystems, School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, United States
| | - Fatemeh Ijadi
- Department of Chemistry and Nanotechnology, School of Engineering and Science, Tecnológico de Monterrey, Monterrey, Nuevo León 64849, México
| | - Mohammad Hadi Norahan
- Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Monterrey, Nuevo León 64849, México
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Ramezani G, Stiharu I, van de Ven TGM, Nerguizian V. Advancements in Hybrid Cellulose-Based Films: Innovations and Applications in 2D Nano-Delivery Systems. J Funct Biomater 2024; 15:93. [PMID: 38667550 PMCID: PMC11051498 DOI: 10.3390/jfb15040093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 03/29/2024] [Accepted: 03/31/2024] [Indexed: 04/28/2024] Open
Abstract
This review paper delves into the realm of hybrid cellulose-based materials and their applications in 2D nano-delivery systems. Cellulose, recognized for its biocompatibility, versatility, and renewability, serves as the core matrix for these nanomaterials. The paper offers a comprehensive overview of the latest advancements in the creation, analysis, and application of these materials, emphasizing their significance in nanotechnology and biomedical domains. It further illuminates the integration of nanomaterials and advanced synthesis techniques that have significantly improved the mechanical, chemical, and biological properties of hybrid cellulose-based materials.
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Affiliation(s)
- Ghazaleh Ramezani
- Department of Mechanical, Industrial, and Aerospace Engineering, Concordia University, Montreal, QC H3G 1M8, Canada;
| | - Ion Stiharu
- Department of Mechanical, Industrial, and Aerospace Engineering, Concordia University, Montreal, QC H3G 1M8, Canada;
| | - Theo G. M. van de Ven
- Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada;
| | - Vahe Nerguizian
- Department of Electrical Engineering, École de Technologie Supérieure, 1100 Notre Dame West, Montreal, QC H3C 1K3, Canada;
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Khatri NR, Egan PF. Energy Absorption of 3D Printed ABS and TPU Multimaterial Honeycomb Structures. 3D PRINTING AND ADDITIVE MANUFACTURING 2024; 11:e840-e850. [PMID: 38689900 PMCID: PMC11057531 DOI: 10.1089/3dp.2022.0196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
Advances in multimaterial 3D printing are enabling the construction of advantageous engineering structures that benefit from material synergies. Cellular structures, such as honeycombs, provide high-energy absorption to weight ratios that could benefit from multimaterial strategies to improve the safety and performance of engineered systems. In this study, we investigate the energy absorption for honeycombs with square and hexagonal unit cells constructed from acrylonitrile butadiene styrene (ABS) and thermoplastic polyurethane (TPU). Honeycombs were fabricated and tested for out-of-plane and in-plane compression using ABS, TPU, and a combination of ABS with a central TPU band of tunable height. Out-of-plane energy absorption for square honeycombs increased from 2.2 kN·mm for TPU samples to 11.5 kN·mm for ABS samples and energy absorption of hexagonal honeycombs increased from 2.9 to 15.1 kN·mm as proportions of TPU/ABS were altered. In-plane loading demonstrated a sequential collapse of unit cell rows in square honeycombs with energy absorption of 0.1 to 2.6 kN·mm and a gradual failure of hexagonal honeycombs with energy absorption of 0.6 to 2.0 kN·mm. These results demonstrate how multimaterial combinations affect honeycomb compressive response by highlighting their benefits for controlled energy absorption and deformation for tunable performance in diverse engineering applications.
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Affiliation(s)
- Nava Raj Khatri
- Department of Mechanical Engineering, Texas Tech University, Lubbock, Texas, USA
| | - Paul F. Egan
- Department of Mechanical Engineering, Texas Tech University, Lubbock, Texas, USA
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Maghsoudi MAF, Aghdam RM, Asbagh RA, Moghaddaszadeh A, Ghaee A, Tafti SMA, Foroutani L, Tafti SHA. 3D-printing of alginate/gelatin scaffold loading tannic acid@ZIF-8 for wound healing: In vitro and in vivo studies. Int J Biol Macromol 2024; 265:130744. [PMID: 38493825 DOI: 10.1016/j.ijbiomac.2024.130744] [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: 10/17/2023] [Revised: 03/06/2024] [Accepted: 03/07/2024] [Indexed: 03/19/2024]
Abstract
In the present study, ZIF-8 metal-organic framework (MOF) modified with Tannic acid (TA@ZIF-8) was synthesized and impregnated in alginate-gelatin (Alg-Gel) hydrogel. The Alg-Gel scaffolds containing 0, 5, and 10 % of TA@ZIF-8 were fabricated through the 3D printing method specifically denoted as Alg-Gel 0 %, Alg-Gel 5 %, and Alg-Gel 10 %. XRD, FTIR, FESEM, and EDX physically and chemically characterized the synthesized ZIF-8 and TA@ZIF-8 MOFs. Besides, Alg-Gel containing TA@ZIF-8 prepared scaffolds and their biological activity were also evaluated. SEM images verified the nano-size formation of MOFs. Improved swelling and decreased degradation rates after adding TA@ZIF-8 were also reported. Increased compression strength from 0.628 to 1.63 MPa in Alg-Gel 0 % and Alg-Gel 10 %, respectively, and a 2.19 increase in elastic modulus in Alg-Gel 10 % scaffolds were exhibited. Biological activity of scaffolds, including Live-dead and Cell adhesion, antibacterial, in-vivo, and immunohistochemistry assays, demonstrated desirable fibroblast cell proliferation and adhesion, increased bacterial growth inhibition zone, accelerated wound closure and improved expression of anti-inflammatory cytokines in Alg-Gel 10 % scaffolds. The findings of this study confirm that Alg-Gel 10 % scaffolds promote full-thickness wound healing and could be considered a potential candidate for full-thickness wound treatment purposes.
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Affiliation(s)
| | | | - Reza Akbari Asbagh
- Research Center for Advanced Technologies In Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Moghaddaszadeh
- School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | - Azadeh Ghaee
- Faculty of New Science and Technologies, University of Tehran, Tehran, Iran
| | - Seyed Mohsen Ahmadi Tafti
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Science, Tehran, Iran
| | - Laleh Foroutani
- Research Center for Advanced Technologies In Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Hossein Ahmadi Tafti
- Research Center for Advanced Technologies In Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Khiari Z. Recent Developments in Bio-Ink Formulations Using Marine-Derived Biomaterials for Three-Dimensional (3D) Bioprinting. Mar Drugs 2024; 22:134. [PMID: 38535475 PMCID: PMC10971850 DOI: 10.3390/md22030134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/12/2024] [Accepted: 03/13/2024] [Indexed: 05/01/2024] Open
Abstract
3D bioprinting is a disruptive, computer-aided, and additive manufacturing technology that allows the obtention, layer-by-layer, of 3D complex structures. This technology is believed to offer tremendous opportunities in several fields including biomedical, pharmaceutical, and food industries. Several bioprinting processes and bio-ink materials have emerged recently. However, there is still a pressing need to develop low-cost sustainable bio-ink materials with superior qualities (excellent mechanical, viscoelastic and thermal properties, biocompatibility, and biodegradability). Marine-derived biomaterials, including polysaccharides and proteins, represent a viable and renewable source for bio-ink formulations. Therefore, the focus of this review centers around the use of marine-derived biomaterials in the formulations of bio-ink. It starts with a general overview of 3D bioprinting processes followed by a description of the most commonly used marine-derived biomaterials for 3D bioprinting, with a special attention paid to chitosan, glycosaminoglycans, alginate, carrageenan, collagen, and gelatin. The challenges facing the application of marine-derived biomaterials in 3D bioprinting within the biomedical and pharmaceutical fields along with future directions are also discussed.
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Affiliation(s)
- Zied Khiari
- National Research Council of Canada, Aquatic and Crop Resource Development Research Centre, 1411 Oxford Street, Halifax, NS B3H 3Z1, Canada
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Amaya-Rivas JL, Perero BS, Helguero CG, Hurel JL, Peralta JM, Flores FA, Alvarado JD. Future trends of additive manufacturing in medical applications: An overview. Heliyon 2024; 10:e26641. [PMID: 38444512 PMCID: PMC10912264 DOI: 10.1016/j.heliyon.2024.e26641] [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: 12/13/2022] [Revised: 12/07/2023] [Accepted: 02/16/2024] [Indexed: 03/07/2024] Open
Abstract
Additive Manufacturing (AM) has recently demonstrated significant medical progress. Due to advancements in materials and methodologies, various processes have been developed to cater to the medical sector's requirements, including bioprinting and 4D, 5D, and 6D printing. However, only a few studies have captured these emerging trends and their medical applications. Therefore, this overview presents an analysis of the advancements and achievements obtained in AM for the medical industry, focusing on the principal trends identified in the annual report of AM3DP.
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Affiliation(s)
- Jorge L. Amaya-Rivas
- Advanced Manufacturing and Prototyping Laboratory (CAMPRO), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
- Faculty of Mechanical Engineering and Production Sciences (FIMCP), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
| | - Bryan S. Perero
- Faculty of Mechanical Engineering and Production Sciences (FIMCP), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
| | - Carlos G. Helguero
- Advanced Manufacturing and Prototyping Laboratory (CAMPRO), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
- Faculty of Mechanical Engineering and Production Sciences (FIMCP), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
| | - Jorge L. Hurel
- Faculty of Mechanical Engineering and Production Sciences (FIMCP), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
| | - Juan M. Peralta
- Faculty of Mechanical Engineering and Production Sciences (FIMCP), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
| | - Francisca A. Flores
- Faculty of Natural Sciences and Mathematics (FCNM), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
| | - José D. Alvarado
- Faculty of Mechanical Engineering and Production Sciences (FIMCP), ESPOL Polytechnic University, Km 30.5 Vía Perimetral, P.O. Box: 09-01-5863, Guayaquil, Ecuador
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50
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Jain N, Shashi Bhushan BL, Natarajan M, Mehta R, Saini DK, Chatterjee K. Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks. ACS Biomater Sci Eng 2024; 10:1235-1261. [PMID: 38335198 DOI: 10.1021/acsbiomaterials.3c01499] [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: 02/12/2024]
Abstract
Fibrosis has been characterized as a global health problem and ranks as one of the primary causes of organ dysfunction. Currently, there is no cure for pulmonary fibrosis, and limited therapeutic options are available due to an inadequate understanding of the disease pathogenesis. The absence of advanced in vitro models replicating dynamic temporal changes observed in the tissue with the progression of the disease is a significant impediment in the development of novel antifibrotic treatments, which has motivated research on tissue-mimetic three-dimensional (3D) models. In this review, we summarize emerging trends in preparing advanced lung models to recapitulate biochemical and biomechanical processes associated with lung fibrogenesis. We begin by describing the importance of in vivo studies and highlighting the often poor correlation between preclinical research and clinical outcomes and the limitations of conventional cell culture in accurately simulating the 3D tissue microenvironment. Rapid advancement in biomaterials, biofabrication, biomicrofluidics, and related bioengineering techniques are enabling the preparation of in vitro models to reproduce the epithelium structure and operate as reliable drug screening strategies for precise prediction. Improving and understanding these model systems is necessary to find the cross-talks between growing cells and the stage at which myofibroblasts differentiate. These advanced models allow us to utilize the knowledge and identify, characterize, and hand pick medicines beneficial to the human community. The challenges of the current approaches, along with the opportunities for further research with potential for translation in this field, are presented toward developing novel treatments for pulmonary fibrosis.
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Affiliation(s)
- Nipun Jain
- Department of Materials Engineering, Indian Institute of Science, C.V Raman Avenue, Bangalore 560012 India
| | - B L Shashi Bhushan
- Department of Pulmonary Medicine, Victoria Hospital, Bangalore Medical College and Research Institute, Bangalore 560002 India
| | - M Natarajan
- Department of Pathology, Victoria Hospital, Bangalore Medical College and Research Institute, Bangalore 560002 India
| | - Ravi Mehta
- Department of Pulmonology and Critical Care, Apollo Hospitals, Jayanagar, Bangalore 560011 India
| | - Deepak Kumar Saini
- Department of Developmental Biology and Genetics, Indian Institute of Science, C.V Raman Avenue, Bangalore 560012 India
| | - Kaushik Chatterjee
- Department of Materials Engineering, Indian Institute of Science, C.V Raman Avenue, Bangalore 560012 India
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