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Zhu S, Diao S, Liu X, Zhang Z, Liu F, Chen W, Lu X, Luo H, Cheng X, Liao Q, Li Z, Chen J. Biomaterial-based strategies: a new era in spinal cord injury treatment. Neural Regen Res 2025; 20:3476-3500. [PMID: 40095657 PMCID: PMC11974648 DOI: 10.4103/nrr.nrr-d-24-00844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/02/2024] [Accepted: 12/16/2024] [Indexed: 03/19/2025] Open
Abstract
Enhancing neurological recovery and improving the prognosis of spinal cord injury have gained research attention recently. Spinal cord injury is associated with a complex molecular and cellular microenvironment. This complexity has prompted researchers to elucidate the underlying pathophysiological mechanisms and changes and to identify effective treatment strategies. Traditional approaches for spinal cord injury repair include surgery, oral or intravenous medications, and administration of neurotrophic factors; however, the efficacy of these approaches remains inconclusive, and serious adverse reactions continue to be a concern. With advancements in tissue engineering and regenerative medicine, emerging strategies for spinal cord injury repair now involve nanoparticle-based nanodelivery systems, scaffolds, and functional recovery techniques that incorporate biomaterials, bioengineering, stem cell, and growth factors as well as three-dimensional bioprinting. Ideal biomaterial scaffolds should not only provide structural support for neuron migration, adhesion, proliferation, and differentiation but also mimic the mechanical properties of natural spinal cord tissue. Additionally, these scaffolds should facilitate axon growth and neurogenesis by offering adjustable topography and a range of physical and biochemical cues. The three-dimensionally interconnected porous structure and appropriate physicochemical properties enabled by three-dimensional biomimetic printing technology can maximize the potential of biomaterials used for treating spinal cord injury. Therefore, correct selection and application of scaffolds, coupled with successful clinical translation, represent promising clinical objectives to enhance the treatment efficacy for and prognosis of spinal cord injury. This review elucidates the key mechanisms underlying the occurrence of spinal cord injury and regeneration post-injury, including neuroinflammation, oxidative stress, axon regeneration, and angiogenesis. This review also briefly discusses the critical role of nanodelivery systems used for repair and regeneration of injured spinal cord, highlighting the influence of nanoparticles and the factors that affect delivery efficiency. Finally, this review highlights tissue engineering strategies and the application of biomaterial scaffolds for the treatment of spinal cord injury. It discusses various types of scaffolds, their integrations with stem cells or growth factors, and approaches for optimization of scaffold design.
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Affiliation(s)
- Shihong Zhu
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
| | - Sijun Diao
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaoyin Liu
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhujun Zhang
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
| | - Fujun Liu
- Department of Ophthalmology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Wei Chen
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiyue Lu
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Huiyang Luo
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xu Cheng
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qiang Liao
- Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhongyu Li
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
| | - Jing Chen
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
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Liu YB, Liu X, Li XF, Qiao L, Wang HL, Dong YF, Zhang F, Liu Y, Liu HY, Ji ML, Li L, Jiang Q, Lu J. Multifunctional piezoelectric hydrogels under ultrasound stimulation boost chondrogenesis by recruiting autologous stem cells and activating the Ca 2+/CaM/CaN signaling pathway. Bioact Mater 2025; 50:344-363. [PMID: 40297641 PMCID: PMC12036080 DOI: 10.1016/j.bioactmat.2025.04.009] [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: 01/20/2025] [Revised: 03/25/2025] [Accepted: 04/10/2025] [Indexed: 04/30/2025] Open
Abstract
Articular cartilage, owing to the lack of undifferentiated stem cells after injury, faces significant challenges in reconstruction and repair, making it a major clinical challenge. Therefore, there is an urgent need to design a multifunctional hydrogels capable of recruiting autologous stem cells to achieve in situ cartilage regeneration. Here, our study investigated the potential of a piezoelectric hydrogel (Hyd6) for enhancing cartilage regeneration through ultrasound (US) stimulation. Hyd6 has multiple properties including injectability, self-healing capabilities, and piezoelectric characteristics. These properties synergistically promote stem cell chondrogenesis. The fabrication and characterization of Hyd6 revealed its excellent biocompatibility, biodegradability, and electromechanical conversion capabilities. In vitro and in vivo experiments revealed that Hyd6, when combined with US stimulation, significantly promotes the recruitment of autologous stem cells and enhances chondrogenesis by generating electrical signals that promote the influx of Ca2+, activating downstream CaM/CaN signaling pathways and accelerating cartilage formation. An in vivo study in a rabbit model of chondral defects revealed that Hyd6 combined with US treatment significantly improved cartilage regeneration, as evidenced by better integration of the regenerated tissue with the surrounding cartilage, greater collagen type II expression, and improved mechanical properties. The results highlight the potential of Hyd6 as a novel therapeutic approach for treating cartilage injuries, offering a self-powered, noninvasive, and effective strategy for tissue engineering and regenerative medicine.
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Affiliation(s)
- Yu-Bao Liu
- The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Xu Liu
- Department of Orthopedics, The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, 225009, China
- Orthopedics Department, Nanjing Drum Tower Hospital & Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Suqian, 223800, China
| | - Xiao-Fei Li
- The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Liang Qiao
- Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Hao-Liang Wang
- The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Yue-Fu Dong
- Department of Joint Surgery, The First People's Hospital of Lianyungang City, Lianyungang, 222000, China
| | - Feng Zhang
- Orthopedics Department, Xuyi County People's Hospital, Huai'an, 211700, China
| | - Yang Liu
- Orthopedics Department, Dan Yang Third People's Hospital, Zhenjiang, 212300, China
| | - Hao-Yang Liu
- The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Ming-Liang Ji
- The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Lan Li
- Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
- Institute of Medical 3D Printing, Nanjing University, Nanjing, 210093, China
| | - Qing Jiang
- Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
- Institute of Medical 3D Printing, Nanjing University, Nanjing, 210093, China
| | - Jun Lu
- The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
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Wahba NKO, Bahnasy SSEL, ElMakawi YM, Dummer PMH, Nagendrababu V, Rossi-Fedele G, Sans FA, Pasqualini D, Alovisi M, Turky M, Ahmed EF, Elheeny AAH. Change in the size of apical radiolucencies in adolescent's mature maxillary incisors following retreatment with two regenerative endodontic techniques: a 12-month randomised clinical trial using volume-based cone-beam computed tomography. Clin Oral Investig 2025; 29:283. [PMID: 40319119 PMCID: PMC12049306 DOI: 10.1007/s00784-025-06344-y] [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: 01/13/2025] [Accepted: 04/14/2025] [Indexed: 05/07/2025]
Abstract
OBJECTIVES The primary aim of this randomised clinical trial was to compare the one year clinical and radiographic outcome of mature permanent central incisors with periapical radiolucencies in adolescents after root canal retreatment using two regenerative endodontic procedures (REPs) with revitalization using induced blood clot formation (BC) or platelet-rich fibrin (PRF) evaluated with cone-beam computed tomography (CBCT). The secondary aim was to assess the responses of the teeth to thermal and electric pulp tests. MATERIALS AND METHODS Fifty-four root filled maxillary central incisors with post-treatment endodontic disease and periapical radiolucencies in 48 adolescents were allocated into two groups (n = 27) using permuted block randomisation. The teeth in one group were root canal retreated with induced BC formation and teeth in the other with PRF. At baseline and at one year, teeth were evaluated clinically and radiographically using periapical radiographs and CBCT scans. Changes in the maximum diameter and volume of the periapical lesions were assessed and pulp sensibility was assessed at one year using thermal and electrical tests. Differences in lesion diameter and volume between the two groups were tested using the Mann-Whitney U test. A linear regression model explored the relationship between independent variables and lesion size. The significant level was set at 5%. RESULTS Reduction in periapical lesion size in the BC and PRF techniques occurred in 85% and 100% of teeth, respectively, with no significant difference. In the BC group, the mean lesion volume diminished from 0.33 ± 0.18 cm3 to 0.13 ± 0.20 cm3, while the mean volume of lesions in the PRF group decreased from 0.27 ± 0.16 cm3 to 0.04 ± 0.06 cm3 with no significant difference between the groups (P > 0.05). Significantly more teeth responded positively to thermal (P = 0.028) and electric (P = 0.032) tests in the PRF group compared to the BC group. CONCLUSIONS REPs using BC or PRF techniques when retreating root canal-treated mature permanent central incisors in adolescents with apical radiolucencies had comparable clinical and radiographic outcomes one year following treatment associated with significantly more positive responses to thermal and electric pulp tests in the PRF group. CLINICAL RELEVANCE Retreatment of mature permanent teeth with apical periodontitis using regenerative endodontic procedures (REPs) is a new and promising approach. REPs with platelet-rich fibrin (PRF) and revascularization techniques provided high and comparable clinical and radiographic success rates.
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Affiliation(s)
- Norhan Khaled Omar Wahba
- Demonstrator of Paediatric and Community Dentistry, Faculty of Oral and Dental Medicine, Nahda University, New Bani Suef, Egypt
| | - Sherif Shafik E L Bahnasy
- Lecturer of Oral Radiology, Faculty of Dentistry, The British University in Egypt, Al Shorouk City, Egypt
| | - Yassmin Mohamed ElMakawi
- Lecturer of Paediatric and Community Dentistry, Faculty of Oral and Dental Medicine, Nahda University, New Bani Suef, Egypt
| | - Paul M H Dummer
- School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
| | - Venkateshbabu Nagendrababu
- Department of Preventive and Restorative Dentistry, College of Dental Medicine, University of Sharjah, Sharjah, UAE
| | | | - Francesc Abella Sans
- Department of Endodontics, School of Dentistry, Universitat International de Catalunya, Sant Cugat del Valles, Barcelona, Spain
| | - Damiano Pasqualini
- Department of Surgical Sciences, Dental School, University of Turin, Turin, Italy
| | - Mario Alovisi
- Department of Surgical Sciences, Dental School, University of Turin, Turin, Italy
| | - Mohammed Turky
- Department of Endodontics, Faculty of Dentistry, Minia University, Minia, Egypt
- Department of Endodontics, Faculty of Dentistry, Sphinx University, Assiut, Egypt
| | - Eman Farouk Ahmed
- Microbiology and Immunology Department, Faculty of Pharmacy, Sohag University, Sohag, 82524, Province, Egypt
| | - Ahmad Abdel Hamid Elheeny
- Paediatric and Community Dentistry, Faculty of Dentistry, Minia University, Province, 61519, Minya, Egypt.
- Paediatric and Community Dentistry, Faculty of Dentistry, Sphinx University, Asyut Al Gadida City, Egypt.
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Cho J, Park JJ, Seo E, Lee OH, Cho TJ, Kim JY, Bae HC, Lee E, Park Y, Jang H, Sun W, Han HS, Lee DS. Self-assembled organoid-tissue modules for scalable organoid engineering: Application to chondrogenic regeneration. Acta Biomater 2025; 197:152-166. [PMID: 40097127 DOI: 10.1016/j.actbio.2025.03.028] [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: 09/20/2024] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 03/19/2025]
Abstract
Tissue engineering has made significant strides in creating biomimetic grafts for the repair and regeneration of damaged tissues; however, the scalability of engineered tissue constructs remains a major technical hurdle. This study introduces a method for generating organoid-tissue modules (Organoid-TMs) through scaffold-free self-assembly of microblocks (MiBs) derived from adipose-derived mesenchymal stem cells (ADMSCs). The key parameters influencing Organoid-TM formation were identified as the density of MiBs and the controlled mixing ratio of large and small MiBs. The resulting Organoid-TM exhibited a distinctive cup-shaped morphology, a millimeter-scale structure with enhanced nutrient and oxygen diffusion compared to conventional spherical aggregates. Despite their larger size, Organoid-TMs maintained ADMSC stemness and differentiation potential, while stemness and differentiation were halted during fabrication. Organoid-TMs receiving chondrogenic cues during fabrication were transplanted into cartilage defect sites in animal models, demonstrating cartilage regeneration efficacy in a scaffold-independent and xeno-free manner. This fabrication method represents a highly reproducible and consistent process for developing spheroids or organoids, offering a robust platform for regenerative medicine applications. Specifically, Organoid-TMs provide a foundational framework for therapeutic strategies targeting cartilage defects and osteoarthritis, paving the way for advancements in tissue-engineered therapeutics. STATEMENT OF SIGNIFICANCE: This study introduces a distinct approach in tissue engineering, utilizing self-assembled Organoid-Tissue Modules (Organoid-TMs) to address persistent challenges in scalable organoid production and cartilage regeneration. By leveraging adipose-derived mesenchymal stem cells (ADMSCs) and carefully optimizing the size, ratio, and spatial organization of microblocks (MiBs), we successfully generated millimeter-scale Organoid-TMs. The distinctive cup-shaped architecture of these Organoid-TMs enhances oxygen and nutrient diffusion, effectively overcoming limitations such as core necrosis typically encountered in large-scale organoid culture. This system demonstrated substantial regenerative potential, particularly in chondrogenic differentiation and cartilage repair in both rabbit and pig models, without the use of artificial scaffolds or xenogenic materials.
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Affiliation(s)
- Jaejin Cho
- Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea; Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
| | - Jin Ju Park
- Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea; Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea
| | - Eunjeong Seo
- Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea; Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea
| | - Ok-Hee Lee
- Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea; Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea
| | - Tae-Jun Cho
- Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea; Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea
| | - Ji Yoon Kim
- Department of Orthopedic Surgery, College of Medicine, Seoul National University 101, Seoul, 03080, Republic of Korea
| | - Hyun Cheol Bae
- Department of Orthopedic Surgery, College of Medicine, Seoul National University 101, Seoul, 03080, Republic of Korea
| | - Eunsoo Lee
- Fluorescence Core Imaging Center (FCIC), Bioimaging Data Curation Center (BDCC), Ewha Womans University, Seoul 03760, Republic of Korea
| | - Yongdoo Park
- Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Hwanseok Jang
- Department of Mechanical Engineering, Korea University College of Engineering, Seoul 02841, Republic of Korea
| | - Woong Sun
- Department of Anatomy, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Hyuk-Soo Han
- Department of Orthopedic Surgery, College of Medicine, Seoul National University 101, Seoul, 03080, Republic of Korea
| | - Dong-Sup Lee
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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Meshry N, Carneiro KMM. DNA as a promising biomaterial for bone regeneration and potential mechanisms of action. Acta Biomater 2025; 197:68-86. [PMID: 40090507 DOI: 10.1016/j.actbio.2025.03.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 02/25/2025] [Accepted: 03/13/2025] [Indexed: 03/18/2025]
Abstract
DNA nanotechnology has created new possibilities for the use of DNA in tissue regeneration - an important advance for DNA use beyond its paradigmatic role as the hereditary biomacromolecule. Biomaterials containing synthetic or natural DNA have been proposed for several applications including drug and gene delivery, and more recently, as osteoconductive biomaterials. This review provides an in-depth discussion of studies that have used DNA-based materials for biomineralization and/or bone repair, with expansion on the topic of DNA hydrogels specifically, and the advantages they offer for advancing the field of bone regeneration. Four mechanisms of action for the osteoconductive capabilities of DNA-based materials are discussed, and a proposed model for degradation of these materials and its link to their osteoconductive properties is later presented. Finally, the review considers current limitations of DNA-based materials and summarizes important aspects that need to be addressed for future application of DNA nanotechnology in tissue repair. STATEMENT OF SIGNIFICANCE: Herein we summarize the developing field of DNA-based materials for biomineralization and bone repair, with a focus on DNA hydrogels. We first provide a comprehensive review of different forms of DNA-based materials described thus far which have been shown to enhance bone repair and mineralization (namely DNA coatings, DNA-containing pastes, DNA nanostructures and DNA hydrogels). Next, we describe four different mechanisms by which DNA-based materials could be exerting their osteogenic effect. Then, we propose a novel model that links DNA degradation and osteoconductivity. Lastly, we suggest possible research directions to enhance DNA-based materials for future clinical application. The suggested mechanisms and the proposed model can guide future research to better understand how DNA functions as a mineral- and bone-promoting molecule.
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Affiliation(s)
- Nadeen Meshry
- Faculty of Dentistry, University of Toronto, Toronto, Canada, 124 Edward Street, Toronto, ON M5G 1G6, Canada
| | - Karina M M Carneiro
- Faculty of Dentistry, University of Toronto, Toronto, Canada, 124 Edward Street, Toronto, ON M5G 1G6, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada, 164 College St, Toronto, ON M5S 3G9, Canada.
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Shan Y, Zhu J, Lu Y, Shen Z, Pan S, Chen H, Chen W, Shi H. Construction of multifunctional tracheal substitute based on silk fibroin methacryloyl and hyaluronic acid methacryloyl with decellularized cartilaginous matrix for tracheal defect repair. Int J Biol Macromol 2025; 308:142564. [PMID: 40154699 DOI: 10.1016/j.ijbiomac.2025.142564] [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: 01/15/2025] [Revised: 03/06/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
The regeneration and functional recovery of tracheal tissue are of paramount importance in the research of tissue-engineered trachea. Current constructs still face some limitations in simulating the complex natural microenvironment and achieving better regenerative capacity and functional recovery. To address these challenges, the application of hydrogels with three-dimensional (3D) network structure and extracellular matrix derived from decellularized tissues and cells has become a more promising strategy. This study aims to introduce a novel bilayer multifunctional tissue-engineered tracheal substitute. Firstly, the mesh polycaprolactone (PCL) scaffold was printed by 3D printing technology, and the concentration of Silk Fibroin Methacryloyl (SilMA) hydrogel suitable for cell adhesion and proliferation and the concentration of Hyaluronic Acid Methacryloyl (HAMA) hydrogel suitable for 3D culture of chondrocytes were selected. Subsequently, the decellularized cartilaginous matrix (DCM) solution was obtained and the concentration that promotes chondrocyte proliferation and migration was screened. Finally, the multifunctional tracheal substitute, which features a HAMA-DCM composite hydrogel loaded with autologous chondrocytes as the basic framework to simulate the outer cartilaginous layer, and a 3D-printed PCL mesh scaffold coated with SilMA hydrogel loaded with autologous epithelial cells serves as internal support to simulate the inner airway epithelial layer, was prepared. Whether it was for repairing window-shape defect for 8 w or conducting long-segment in situ transplantation for 12 w, it achieved satisfactory surgical outcomes, including epithelial crawling, cartilage regeneration, and vascular remodeling.
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Affiliation(s)
- Yibo Shan
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China; Medical College, Yangzhou University, Yangzhou 225009, China
| | - Jianwei Zhu
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China; Medical College, Yangzhou University, Yangzhou 225009, China
| | - Yi Lu
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China; Medical College, Yangzhou University, Yangzhou 225009, China
| | - Zhiming Shen
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui, China
| | - Shu Pan
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu, China
| | - Hao Chen
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China; Medical College, Yangzhou University, Yangzhou 225009, China
| | - Wenxuan Chen
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China; Medical College, Yangzhou University, Yangzhou 225009, China
| | - Hongcan Shi
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China; Medical College, Yangzhou University, Yangzhou 225009, China.
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Hoang VT, Nguyen QT, Phan TTK, Pham TH, Dinh NTH, Anh LPH, Dao LTM, Bui VD, Dao H, Le DS, Ngo ATL, Le Q, Nguyen Thanh L. Tissue Engineering and Regenerative Medicine: Perspectives and Challenges. MedComm (Beijing) 2025; 6:e70192. [PMID: 40290901 PMCID: PMC12022429 DOI: 10.1002/mco2.70192] [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: 07/06/2024] [Revised: 12/30/2024] [Accepted: 03/04/2025] [Indexed: 04/30/2025] Open
Abstract
From the pioneering days of cell therapy to the achievement of bioprinting organs, tissue engineering, and regenerative medicine have seen tremendous technological advancements, offering solutions for restoring damaged tissues and organs. However, only a few products and technologies have received United States Food and Drug Administration approval. This review highlights significant progress in cell therapy, extracellular vesicle-based therapy, and tissue engineering. Hematopoietic stem cell transplantation is a powerful tool for treating many diseases, especially hematological malignancies. Mesenchymal stem cells have been extensively studied. The discovery of induced pluripotent stem cells has revolutionized disease modeling and regenerative applications, paving the way for personalized medicine. Gene therapy represents an innovative approach to the treatment of genetic disorders. Additionally, extracellular vesicle-based therapies have emerged as rising stars, offering promising solutions in diagnostics, cell-free therapeutics, drug delivery, and targeted therapy. Advances in tissue engineering enable complex tissue constructs, further transforming the field. Despite these advancements, many technical, ethical, and regulatory challenges remain. This review addresses the current bottlenecks, emphasizing novel technologies and interdisciplinary research to overcome these hurdles. Standardizing practices and conducting clinical trials will balance innovation and regulation, improving patient outcomes and quality of life.
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Affiliation(s)
- Van T. Hoang
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Quyen Thi Nguyen
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Trang Thi Kieu Phan
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Trang H. Pham
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Nhung Thi Hong Dinh
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Le Phuong Hoang Anh
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Lan Thi Mai Dao
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Van Dat Bui
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- School of Chemical EngineeringCollege of EngineeringSungkyunkwan University (SKKU)SuwonRepublic of Korea
| | - Hong‐Nhung Dao
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Duc Son Le
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Anh Thi Lan Ngo
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Quang‐Duong Le
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
| | - Liem Nguyen Thanh
- Vinmec Research Institute of Stem Cell and Gene TechnologyCollege of Health SciencesVinUniversityVinhomes Ocean ParkHanoiVietnam
- Vinmec Health Care SystemHanoiVietnam
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Tian Z, Zhao Z, Rausch MA, Behm C, Tur D, Shokoohi-Tabrizi HA, Andrukhov O, Rausch-Fan X. A comparative study of the epithelial regeneration capacities of two biomaterials in vitro. BMC Oral Health 2025; 25:640. [PMID: 40281524 PMCID: PMC12023557 DOI: 10.1186/s12903-025-06026-x] [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: 01/15/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Regeneration of periodontal epithelium remains a major focus in current dental research, with various exogenous substitute materials being applied in clinical practice. Yet, the highly organized structure of native tissue still poses considerable challenges for biomaterials attempting to mimic the original environment. In this study, we investigated the effects of a newly developed gelatin/polycaprolactone nanofiber (GPF) and a micro-scaled collagen matrix (CM) on the biological behavior of oral epithelial Ca9-22 cells, aiming to assess the clinical applicability of the materials and conducted a preliminary exploration of the interplay between the Ca9-22 cells and the material properties. METHODS The oral epithelial Ca9-22 cell line was cultured onto the GPF, CM, and tissue culture plate (TCP) for 3, 7, and 14 days. Cell morphology, attachment proliferation/viability, the gene expression of keratin 14 (KRT14), keratin 10 (KRT10), integrin β-1 (ITGB-1), intercellular adhesion molecule 1 (ICAM-1), interleukin 8 (IL-8) and interleukin 1β (IL-1β), the levels of IL-8 proteins were evaluated. RESULTS Ca9-22 cells exhibited distinct adhesion morphology and distribution patterns on two biomaterials. After 3 days of culturing on GPF, Ca9-22 cells demonstrated higher levels of proliferation/viability compared to those on CM. In most situations, except KRT10, both materials effectively stimulated gene and protein expression related to epithelial regeneration and wound healing, especially in the early stage of culture. Compared to CM, GPF demonstrated a stronger stimulation of KRT14 expression at day 3 and a more significant enhancement of KRT10 expression after 7 and 14 days. However, it was less effective at promoting IL-8 expression after 3 days than the former. The gene expression of KRT10 was suppressed by CM at day 7. The IL-8 protein production was the highest in cells grown on CM. CONCLUSION The morphology and cellular functions of oral epithelial cells differed between GPF and CM. Both materials are capable of promoting epithelial regeneration; however, GPF is more conducive to functional stratification of newly formed epithelium, while CM holds a more sustained effect on epithelial proliferation.
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Affiliation(s)
- Zhiwei Tian
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Zhongqi Zhao
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Marco Aoqi Rausch
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
- Clinical Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Christian Behm
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Dino Tur
- Clinical Division of Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Hassan Ali Shokoohi-Tabrizi
- Core Facility Applied Physics, Laser and CAD/CAM Technology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Oleh Andrukhov
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
| | - Xiaohui Rausch-Fan
- Clinical Division of Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
- Center for Clinical Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
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9
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Öksüz KE, Arslan S. Sustainable Synthesis of Multifunctionalized Amoxicillin-Loaded Biopolymer Foams. ACS OMEGA 2025; 10:15525-15539. [PMID: 40290945 PMCID: PMC12019502 DOI: 10.1021/acsomega.5c00442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/15/2025] [Accepted: 03/24/2025] [Indexed: 04/30/2025]
Abstract
The development of biocompatible biopolymer foams loaded with antibiotics is crucial to advancing drug delivery systems in biomedical engineering. These materials offer controlled drug release and specialized functionalities for improved therapeutic outcomes. This study presents the development and characterization of antimicrobial polymeric biofoam materials loaded with the drug amoxicillin (AMX). The sustainable synthesis of these biopolymer foams involves a cost-effective, eco-friendly method that incorporates natural starch within poly(vinyl alcohol) (PVA) through an aldehyde cross-linking/stabilizing process. The highly porous structure of the biofoams enabled effective impregnation of the AMX drug using an innovative process involving ultrasonication and vacuum pressure to maximize efficiency and minimize biomaterial loss. The findings demonstrate the potential of these PVA/starch-based biofoams as versatile drug delivery systems with desirable physicochemical and biological characteristics. Detailed investigations were conducted to evaluate morphological features, chemical properties, swelling behavior, in vitro biodegradability, drug release profiles, cell culture, and antimicrobial activity tests of the prepared biofoam samples. Investigating the effect of controlled loading of AMX under laboratory conditions on its release profile and studying its biodegradation in various environments over time represent a critical aspect of this research. The optimal release profile under physiological conditions and the potent inhibition of bacterial growth against Escherichia coli and Staphylococcus aureus microorganisms by AMX-loaded biofoam materials highlight their potential for biomedical applications. These materials show promise for the in vivo administration and local treatment of bacterial infections.
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Affiliation(s)
- Kerim Emre Öksüz
- Department
of Metallurgical and Materials Engineering, Sivas Cumhuriyet University, Sivas 58140, Türkiye
- Institute
of Science and Technology, Department of Bioengineering, Sivas Cumhuriyet University, Sivas 58140, Türkiye
| | - Saynur Arslan
- Department
of Metallurgical and Materials Engineering, Sivas Cumhuriyet University, Sivas 58140, Türkiye
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10
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Scărișoreanu A, Demeter M, Călina I, Raza MA. Non-ionizing (UV and MW)-assisted synthesis of polymeric hydrogels for advanced tissue engineering applications. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2025:1-33. [PMID: 40219715 DOI: 10.1080/09205063.2025.2486866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025]
Abstract
Significant efforts are underway to develop next-generation biomaterials through clean processes, accelerating the transition from innovative materials to tissue engineering (TE) applications and providing new alternatives for complex tissue repair. A crucial aspect of TE is selecting appropriate matrix materials with optimal physical and bioactive properties for scaffold development. For this purpose, polymers have repeatedly proven effective in creating suitable structures for successful TE applications. In this respect, ultraviolet (UV) and microwave (MW)-assisted synthesis has emerged as promising approaches in TE, offering improved material properties and reduced processing times. UV-assisted synthesis provides advantages, such as rapid gelation, customizable characteristics, and compatibility with various biological materials. MW-assisted synthesis accelerates chemical reactions through localized heating, elimination of side reaction products, and enhanced molecular interactions, enabling rapid fabrication of biocompatible materials such as hydrogels, ceramics, and composites. This review explores the effect of UV and MW-assisted synthesis on polymeric hydrogels for advancing novel materials in TE. The paper outlines the advantages of each technique, including technical specifications of reaction synthesis and recent advancements in UV and MW equipment developments. Additionally, each technique is carefully stated, highlighting hydrogels with enhanced biocompatibility through biological testing, and enhanced efficacy in regenerating soft and hard tissues.
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Affiliation(s)
- Anca Scărișoreanu
- National Institute for Laser, Plasma and Radiation Physics, Măgurele, Romania
| | - Maria Demeter
- National Institute for Laser, Plasma and Radiation Physics, Măgurele, Romania
| | - Ion Călina
- National Institute for Laser, Plasma and Radiation Physics, Măgurele, Romania
| | - Muhammad Asim Raza
- School of Chemical Engineering, Yeungnam University, Gyeongsan, Republic of Korea
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11
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Mithra S, Abdul Majeed S, Eisa Abdullah SA, Ajay Pathra G, Taju G, Bright Singh IS, Santhanam P, Sahul Hameed AS. Production of small-scale laboratory-grown cell-based fish meat from Asian seabass muscle and fin cell lines. In Vitro Cell Dev Biol Anim 2025:10.1007/s11626-025-01040-3. [PMID: 40198432 DOI: 10.1007/s11626-025-01040-3] [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: 01/07/2025] [Accepted: 02/23/2025] [Indexed: 04/10/2025]
Abstract
Aquaculture is essential to satisfying the world's increasing demand for seafood. Likewise, overfishing is becoming more common across the world, inflicting tremendous damage to the marine environment. There is a critical need for protecting sustainable fishing resources to fulfil the increasing demand for seafood. The current work focuses on the cells derived from Asian seabass muscle (SBM) and Asian seabass fin (SBF) for producing cell-based fish meat. SBM and SBF cells were seeded separately in the TubeSpin bioreactor and placed on a 3D orbital rocker. Cell sheets formed on the TubeSpin were detached and formed spheroid-like structures. These structures aggregated and formed visible tissue-like structures on 45 d of culture. Immunotyping results revealed that the presence of myosin in the cells of muscle and fin tissue, and indicating that these cells might have originated from myoblasts. The origin of cultured tissue from SBM and SBF cell lines was confirmed by amplification and sequencing of the L. calcarifer specific mitochondrial larger subunit rRNA gene. Additionally, these cells could be cultivated in multilayered forms that were appropriate for large-scale production. This approach provides a new method for the production of cell-based, laboratory-grown meat from the Asian seabass muscle and fin cell lines.
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Affiliation(s)
- Sivaraj Mithra
- Aquatic Animal Health Laboratory, PG & Research Department of Zoology, C. Abdul Hakeem College (Affiliated to Thiruvalluvar University), Melvisharam, Tamil Nadu, 632509, India
| | - Seepoo Abdul Majeed
- Aquatic Animal Health Laboratory, PG & Research Department of Zoology, C. Abdul Hakeem College (Affiliated to Thiruvalluvar University), Melvisharam, Tamil Nadu, 632509, India.
| | - Shaik Abdullah Eisa Abdullah
- Aquatic Animal Health Laboratory, PG & Research Department of Zoology, C. Abdul Hakeem College (Affiliated to Thiruvalluvar University), Melvisharam, Tamil Nadu, 632509, India
| | - Ganesan Ajay Pathra
- Aquatic Animal Health Laboratory, PG & Research Department of Zoology, C. Abdul Hakeem College (Affiliated to Thiruvalluvar University), Melvisharam, Tamil Nadu, 632509, India
| | - Gani Taju
- Aquatic Animal Health Laboratory, PG & Research Department of Zoology, C. Abdul Hakeem College (Affiliated to Thiruvalluvar University), Melvisharam, Tamil Nadu, 632509, India
| | - Isaac Sarojini Bright Singh
- National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Kochi, Kerala, 682016, India
| | - Perumal Santhanam
- Department of Marine Science, School of Marine Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India
| | - Azeez Sait Sahul Hameed
- Aquatic Animal Health Laboratory, PG & Research Department of Zoology, C. Abdul Hakeem College (Affiliated to Thiruvalluvar University), Melvisharam, Tamil Nadu, 632509, India.
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12
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Zeng Y, Yan C, Chen G, Chen Z, Wang F. Advances in oxygen-releasing matrices for regenerative engineering applications. Med Biol Eng Comput 2025:10.1007/s11517-025-03354-6. [PMID: 40183849 DOI: 10.1007/s11517-025-03354-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 03/23/2025] [Indexed: 04/05/2025]
Abstract
In recent years, the effects of hypoxia on tissue repair have received wider attention with the deepening of tissue engineering research. Various oxygen supply strategies have wider applications in the field of tissue repair. Currently, commonly used methods of oxygen supply for defective tissues include hyperbaric oxygen (HBO) and oxygen-releasing materials. Between them, oxygen-releasing materials continuously and efficiently release oxygen from within the defective tissue. Compared with HBO, which may cause oxidative stress in healthy tissues, supplying oxygen via oxygen-releasing materials is safer because of their oxygen-releasing in situ and specific oxygen supply characteristics. However, there still exist some problems in the study of oxygen-releasing materials, such as cytotoxicity and the shortage of oxygen-releasing time. The current reviews on oxygen-releasing materials mostly elaborate on the principles of oxygen-releasing materials and lack a review of their preparation methods and applications. In this paper, different types of oxygen-releasing materials, such as hydrogels, microspheres, and layers, are reviewed concerning their applications, structures, current development status, and challenges.
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Affiliation(s)
- Yihong Zeng
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Banan District, No. 69 Hongguang Avenue, Chongqing, 400054, P.R. China
| | - Can Yan
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Banan District, No. 69 Hongguang Avenue, Chongqing, 400054, P.R. China
| | - Guobao Chen
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Banan District, No. 69 Hongguang Avenue, Chongqing, 400054, P.R. China.
| | - Zhongmin Chen
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Banan District, No. 69 Hongguang Avenue, Chongqing, 400054, P.R. China
| | - Fuping Wang
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Banan District, No. 69 Hongguang Avenue, Chongqing, 400054, P.R. China
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13
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Chansaenroj J, Kornsuthisopon C, Chansaenroj A, Samaranayake LP, Fan Y, Osathanon T. Potential of Dental Pulp Stem Cell Exosomes: Unveiling miRNA-Driven Regenerative Mechanisms. Int Dent J 2025; 75:415-425. [PMID: 39368923 PMCID: PMC11976581 DOI: 10.1016/j.identj.2024.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/21/2024] [Accepted: 08/24/2024] [Indexed: 10/07/2024] Open
Abstract
Human dental pulp stem cells (hDPSCs) have emerged as a promising resource in regenerative medicine due to their unique ability to secrete exosomes containing a diverse array of bioactive molecules, particularly microRNAs (miRNAs). These exosomes appear to be essential for stimulating regenerative mechanisms, especially those associated with stem cell pluripotency and tissue repair. However, several challenges such as cargo specificity and delivery efficiency need to be addressed to maximise the therapeutic potential of hDPSC-derived exosomes and miRNA-based therapies. This narrative review explores hDPSCs' potential in regenerative medicine by examining their role in tissue engineering, secretome composition, exosome function, exosomal miRNA in diverse models, and miRNA profiling. Therefore, it is imperative to sustain ongoing research on miRNA to advance clinical applications in the field of regenerative medicine and dentistry. A comprehensive understanding of the specific miRNA composition within hDPSC-derived exosomes is essential to elucidate their mechanistic roles in diverse disease states and to inform the development of innovative therapeutic strategies. These findings hold significant potential for the development of innovative regenerative therapies and emphasises the importance of establishing a strong connection between translational research discoveries and clinical applications. hDPSC-derived exosomes and miRNA-based therapies play a crucial role in immune modulation, regenerative dentistry, and tissue repair.
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Affiliation(s)
- Jira Chansaenroj
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Chatvadee Kornsuthisopon
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
| | - Ajjima Chansaenroj
- Department of Animal Husbandry, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand
| | - Lakshman P Samaranayake
- Office of Research Affairs, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Yi Fan
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Thanaphum Osathanon
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
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14
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Ullah S, Zainol I. Fabrication and applications of biofunctional collagen biomaterials in tissue engineering. Int J Biol Macromol 2025; 298:139952. [PMID: 39824416 DOI: 10.1016/j.ijbiomac.2025.139952] [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: 10/23/2024] [Revised: 01/12/2025] [Accepted: 01/14/2025] [Indexed: 01/20/2025]
Abstract
Collagen is extensively used in tissue engineering for various organ tissue regeneration due to the main component of human organ extracellular matrix (ECM) and their inherent nature bioactivity. Collagen various types naturally exist in different organ ECMs. Collagen fabricated with natural ECM mimics architecture, composition and mechanical properties for various organ tissue regeneration. Collagen fabrication with organ-specific biofunctionality facilitated organ tissue engineering as compared to unmodified collagen biomaterials. Collagen biofunctionality improved by subjecting collagen to synthesis, fibers and surface modifications, and blending with other components. Furthermore, collagen is loaded with bioactive molecules, growth factors, drugs and cells also enhancing the biofunctionality of collagen biomaterials. In this review, we will explore the recent advancements in biofunctional collagen biomaterials fabrication with organ-specific biofunctionality in tissue engineering to resolve various organ tissue engineering issues and regeneration challenges. Biofunctional collagen biomaterials stimulate microenvironments inside and around the implants to excellently regulate cellular activities, differentiate cells into organ native cells, enhanced ECM production and remodeling to regenerate organ tissues with native structure, function and maturation. This review critically explored biofunctional collagen biomaterials fabrication in resolving various organ tissue engineering issues and regeneration challenges, and opening new directions of biofunctional collagen biomaterials fabrication, design and applications.
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Affiliation(s)
- Saleem Ullah
- Polymer Lab, Chemistry Department, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak, Darul Ridzuan, Malaysia.
| | - Ismail Zainol
- Polymer Lab, Chemistry Department, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak, Darul Ridzuan, Malaysia.
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15
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Scholpp S, Hoffmann L, Schätzlein E, Gries T, Emonts C, Blaeser A. Interlacing biology and engineering: An introduction to textiles and their application in tissue engineering. Mater Today Bio 2025; 31:101617. [PMID: 40124339 PMCID: PMC11926717 DOI: 10.1016/j.mtbio.2025.101617] [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: 12/19/2024] [Revised: 02/15/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
Tissue engineering (TE) aims to provide personalized solutions for tissue loss caused by trauma, tumors, or congenital defects. While traditional methods like autologous and homologous tissue transplants face challenges such as donor shortages and risk of donor site morbidity, TE provides a viable alternative using scaffolds, cells, and biologically active molecules. Textiles represent a promising scaffold option for both in-vitro and in-situ TE applications. Textile engineering is a broad field and can be divided into fiber-based textiles and yarn-based textiles. In fiber-based textiles the textile fabric is produced in the same step as the fibers (e.g. non-wovens, electrospun mats and 3D-printed). For yarn-based textiles, yarns are produced from fibers or filaments first and then, a textile fabric is produced (e.g. woven, weft-knitted, warp-knitted and braided fabrics). The selection of textile scaffold technology depends on the target tissue, mechanical requirements, and fabrication methods, with each approach offering distinct advantages. Braided scaffolds, with their high tensile strength, are ideal for load-bearing tissues like tendons and ligaments, while their ability to form stable hollow lumens makes them suitable for vascular applications. Weaving, weft-, and warp-knitting provide tunable structural properties, with warp-knitting offering the greatest design flexibility. Spacer fabrics enable complex 3D architecture, benefiting applications such as skin grafts and multilayered tissues. Electrospinning, though highly effective in mimicking the ECM, is structurally limited. The complex interactions between materials, fiber properties, and textile technologies allows for scaffolds with a wide range of morphological and mechanical characteristics (e.g., tensile strength of woven textiles ranging from 0.64 to 180.4 N/mm2). With in-depth knowledge, textiles can be tailored to obtain specific mechanical properties as accurately as possible and aid the formation of functional tissue. However, as textile structures inherently differ from biological tissues, careful optimization is required to enhance cell behavior, mechanical performance, and clinical applicability. This review is intended for TE experts interested in using textiles as scaffolds and provides a detailed analysis of the available options, their characteristics and known applications. For this, first the major fiber formation methods are introduced, then subsequent used automated textile technologies are presented, highlighting their strengths and limitations. Finally, we analyze how these textile and fiber structures are utilized in TE, organized by the use of textiles in TE across major organ systems, including the nervous, skin, cardiovascular, respiratory, urinary, digestive, and musculoskeletal systems.
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Affiliation(s)
- S. Scholpp
- Institute for BioMedical Printing Technology, Technical University of Darmstadt, Darmstadt, Germany
| | - L.A. Hoffmann
- Institut für Textiltechnik, RWTH Aachen University, Aachen, Germany
| | - E. Schätzlein
- Institute for BioMedical Printing Technology, Technical University of Darmstadt, Darmstadt, Germany
| | - T. Gries
- Institut für Textiltechnik, RWTH Aachen University, Aachen, Germany
| | - C. Emonts
- Institut für Textiltechnik, RWTH Aachen University, Aachen, Germany
| | - A. Blaeser
- Institute for BioMedical Printing Technology, Technical University of Darmstadt, Darmstadt, Germany
- Centre for Synthetic Biology, Technical University of Darmstadt, Darmstadt, Germany
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16
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Liu J, Wang Q, Le Y, Hu M, Li C, An N, Song Q, Yin W, Ma W, Pan M, Feng Y, Wang Y, Han L, Liu J. 3D-Bioprinting for Precision Microtissue Engineering: Advances, Applications, and Prospects. Adv Healthc Mater 2025; 14:e2403781. [PMID: 39648541 DOI: 10.1002/adhm.202403781] [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: 10/01/2024] [Revised: 11/18/2024] [Indexed: 12/10/2024]
Abstract
Microtissues, engineered to emulate the complexity of human organs, are revolutionizing the fields of regenerative medicine, disease modelling, and drug screening. Despite the promise of traditional microtissue engineering, it has yet to achieve the precision required to fully replicate organ-like structures. Enter 3D bioprinting, a transformative approach that offers unparalleled control over the microtissue's spatial arrangement and mechanical properties. This cutting-edge technology enables the detailed layering of bioinks, crafting microtissues with tissue-like 3D structures. It allows for the direct construction of organoids and the fine-tuning of the mechanical forces vital for tissue maturation. Moreover, 3D-printed devices provide microtissues with the necessary guidance and microenvironments, facilitating sophisticated tissue interactions. The applications of 3D-printed microtissues are expanding rapidly, with successful demonstrations of their functionality in vitro and in vivo. This technology excels at replicating the intricate processes of tissue development, offering a more ethical and controlled alternative to traditional animal models. By simulating in vivo conditions, 3D-printed microtissues are emerging as powerful tools for personalized drug screening, offering new avenues for pharmaceutical development and precision medicine.
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Affiliation(s)
- Jinrun Liu
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
| | - Qi Wang
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
| | - Yinpeng Le
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
| | - Min Hu
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
| | - Chen Li
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
| | - Ni An
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China
| | - Qingru Song
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China
| | - Wenzhen Yin
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China
| | - Wenrui Ma
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China
| | - Mingyue Pan
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
| | - Yutian Feng
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
| | - Yunfang Wang
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China
| | - Lu Han
- Beijing Institute of Graphic Communication, Beijing, 102600, China
| | - Juan Liu
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 102218, China
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17
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Felix RB, Shabazz A, Holeman WP, Han S, Wyble M, Uzoukwu M, Gomes LA, Nho L, Litman MZ, Hu P, Fisher JP. From Promise to Practice: Recent Growth in 30 Years of Tissue Engineering Commercialization. Tissue Eng Part A 2025; 31:285-302. [PMID: 38818800 DOI: 10.1089/ten.tea.2024.0112] [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: 06/01/2024] Open
Abstract
This perspective, marking the 30th anniversary of the Tissue Engineering journal, discusses the exciting trends in the global commercialization of tissue engineering technology. Within a historical context, we present an evolution of challenges and a discussion of the last 5 years of global commercial successes and emerging market trends, highlighting the continued expansion of the field in the northeastern United States. This leads to an overview of the last 5 years' progress in clinical trials for tissue-engineered therapeutics, including an analysis of trends in success and failure. Finally, we provide a broad overview of preclinical research and a perspective on where the state-of-the-art lies on the horizon.
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Affiliation(s)
- Ryan B Felix
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Amal Shabazz
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - William Pieper Holeman
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Sarang Han
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Matthew Wyble
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Marylyn Uzoukwu
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Lauren Audrey Gomes
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Laena Nho
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Mark Zachary Litman
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Peter Hu
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - John P Fisher
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
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18
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Chen S, Yoo JJ, Wang M. The application of tissue engineering strategies for uterine regeneration. Mater Today Bio 2025; 31:101594. [PMID: 40070871 PMCID: PMC11894340 DOI: 10.1016/j.mtbio.2025.101594] [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: 01/16/2025] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
Uterine injuries, particularly damages to endometrium, are usually associated with abnormal menstruation, recurrent miscarriage, pregnancy complications, and infertility. Tissue engineering using cell-based, biomolecule-based, or biomaterial and scaffold-based strategies has emerged as a novel and promising approach for uterine regeneration. Stem cells, biomolecules, and porous scaffolds used alone or, very often, used in combination as a more effective treatment means have shown great potential in promoting uterine regeneration. The reported preclinical studies have indicated that appropriate tissue engineering strategies could safely and effectively reconstruct not only endometrium but also partial or even the whole uterine structure. However, the progress in the uterine regeneration area is slow in comparison to that of regenerating many other body tissues and hence it still remains a great challenge to apply uterine tissue engineering for clinical applications. In this review, conventional treatments for uterine-related diseases are briefly reviewed and discussed first. Subsequently, tissue engineering strategies (cell-based, biomolecule-based, biomaterial and scaffold-based, or their combinations) for uterine repair in preclinical studies and clinical trials are presented and analyzed. Finally, the challenges and perspectives in uterine regeneration are pointed and discussed. Despite various limitations and obstacles, the tissue engineering approach is viable and holds high promise for uterine regeneration.
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Affiliation(s)
- Shangsi Chen
- Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong
| | - James J. Yoo
- Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC, 27157, USA
| | - Min Wang
- Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong
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19
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Tosaka R, Eguchi T, Ishizuka T, Kawaguchi K, Nagashima T, Nakayama R, Hamada Y. The effects of silk sheets derived from germ-free silkworms on wound healing of full-thickness epithelial defects. Burns 2025; 51:107470. [PMID: 40327970 DOI: 10.1016/j.burns.2025.107470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 02/24/2025] [Accepted: 03/24/2025] [Indexed: 05/08/2025]
Abstract
Collagen is widely used as a scaffold for full-thickness epithelial defects but has poor biostability and often induces hypertrophic scarring. Silk, especially silk derived from germ-free silkworms (SGFS), has high biocompatibility and controllable durability. Therefore, SGFS is possibly for medicine. Herein, we evaluated the effects of SGFS as a scaffold in the wound healing of full-thickness epithelial defects. Epithelial defects were made in the dorsal skin of C57BL/6 J mice, and an SGFS or a collagen sheet was applied to each defect and compared. On days 1, 3, 7, and 14 after surgery, re-epithelialization, inflammatory responses, and granulation tissue formation of each wound were assessed and compared between the groups. Re-epithelialization was observed in the SGFS group on day 3 but no re-epithelialization occurred in the collagen group. Histopathological examination showed less granulation tissue formation in the SGFS group than in the collagen group. IL-6 expression was significantly higher in the SGFS group than in the collagen group on day 1. TGF-β1 expression in the SGFS group was significantly lower than that in the collagen sheet group on days 7 and 14. Based on these results, SGFS promoted re-epithelialization and reduced hypertrophic scarring in the wound healing process compared with collagen.
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Affiliation(s)
- Ryo Tosaka
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Takanori Eguchi
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Tadatoshi Ishizuka
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Koji Kawaguchi
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Takayuki Nagashima
- Department of Human Animal Relations, Yamazaki University of Animal Health Technology, 4-7-2, Minami-Osawa, Hachioji-shi, Tokyo 192-0364, Japan.
| | - Ryoko Nakayama
- Department of Pathology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Yoshiki Hamada
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
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20
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Chen Y, Wei J. Application of 3D Printing Technology in Dentistry: A Review. Polymers (Basel) 2025; 17:886. [PMID: 40219277 PMCID: PMC11991056 DOI: 10.3390/polym17070886] [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: 02/08/2025] [Revised: 03/20/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025] Open
Abstract
Three-dimensional (3D) printing is a cutting-edge technology that is widely used in biomedical fields to construct various commercial products or scaffolds for theoretical research. In this review, 3D printing technologies with different principles are briefly introduced, including selective laser melting (SLM), selective laser sintering (SLS), fused deposition modeling (FDM), stereolithography (SLA), and digital light processing (DLP). In addition, the applications of 3D printing in dentistry, such as dental implantology, prosthodontics, orthodontics, maxillofacial surgery, and dental tissue regeneration, were summarized. Furthermore, the perspective and challenges of 3D printing were also addressed to help the readers obtain a clear map for the development of 3D printing in dentistry.
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Affiliation(s)
- Yangqing Chen
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China;
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031, China
- Jiangxi Provincial Key Laboratory of Oral Disease, Nanchang 330006, China
| | - Junchao Wei
- School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China;
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031, China
- Jiangxi Provincial Key Laboratory of Oral Disease, Nanchang 330006, China
- Jiangxi Province Clinical Research Center for Oral Disease, Nanchang 330006, China
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21
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Shepherd J. Biomimetic Approaches in the Development of Optimised 3D Culture Environments for Drug Discovery in Cardiac Disease. Biomimetics (Basel) 2025; 10:204. [PMID: 40277603 PMCID: PMC12024959 DOI: 10.3390/biomimetics10040204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 03/09/2025] [Accepted: 03/21/2025] [Indexed: 04/26/2025] Open
Abstract
Cardiovascular disease remains the leading cause of death worldwide, yet despite massive investment in drug discovery, the progress of cardiovascular drugs from lab to clinic remains slow. It is a complex, costly pathway from drug discovery to the clinic and failure becomes more expensive as a drug progresses along this pathway. The focus has begun to shift to optimisation of in vitro culture methodologies, not only because these must be undertaken are earlier on in the drug discovery pathway, but also because the principles of the 3Rs have become embedded in national and international legislation and regulation. Numerous studies have shown myocyte cell behaviour to be much more physiologically relevant in 3D culture compared to 2D culture, highlighting the advantages of using 3D-based models, whether microfluidic or otherwise, for preclinical drug screening. This review aims to provide an overview of the challenges in cardiovascular drug discovery, the limitations of traditional routes, and the successes in the field of preclinical models for cardiovascular drug discovery. It focuses on the particular role biomimicry can play, but also the challenges around implementation within commercial drug discovery.
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Affiliation(s)
- Jenny Shepherd
- School of Engineering, University of Leicester, Leicester LE1 7RH, UK
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22
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Nagase K, Watanabe M, Kikuchi A, Okano T. Effective cell sheet preparation using thermoresponsive polymer brushes with various graft densities and chain lengths. Biomater Sci 2025; 13:1657-1670. [PMID: 39996321 DOI: 10.1039/d4bm01705f] [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: 02/26/2025]
Abstract
Various cell sheets have been used as effective and useful cellular tissues in tissue engineering and regenerative therapy. Poly(N-isopropylacrylamide) (PNIPAAm)-modified surfaces have been investigated for effective cell sheet preparation. In this study, the effective PNIPAAm graft density and chain length of PNIPAAm brushes for various cell types were investigated. The PNIPAAm brush-grafted glass was prepared via silanization and subsequent atom transfer radical polymerization (ATRP). The density of the PNIPAAm brushes was modulated by changing the ATRP initiator and co-adsorber composition, while the PNIPAAm brush length was modulated by changing the monomer concentration in the ATRP. The hydrophilicity of the PNIPAAm brushes increased with increasing PNIPAAm brush length because long PNIPAAm brushes tended to hydrate. Fibronectin adsorption increased with decreasing PNIPAAm brush concentration because the exposed hydrophobic co-adsorber in the dilute PNIPAAm brush enhanced the adsorption of fibronectin. The cell-sheet fabrication ability was investigated using six types of PNIPAAm brushes. An endothelial cell sheet was fabricated using a dense, short PNIPAAm brush. NIH/3T3 sheets can be fabricated using three types of PNIPAAm brushes: dense-long PNIPAAm brushes, moderately dense-short PNIPAAm brushes, and dilute-long PNIPAAm brushes. MDCK cell sheets could not be prepared using the PNIPAAm brushes. A549 cell sheets were prepared using a dense-short PNIPAAm brush and moderately dense-short PNIPAAm brushes. These results indicate that the optimal PNIPAAm brush conditions for cell sheet preparation vary depending on cell type. Thus, modulation of PNIPAAm brush density and length is an effective approach for preparing target cell sheets.
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Affiliation(s)
- Kenichi Nagase
- Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, 734-8553, Japan.
- Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
| | - Minami Watanabe
- Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
- Department of Materials Science and Technology, Graduate School of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, Katsushika, Tokyo 125-8585, Japan
| | - Akihiko Kikuchi
- Department of Materials Science and Technology, Graduate School of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, Katsushika, Tokyo 125-8585, Japan
| | - Teruo Okano
- Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
- Cell Sheet Tissue Engineering Center, Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, UT84112, Utah, USA
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23
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Li Q, Shi H, Wang Y, Hu R, Feng C, Ma X, Wang Y, Li X, Zhu X, Zhang X. Enhancing the mechanical and antibacterial properties of hydroxyapatite bioceramics by in situ graphene doping to promote osseointegration in infected bone defects. J Mater Chem B 2025; 13:3930-3944. [PMID: 40013324 DOI: 10.1039/d4tb02330g] [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: 02/28/2025]
Abstract
Hydroxyapatite (HA) bioceramics are extensively utilized in the field of bone repair owing to their remarkable biocompatibility, bioactivity, and osteoconductivity. However, their applications in load-bearing bones are significantly limited because of their inherent brittleness. Achieving a suitable balance between mechanical strength and osteogenic activity remains a critical challenge. In this work, HA ceramics with in situ graphene doping were fabricated via ball-milling and vacuum sintering processes in a convenient way, thereby increasing their fracture toughness and flexural strength to the levels of natural cortical bone. Furthermore, in situ graphene doping imparted outstanding photothermal property to HA bioceramics, achieving wet temperatures exceeding 60 °C under near-infrared radiation at 808 nm and exhibiting excellent antibacterial efficacy with a bacteriostasis rate of approximately 96% against S. aureus. Additionally, HA bioceramics with in situ graphene doping promoted the proliferation and differentiation of bone marrow stem cells (BMSCs). The anti-infective capability and osseointegration potential of these doped HA bioceramics were further validated using an infected bone defect model in the rabbit femur. In summary, these findings indicate that in situ graphene doping holds immense potential for broadening the applications of HA bioceramics in the repair of load-bearing and infected bone defects.
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Affiliation(s)
- Qipeng Li
- College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
| | - Hao Shi
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
| | - Yuyi Wang
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
| | - Ruitao Hu
- Pittsburgh Institute, Sichuan University, Chengdu, 610065, China
| | - Cong Feng
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
| | - Xiaodong Ma
- School of Chemical Engineering, University of Queensland, Brisbane, QLD, 4072, Australia
| | - Ye Wang
- College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
| | - Xiangfeng Li
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
| | - Xiangdong Zhu
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
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24
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Yoon S, Chen B. Biomimetic Elastomer-Clay Nanocomposite Hydrogels with Control of Biological Chemicals for Soft Tissue Engineering and Wound Healing. ACS APPLIED BIO MATERIALS 2025; 8:2492-2505. [PMID: 39976353 PMCID: PMC11921026 DOI: 10.1021/acsabm.4c01944] [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: 12/20/2024] [Revised: 02/10/2025] [Accepted: 02/11/2025] [Indexed: 02/21/2025]
Abstract
Resilient hydrogels are of great interest in soft tissue applications, such as soft tissue engineering and wound healing, with their biomimetic mechanical and hydration properties. A critical aspect in designing hydrogels for healthcare is their functionalities to control the surrounding biological environments to optimize the healing process. Herein, we have created an elastomer-clay nanocomposite hydrogel system with biomimetic mechanical behavior and sustained drug delivery of bioactive components and malodorous diamine-controlling properties. These hydrogels were prepared by a combined approach of melt intercalation of poly(ethylene glycol) and montmorillonite clay, followed by in situ cross-linking with a branched poly(glycerol sebacate) prepolymer. The hydration, vapor transmission, and surface wettability of the hydrogels were readily controlled by varying the clay content. Their mechanical properties were also modulated to mimic the Young's moduli (ranging between 12.6 and 105.2 kPa), as well as good flexibility and stretchability of soft tissues. A porous scaffold with interconnected pore structures as well as full and instant shape recovery was fabricated from a selected nanocomposite to demonstrate its potential applications as soft tissue scaffolds and wound healing materials. Biodegradability and biocompatibility were tested in vitro, showing controllable degradation kinetics with clay and no evidence of cytotoxicity. With the high surface area and absorption capacity of the clay, sustained drug delivery of a proangiogenic agent of 17β-estradiol as a model drug and the ability to control the malodorous diamines were both achieved. This elastomer-clay nanocomposite hydrogel system with a three-dimensional interconnected porous scaffold architecture and controllable hydration, mechanical, and biodegradable properties, as well as good biocompatibility and the ability to control the biological chemical species of the surrounding environments, has great potential in soft tissue engineering and wound healing.
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Affiliation(s)
- Sungkwon Yoon
- School of
Mechanical and Aerospace Engineering, Queen’s
University Belfast, Stranmillis Road, Belfast BT9 5AH, United Kingdom
- Department
of Materials Science and Engineering, University
of Sheffield, Mappin
Street, Sheffield S1 3JD, United Kingdom
| | - Biqiong Chen
- School of
Mechanical and Aerospace Engineering, Queen’s
University Belfast, Stranmillis Road, Belfast BT9 5AH, United Kingdom
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25
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Shi J, Wan Y, Jia H, Skeldon G, Jan Cornelissen D, Wesencraft K, Wu J, McConnell G, Chen Q, Liu D, Shu W. Printing Cell Embedded Sacrificial Strategy for Microvasculature using Degradable DNA Biolubricant. Angew Chem Int Ed Engl 2025; 64:e202417510. [PMID: 39460720 PMCID: PMC11914955 DOI: 10.1002/anie.202417510] [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: 10/04/2024] [Revised: 10/22/2024] [Accepted: 10/24/2024] [Indexed: 10/28/2024]
Abstract
Microvasculature is essential for the continued function of cells in tissue and is fundamental in the fields of tissue engineering, organ repair and drug screening. However, the fabrication of microvasculature is still challenging using existing strategies. Here, we developed a general PRINting Cell Embedded Sacrificial Strategy (PRINCESS) and successfully fabricated microvasculatures using degradable DNA biolubricant. This is the first demonstration of direct cell printing to fabricate microvasculature, which eliminates the need for a subsequent cell seeding process and the associated deficiencies. Utilizing the shear-thinning property of DNA hydrogels as a novel sacrificial, cell-laden biolubricant, we can print a 70 μm endothelialized microvasculature, breaking the limit of 100 μm. To our best knowledge, this is the smallest endothelialized microvasculature that has ever been bioprinted so far. In addition, the self-healing property of DNA hydrogels allows the creation of continuous branched structures. This strategy provides a new platform for constructing complex hierarchical vascular networks and offers new opportunity towards engineering thick tissues. The extremely low volume of sacrificial biolubricant paves the way for DNA hydrogels to be used in practical tissue engineering applications. The high-resolution bioprinting technique also exhibits great potential for printing lymphatics, retinas and neural networks in the future.
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Affiliation(s)
- Jiezhong Shi
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education)Department of Chemistry Tsinghua UniversityBeijing100084China
- Department of Biomedical EngineeringUniversity of StrathclydeGlasgowG4 0NWUnited Kingdom
- SINOPEC Key Laboratory of Research and Application of Medical and Hygienic MaterialsSINOPEC Beijing Research Institute of Chemical Industry Co., Ltd.Beijing, 100013China
| | - Yifei Wan
- Department of Biomedical EngineeringUniversity of StrathclydeGlasgowG4 0NWUnited Kingdom
| | - Haoyang Jia
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education)Department of Chemistry Tsinghua UniversityBeijing100084China
| | - Gregor Skeldon
- Department of Biomedical EngineeringUniversity of StrathclydeGlasgowG4 0NWUnited Kingdom
| | - Dirk Jan Cornelissen
- Department of Biomedical EngineeringUniversity of StrathclydeGlasgowG4 0NWUnited Kingdom
| | - Katrina Wesencraft
- Department of Physics, SUPAUniversity of StrathclydeGlasgowG4 0NGUnited Kingdom
| | - Junxi Wu
- Department of Biomedical EngineeringUniversity of StrathclydeGlasgowG4 0NWUnited Kingdom
| | - Gail McConnell
- Department of Physics, SUPAUniversity of StrathclydeGlasgowG4 0NGUnited Kingdom
| | - Quan Chen
- State Key Laboratory of Polymer Physics and ChemistryChangchun Institute of Applied Chemistry, Chinese Academy of SciencesChangchun130022China
| | - Dongsheng Liu
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education)Department of Chemistry Tsinghua UniversityBeijing100084China
| | - Wenmiao Shu
- Department of Biomedical EngineeringUniversity of StrathclydeGlasgowG4 0NWUnited Kingdom
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26
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Rajab TK, Kalfa DM, Mery CM, Emani SM, Reemtsen BL. Indications and Practical Considerations for Partial Heart Transplantation. Ann Thorac Surg 2025:S0003-4975(25)00203-6. [PMID: 40107593 DOI: 10.1016/j.athoracsur.2025.01.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 12/17/2024] [Accepted: 01/19/2025] [Indexed: 03/22/2025]
Abstract
Partial heart transplantation is a new approach to deliver growing heart valve substitutes for children. The rationale for partial heart transplantation is that the valves contained in heart transplants grow. Partial heart transplants differ from heart transplants because only the part of the heart containing the necessary valve is transplanted, while the native ventricles are preserved. Preserving the native ventricles eliminates the risk of graft ventricular dysfunction and allows for utilization of donor hearts with ventricular dysfunction. Here we outline practical considerations for partial heart transplantation, including indications, sources for donor hearts, graft procurement, graft preservation, implantation, recipient immunosuppression, and reimbursement. This invited expert review is intended to help clinical teams implement partial heart transplantation.
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Affiliation(s)
- Taufiek Konrad Rajab
- Division of Cardiovascular Surgery, Department of Surgery, Arkansas Children's Hospital, Little Rock, Arkansas.
| | - David M Kalfa
- Section of Pediatric and Congenital Cardiac Surgery, Division of Cardiac, Thoracic, and Vascular Surgery, Department of Surgery, Morgan Stanley Children's Hospital, New York, New York
| | - Carlos M Mery
- Division of Pediatric Cardiac Surgery, Department of Cardiac Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Sitaram M Emani
- Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts
| | - Brian L Reemtsen
- Division of Cardiovascular Surgery, Department of Surgery, Arkansas Children's Hospital, Little Rock, Arkansas
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27
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Liu J, Li Y, Zhang Y, Zhao Z, Liu B. Engineered stromal vascular fraction for tissue regeneration. Front Pharmacol 2025; 16:1510508. [PMID: 40183080 PMCID: PMC11966044 DOI: 10.3389/fphar.2025.1510508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 02/19/2025] [Indexed: 04/05/2025] Open
Abstract
The treatment of various tissue injuries presents significant challenges, particularly in the reconstruction of large and severe tissue defects, with conventional clinical methods often yielding suboptimal results. However, advances in engineering materials have introduced new possibilities for tissue repair. Bioactive components are commonly integrated with synthetic materials to enhance tissue reconstruction. Stromal vascular fraction (SVF), an adipose-derived cell cluster, has shown considerable potential in tissue regeneration due to its simple and efficient way of obtaining and its richness in growth factors. Therefore, this review illustrated the preparation, characterization, mechanism of action, and applications of engineered SVF in various tissue repair processes, to provide some references for the option of better methods for tissue defect reconstruction.
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Affiliation(s)
- Jianfeng Liu
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Yiwei Li
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Yanan Zhang
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Zhiwei Zhao
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
| | - Bin Liu
- Department of Hand and Foot Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, China
- Engineering Laboratory of Tissue Engineering Biomaterials of Jilin Province, Changchun, China
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28
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Xiong X, Zhou X, Zhang H, Aizenberg M, Yao Y, Hu Y, Aizenberg J, Cui J. Controlled macroscopic shape evolution of self-growing polymeric materials. Nat Commun 2025; 16:2131. [PMID: 40032829 PMCID: PMC11876608 DOI: 10.1038/s41467-025-57030-2] [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: 10/10/2024] [Accepted: 02/10/2025] [Indexed: 03/05/2025] Open
Abstract
Living organisms absorb external nutrients to grow, changing their macroscopic shapes to meet various challenges through mass transport and integration. While several strategies have been developed to create dynamic polymers that allow for mainchain remodelings to mimic the growing ability of living organisms, most are limited to simple homogeneous growth without complex control of global geometric transformation during growth. Herein, we report an approach to design controlled, growth-induced shape transformation in synthetic materials, in which significant mass transport within the materials is induced by spatially controlled polymerization leading to reshaping the materials. This method is demonstrated using silicone systems made through anionic ring-opening polymerization (anionic ROP) of octamethylcyclotetrasiloxane (D4) with a strong base as the catalyst. We show that a flat square sample can be transformed into a sphere through growth without the need for remolding and preprogramming. By varying the composition of the monomer mixture provided to the samples, and the modes of triggering and shutting down polymerization, we achieve exquisite control over growing polymeric objects into various sizes and shapes, modulating their mechanical properties, self-healing ability, and availability of active sites for further growth from a desired location. We envision this strategy opening an innovative direction in preparing soft materials with specific shapes or surface morphologies.
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Affiliation(s)
- Xinhong Xiong
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Yangtze Delta Region Institute (Huzhou), University of Electronic Science and Technology of China, Huzhou, China
| | - Xiaozhuang Zhou
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Yangtze Delta Region Institute (Huzhou), University of Electronic Science and Technology of China, Huzhou, China
| | - Haohui Zhang
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
| | - Michael Aizenberg
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
| | - Yuxing Yao
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
| | - Yuhang Hu
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
- The School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA
| | - Joanna Aizenberg
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
| | - Jiaxi Cui
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
- Yangtze Delta Region Institute (Huzhou), University of Electronic Science and Technology of China, Huzhou, China.
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Luo X, Zhang Y, Zeng Y, Yang D, Zhou Z, Zheng Z, Xiao P, Ding X, Li Q, Chen J, Deng Q, Zhong X, Qiu S, Yan W. Nanotherapies Based on ROS Regulation in Oral Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2409087. [PMID: 39887942 PMCID: PMC11884622 DOI: 10.1002/advs.202409087] [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: 08/03/2024] [Revised: 12/28/2024] [Indexed: 02/01/2025]
Abstract
Oral diseases rank among the most prevalent clinical conditions globally, typically involving detrimental factors such as infection, inflammation, and injury in their occurrence, development, and outcomes. The concentration of reactive oxygen species (ROS) within cells has been demonstrated as a pivotal player in modulating these intricate pathological processes, exerting significant roles in restoring oral functionality and maintaining tissue structural integrity. Due to their enzyme-like catalytic properties, unique composition, and intelligent design, ROS-based nanomaterials have garnered considerable attention in oral nanomedicine. Such nanomaterials have the capacity to influence the spatiotemporal dynamics of ROS within biological systems, guiding the evolution of intra-ROS to facilitate therapeutic interventions. This paper reviews the latest advancements in the design, functional customization, and oral medical applications of ROS-based nanomaterials. Through the analysis of the components and designs of various novel nanozymes and ROS-based nanoplatforms responsive to different stimuli dimensions, it elaborates on their impacts on the dynamic behavior of intra-ROS and their potential regulatory mechanisms within the body. Furthermore, it discusses the prospects and strategies of nanotherapies based on ROS scavenging and generation in oral diseases, offering alternative insights for the design and development of nanomaterials for treating ROS-related conditions.
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Affiliation(s)
- Xin Luo
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Yanli Zhang
- Stomatological HospitalSchool of StomatologySouthern Medical UniversityGuangzhou510280China
| | - Yuting Zeng
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Dehong Yang
- Department of Orthopedics Spinal SurgeryNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Zhiyan Zhou
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Ziting Zheng
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Ping Xiao
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Xian Ding
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Qianlin Li
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Jiaping Chen
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Qianwen Deng
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Xincen Zhong
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Sijie Qiu
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
| | - Wenjuan Yan
- Department of StomatologyNanfang HospitalSouthern Medical UniversityGuangzhou510515China
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Hayam R, Hamias S, Skitel Moshe M, Davidov T, Yen FC, Baruch L, Machluf M. Porcine Bone Extracellular Matrix Hydrogel as a Promising Graft for Bone Regeneration. Gels 2025; 11:173. [PMID: 40136879 PMCID: PMC11942433 DOI: 10.3390/gels11030173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/18/2025] [Accepted: 02/24/2025] [Indexed: 03/27/2025] Open
Abstract
Bone defects resulting from trauma, tumors, or congenital conditions pose significant challenges for natural healing and often require grafting solutions. While autografts remain the gold standard, their limitations, such as restricted availability and donor site complications, underscore the need for alternative approaches. The present research investigates the potential of porcine-derived bone extracellular matrix (pbECM) hydrogel as a highly promising bioactive scaffold for bone regeneration, comparing it to the human-derived bECM (hbECM). Porcine and human cancellous bones were decellularized and characterized in terms of their composition and structure. Further, the ECMs were processed into hydrogels, and their rheological properties and cytocompatibility were studied in vitro while their biocompatibility was studied in vivo using a mouse model. The potential of the pbECM hydrogel as a bone graft was evaluated in vivo using a rat femoral defect model. Our results demonstrated the excellent preservation of essential ECM components in both the pbECM and hbECM with more than 90% collagen out of all proteins. Rheological analyses revealed the superior mechanical properties of the pbECM hydrogel compared to the hbECM, with an approximately 10-fold higher storage modulus and a significantly later deformation point. These stronger gel properties of the pbECM were attributed to the higher content of structural proteins and residual minerals. Both the pbECM and hbECM effectively supported mesenchymal stem cell adhesion, viability, and proliferation, achieving a 20-fold increase in cell number within 10 days and highlighting their strong bioactive potential. In vivo, pbECM hydrogels elicited a minimal immunogenic response. Most importantly, when implanted in a rat femoral defect model, pbECM hydrogel had significantly enhanced bone regeneration through graft integration, stem cell recruitment, and differentiation. New bone formation was observed at an average of 50% of the defect volume, outperforming the commercial demineralized bone matrix (DBM), in which the new bone filled only 35% of the defect volume. These results position pbECM hydrogel as a highly effective and biocompatible scaffold for bone tissue engineering, offering a promising alternative to traditional grafting methods and paving the way for future clinical applications in bone repair.
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Affiliation(s)
- Rotem Hayam
- Faculty of Biotechnology & Food Engineering, Technion—Israel Institute of Technology (IIT), Haifa 3200003, Israel; (R.H.); (S.H.); (T.D.); (F.-C.Y.); (L.B.)
| | - Shani Hamias
- Faculty of Biotechnology & Food Engineering, Technion—Israel Institute of Technology (IIT), Haifa 3200003, Israel; (R.H.); (S.H.); (T.D.); (F.-C.Y.); (L.B.)
| | - Michal Skitel Moshe
- The Interdisciplinary Program for Biotechnology, Technion—Israel Institute of Technology, Haifa 3200003, Israel;
| | - Tzila Davidov
- Faculty of Biotechnology & Food Engineering, Technion—Israel Institute of Technology (IIT), Haifa 3200003, Israel; (R.H.); (S.H.); (T.D.); (F.-C.Y.); (L.B.)
| | - Feng-Chun Yen
- Faculty of Biotechnology & Food Engineering, Technion—Israel Institute of Technology (IIT), Haifa 3200003, Israel; (R.H.); (S.H.); (T.D.); (F.-C.Y.); (L.B.)
| | - Limor Baruch
- Faculty of Biotechnology & Food Engineering, Technion—Israel Institute of Technology (IIT), Haifa 3200003, Israel; (R.H.); (S.H.); (T.D.); (F.-C.Y.); (L.B.)
| | - Marcelle Machluf
- Faculty of Biotechnology & Food Engineering, Technion—Israel Institute of Technology (IIT), Haifa 3200003, Israel; (R.H.); (S.H.); (T.D.); (F.-C.Y.); (L.B.)
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Jenkins TL, Venkataraman S, Saleh A, Calve S, Pourdeyhimi B, Little D. Application of Tendon-Derived Matrix and Carbodiimide Crosslinking Matures the Engineered Tendon-Like Proteome on Meltblown Scaffolds. J Tissue Eng Regen Med 2025; 2025:2184723. [PMID: 40224957 PMCID: PMC11985250 DOI: 10.1155/term/2184723] [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: 07/23/2024] [Accepted: 01/20/2025] [Indexed: 04/15/2025]
Abstract
Background: Tendon injuries are increasingly common and heal by fibrosis rather than scar-less regeneration. Tissue engineering seeks to improve repair using synthetic polymer scaffolds with biomimetic factors to enhance the regenerative potential. Methods: In this study, we compared three groups, namely, poly(lactic acid) (PLA) meltblown scaffolds, PLA meltblown scaffolds coated with tendon-derived matrix (TDM), and PLA meltblown scaffolds with carbodiimide crosslinked TDM (2.5:1:1 EDC:NHS:COOH ratio) (EDC-TDM) and determined their potential for engineered tendon development. We cultured human adipose stem cells (hASCs) for 28 days on meltblown scaffolds (n = 4-6/group) and measured tensile mechanical function, matrix synthesis, and matrix composition using biochemical assays and proteomics. Results: Coating PLA meltblown scaffolds with TDM improved yield stretch and stress at 28 days compared with PLA. Matrix synthesis rates for TDM or EDC-TDM were similar to PLA. Proteomic analysis revealed that hASCs produced a collagen-rich extracellular matrix, with many tendon-related matrix proteins. Coating scaffolds with TDM led to an increase in collagen type I whereas EDC-TDM scaffolds had an increase in glycoproteins and ECM regulators compared with other groups, consistent with increased maturity of the newly deposited matrix. Conclusions: TDM coating and crosslinking of meltblown scaffolds demonstrated matricellular benefits for the proteome of engineered tendon development but provided fewer clear benefits toward mechanical, biochemical, and rate of matrix accumulation than expected, and that previous work with electrospun scaffolds would suggest. However, electrospun scaffolds have different fiber structure and microarchitecture than meltblown, suggesting that further consideration of these differences and refinement of TDM application methods to meltblown scaffolds is required.
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Affiliation(s)
- Thomas Lee Jenkins
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
| | - Sadhana Venkataraman
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
| | - Aya Saleh
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
| | - Sarah Calve
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
- Department of Mechanical Engineering, University of Colorado-Boulder, Boulder, Colorado, USA
| | - Behnam Pourdeyhimi
- The Nonwovens Institute, North Carolina State University, Raleigh, North Carolina, USA
| | - Dianne Little
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
- Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA
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Saadh MJ, Jasim NY, Ahmed MH, Ballal S, Kumar A, Atteri S, Vashishth R, Rizaev J, Alhili A, Jawad MJ, Yazdi F, Salajegheh A, Akhavan-Sigari R. Critical roles of miR-21 in promotions angiogenesis: friend or foe? Clin Exp Med 2025; 25:66. [PMID: 39998742 PMCID: PMC11861128 DOI: 10.1007/s10238-025-01600-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 02/11/2025] [Indexed: 02/27/2025]
Abstract
MiRNAs are small RNA strands that are managed following transcription and are of substantial importance in blood vessel formation. It is essential to oversee the growth, differentiation, death, movement and construction of tubes by angiogenesis-affiliated cells. If miRNAs are not correctly regulated in regard to angiogenesis, it can deteriorate the health and lead to various illnesses, which include cancer, cardiovascular disorder, critical limb ischemia, Crohn's disease, ocular diseases, diabetic microvascular complications, and more. Consequently, it is vital to understand the crucial part that miRNAs play in the development of blood vessels, so we can develop reliable treatment plans for vascular diseases. This write-up will assess the critical role of miR-21/exosomal miR-21 in managing angiogenesis associated with bone growth, wound recovery, and other pathological conditions like tumor growth, ocular illnesses, diabetes, and other diseases connected to formation of blood vessels. Previous investigations have demonstrated that miR-21 is present at higher amounts in certain cancerous cells, and it influences a multitude of genes that moderate the increased creation of blood vessels. Furthermore, studies demonstrated that exosomal miR-21 has the capacity to interact with endothelial cells to foster tumor angiogenesis. For that reason, this review explains the critical importance of miR-21/exosomal miR-21 in managing both healthy and diseased states of angiogenesis.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | - Nisreen Yasir Jasim
- College of Nursing, National University of Science and Technology, Nasiriyah, Dhi Qar, Iraq
| | | | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Abhishek Kumar
- School of Pharmacy-Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Gangoh, Uttar Pradesh, 247341, India
- Department of Pharmacy, Arka Jain University, Jamshedpur, Jharkhand, 831001, India
| | - Shikha Atteri
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjheri, Mohali, Punjab, 140307, India
| | - Raghav Vashishth
- Department of Surgery, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, India
| | - Jasur Rizaev
- Department of Public Health and Healthcare Management, Rector, Samarkand State Medical University, 18, Amir Temur Street, Samarkand, Uzbekistan
| | - Ahmed Alhili
- Medical Technical College, Al-Farahidi University, Baghdad, Iraq
| | | | - Farzaneh Yazdi
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
| | | | - Reza Akhavan-Sigari
- Dr. Schneiderhan GmbH and ISAR Klinikum, Munich, Germany
- Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw, Management University Warsaw, Warsaw, Poland
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Turker B. Redesigning FDM Platforms for Bio-Printing Applications. MICROMACHINES 2025; 16:226. [PMID: 40047710 PMCID: PMC11857145 DOI: 10.3390/mi16020226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/06/2025] [Accepted: 02/14/2025] [Indexed: 03/09/2025]
Abstract
Fused Deposition Modeling (FDM) is a prominent additive manufacturing technique known for its ability to provide cost-effective and fast printing solutions. FDM enables the production of computer-aided 3D designs as solid objects at macro scales with high-precision alignment while sacrificing excellent surface smoothness compared to other 3D printing techniques such as SLA (Stereolithography) and SLS (Selective Laser Sintering). Electro-Spinning (ES) is another technique for producing soft-structured nonwoven micro-scale materials, such as nanofibers. However, compared to the FDM technique, it has limited accuracy and sensitivity regarding high-precision alignment. The need for high-precision alignment of micro-scaled soft structures during the printing process raises the question of whether FDM and ES techniques can be combined. Today, the printing technique with such capability is called Melt Electro Writing (MEW), and in practice, it refers to the basic working principle on which bio-printers are based. This paper aims to examine how these two techniques can be combined affordably. Comparatively, it presents output production processes, design components, parameters, and materials used in output production. It discusses the limitations and advantages of such a hybrid platform, specifically from the perspective of engineering design and its biomedical applications.
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Affiliation(s)
- Burak Turker
- Department of Biomedical Engineering, Engineering Faculty, Ahmet Necdet Sezer Campus, Afyon Kocatepe University, Afyonkarahisar 03200, Turkey
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Evangelista RAA, Pires ALR, Nogueira BV. A chronological history of heart valve prostheses to offer perspectives of their limitations. Front Bioeng Biotechnol 2025; 13:1533421. [PMID: 40028289 PMCID: PMC11868121 DOI: 10.3389/fbioe.2025.1533421] [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: 11/23/2024] [Accepted: 01/23/2025] [Indexed: 03/05/2025] Open
Abstract
Prosthetic heart valves (PHV) have been studied for around 70 years. They are the best alternative to save the life of patients with cardiac valve diseases. However, current PHVs may still cause significant disadvantages to patients. In general, native heart valves show complex structures and reproducing their functions challenges scientists. Valve repair and replacement are the options to heal heart valve diseases (VHDs), such as stenosis and regurgitation, which show high morbidity and mortality worldwide. Valve repair contributes to the performance of cardiac cycles. However, it fails to restore valve anatomy to its normal condition. On the other hand, replacement is the only alternative to treat valve degeneration. It may do so by mechanical or bioprosthetic valves. Although prostheses may restructure patients' cardiac cycle, both prostheses may show limitations and potential disadvantages, such as mechanical valves causing thrombogenicity or bioprosthetic valves, calcification. Thus, prostheses require constant improvements to remedy these limitations. Although the design of mechanical valve structures has improved, their raw materials cause great disadvantages, and alternatives for this problem remain scarce. Cardiac valve tissue engineering emerged 30 years ago and has improved over time, e.g., xenografts and fabricated heart valves serving as scaffolds for cell seeding. Thus, this review describes cardiac valve substitutes, starting with the history of valvular prosthesis transplants and ending with some perspectives to alleviate the limitations of artificial valves.
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Affiliation(s)
| | - Ana Luiza Resende Pires
- Graduate Program in Biotechnology, Federal University of Espírito Santo. Av. Marechal Campos, Vitória, Brazil
| | - Breno Valentim Nogueira
- Rede Nordeste de Biotecnologia (RENORBIO), Federal University of Espírito Santo (UFES), Vitória, Brazil
- Graduate Program in Biotechnology, Federal University of Espírito Santo. Av. Marechal Campos, Vitória, Brazil
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35
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Olevsky LM, Jacques MG, Hixon KR. PoreVision: A Program for Enhancing Efficiency and Accuracy in SEM Pore Analyses of Gels and Other Porous Materials. Gels 2025; 11:132. [PMID: 39996675 PMCID: PMC11855315 DOI: 10.3390/gels11020132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/08/2025] [Accepted: 01/13/2025] [Indexed: 02/26/2025] Open
Abstract
Porous gels are frequently utilized as cell scaffolds in tissue engineering. Previous studies have highlighted the significance of scaffold pore size and pore orientation in influencing cell migration and differentiation. Moreover, there exists a considerable body of research focused on optimizing pore characteristics to enhance scaffold performance. However, current methods for numerical pore characterization typically involve expensive machines or manual size measurements using image manipulation software. In this project, our objective is to develop a user-friendly, versatile, and freely accessible software tool using Python scripting. This tool aims to streamline and objectify pore characterization, thereby accelerating research efforts and providing a standardized framework for researchers working with porous gels. Our group found that first-time users of PoreVision and ImageJ take similar amounts of time to use both programs; however, PoreVision is capable of handling larger datasets with reduced variability. Further, PoreVision users exhibited lower variability in area and orientation measurements compared to ImageJ, while perimeter variability was similar between the two. PoreVision showed higher variability in average measurements, likely due to its larger sample size and broader range of pore sizes, which may be missed in ImageJ's manual scanning approach. By facilitating quantitative analysis of pore size, shape, and orientation, our software tool will contribute to a more comprehensive understanding of scaffold properties and their impact on cellular behavior. Ultimately, we aim to aid researchers in the field of tissue engineering with a user-friendly tool that enhances the reproducibility and reliability of pore characterization analyses.
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Affiliation(s)
- Levi M. Olevsky
- Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA;
| | - Mason G. Jacques
- College of Engineering and Physical Sciences, University of New Hampshire, Durham, NH 03824, USA;
| | - Katherine R. Hixon
- Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA;
- Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA
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Hsu YW, Ma L, Tang Y, Li M, Zhou C, Geng Y, Zhang C, Wang T, Guo W, Li M, Wang Y. The application of aptamers in the repair of bone, nerve, and vascular tissues. J Mater Chem B 2025; 13:1872-1889. [PMID: 39760465 DOI: 10.1039/d4tb02180k] [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: 01/07/2025]
Abstract
Aptamers represent a distinct category of short nucleotide sequences or peptide molecules characterized by their ability to bind to specific targets with high precision. These molecules are predominantly synthesized through SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology. Recent findings indicate that aptamers may have significant applications in regenerative medicine, particularly in the domain of tissue repair. In comparison to other bioactive agents, aptamers exhibit superior specificity and affinity, are more readily accessible, and can be chemically modified, thereby presenting a promising avenue for the functionalization of tissue engineering materials in tissue repair applications. This review delineates the properties of aptamers and examines the methodologies and advancements related to aptamer-functionalized hydrogels, nanoparticles, and electrospun materials. It categorizes the four primary functions of aptamers in tissue repair, namely regeneration, delivery systems, anti-inflammatory actions, and pro-coagulation effects. Furthermore, the review explores the utilization of aptamer-functionalized tissue engineering materials in the repair of bone, nerve, and vascular tissues, highlighting the mechanisms by which aptamers facilitate tissue growth and repair through regenerative properties and their role in transporting substances that promote repair. Lastly, the review addresses the future prospects and challenges associated with the application of aptamers in tissue repair, offering novel insights and directions for further research and application in this domain.
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Affiliation(s)
- Yu-Wei Hsu
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
- Emergency Department, Peking University People's Hospital, Beijing, 100044, China.
| | - Le Ma
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
| | - Ye Tang
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
- Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing, 100044, China
| | - Mengen Li
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
- Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing, 100044, China
| | - Chengkai Zhou
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
| | - Yan Geng
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
| | - Chenxi Zhang
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
| | - Tianbing Wang
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
| | - Wei Guo
- Emergency Department, Peking University People's Hospital, Beijing, 100044, China.
| | - Ming Li
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
| | - Yanhua Wang
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing, 100044, China.
- National Center for Trauma Medicine, Beijing, 100044, China
- Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing, 100044, China
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Zhao X, Yao M, Wang Y, Feng C, Yang Y, Tian L, Bao C, Li X, Zhu X, Zhang X. Neuroregulation during Bone Formation and Regeneration: Mechanisms and Strategies. ACS APPLIED MATERIALS & INTERFACES 2025; 17:7223-7250. [PMID: 39869030 DOI: 10.1021/acsami.4c16786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2025]
Abstract
The skeleton is highly innervated by numerous nerve fibers. These nerve fibers, in addition to transmitting information within the bone and mediating bone sensations, play a crucial role in regulating bone tissue formation and regeneration. Traditional bone tissue engineering (BTE) often fails to achieve satisfactory outcomes when dealing with large-scale bone defects, which is frequently related to the lack of effective reconstruction of the neurovascular network. In recent years, increasing research has revealed the critical role of nerves in bone metabolism. Nerve fibers regulate bone cells through neurotransmitters, neuropeptides, and peripheral glial cells. Furthermore, nerves also coordinate with the vascular and immune systems to jointly construct a microenvironment favorable for bone regeneration. As a signaling driver of bone formation, neuroregulation spans the entire process of bone physiological activities from the embryonic formation to postmaturity remodeling and repair. However, there is currently a lack of comprehensive summaries of these regulatory mechanisms. Therefore, this review sketches out the function of nerves during bone formation and regeneration. Then, we elaborate on the mechanisms of neurovascular coupling and neuromodulation of bone immunity. Finally, we discuss several novel strategies for neuro-bone tissue engineering (NBTE) based on neuroregulation of bone, focusing on the coordinated regeneration of nerve and bone tissue.
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Affiliation(s)
- Xiangrong Zhao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University, Chengdu 610041, Sichuan, China
| | - Meilin Yao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yuyi Wang
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Cong Feng
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Yuhan Yang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University, Chengdu 610041, Sichuan, China
| | - Luoqiang Tian
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Chongyun Bao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University, Chengdu 610041, Sichuan, China
| | - Xiangfeng Li
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Xiangdong Zhu
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
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Zhao Y, Zhang Q, Zhang S, Chen J, Kong L, Gao J, Zhu Q. Adrenomedullin-loaded Gelatin Methacryloyl Hydrogel Promotes Endogenous Dental Pulp Regeneration: An In Vitro and In Vivo Study. J Endod 2025; 51:172-184. [PMID: 39581536 DOI: 10.1016/j.joen.2024.11.011] [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: 08/15/2024] [Revised: 10/22/2024] [Accepted: 11/17/2024] [Indexed: 11/26/2024]
Abstract
INTRODUCTION To prepare a gelatin methacryloyl (GelMA) hydrogel scaffold embedded with adrenomedullin (ADM) and investigate its impact and underlying mechanisms in endogenous pulp regeneration. METHODS ADM was evenly distributed within the GelMA hydrogel through a simple and conventional physical mixing technique. The scaffold underwent characterization via scanning electron microscopy, alongside assessments of swelling, degradation, and release properties. Biocompatibility was evaluated using cytoskeletal and live-dead staining techniques. The hydrogel's influence on dental pulp stem cells' proliferation, migration, and differentiation was assessed with CCK-8 assays, Transwell assays, and alizarin red and alkaline phosphatase staining. Transcriptomics provided insights into potential mechanisms. The angiogenic effects on umbilical vein endothelial cells were examined using scratch and tube formation assays. In vivo, the composite hydrogel's regenerative capacity was tested in a rat model of pulp regeneration. Statistical analysis involved Student's t-test and one-way analysis of variance, with significance set at P < .05. RESULTS The ADM-loaded GelMA (GelMA@ADM) hydrogel displayed a porous architecture under electron microscopy conducive to cell adhesion and demonstrated excellent biocompatibility. In vitro experiments showed that GelMA@ADM significantly boosted dental pulp stem cells' migration, proliferation, and differentiation, and enhanced the angiogenic activity of umbilical vein endothelial cells after one week of treatment. Corresponding in vivo experiments revealed that GelMA@ADM facilitated the formation of new vascularized pulp tissue after 2 weeks of treatment. CONCLUSIONS The GelMA@ADM hydrogel effectively promotes dental pulp stem cells' proliferation and differentiation, augments vascularization by umbilical vein endothelial cells, and fosters the creation of new vascularized pulp tissue. These findings underscore the potential of GelMA@ADM hydrogel for endogenous pulp regeneration.
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Affiliation(s)
- Yangpeng Zhao
- Department of Stomatology, The First Affiliated Hospital of Naval Medical University, Changhai Hospital, Shanghai, China
| | - Qian Zhang
- Department of Stomatology, The First Affiliated Hospital of Naval Medical University, Changhai Hospital, Shanghai, China
| | - Song Zhang
- Department of Orthopedics, The First Affiliated Hospital of Naval Medical University, Changhai Hospital, Shanghai, China
| | - Jianan Chen
- Department of Stomatology, The First Affiliated Hospital of Naval Medical University, Changhai Hospital, Shanghai, China
| | - Lingtong Kong
- Department of Orthopedics, The First Affiliated Hospital of Naval Medical University, Changhai Hospital, Shanghai, China
| | - Jianyong Gao
- Department of Stomatology, The First Affiliated Hospital of Naval Medical University, Changhai Hospital, Shanghai, China.
| | - Qiang Zhu
- Department of Stomatology, The First Affiliated Hospital of Naval Medical University, Changhai Hospital, Shanghai, China.
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Wang Y, Li Z, Yu R, Chen Y, Wang D, Zhao W, Ge S, Liu H, Li J. Metal-phenolic network biointerface-mediated cell regulation for bone tissue regeneration. Mater Today Bio 2025; 30:101400. [PMID: 39759849 PMCID: PMC11699301 DOI: 10.1016/j.mtbio.2024.101400] [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: 11/07/2024] [Revised: 12/07/2024] [Accepted: 12/09/2024] [Indexed: 01/07/2025] Open
Abstract
Bone tissue regeneration presents a significant challenge in clinical treatment due to inadequate coordination between implant materials and reparative cells at the biomaterial-bone interfaces. This gap underscores the necessity of enhancing interaction modulation between cells and biomaterials, which is a crucial focus in bone tissue engineering. Metal-polyphenolic networks (MPN) are novel inorganic-organic hybrid complexes that are formed through coordination interactions between phenolic ligands and metal ions. These networks provide a multifunctional platform for biomedical applications, with the potential for tailored design and modifications. Despite advances in understanding MPN and their role in bone tissue regeneration, a comprehensive overview of the related mechanisms is lacking. Here, we address this gap by focusing on MPN biointerface-mediated cellular regulatory mechanisms during bone regeneration. We begin by reviewing the natural healing processes of bone defects, followed by a detailed examination of MPN, including their constituents and distinctive characteristics. We then explore the regulatory influence of MPN biointerfaces on key cellular activities during bone regeneration. Additionally, we illustrate their primary applications in addressing inflammatory bone loss, regenerating critical-size bone defects, and enhancing implant-bone integration. In conclusion, this review elucidates how MPN-based interfaces facilitate effective bone tissue regeneration, advancing our understanding of material interface-mediated cellular control and the broader field of tissue engineering.
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Affiliation(s)
- Ying Wang
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
| | - Zhibang Li
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
| | - Ruiqing Yu
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
| | - Yi Chen
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
| | - Danyang Wang
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
| | - Weiwei Zhao
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
| | - Shaohua Ge
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
| | - Hong Liu
- State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong, 250100, China
| | - Jianhua Li
- Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China
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Wright C, Zotter SF, Tung WS, Reikersdorfer K, Homer A, Kheir N, Paschos N. Current Concepts and Clinical Applications in Cartilage Tissue Engineering. Tissue Eng Part A 2025; 31:87-99. [PMID: 39812645 DOI: 10.1089/ten.tea.2024.0300] [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: 01/16/2025] Open
Abstract
Cartilage injuries are extremely common in the general population, and conventional interventions have failed to produce optimal results. Tissue engineering (TE) technology has been developed to produce neocartilage for use in a variety of cartilage-related conditions. However, progress in the field of cartilage TE has historically been difficult due to the high functional demand and avascular nature of the tissue. Recent advancements in cell sourcing, biostimulation, and scaffold technology have revolutionized the field and made the clinical application of this technology a reality. Cartilage engineering technology will continue to expand its horizons to fully integrate three-dimensional printing, gene editing, and optimal cell sourcing in the future. This review focuses on the recent advancements in the field of cartilage TE and the landscape of clinical treatments for a variety of cartilage-related conditions.
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Affiliation(s)
- Connor Wright
- University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Orthopaedics, Massachusetts General Brigham, Boston, MA, USA
| | | | - Wei Shao Tung
- Department of Orthopaedics, Massachusetts General Brigham, Boston, MA, USA
| | - Kristen Reikersdorfer
- Department of Orthopaedics, Massachusetts General Brigham, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Andrew Homer
- Department of Orthopaedics, Massachusetts General Brigham, Boston, MA, USA
| | - Nadim Kheir
- Department of Orthopaedics, Massachusetts General Brigham, Boston, MA, USA
| | - Nikolaos Paschos
- Department of Orthopaedics, Massachusetts General Brigham, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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Peng X, Chen X, Zhang Y, Tian Z, Wang M, Chen Z. Advances in the pathology and treatment of osteoarthritis. J Adv Res 2025:S2090-1232(25)00072-4. [PMID: 39889821 DOI: 10.1016/j.jare.2025.01.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 01/27/2025] [Accepted: 01/27/2025] [Indexed: 02/03/2025] Open
Abstract
BACKGROUND Osteoarthritis (OA), a widespread degenerative joint disease, predominantly affects individuals from middle age onwards, exhibiting non-inflammatory characteristics. OA leads to the gradual deterioration of articular cartilage and subchondral bone, causing pain and reduced mobility. The risk of OA increases with age, making it a critical health concern for seniors. Despite significant research efforts and various therapeutic approaches, the precise causes of OA remain unclear. AIM OF REVIEW This paper provides a thorough examination of OA characteristics, pathogenic mechanisms at various levels, and personalized treatment strategies for different OA stages. The review aims to enhance understanding of disease mechanisms and establish a theoretical framework for developing more effective therapeutic interventions. KEY SCIENTIFIC CONCEPTS OF REVIEW This review systematically examines OA through multiple perspectives, integrating current knowledge of clinical presentation, pathological mechanisms, and associated signaling pathways. It assesses diagnostic methods and reviews both pharmacological and surgical treatments for OA, as well as emerging tissue engineering approaches to manage the disease. While therapeutic strategies such as exercise, anti-inflammatory drugs, and surgical interventions are employed to manage symptoms and modify joint structure, none have been able to effectively halt OA's advancement or achieve long-lasting symptom relief. Tissue engineering strategies, such as cell-seeded scaffolds, supportive matrices, and growth factor delivery, have emerged as promising approaches for cartilage repair and OA treatment. To combat the debilitating effects of OA, it is crucial to investigate the molecular basis of its pathogenesis and seek out innovative therapeutic targets for more potent preventive and treatment strategies.
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Affiliation(s)
- Xueliang Peng
- Provincial Key Laboratory of Biotechnology of Shaanxi, Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Faculty of Life Science, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi Province 710069, China
| | - Xuanning Chen
- College of Stomatology, Shanghai Jiao Tong University, Shanghai 200215, China
| | - Yifan Zhang
- Provincial Key Laboratory of Biotechnology of Shaanxi, Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Faculty of Life Science, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi Province 710069, China
| | - Zhichao Tian
- Provincial Key Laboratory of Biotechnology of Shaanxi, Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Faculty of Life Science, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi Province 710069, China
| | - Meihua Wang
- Provincial Key Laboratory of Biotechnology of Shaanxi, Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Faculty of Life Science, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi Province 710069, China
| | - Zhuoyue Chen
- Provincial Key Laboratory of Biotechnology of Shaanxi, Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Faculty of Life Science, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi Province 710069, China.
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Dong DL, Jin GZ. Targeting Chondrocyte Hypertrophy as Strategies for the Treatment of Osteoarthritis. Bioengineering (Basel) 2025; 12:77. [PMID: 39851351 PMCID: PMC11760869 DOI: 10.3390/bioengineering12010077] [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: 11/28/2024] [Revised: 01/08/2025] [Accepted: 01/14/2025] [Indexed: 01/26/2025] Open
Abstract
Osteoarthritis (OA) is a common joint disease characterized by pain and functional impairment, which severely impacts the quality of life of middle-aged and elderly individuals. During normal bone development, chondrocyte hypertrophy is a natural physiological process. However, in the progression of OA, chondrocyte hypertrophy becomes one of its key pathological features. Although there is no definitive evidence to date confirming that chondrocyte hypertrophy is the direct cause of OA, substantial experimental data indicate that it plays an important role in the disease's pathogenesis. In this review, we first explore the mechanisms underlying chondrocyte hypertrophy in OA and offer new insights. We then propose strategies for inhibiting chondrocyte hypertrophy from the perspectives of targeting signaling pathways and tissue engineering, ultimately envisioning the future prospects of OA treatment.
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Affiliation(s)
- Da-Long Dong
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea;
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Guang-Zhen Jin
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea;
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Li T, Zhang L, Qu X, Lei B. Advanced Thermoactive Nanomaterials for Thermomedical Tissue Regeneration: Opportunities and Challenges. SMALL METHODS 2025; 9:e2400510. [PMID: 39588862 DOI: 10.1002/smtd.202400510] [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: 06/04/2024] [Revised: 11/06/2024] [Indexed: 11/27/2024]
Abstract
Nanomaterials usually possess remarkable properties, including excellent biocompatibility, unique physical and chemical characteristics, and bionic attributes, which make them highly promising for applications in tissue regeneration. Thermal therapy has emerged as a versatile approach for wound healing, nerve repair, bone regeneration, tumor therapy, and antibacterial tissue regeneration. By combining nanomaterials with thermal therapy, multifunctional nanomaterials with thermogenic effects and tissue regeneration capabilities can be engineered to achieve enhanced therapeutic outcomes. This study provides a comprehensive review of the effects of thermal stimulation on cellular and tissue regeneration. Furthermore, it highlights the applications of photothermal, magnetothermal, and electrothermal nanomaterials, and thermally responsive drug delivery systems in tissue engineering. In Addition, the bioactivities and biocompatibilities of several representative thermal nanomaterials are discussed. Finally, the challenges facing thermal nanomaterials are outlined, and future prospects in the field are presented with the aim of offering new opportunities and avenues for the utilization of thermal nanomaterials in tissue regeneration.
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Affiliation(s)
- Ting Li
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Long Zhang
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Xiaoyan Qu
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Bo Lei
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China
- State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710054, China
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Wang D, Liu W, Venkatesan JK, Madry H, Cucchiarini M. Therapeutic Controlled Release Strategies for Human Osteoarthritis. Adv Healthc Mater 2025; 14:e2402737. [PMID: 39506433 PMCID: PMC11730424 DOI: 10.1002/adhm.202402737] [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: 07/24/2024] [Revised: 10/15/2024] [Indexed: 11/08/2024]
Abstract
Osteoarthritis is a progressive, irreversible debilitating whole joint disease that affects millions of people worldwide. Despite the availability of various options (non-pharmacological and pharmacological treatments and therapy, orthobiologics, and surgical interventions), none of them can definitively cure osteoarthritis in patients. Strategies based on the controlled release of therapeutic compounds via biocompatible materials may provide powerful tools to enhance the spatiotemporal delivery, expression, and activities of the candidate agents as a means to durably manage the pathological progression of osteoarthritis in the affected joints upon convenient intra-articular (injectable) delivery while reducing their clearance, dissemination, or side effects. The goal of this review is to describe the current knowledge and advancements of controlled release to treat osteoarthritis, from basic principles to applications in vivo using therapeutic recombinant molecules and drugs and more innovatively gene sequences, providing a degree of confidence to manage the disease in patients in a close future.
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Affiliation(s)
- Dan Wang
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Wei Liu
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Jagadeesh K. Venkatesan
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Henning Madry
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Magali Cucchiarini
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
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Capandova M, Sedlakova V, Vorac Z, Kotasova H, Dumkova J, Moran L, Jaros J, Antol M, Bohaciakova D, Hampl A. Using Polycaprolactone Nanofibers for the Proof-of-Concept Construction of the Alveolar-Capillary Interface. J Biomed Mater Res A 2025; 113:e37824. [PMID: 39474705 DOI: 10.1002/jbm.a.37824] [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: 05/29/2024] [Revised: 09/14/2024] [Accepted: 10/14/2024] [Indexed: 12/26/2024]
Abstract
The alveolar-capillary interface is the key functional element of gas exchange in the human lung, and disruptions to this interface can lead to significant medical complications. However, it is currently challenging to adequately model this interface in vitro, as it requires not only the co-culture of human alveolar epithelial and endothelial cells but mainly the preparation of a biocompatible scaffold that mimics the basement membrane. This scaffold should support cell seeding from both sides, and maintain optimal cell adhesion, growth, and differentiation conditions. Our study investigates the use of polycaprolactone (PCL) nanofibers as a versatile substrate for such cell cultures, aiming to model the alveolar-capillary interface more accurately. We optimized nanofiber production parameters, utilized polyamide mesh UHELON as a mechanical support for scaffold handling, and created 3D-printed inserts for specialized co-cultures. Our findings confirm that PCL nanofibrous scaffolds are manageable and support the co-culture of diverse cell types, effectively enabling cell attachment, proliferation, and differentiation. Our research establishes a proof-of-concept model for the alveolar-capillary interface, offering significant potential for enhancing cell-based testing and advancing tissue-engineering applications that require specific nanofibrous matrices.
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Affiliation(s)
- Michaela Capandova
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Institute of Computer Science, Masaryk University, Brno, Czech Republic
| | - Veronika Sedlakova
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Zbynek Vorac
- Department of Plasma Physics and Technology, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Hana Kotasova
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Jana Dumkova
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Lukas Moran
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Josef Jaros
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic
| | - Matej Antol
- Institute of Computer Science, Masaryk University, Brno, Czech Republic
| | - Dasa Bohaciakova
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic
| | - Ales Hampl
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic
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Park JH, Bae HS, Kim I, Jung J, Roh Y, Lee D, Hwang TS, Lee HC, Byun JH. Efficacy of Bone Regeneration Cell Therapy Using Mesenchymal Stem Cells Originating from Embryonic Stem Cells in Animal Models; Bone Defects and Osteomyelitis. Tissue Eng Regen Med 2025; 22:145-157. [PMID: 39612134 PMCID: PMC11712062 DOI: 10.1007/s13770-024-00683-9] [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: 09/12/2024] [Revised: 10/31/2024] [Accepted: 11/08/2024] [Indexed: 11/30/2024] Open
Abstract
BACKGROUND Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture. METHODS This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DW-MSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts. RESULTS Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring. CONCLUSION Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.
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Affiliation(s)
- Jin-Ho Park
- Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Medical Sciences, Gyeongsang National University, Jinju, 52727, Republic of Korea
- Department of Nutritional Science, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA
| | - Han-Sol Bae
- Cell Therapy Center, Daewoong Pharmaceutical, Co., Ltd., Yongin, 17028, Republic of Korea
| | - Ingeun Kim
- Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - Jiwoon Jung
- Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - Yoonho Roh
- Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - Dongbin Lee
- Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - Tae Sung Hwang
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - Hee-Chun Lee
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - June-Ho Byun
- Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Medical Sciences, Gyeongsang National University, Jinju, 52727, Republic of Korea.
- Department of Convergence Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea.
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Sun M, LaSala VR, Giuglaris C, Blitzer D, Jackman S, Ustunel S, Rajesh K, Kalfa D. Cardiovascular patches applied in congenital cardiac surgery: Current materials and prospects. Bioeng Transl Med 2025; 10:e10706. [PMID: 39801761 PMCID: PMC11711229 DOI: 10.1002/btm2.10706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 06/12/2024] [Accepted: 07/17/2024] [Indexed: 01/16/2025] Open
Abstract
Congenital Heart Defects (CHDs) are the most common congenital anomalies, affecting between 4 and 75 per 1000 live births. Cardiovascular patches (CVPs) are frequently used as part of the surgical armamentarium to reconstruct cardiovascular structures to correct CHDs in pediatric patients. This review aims to evaluate the history of cardiovascular patches, currently available options, clinical applications, and important features of these patches. Performance and outcomes of different patch materials are assessed to provide reference points for clinicians. The target audience includes clinicians seeking data on clinical performance as they make choices between different patch products, as well as scientists and engineers working to develop patches or synthesize new patch materials.
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Affiliation(s)
- Mingze Sun
- Department of SurgeryColumbia UniversityNew YorkNew YorkUSA
| | | | - Caroline Giuglaris
- Department of SurgeryColumbia UniversityNew YorkNew YorkUSA
- UMR 168 Laboratoire Physique des Cellules et CancerInstitut Curie, PSL Research University, Sorbonne Université, CNRSParisFrance
| | - David Blitzer
- Department of SurgeryColumbia UniversityNew YorkNew YorkUSA
| | - Sophia Jackman
- Department of SurgeryColumbia UniversityNew YorkNew YorkUSA
| | - Senay Ustunel
- Department of SurgeryColumbia UniversityNew YorkNew YorkUSA
| | - Kavya Rajesh
- Department of SurgeryColumbia UniversityNew YorkNew YorkUSA
| | - David Kalfa
- Department of SurgeryColumbia UniversityNew YorkNew YorkUSA
- Division of Cardiac, Thoracic and Vascular Surgery, Section of Pediatric and Congenital Cardiac SurgeryNew‐York Presbyterian—Morgan Stanley Children's Hospital, Columbia University Irving Medical CenterNew YorkNew YorkUSA
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Dogan SE, Ozturk C, Koc B. Design of patient-specific mandibular reconstruction plates and a hybrid scaffold. Comput Biol Med 2025; 184:109380. [PMID: 39602978 DOI: 10.1016/j.compbiomed.2024.109380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 10/24/2024] [Accepted: 11/06/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Managing segmental mandibular defects remains challenging, requiring a multidisciplinary approach despite the remarkable progress in mandibular reconstruction plates, finite element methods, computer-aided design and manufacturing techniques, and novel surgical procedures. Complex surgeries require a comprehensive approach, as using only reconstruction plates or tissue scaffolds may not be adequate for optimal results. The limitations of the treatment options should be investigated towards a patient-specific trend to provide shorter surgery time, better healing, and lower costs. Integrated hybrid scaffold systems are promising in improving mechanical properties and facilitating healing. By combining different materials and structures, hybrid scaffolds can provide enhanced support and stability to the tissue regeneration process, leading to better patient outcomes. The use of such systems represents a significant advancement in tissue engineering and a wide range of medical procedures. MATERIALS AND METHODS A head and neck computed tomography (CT) data of a patient with odontogenic myxoma was used for creating a three-dimensional (3D) mandible model. Virtual osteotomies were performed to create a segmental defect model, including the angulus mandibulae region. The first mandibular reconstruction plate was designed. Finite elemental analyses (FEA) and topology optimizations were performed to create two different reconstruction plates for different treatment scenarios. The FEA were performed for the resulting two plates to assess their biomechanical performance. To provide osteoconductive and osteoinductive properties a scaffold was designed using the defect area. A biomimetic Tricalcium phosphate-Polycaprolactone (TCP-PCL) hybrid bone scaffold enhanced with Hyaluronic acid dipping was manufactured. RESULTS The results of the in-silico analysis indicate that the designed reconstruction plates possess robust biomechanical performance and demonstrate remarkable stability under the most rigorous masticatory activities. Using the Voronoi pattern decreased the mass by %37 without losing endurance. Using reconstruction plates and hybrid scaffolds exhibits promising potential for clinical applications, subject to further in vivo and clinical studies.
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Affiliation(s)
- Sait Emre Dogan
- Bogazici University, Institute of Biomedical Engineering, Istanbul, 34684, Turkiye.
| | - Cengizhan Ozturk
- Bogazici University, Institute of Biomedical Engineering, Istanbul, 34684, Turkiye.
| | - Bahattin Koc
- 3D Bioprinting Laboratory, Sabanci University Nanotechnology Research and Application Center, Istanbul, 34956, Turkiye; Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, 34956, Turkiye.
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Huang W, Dong H, Yan Q, Deng T, Li X, Zhao Z, Li Z, Wang M, Zhang C, Kong B, Shi J, Yuan D. Disulfide-Rich Self-Assembling Peptides Based on Aromatic Amino Acid. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2407464. [PMID: 39491516 DOI: 10.1002/smll.202407464] [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: 08/23/2024] [Revised: 10/18/2024] [Indexed: 11/05/2024]
Abstract
Aromatic residues in assembling peptides play a crucial role in driving peptide self-assembly through π-π stacking and hydrophobic interactions. Although various aromatic capping groups have been extensively studied, systematic investigations into the effects of single aromatic amino acids in assembling peptides remain limited. In this study, the influence of aromatic-aromatic interactions on disulfide-rich assembling peptides is systematically investigated by incorporating three different aromatic amino acids. Their folding propensity, self-assembling properties, and rheological behaviors are evaluated. These results indicate that different aromatic-aromatic interactions have a significant effect on self-assembly abilities, as determined by critical aggregation concentration (CAC) measurements. Furthermore, the biocompatibility of these hydrogels is assessed, and their potential for 3D cell culture is explored. The injectable F1-ox hydrogel demonstrate excellent biocompatibility for SHED and NIH3T3 cells and exhibit a porous structure that facilitates nutrient and cellular metabolic waste exchange. This work provides new insights into the molecular design of peptide-based biomaterials, with a focus on the impact of aromatic residues on disulfide-rich assembling peptides.
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Affiliation(s)
- Wenjing Huang
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Huilei Dong
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Qipeng Yan
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Tingfen Deng
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Xiaoxu Li
- China Tobacco Hunan Industrial CO., Ltd., Changsha, Hunan, 410019, P. R. China
- Beijing Life Science Academy, Beijing, 102209, P. R. China
| | - Zhe Zhao
- Technology Center, China Tobacco Shandong Industrial Co., Ltd., Jinan, 250014, P. R. China
| | - Zenghui Li
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Mingshui Wang
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Chunhui Zhang
- College of Biology, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Bo Kong
- China Tobacco Hunan Industrial CO., Ltd., Changsha, Hunan, 410019, P. R. China
| | - Junfeng Shi
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
| | - Dan Yuan
- The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, P. R. China
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50
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Pitol-Palin L, Moura J, Frigério PB, de Souza Batista FR, Saska S, Oliveira LJM, Matsubara EY, Pilatti L, Câmara D, Lizier N, Blay A, Shibli JA, Okamoto R. A preliminary study of cell-based bone tissue engineering into 3D-printed β-tricalcium phosphate scaffolds and polydioxanone membranes. Sci Rep 2024; 14:31184. [PMID: 39732806 PMCID: PMC11682175 DOI: 10.1038/s41598-024-82334-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 12/04/2024] [Indexed: 12/30/2024] Open
Abstract
Treatment of complex craniofacial deformities is still a challenge for medicine and dentistry because few approach therapies are available on the market that allow rehabilitation using 3D-printed medical devices. Thus, this study aims to create a scaffold with a morphology that simulates bone tissue, able to create a favorable environment for the development and differentiation of osteogenic cells. Moreover, its association with Plenum Guide, through cell-based tissue engineering (ASCs) for guided bone regeneration in critical rat calvarial defects. The manufacturing and characterization of 3D-printed β-TCP scaffolds for experimental surgery was performed. Nine male rats were divided into three groups: β-TCP + PDO membrane (TCP/PG), β-TCP/ASCs + PDO membrane (TCPasc/PG), and β-TCP/ASCs + PDO membrane/ASCs (TCPasc/PGasc). A surgical defect with a 5-mm diameter was performed in the right parietal bone, and the defect was filled with the 3D-printed β-TCP scaffold and PDO membrane with or without ASCs. The animals were euthanized 7, 14, and 30 days after the surgical procedure for histomorphometric and immunolabeling analyses. 3D-printed β-TCP scaffolds were created with a 404 ± 0.0238 μm gyroid macro-pore and, the association to cell-based therapy promotes, especially in the TCPasc/PGasc group, a bone area formation at the defect border region and the center of the defect. The use of 3D-printed β-TCP scaffolds and PDO membranes associated with cell-based therapy could improve and accelerate guided bone regeneration, promoting an increase in osteogenic capacity and reducing the time involved in the bone formation process. Moreover, using ASCs optimized the bioceramics by increasing its osteoinductive and osteoprogenitor capacity and, even with the resorption of the printed scaffold, aided as a scaffold for mesenchymal cell differentiation, as well as in bone tissue formation.
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Affiliation(s)
- L Pitol-Palin
- Department of Diagnosis and Surgery, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, 16015-050, Brazil
| | - J Moura
- Department of Diagnosis and Surgery, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, 16015-050, Brazil
| | - P B Frigério
- Department of Diagnosis and Surgery, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, 16015-050, Brazil
| | - F R de Souza Batista
- Department of Diagnosis and Surgery, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, 16015-050, Brazil
| | - S Saska
- M3 Health Ind. Com. De Prod. Med. Odont. e Correlatos S.A., 640 Ain Ata, Jundiaí, 13212- 213, Brazil
| | - L J M Oliveira
- M3 Health Ind. Com. De Prod. Med. Odont. e Correlatos S.A., 640 Ain Ata, Jundiaí, 13212- 213, Brazil
| | - E Y Matsubara
- M3 Health Ind. Com. De Prod. Med. Odont. e Correlatos S.A., 640 Ain Ata, Jundiaí, 13212- 213, Brazil
| | - L Pilatti
- M3 Health Ind. Com. De Prod. Med. Odont. e Correlatos S.A., 640 Ain Ata, Jundiaí, 13212- 213, Brazil
| | - D Câmara
- Nicell Pesquisa e Desenvolvimento Científico Ltda., 2721, Indianópolis, São Paulo, 04063-005, Brazil
| | - N Lizier
- Nicell Pesquisa e Desenvolvimento Científico Ltda., 2721, Indianópolis, São Paulo, 04063-005, Brazil
| | - A Blay
- M3 Health Ind. Com. De Prod. Med. Odont. e Correlatos S.A., 640 Ain Ata, Jundiaí, 13212- 213, Brazil
| | - J A Shibli
- Department of Periodontology and Oral Implantology, Dental Research Division, Guarulhos University - UNG, Guarulhos, 07011-080, Brazil.
| | - R Okamoto
- Department of Basic Sciences, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, 16066-840, Brazil.
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