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Bosch-Rué E, Zhang Q, Truskey GA, Olmos Buitrago J, M Bosch B, Pérez RA. Development of small tissue engineered blood vessels and their clinical and research applications. Biofabrication 2025; 17:032005. [PMID: 40341214 DOI: 10.1088/1758-5090/add626] [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: 07/02/2024] [Accepted: 05/08/2025] [Indexed: 05/10/2025]
Abstract
Since the first tissue engineered blood vessel (TEBV) was developed, different approaches, biomaterial scaffolds and cell sources have been used to obtain an engineered vessel as much similar as native vessels in terms of structure, functionality and mechanical properties. At the same time, diverse needs to obtain a functional TEBV have emerged, such as for blood vessel replacement for cardiovascular diseases (CVDs) to be used as artery bypass, to vascularize tissue engineered constructs, or even to model vascular diseases or drug testing. In this review, after briefly describing the native structure and function of arteries, we will give an overview of different biomaterials, cells and methods that have been used during the last years for the development of small TEBV (1-6 mm diameter). The importance of perfusing the TEBV to acquire functionality and maturation will be also discussed. Finally, we will center the review on TEBV applications beyond their use as vascular graft for CVDs.
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Affiliation(s)
- Elia Bosch-Rué
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
| | - Qiao Zhang
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States of America
| | - George A Truskey
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States of America
| | - Jenifer Olmos Buitrago
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
| | - Begoña M Bosch
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
| | - Román A Pérez
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
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2
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Helms F, Käding D, Aper T, Ruhparwar A, Wilhelmi M. An Arteriovenous Bioreactor Perfusion System for Physiological In Vitro Culture of Complex Vascularized Tissue Constructs. Bioengineering (Basel) 2024; 11:1147. [PMID: 39593807 PMCID: PMC11591738 DOI: 10.3390/bioengineering11111147] [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: 10/15/2024] [Revised: 11/05/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND The generation and perfusion of complex vascularized tissues in vitro requires sophisticated perfusion techniques. For multiscale arteriovenous networks, not only the arterial, but also the venous, biomechanical and biochemical conditions that physiologically exist in the human body must be accurately emulated. For this, we here present a modular arteriovenous perfusion system for the in vitro culture of a multi-scale bioartificial vascular network. METHODS The custom-built perfusion system consisted of two circuits: in the arterial circuit, physiological arterial biomechanical and biochemical conditions were simulated using a modular set-up with a pulsatile peristaltic pump, compliance chambers, and resistors. In the venous circuit, venous conditions were emulated accordingly. In the center of the system, a bioartificial multi-scale vascularized fibrin-based tissue was perfused by both circuits simultaneously under biomimetic arteriovenous conditions. Culture conditions were monitored continuously using a multi-sensor monitoring system. RESULTS The physiological arterial and venous pressure- and flow-curves, as well as the microvascular arteriovenous oxygen partial pressure gradient, were accurately emulated in the perfusion system. The multi-sensor monitoring system facilitated live monitoring of the respective parameters and data-logging. In a proof-of-concept experiment, vascularized three-dimensional fibrin tissues showed sustained cell viability and homogenous microvessel formation after culture in the perfusion system. CONCLUSIONS The arteriovenous perfusion system facilitated the in vitro culture of a multiscale vascularized tissue under physiological pressure-, flow-, and oxygen-gradient conditions. With that, it presents a promising technique for the in vitro generation and culture of complex large-scale vascularized tissues.
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Affiliation(s)
- Florian Helms
- Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625 Hannover, Germany
- Division for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany
| | - Delia Käding
- Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625 Hannover, Germany
| | - Thomas Aper
- Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625 Hannover, Germany
- Division for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany
| | - Arjang Ruhparwar
- Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625 Hannover, Germany
- Division for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany
| | - Mathias Wilhelmi
- Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625 Hannover, Germany
- Department of Vascular and Endovascular Surgery, St. Bernward Hospital, 31134 Hildesheim, Germany
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Zimmerling A, Boire J, Zhou Y, Chen X. Influence of Breath-Mimicking Ventilated Incubation on Three-Dimensional Bioprinted Respiratory Tissue Scaffolds. J Biomech Eng 2024; 146:091004. [PMID: 38557592 DOI: 10.1115/1.4065214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 03/28/2024] [Indexed: 04/04/2024]
Abstract
Development of respiratory tissue constructs is challenging due to the complex structure of native respiratory tissue and the unique biomechanical conditions induced by breathing. While studies have shown that the inclusion of biomechanical stimulus mimicking physiological conditions greatly benefits the development of engineered tissues, to our knowledge no studies investigating the influence of biomechanical stimulus on the development of respiratory tissue models produced through three-dimensional (3D) bioprinting have been reported. This paper presents a study on the utilization of a novel breath-mimicking ventilated incubator to impart biomechanical stimulus during the culture of 3D respiratory bioprinted constructs. Constructs were bioprinted using an alginate/collagen hydrogel containing human primary pulmonary fibroblasts with further seeding of human primary bronchial epithelial cells. Biomechanical stimulus was then applied via a novel ventilated incubator capable of mimicking the pressure and airflow conditions of multiple breathing conditions: standard incubation, shallow breathing, normal breathing, and heavy breathing, over a two-week time period. At time points between 1 and 14 days, constructs were characterized in terms of mechanical properties, cell proliferation, and morphology. The results illustrated that incubation conditions mimicking normal and heavy breathing led to greater and more continuous cell proliferation and further indicated a more physiologically relevant respiratory tissue model.
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Affiliation(s)
- Amanda Zimmerling
- Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, 57 Campus Drive, Saskatoon, SK S7N 5A9, Canada; Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
| | - Jim Boire
- Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, 57 Campus Drive, Saskatoon, SK S7N 5A9, Canada; RMD Engineering Inc., #1 Cory Place East Cory Industrial Park, RM Corman Park, Saskatoon, SK S7K 3J7, Canada
| | - Yan Zhou
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
| | - Xiongbiao Chen
- Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, 57 Campus Drive, Saskatoon, SK S7N 5A9, Canada; Department of Mechanical Engineering, College of Engineering, University of Saskatchewan, 57 Campus Drive, Saskatoon, SK S7N 5A9, Canada
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4
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Schot M, Becker M, Paggi CA, Gomes F, Koch T, Gensheimer T, Johnbosco C, Nogueira LP, van der Meer A, Carlson A, Haugen H, Leijten J. Photoannealing of Microtissues Creates High-Density Capillary Network Containing Living Matter in a Volumetric-Independent Manner. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2308949. [PMID: 38095242 DOI: 10.1002/adma.202308949] [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: 09/01/2023] [Revised: 11/21/2023] [Indexed: 07/13/2024]
Abstract
The vascular tree is crucial for the survival and function of large living tissues. Despite breakthroughs in 3D bioprinting to endow engineered tissues with large blood vessels, there is currently no approach to engineer high-density capillary networks into living tissues in a scalable manner. Here, photoannealing of living microtissue (PALM) is presented as a scalable strategy to engineer capillary-rich tissues. Specifically, in-air microfluidics is used to produce living microtissues composed of cell-laden microgels in ultrahigh throughput, which can be photoannealed into a monolithic living matter. Annealed microtissues inherently give rise to an open and interconnected pore network within the resulting living matter. Interestingly, utilizing soft microgels enables microgel deformation, which leads to the uniform formation of capillary-sized pores. Importantly, the ultrahigh throughput nature underlying the microtissue formation uniquely facilitates scalable production of living tissues of clinically relevant sizes (>1 cm3) with an integrated high-density capillary network. In short, PALM generates monolithic, microporous, modular tissues that meet the previously unsolved need for large engineered tissues containing high-density vascular networks, which is anticipated to advance the fields of engineered organs, regenerative medicine, and drug screening.
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Affiliation(s)
- Maik Schot
- Leijten lab, Department of Developmental BioEngineering, TechMed Centre, University of Twente, Enschede, 7522AE, The Netherlands
| | - Malin Becker
- Leijten lab, Department of Developmental BioEngineering, TechMed Centre, University of Twente, Enschede, 7522AE, The Netherlands
| | - Carlo Alberto Paggi
- Leijten lab, Department of Developmental BioEngineering, TechMed Centre, University of Twente, Enschede, 7522AE, The Netherlands
| | - Francisca Gomes
- Leijten lab, Department of Developmental BioEngineering, TechMed Centre, University of Twente, Enschede, 7522AE, The Netherlands
| | - Timo Koch
- Department of Mathematics, University of Oslo, Oslo, 0316, Norway
| | - Tarek Gensheimer
- Department of Applied Stem Cell Technology, TechMed Centre, University of Twente, Enschede, 7500AE, The Netherlands
| | - Castro Johnbosco
- Leijten lab, Department of Developmental BioEngineering, TechMed Centre, University of Twente, Enschede, 7522AE, The Netherlands
| | | | - Andries van der Meer
- Department of Applied Stem Cell Technology, TechMed Centre, University of Twente, Enschede, 7500AE, The Netherlands
| | - Andreas Carlson
- Department of Mathematics, University of Oslo, Oslo, 0316, Norway
| | - Håvard Haugen
- Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, 0316, Norway
| | - Jeroen Leijten
- Leijten lab, Department of Developmental BioEngineering, TechMed Centre, University of Twente, Enschede, 7522AE, The Netherlands
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Rosellini E, Giordano C, Guidi L, Cascone MG. Biomimetic Approaches in Scaffold-Based Blood Vessel Tissue Engineering. Biomimetics (Basel) 2024; 9:377. [PMID: 39056818 PMCID: PMC11274842 DOI: 10.3390/biomimetics9070377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/15/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
Cardiovascular diseases remain a leading cause of mortality globally, with atherosclerosis representing a significant pathological means, often leading to myocardial infarction. Coronary artery bypass surgery, a common procedure used to treat coronary artery disease, presents challenges due to the limited autologous tissue availability or the shortcomings of synthetic grafts. Consequently, there is a growing interest in tissue engineering approaches to develop vascular substitutes. This review offers an updated picture of the state of the art in vascular tissue engineering, emphasising the design of scaffolds and dynamic culture conditions following a biomimetic approach. By emulating native vessel properties and, in particular, by mimicking the three-layer structure of the vascular wall, tissue-engineered grafts can improve long-term patency and clinical outcomes. Furthermore, ongoing research focuses on enhancing biomimicry through innovative scaffold materials, surface functionalisation strategies, and the use of bioreactors mimicking the physiological microenvironment. Through a multidisciplinary lens, this review provides insight into the latest advancements and future directions of vascular tissue engineering, with particular reference to employing biomimicry to create systems capable of reproducing the structure-function relationships present in the arterial wall. Despite the existence of a gap between benchtop innovation and clinical translation, it appears that the biomimetic technologies developed to date demonstrate promising results in preventing vascular occlusion due to blood clotting under laboratory conditions and in preclinical studies. Therefore, a multifaceted biomimetic approach could represent a winning strategy to ensure the translation of vascular tissue engineering into clinical practice.
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Affiliation(s)
- Elisabetta Rosellini
- Department of Civil and Industrial Engineering, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy; (C.G.); (L.G.)
| | | | | | - Maria Grazia Cascone
- Department of Civil and Industrial Engineering, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy; (C.G.); (L.G.)
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Hernandez-Sanchez D, Comtois-Bona M, Muñoz M, Ruel M, Suuronen EJ, Alarcon EI. Manufacturing and validation of small-diameter vascular grafts: A mini review. iScience 2024; 27:109845. [PMID: 38799581 PMCID: PMC11126982 DOI: 10.1016/j.isci.2024.109845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2024] Open
Abstract
The field of small-diameter vascular grafts remains a challenge for biomaterials scientists. While decades of research have brought us much closer to developing biomimetic materials for regenerating tissues and organs, the physiological challenges involved in manufacturing small conduits that can transport blood while not inducing an immune response or promoting blood clots continue to limit progress in this area. In this short review, we present some of the most recent methods and advancements made by researchers working in the field of small-diameter vascular grafts. We also discuss some of the most critical aspects biomaterials scientists should consider when developing lab-made small-diameter vascular grafts.
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Affiliation(s)
- Deyanira Hernandez-Sanchez
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
| | - Maxime Comtois-Bona
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
| | - Marcelo Muñoz
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
| | - Marc Ruel
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, 451 Smyth Road, Ottawa ON K1H8M5, Canada
| | - Erik J. Suuronen
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, 451 Smyth Road, Ottawa ON K1H8M5, Canada
| | - Emilio I. Alarcon
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H8M5, Canada
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7
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Ding H, Hou X, Gao Z, Guo Y, Liao B, Wan J. Challenges and Strategies for Endothelializing Decellularized Small-Diameter Tissue-Engineered Vessel Grafts. Adv Healthc Mater 2024; 13:e2304432. [PMID: 38462702 DOI: 10.1002/adhm.202304432] [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: 12/13/2023] [Revised: 02/26/2024] [Indexed: 03/12/2024]
Abstract
Vascular diseases are the leading cause of ischemic necrosis in tissues and organs, necessitating using vascular grafts to restore blood supply. Currently, small vessels for coronary artery bypass grafts are unavailable in clinical settings. Decellularized small-diameter tissue-engineered vessel grafts (SD-TEVGs) hold significant potential. However, they face challenges, as simple implantation of decellularized SD-TEVGs in animals leads to thrombosis and calcification due to incomplete endothelialization. Consequently, research and development focus has shifted toward enhancing the endothelialization process of decellularized SD-TEVGs. This paper reviews preclinical studies involving decellularized SD-TEVGs, highlighting different strategies and their advantages and disadvantages for achieving rapid endothelialization of these vascular grafts. Methods are analyzed to improve the process while addressing potential shortcomings. This paper aims to contribute to the future commercial viability of decellularized SD-TEVGs.
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Affiliation(s)
- Heng Ding
- Department of Cardiovascular Surgery, The Affiliated Hospital, Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of cardiovascular remodeling and dysfunction, Luzhou, Sichuan, 646000, China
- Nanjing Medical University, Nanjing, 211166, P. R. China
| | - Xiaojie Hou
- Department of Cardiovascular Surgery and Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Zhen Gao
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100069, China
| | - Yingqiang Guo
- Department of Cardiovascular Surgery and Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Bin Liao
- Department of Cardiovascular Surgery, The Affiliated Hospital, Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of cardiovascular remodeling and dysfunction, Luzhou, Sichuan, 646000, China
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Juyi Wan
- Department of Cardiovascular Surgery, The Affiliated Hospital, Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of cardiovascular remodeling and dysfunction, Luzhou, Sichuan, 646000, China
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China
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8
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Glomb C, Wilhelmi M, Strauß S, Zippusch S, Klingenberg M, Aper T, Vogt PM, Ruhparwar A, Helms F. Fabrication and biomechanical characterization of a spider silk reinforced fibrin-based vascular prosthesis. J Mech Behav Biomed Mater 2024; 152:106433. [PMID: 38316085 DOI: 10.1016/j.jmbbm.2024.106433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/15/2024] [Accepted: 01/25/2024] [Indexed: 02/07/2024]
Abstract
With fibrin-based vascular prostheses, vascular tissue engineering offers a promising approach for the fabrication of biologically active regenerative vascular grafts. As a potentially autologous biomaterial, fibrin exhibits excellent hemo- and biocompatibility. However, the major problem in the use of fibrin constructs in vascular tissue engineering, which has so far prevented their widespread clinical application, is the insufficient biomechanical stability of unprocessed fibrin matrices. In this proof-of-concept study, we investigated to what extent the addition of a spider silk network into the wall structure of fibrin-based vascular prostheses leads to an increase in biomechanical stability and an improvement in the biomimetic elastic behavior of the grafts. For the fabrication of hybrid prostheses composed of fibrin and spider silk, a statically cast tubular fibrin matrix was surrounded with an envelope layer of Trichonephila edulis silk using a custom built coiling machine. The fibrin matrix was then compacted and pressed into the spider silk network by transluminal balloon compression. This manufacturing process resulted in a hybrid prosthesis with a luminal diameter of 4 mm. Biomechanical characterization revealed a significant increase in biomechanical stability of spider silk reinforced grafts compared to exclusively compacted fibrin segments with a mean burst pressure of 362 ± 74 mmHg vs. 213 ± 14 mmHg (p < 0.05). Dynamic elastic behavior of the spider silk reinforced grafts was similar to native arteries. In addition, the coiling with spider silk allowed a significant increase in suture retention strength and resistance to external compression without compromising the endothelialization capacity of the grafts. Thus, spider silk reinforcement using the abluminal coiling technique represents an efficient and reproducible technique to optimize the biomechanical behavior of small-diameter fibrin-based vascular grafts.
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Affiliation(s)
- Clara Glomb
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany
| | - Mathias Wilhelmi
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany; Department of Vascular- and Endovascular Surgery, St. Bernward Hospital, Hildesheim, Germany
| | - Sarah Strauß
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Sarah Zippusch
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany; Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Melanie Klingenberg
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany; Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Thomas Aper
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany; Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Peter M Vogt
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Arjang Ruhparwar
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany; Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Florian Helms
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany; Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.
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9
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Margolis EA, Friend NE, Rolle MW, Alsberg E, Putnam AJ. Manufacturing the multiscale vascular hierarchy: progress toward solving the grand challenge of tissue engineering. Trends Biotechnol 2023; 41:1400-1416. [PMID: 37169690 PMCID: PMC10593098 DOI: 10.1016/j.tibtech.2023.04.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 04/05/2023] [Accepted: 04/14/2023] [Indexed: 05/13/2023]
Abstract
In human vascular anatomy, blood flows from the heart to organs and tissues through a hierarchical vascular tree, comprising large arteries that branch into arterioles and further into capillaries, where gas and nutrient exchange occur. Engineering a complete, integrated vascular hierarchy with vessels large enough to suture, strong enough to withstand hemodynamic forces, and a branching structure to permit immediate perfusion of a fluidic circuit across scales would be transformative for regenerative medicine (RM), enabling the translation of engineered tissues of clinically relevant size, and perhaps whole organs. How close are we to solving this biological plumbing problem? In this review, we highlight advances in engineered vasculature at individual scales and focus on recent strategies to integrate across scales.
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Affiliation(s)
- Emily A Margolis
- University of Michigan, Department of Biomedical Engineering, Ann Arbor, MI, USA
| | - Nicole E Friend
- University of Michigan, Department of Biomedical Engineering, Ann Arbor, MI, USA
| | - Marsha W Rolle
- Worcester Polytechnic Institute, Department of Biomedical Engineering, Worcester, MA, USA
| | - Eben Alsberg
- University of Illinois at Chicago, Department of Biomedical Engineering, Chicago, IL, USA
| | - Andrew J Putnam
- University of Michigan, Department of Biomedical Engineering, Ann Arbor, MI, USA.
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10
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Di Francesco D, Pigliafreddo A, Casarella S, Di Nunno L, Mantovani D, Boccafoschi F. Biological Materials for Tissue-Engineered Vascular Grafts: Overview of Recent Advancements. Biomolecules 2023; 13:1389. [PMID: 37759789 PMCID: PMC10526356 DOI: 10.3390/biom13091389] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/11/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
The clinical demand for tissue-engineered vascular grafts is still rising, and there are many challenges that need to be overcome, in particular, to obtain functional small-diameter grafts. The many advances made in cell culture, biomaterials, manufacturing techniques, and tissue engineering methods have led to various promising solutions for vascular graft production, with available options able to recapitulate both biological and mechanical properties of native blood vessels. Due to the rising interest in materials with bioactive potentials, materials from natural sources have also recently gained more attention for vascular tissue engineering, and new strategies have been developed to solve the disadvantages related to their use. In this review, the progress made in tissue-engineered vascular graft production is discussed. We highlight, in particular, the use of natural materials as scaffolds for vascular tissue engineering.
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Affiliation(s)
- Dalila Di Francesco
- Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, Italy; (D.D.F.); (S.C.); (L.D.N.)
- Laboratory for Biomaterials and Bioengineering, CRC-I, Department of Min-Met-Materials Engineering, University Hospital Research Center, Regenerative Medicine, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Alexa Pigliafreddo
- Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, Italy; (D.D.F.); (S.C.); (L.D.N.)
| | - Simona Casarella
- Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, Italy; (D.D.F.); (S.C.); (L.D.N.)
| | - Luca Di Nunno
- Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, Italy; (D.D.F.); (S.C.); (L.D.N.)
| | - Diego Mantovani
- Laboratory for Biomaterials and Bioengineering, CRC-I, Department of Min-Met-Materials Engineering, University Hospital Research Center, Regenerative Medicine, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Francesca Boccafoschi
- Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, Italy; (D.D.F.); (S.C.); (L.D.N.)
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11
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Jafari A, Behjat E, Malektaj H, Mobini F. Alignment behavior of nerve, vascular, muscle, and intestine cells in two- and three-dimensional strategies. WIREs Mech Dis 2023; 15:e1620. [PMID: 37392045 DOI: 10.1002/wsbm.1620] [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: 07/31/2022] [Revised: 02/28/2023] [Accepted: 05/23/2023] [Indexed: 07/02/2023]
Abstract
By harnessing structural hierarchical insights, plausibly simulate better ones imagination to figure out the best choice of methods for reaching out the unprecedented developments of the tissue engineering products as a next level. Constructing a functional tissue that incorporates two-dimensional (2D) or higher dimensions requires overcoming technological or biological limitations in order to orchestrate the structural compilation of one-dimensional and 2D sheets (microstructures) simultaneously (in situ). This approach enables the creation of a layered structure that can be referred to as an ensemble of layers or, after several days of maturation, a direct or indirect joining of layers. Here, we have avoided providing a detailed methodological description of three-dimensional and 2D strategies, except for a few interesting examples that highlight the higher alignment of cells and emphasize rarely remembered facts associated with vascular, peripheral nerve, muscle, and intestine tissues. The effective directionality of cells in conjunction with geometric cues (in the range of micrometers) is well known to affect a variety of cell behaviors. The curvature of a cell's environment is one of the factors that influence the formation of patterns within tissues. The text will cover cell types containing some level of stemness, which will be followed by their consequences for tissue formation. Other important considerations pertain to cytoskeleton traction forces, cell organelle positioning, and cell migration. An overview of cell alignment along with several pivotal molecular and cellular level concepts, such as mechanotransduction, chirality, and curvature of structure effects on cell alignments will be presented. The mechanotransduction term will be used here in the context of the sensing capability that cells show as a result of force-induced changes either at the conformational or the organizational levels, a capability that allows us to modify cell fate by triggering downstream signaling pathways. A discussion of the cells' cytoskeleton and of the stress fibers involvement in altering the cell's circumferential constitution behavior (alignment) based on exposed scaffold radius will be provided. Curvatures with size similarities in the range of cell sizes cause the cell's behavior to act as if it was in an in vivo tissue environment. The revision of the literature, patents, and clinical trials performed for the present study shows that there is a clear need for translational research through the implementation of clinical trial platforms that address the tissue engineering possibilities raised in the current revision. This article is categorized under: Infectious Diseases > Biomedical Engineering Neurological Diseases > Biomedical Engineering Cardiovascular Diseases > Biomedical Engineering.
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Affiliation(s)
- Amir Jafari
- Laboratório de Neurofisiologia, Instituto de Biologia Roberto Alcantara Gomes, Centro Biomédico, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Erfan Behjat
- Department of Biomaterials, School of Metallurgy & Materials Engineering, Iran University of Science and Technology, Tehran, Iran
| | - Haniyeh Malektaj
- Department of Materials and Production, Aalborg University, Aalborg, Denmark
| | - Faezeh Mobini
- Molecular Simulation Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
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12
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Afzal Z, Huguet EL. Bioengineering liver tissue by repopulation of decellularised scaffolds. World J Hepatol 2023; 15:151-179. [PMID: 36926238 PMCID: PMC10011915 DOI: 10.4254/wjh.v15.i2.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/22/2022] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Liver transplantation is the only curative therapy for end stage liver disease, but is limited by the organ shortage, and is associated with the adverse consequences of immunosuppression. Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact, as well as retaining the instructive cell fate determining biochemicals contained therein. Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models, using a wide range of cell types including primary cells, cell lines, foetal stem cells, and induced pluripotent stem cells. Within these models, a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo. Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes, though advances in organoid culture may help address this. Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo, but with cell types that would limit clinical applications, and which have not been shown to have the specific functions of liver sinusoidal endothelial cells. Minority cell groups such as Kupffer cells and stellate cells have not been repopulated. Bioengineering by repopulation of decellularised scaffolds has significantly progressed, but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.
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Affiliation(s)
- Zeeshan Afzal
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Laurent Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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13
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Obed D, Dastagir N, Liebsch C, Bingoel AS, Strauss S, Vogt PM, Dastagir K. In Vitro Differentiation of Myoblast Cell Lines on Spider Silk Scaffolds in a Rotating Bioreactor for Vascular Tissue Engineering. J Pers Med 2022; 12:jpm12121986. [PMID: 36556206 PMCID: PMC9783533 DOI: 10.3390/jpm12121986] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 12/02/2022] Open
Abstract
Functional construction of tissue-engineered vessels as an alternative to autologous vascular grafts has been shown to be feasible, however the proliferation of seeded smooth-muscle cells remains a limiting factor. We employed a rotating bioreactor system to improve myoblast cell differentiation on a spider silk scaffold for tissue-engineered vessel construction. C2C12 myofibroblast cells were seeded on the surface of spider silk scaffold constructs and cultivated in a rotating bioreactor system with a continuous rotation speed (1 rpm). Cell function, cell growth and morphological structure and expression of biomarkers were analyzed using scanning electron microscopy, the LIVE/DEAD® assay, Western blot and quantitative real-time PCR analyses. A dense myofibroblast cell sheet could be developed which resembled native blood vessel muscular tissue in morphological structure and in function. Bioreactor perfusion positively affected cell morphology, and increased cell viability and cell differentiation. The expression of desmin, MYF5 and MEF2D surged as an indication of myoblast differentiation. Cell-seeded scaffolds showed a tear-down at 18 N when strained at a set speed (20 mm min-1). Spider silk scaffolds appear to offer a reliable basis for engineered vascular constructs and rotating bioreactor cultivation may be considered an effective alternative to complex bioreactor setups to improve cell viability and biology.
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Affiliation(s)
- Doha Obed
- Correspondence: ; Tel.: +49-511-532-8894; Fax: +49-511-532-8864
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14
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Du J, Hu X, Su Y, Wei T, Jiao Z, Liu T, Wang H, Nie Y, Li X, Song K. Gelatin/sodium alginate hydrogel-coated decellularized porcine coronary artery to construct bilayer tissue engineered blood vessels. Int J Biol Macromol 2022; 209:2070-2083. [PMID: 35500770 DOI: 10.1016/j.ijbiomac.2022.04.188] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 04/22/2022] [Accepted: 04/25/2022] [Indexed: 11/05/2022]
Abstract
Cardiovascular diseases and vascular trauma can be commonly found in the population. Scholars worldwide hope to develop small-diameter vascular grafts that can replace autologous vessels for clinical use. Decellularized blood vessels can retain the original morphology, structure, and physical properties of blood vessels, which is conducive to cell growth, proliferation, and differentiation. In this study, porcine coronary arteries (PCAs) were decellularized to prepare decellularized porcine coronary artery (DPCA), and bilayer hybrid scaffolds were prepared by coating gelatin and sodium alginate mixed hydrogel of seven different proportions and combined with mouse fibroblasts (L929 cells) to study the construction of tissue engineering vessels in vitro. The obtained bilayer hybrid scaffolds were 3-7 cm in length, 5 mm in external diameter, and 1 mm in average wall thickness. All seven bilayer hybrid scaffolds showed good biocompatibility after cell inoculation. Compared with 2D culture, cells on 3D scaffolds grew relatively slowly in the first 4 days, and the number of cells proliferated rapidly at 7 days. In the same culture days, different concentrations of hydrogel also had an impact on cell proliferation. With the increase of hydrogel content, cells on the 3D scaffold formed cell colonies faster. The results showed that the scaffold had good biocompatibility and could meet the needs of artificial blood vessel construction.
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Affiliation(s)
- Jing Du
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Xueyan Hu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Ya Su
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Tuo Wei
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Zeren Jiao
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA
| | - Tianqing Liu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Hong Wang
- Department of orthopeadics, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116033, China.
| | - Yi Nie
- Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, China; Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
| | - Xiangqin Li
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
| | - Kedong Song
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
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15
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Helms F, Zippusch S, Aper T, Kalies S, Heisterkamp A, Haverich A, Böer U, Wilhelmi M. Mechanical stimulation induces vasa vasorum capillary alignment in a fibrin-based tunica adventitia. Tissue Eng Part A 2022; 28:818-832. [PMID: 35611972 DOI: 10.1089/ten.tea.2022.0042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Generation of bioartificial blood vessels with a physiological three-layered wall architecture is a long pursued goal in vascular tissue engineering. While considerable advances have been made to resemble the physiological tunica intima and media morphology and function in bioartificial vessels, only very few studies have targeted the generation of a tunica adventitia including its characteristic vascular network known as the vasa vasorum, which are essential for graft nutrition and integration. In healthy native blood vessels, capillary vasa vasorum are aligned longitudinally to the vessel axis. Thus, inducing longitudinal alignment of capillary tubes to generate a physiological tunica adventitia morphology and function may be advantageous in bioengineered vessels as well. In this study, we investigated the effect of two biomechanical stimulation parameters, longitudinal tension and physiological cyclic stretch, on tube alignment in capillary networks formed by self-assembly of human umbilical vein endothelial cells in tunica adventitia-equivalents of fibrin-based bioartificial blood vessels. Moreover, the effect of changes of the biomechanical environment on network remodeling after initial tube formation was analyzed. Both, longitudinal tension and cyclic stretch by pulsatile perfusion induced physiological capillary tube alignment parallel to the longitudinal vessel axis. This effect was even more pronounced when both biomechanical factors were applied simultaneously, which resulted in alignment of 57.2% ± 5.2% within 5° of the main vessel axis. Opposed to that, random tube orientation was observed in vessels incubated statically. Scanning electron microscopy showed that longitudinal tension also resulted in longitudinal alignment of fibrin fibrils, which may function as a guidance structure for directed capillary tube formation. Moreover, existing microvascular networks showed distinct remodeling in response to addition or withdrawal of mechanical stimulation with corresponding increase or decrease of the degree of alignment. With longitudinal tension and cyclic stretch, we identified two mechanical stimuli that facilitate the generation of a pre-vascularized tunica adventitia-equivalent with physiological tube alignment in bioartificial vascular grafts.
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Affiliation(s)
- Florian Helms
- Hannover Medical School, 9177, Lower Saxony centre of biotechnology implant research and development (NIFE), Hannover, Niedersachsen, Germany.,Hannover Medical School, 9177, Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover, Niedersachsen, Germany;
| | - Sarah Zippusch
- Hannover Medical School, 9177, Lower Saxony centre of biotechnology implant research and development (NIFE), Hannover, Niedersachsen, Germany.,Hannover Medical School, 9177, Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover, Niedersachsen, Germany;
| | - Thomas Aper
- Hannover Medical School, 9177, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Niedersachsen, Germany.,Hannover Medical School, 9177, Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover, Niedersachsen, Germany;
| | - Stefan Kalies
- Hannover Medical School, 9177, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Niedersachsen, Germany.,Leibniz University Hannover, 26555, Institute of Quantum Optics, Hannover, Niedersachsen, Germany;
| | - Alexander Heisterkamp
- Hannover Medical School, 9177, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Niedersachsen, Germany.,Leibniz University Hannover, 26555, Institure of Quantum Optics, Hannover, Niedersachsen, Germany;
| | - Axel Haverich
- Hannover Medical School, 9177, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Niedersachsen, Germany.,Hannover Medical School, 9177, Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover, Niedersachsen, Germany;
| | - Ulrike Böer
- Hannover Medical School, 9177, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Niedersachsen, Germany.,Hannover Medical School, 9177, Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover, Niedersachsen, Germany;
| | - Mathias Wilhelmi
- Hannover Medical School, 9177, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Niedersachsen, Germany.,St Bernward Hospital, 14966, Department of Vascular- and Endovascular Surgery, Hildesheim, Niedersachsen, Germany;
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16
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Helms F, Zippusch S, Theilen J, Haverich A, Wilhelmi M, Böer U. An encapsulated fibrin-based bioartificial tissue construct with integrated macrovessels, microchannels and capillary tubes. Biotechnol Bioeng 2022; 119:2239-2249. [PMID: 35485750 DOI: 10.1002/bit.28111] [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: 11/05/2021] [Revised: 04/01/2022] [Accepted: 04/06/2022] [Indexed: 11/06/2022]
Abstract
Facilitating sufficient nutrient and oxygen supply in large-scale bioartificial constructs is a critical step in organ bioengineering. Immediate perfusion not only depends on a dense capillary network, but also requires integrated large-diameter vessels that allow vascular anastomoses during implantation. These requirements set high demands for matrix generation as well as for in vitro cultivation techniques and remain mostly unsolved challenges up until today. Additionally, bioartificial constructs must have sufficient biomechanical stability to withstand mechanical stresses during and after implantation. We developed a bioartificial tissue construct with a fibrin matrix containing human umbilical vein endothelial cells and adipose tissue-derived stem cells facilitating capillary-like network formation. This core matrix was surrounded by a dense acellular fibrin capsule providing biomechanical stability. Two fibrin-based macrovessels were integrated on each side of the construct and interconnected via four 1.2 mm thick microchannels penetrating the cellularized core matrix. After four days of perfusion in a custom-built bioreactor, homogenous capillary-like network formation throughout the core matrix was observed. The fibrin capsule stabilized the core matrix and facilitated the generation of a self-supporting construct. Thus, the encapsulated fibrin tissue construct could provide a universal pre-vascularized matrix for seeding with different cell types in various tissue engineering approaches. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Florian Helms
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Hannover, Germany, Stadtfelddamm 34, 30625, Hannover, Germany.,Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Sarah Zippusch
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Hannover, Germany, Stadtfelddamm 34, 30625, Hannover, Germany.,Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Jonathan Theilen
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Hannover, Germany, Stadtfelddamm 34, 30625, Hannover, Germany
| | - Axel Haverich
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Hannover, Germany, Stadtfelddamm 34, 30625, Hannover, Germany.,Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Mathias Wilhelmi
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Hannover, Germany, Stadtfelddamm 34, 30625, Hannover, Germany.,Department of Vascular- and Endovascular Surgery, St. Bernward Hospital, Hildesheim, Germany
| | - Ulrike Böer
- Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Hannover, Germany, Stadtfelddamm 34, 30625, Hannover, Germany.,Division for Cardiothoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
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17
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Jiao Y, Zhang Y, Xiao Y, Xing Y, Cai Z, Wang C, Zhou Z, Feng Z, Gu Y. The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor. Bioengineered 2022; 13:7925-7938. [PMID: 35358008 PMCID: PMC9278976 DOI: 10.1080/21655979.2022.2039502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.
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Affiliation(s)
- Yuhao Jiao
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yuanguo Zhang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yonghao Xiao
- School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China
| | - Yuehao Xing
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zhiwen Cai
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Cong Wang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zhengtong Zhou
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zengguo Feng
- School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China
| | - Yongquan Gu
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
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18
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Devillard CD, Marquette CA. Vascular Tissue Engineering: Challenges and Requirements for an Ideal Large Scale Blood Vessel. Front Bioeng Biotechnol 2021; 9:721843. [PMID: 34671597 PMCID: PMC8522984 DOI: 10.3389/fbioe.2021.721843] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 09/20/2021] [Indexed: 01/05/2023] Open
Abstract
Since the emergence of regenerative medicine and tissue engineering more than half a century ago, one obstacle has persisted: the in vitro creation of large-scale vascular tissue (>1 cm3) to meet the clinical needs of viable tissue grafts but also for biological research applications. Considerable advancements in biofabrication have been made since Weinberg and Bell, in 1986, created the first blood vessel from collagen, endothelial cells, smooth muscle cells and fibroblasts. The synergistic combination of advances in fabrication methods, availability of cell source, biomaterials formulation and vascular tissue development, promises new strategies for the creation of autologous blood vessels, recapitulating biological functions, structural functions, but also the mechanical functions of a native blood vessel. In this review, the main technological advancements in bio-fabrication are discussed with a particular highlights on 3D bioprinting technologies. The choice of the main biomaterials and cell sources, the use of dynamic maturation systems such as bioreactors and the associated clinical trials will be detailed. The remaining challenges in this complex engineering field will finally be discussed.
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Affiliation(s)
- Chloé D Devillard
- 3d.FAB, CNRS, INSA, Univ Lyon, CPE-Lyon, UMR5246, ICBMS, Université Lyon 1, Villeurbanne Cedex, France
| | - Christophe A Marquette
- 3d.FAB, CNRS, INSA, Univ Lyon, CPE-Lyon, UMR5246, ICBMS, Université Lyon 1, Villeurbanne Cedex, France
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19
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Transluminal compression increases mechanical stability, stiffness and endothelialization capacity of fibrin-based bioartificial blood vessels. J Mech Behav Biomed Mater 2021; 124:104835. [PMID: 34530301 DOI: 10.1016/j.jmbbm.2021.104835] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 08/15/2021] [Accepted: 09/08/2021] [Indexed: 01/06/2023]
Abstract
Fibrin is used successfully as a biological matrix in various bioengineering approaches. Its unique combination of autologous availability, hemocompatibility and biological activity makes it an almost ideal matrix material for vascular tissue engineering. However, clinical application of fibrin-based bioartificial blood vessels is still limited due to insufficient mechanical stability and stiffness of fibrin matrices. Biomechanical properties of fibrin-based constructs can potentially be modified by adjusting matrix density. Thus, as an attempt to optimize strength and elasticity of fibrin matrices for vascular tissue engineering applications, we developed a simple and reproducible method for transluminal compression of small-diameter fibrin-based vessels: After initial polymerization of high-concentration fibrin matrices in a vascular mold, vessels were compressed using an intraluminal angioplasty balloon. Vessels compacted with different pressures were compared for ultimate strength, elastic and structural properties and cellularization capacity. Transluminal compression increased fibrin network density and facilitated rapid production of homogenous vessels with a length of 10 cm. Compared to non-compressed controls, compacted fibrin vessels showed superior maximal burst pressure (199.8 mmHg vs. 94.0 mmHg), physiological elastic properties similar to the elastic behavior of natural arteries and higher luminal endothelial cell coverage (98.6% vs. 34.6%). Thus, transluminal compaction represents a suitable technique to enhance biomechanical properties of fibrin-based bioartificial vessels while preserving the biological advantages of this promising biomaterial.
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