|
1
|
Rohringer S, Grasl C, Ehrmann K, Hager P, Hahn C, Specht SJ, Walter I, Schneider KH, Zopf LM, Baudis S, Liska R, Schima H, Podesser BK, Bergmeister H. Biodegradable, Self-Reinforcing Vascular Grafts for In Situ Tissue Engineering Approaches. Adv Healthc Mater 2023; 12:e2300520. [PMID: 37173073 PMCID: PMC11468867 DOI: 10.1002/adhm.202300520] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 04/21/2023] [Indexed: 05/15/2023]
Abstract
Clinically available small-diameter synthetic vascular grafts (SDVGs) have unsatisfactory patency rates due to impaired graft healing. Therefore, autologous implants are still the gold standard for small vessel replacement. Bioresorbable SDVGs may be an alternative, but many polymers have inadequate biomechanical properties that lead to graft failure. To overcome these limitations, a new biodegradable SDVG is developed to ensure safe use until adequate new tissue is formed. SDVGs are electrospun using a polymer blend composed of thermoplastic polyurethane (TPU) and a new self-reinforcing TP(U-urea) (TPUU). Biocompatibility is tested in vitro by cell seeding and hemocompatibility tests. In vivo performance is evaluated in rats over a period for up to six months. Autologous rat aortic implants serve as a control group. Scanning electron microscopy, micro-computed tomography (µCT), histology, and gene expression analyses are applied. TPU/TPUU grafts show significant improvement of biomechanical properties after water incubation and exhibit excellent cyto- and hemocompatibility. All grafts remain patent, and biomechanical properties are sufficient despite wall thinning. No inflammation, aneurysms, intimal hyperplasia, or thrombus formation are observed. Evaluation of graft healing shows similar gene expression profiles of TPU/TPUU and autologous conduits. These new biodegradable, self-reinforcing SDVGs may be promising candidates for clinical use in the future.
Collapse
Affiliation(s)
- Sabrina Rohringer
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Christian Grasl
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
- Center for Medical Physics and Biomedical EngineeringMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
| | - Katharina Ehrmann
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Institute of Applied Synthetic ChemistryTechnical University of ViennaGetreidemarkt 9/163Vienna1060Austria
| | - Pia Hager
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Clemens Hahn
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Sophie J. Specht
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Ingrid Walter
- Department of PathobiologyUniversity of Veterinary MedicineVeterinaerplatz 1Vienna1210Austria
| | - Karl H. Schneider
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Lydia M. Zopf
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for TraumatologyDonaueschingenstraße 13Vienna1200Austria
| | - Stefan Baudis
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Institute of Applied Synthetic ChemistryTechnical University of ViennaGetreidemarkt 9/163Vienna1060Austria
| | - Robert Liska
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Institute of Applied Synthetic ChemistryTechnical University of ViennaGetreidemarkt 9/163Vienna1060Austria
| | - Heinrich Schima
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
- Center for Medical Physics and Biomedical EngineeringMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
| | - Bruno K. Podesser
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Helga Bergmeister
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| |
Collapse
|
|
2
|
Um S, Ha J, Choi SJ, Oh W, Jin HJ. Prospects for the therapeutic development of umbilical cord blood-derived mesenchymal stem cells. World J Stem Cells 2020; 12:1511-1528. [PMID: 33505598 PMCID: PMC7789129 DOI: 10.4252/wjsc.v12.i12.1511] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/23/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
Umbilical cord blood (UCB) is a primitive and abundant source of mesenchymal stem cells (MSCs). UCB-derived MSCs have a broad and efficient therapeutic capacity to treat various diseases and disorders. Despite the high latent self-renewal and differentiation capacity of these cells, the safety, efficacy, and yield of MSCs expanded for ex vivo clinical applications remains a concern. However, immunomodulatory effects have emerged in various disease models, exhibiting specific mechanisms of action, such as cell migration and homing, angiogenesis, anti-apoptosis, proliferation, anti-cancer, anti-fibrosis, anti-inflammation and tissue regeneration. Herein, we review the current literature pertaining to the UCB-derived MSC application as potential treatment strategies, and discuss the concerns regarding the safety and mass production issues in future applications.
Collapse
Affiliation(s)
- Soyoun Um
- Research Team for Immune Cell Therapy, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Jueun Ha
- Research Team for Osteoarthritis, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Soo Jin Choi
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Wonil Oh
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Hye Jin Jin
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| |
Collapse
|
|
3
|
Pérez-Tanoira R, Han X, Soininen A, Aarnisalo AA, Tiainen VM, Eklund KK, Esteban J, Kinnari TJ. Competitive colonization of prosthetic surfaces by staphylococcus aureus and human cells. J Biomed Mater Res A 2016; 105:62-72. [PMID: 27513443 DOI: 10.1002/jbm.a.35863] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 07/26/2016] [Accepted: 08/08/2016] [Indexed: 12/31/2022]
Abstract
Implantation of a biomaterial provides an adhesion substratum both to host cell integration and to contaminating bacteria. We studied simultaneous competitive adhesion of Staphylococcus aureus in serial 1:10 dilutions of 108 colony forming units (CFU)/mL and human osteogenic sarcoma (SaOS-2) or primary osteoblast (hOB) cells, both 1x105 cells/mL, to the surfaces of titanium, polydimethylsiloxane and polystyrene. The bacterial adherence and human cell proliferation, cytotoxicity and production of reactive oxygen species (ROS) were studied using fluorometric (fluorescent microscopy and flow cytometry) and colorimetric methods (MTT, LDH and crystal violet). The bacterial cell viability was also evaluated using the drop plate method. The presence of bacteria resulted in reduced adherence of human cells to the surface of the biomaterials, increased production of ROS, and into increased apoptosis. On the other hand, the presence of either type of human cells was associated with a reduction of bacterial colonization of the biomaterial with Staphylococcus aureus. These results suggest that increasing colonization of the biomaterial surface in vitro by one negatively affects colonization by the other. Host cell integration to an implant surface reduces bacterial contamination, which opens novel opportunities for the design of infection-resistant biomaterials in current implantology and future regenerative medicine. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 62-72, 2017.
Collapse
Affiliation(s)
- Ramón Pérez-Tanoira
- Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Xia Han
- Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Antti Soininen
- ORTON Research Institute, Helsinki, Finland.,ORTON Orthopedic Hospital, Helsinki, Finland
| | - Antti A Aarnisalo
- Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Veli-Matti Tiainen
- ORTON Research Institute, Helsinki, Finland.,ORTON Orthopedic Hospital, Helsinki, Finland
| | - Kari K Eklund
- Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Rheumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Jaime Esteban
- Clinical Microbiology, IIS-Fundación Jiménez Díaz, Madrid, Spain
| | - Teemu J Kinnari
- Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| |
Collapse
|
|
4
|
Lueders C, Jastram B, Hetzer R, Schwandt H. Rapid manufacturing techniques for the tissue engineering of human heart valves. Eur J Cardiothorac Surg 2014; 46:593-601. [PMID: 25063052 DOI: 10.1093/ejcts/ezt510] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Three-dimensional (3D) printing technologies have reached a level of quality that justifies considering rapid manufacturing for medical applications. Herein, we introduce a new approach using 3D printing to simplify and improve the fabrication of human heart valve scaffolds by tissue engineering (TE). Custom-made human heart valve scaffolds are to be fabricated on a selective laser-sintering 3D printer for subsequent seeding with vascular cells from human umbilical cords. The scaffolds will be produced from resorbable polymers that must feature a number of specific properties: the structure, i.e. particle granularity and shape, and thermic properties must be feasible for the printing process. They must be suitable for the cell-seeding process and at the same time should be resorbable. They must be applicable for implementation in the human body and flexible enough to support the full functionality of the valve. The research focuses mainly on the search for a suitable scaffold material that allows the implementation of both the printing process to produce the scaffolds and the cell-seeding process, while meeting all of the above requirements. Computer tomographic data from patients were transformed into a 3D data model suitable for the 3D printer. Our current activities involve various aspects of the printing process, material research and the implementation of the cell-seeding process. Different resorbable polymeric materials have been examined and used to fabricate heart valve scaffolds by rapid manufacturing. Human vascular cells attached to the scaffold surface should migrate additionally into the inner structure of the polymeric samples. The ultimate intention of our approach is to establish a heart valve fabrication process based on 3D rapid manufacturing and TE. Based on the computer tomographic data of a patient, a custom-made scaffold for a valve will be produced on a 3D printer and populated preferably by autologous cells. The long-term goal is to support the growth of a new valve by a 3D structure resorbed by the human body in the course of the growth process. Our current activities can be characterized as basic research in which the fundamental steps of the technical process and its feasibility are investigated.
Collapse
Affiliation(s)
- Cora Lueders
- Deutsches Herzzentrum Berlin, Laboratory for Tissue Engineering, Berlin, Germany
| | - Ben Jastram
- Faculty of Mathematics and Natural Sciences, 3D Laboratory, Institute of Mathematics, MA 6-4, Technical University of Berlin, Berlin, Germany
| | - Roland Hetzer
- Deutsches Herzzentrum Berlin, Laboratory for Tissue Engineering, Berlin, Germany
| | - Hartmut Schwandt
- Faculty of Mathematics and Natural Sciences, 3D Laboratory, Institute of Mathematics, MA 6-4, Technical University of Berlin, Berlin, Germany
| |
Collapse
|
|
5
|
Han I, Yun M, Kim EO, Kim B, Jung MH, Kim SH. Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/AKT signaling. Stem Cell Res Ther 2014; 5:54. [PMID: 24739733 PMCID: PMC4055109 DOI: 10.1186/scrt443] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Accepted: 03/21/2014] [Indexed: 12/15/2022] Open
Abstract
Introduction Although mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells still remains unclear. Thus, in the present study, we elucidated the antitumor activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo. Methods hUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse. Results We found that hUCMSCs inhibited the proliferation of PC-3 cells in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/ AKT, extracellular signal-regulated kinase (ERK), and the expression of survival genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western blotting assay. Conversely, we found that treatment of specific JNK inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in PC-3 cells by Western blotting and immunofluorescence assay. The homing of hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse. Conclusions These results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment.
Collapse
|
|
6
|
Riescher S, Wehner D, Schmid T, Zimmermann H, Hartmann B, Schmid C, Lehle K. Titaniumcarboxonitride layer increased biocompatibility of medical polyetherurethanes. J Biomed Mater Res B Appl Biomater 2013; 102:141-8. [DOI: 10.1002/jbm.b.32990] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Revised: 03/20/2013] [Accepted: 05/28/2013] [Indexed: 12/12/2022]
Affiliation(s)
- Sebastian Riescher
- Department of Cardiothoracic Surgery; University Medical Centre Regensburg; Franz-Josef-Strauss-Allee 11 93042 Regensburg Germany
| | - Daniel Wehner
- Dualis Medtech GmbH; Am Technologiepark 8+10 82229 Seefeld Germany
| | - Thomas Schmid
- Dualis Medtech GmbH; Am Technologiepark 8+10 82229 Seefeld Germany
| | | | - Björn Hartmann
- pfm medical titanium gmbh; Hoefener Str. 45 90431 Nürnberg Germany
| | - Christof Schmid
- Department of Cardiothoracic Surgery; University Medical Centre Regensburg; Franz-Josef-Strauss-Allee 11 93042 Regensburg Germany
| | - Karla Lehle
- Department of Cardiothoracic Surgery; University Medical Centre Regensburg; Franz-Josef-Strauss-Allee 11 93042 Regensburg Germany
| |
Collapse
|
|
7
|
Hollweck T, Akra B, Häussler S, Uberfuhr P, Schmitz C, Pfeifer S, Eblenkamp M, Wintermantel E, Eissner G. A novel pulsatile bioreactor for mechanical stimulation of tissue engineered cardiac constructs. J Funct Biomater 2011; 2:107-18. [PMID: 24956300 PMCID: PMC4030939 DOI: 10.3390/jfb2030107] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Accepted: 07/18/2011] [Indexed: 11/17/2022] Open
Abstract
After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC) colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.
Collapse
Affiliation(s)
- Trixi Hollweck
- Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
| | - Bassil Akra
- Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
| | - Simon Häussler
- Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
| | - Peter Uberfuhr
- Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
| | - Christoph Schmitz
- Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
| | - Stefan Pfeifer
- Chair of Medical Engineering, Technische Universität München, Boltzmannstrasse 15, 85748 Garching, Germany.
| | - Markus Eblenkamp
- Chair of Medical Engineering, Technische Universität München, Boltzmannstrasse 15, 85748 Garching, Germany.
| | - Erich Wintermantel
- Chair of Medical Engineering, Technische Universität München, Boltzmannstrasse 15, 85748 Garching, Germany.
| | - Günther Eissner
- Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
| |
Collapse
|