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1
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Fenberg R, vonWindheim N, Malara M, Ahmed M, Cowen E, Melaragno L, Vankoevering K. Tissue Engineering: Current Technology for Facial Reconstruction. Facial Plast Surg 2023; 39:489-495. [PMID: 37290454 DOI: 10.1055/s-0043-1769808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023] Open
Abstract
Facial reconstruction is a complex surgical process that requires intricate three-dimensional (3D) concepts for optimal functional and aesthetic outcomes. Conventional reconstruction of structural facial anomalies, such as those including cartilage or bony defects, typically rely on hand-carving autologous constructs harvested from a separate donor site, and shaping that cartilage or bone into a new structural framework. Tissue engineering has emerged in recent decades as a potential approach to mitigate the need for donor site morbidity while improving precision in the design of reconstructive construct. Computer-aided design and computer-aided manufacturing have allowed for a digital 3D workflow to digitally execute the planned reconstruction in virtual space. 3D printing and other manufacturing techniques can then be utilized to create custom-fabricated scaffolds and guides to improve the reconstructive efficiency. Tissue engineering can be paired with custom 3D-manufactured scaffolds to theoretically create an ideal framework for structural reconstruction. In the past decade, there have been several compelling preclinical studies demonstrating the capacity to induce chondrogenesis or osteogenesis in a custom scaffold. However, to date, these preclinical data have not yet translated into significant clinical experience. This translation has been hindered by a lack of consensus on the ideal materials and cellular progenitors to be utilized in these constructs and a lack of regulatory guidance and control to enable clinical application. In this review, we highlight the current state of tissue engineering in facial reconstruction and exciting potential for future applications as the field continues to advance.
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Affiliation(s)
- Rachel Fenberg
- School of Medicine, Albert Einstein College of Medicine, Bronx, New York
| | - Natalia vonWindheim
- Center for Design and Manufacturing Excellence, The Ohio State University College of Engineering, Columbus, Ohio
| | - Megan Malara
- Center for Design and Manufacturing Excellence, The Ohio State University College of Engineering, Columbus, Ohio
| | - Maariyah Ahmed
- Center for Design and Manufacturing Excellence, The Ohio State University College of Engineering, Columbus, Ohio
| | - Erin Cowen
- Center for Design and Manufacturing Excellence, The Ohio State University College of Engineering, Columbus, Ohio
| | - Luigi Melaragno
- Center for Design and Manufacturing Excellence, The Ohio State University College of Engineering, Columbus, Ohio
| | - Kyle Vankoevering
- Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
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Chen D, Wu JY, Kennedy KM, Yeager K, Bernhard JC, Ng JJ, Zimmerman BK, Robinson S, Durney KM, Shaeffer C, Vila OF, Takawira C, Gimble JM, Guo XE, Ateshian GA, Lopez MJ, Eisig SB, Vunjak-Novakovic G. Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration. Sci Transl Med 2021; 12:12/565/eabb6683. [PMID: 33055244 DOI: 10.1126/scitranslmed.abb6683] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 09/16/2020] [Indexed: 12/21/2022]
Abstract
Joint disorders can be detrimental to quality of life. There is an unmet need for precise functional reconstruction of native-like cartilage and bone tissues in the craniofacial space and particularly for the temporomandibular joint (TMJ). Current surgical methods suffer from lack of precision and comorbidities and frequently involve multiple operations. Studies have sought to improve craniofacial bone grafts without addressing the cartilage, which is essential to TMJ function. For the human-sized TMJ in the Yucatan minipig model, we engineered autologous, biologically, and anatomically matched cartilage-bone grafts for repairing the ramus-condyle unit (RCU), a geometrically intricate structure subjected to complex loading forces. Using image-guided micromilling, anatomically precise scaffolds were created from decellularized bone matrix and infused with autologous adipose-derived chondrogenic and osteogenic progenitor cells. The resulting constructs were cultured in a dual perfusion bioreactor for 5 weeks before implantation. Six months after implantation, the bioengineered RCUs maintained their predefined anatomical structure and regenerated full-thickness, stratified, and mechanically robust cartilage over the underlying bone, to a greater extent than either autologous bone-only engineered grafts or acellular scaffolds. Tracking of implanted cells and parallel bioreactor studies enabled additional insights into the progression of cartilage and bone regeneration. This study demonstrates the feasibility of TMJ regeneration using anatomically precise, autologous, living cartilage-bone grafts for functional, personalized total joint replacement. Inclusion of the adjacent tissues such as soft connective tissues and the TMJ disc could further extend the functional integration of engineered RCUs with the host.
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Affiliation(s)
- David Chen
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Josephine Y Wu
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Kelsey M Kennedy
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Keith Yeager
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Jonathan C Bernhard
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Johnathan J Ng
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Brandon K Zimmerman
- Department of Mechanical Engineering, Columbia University, New York, NY 10032, USA
| | - Samuel Robinson
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Krista M Durney
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Courtney Shaeffer
- Department of Mechanical Engineering, Columbia University, New York, NY 10032, USA
| | - Olaia F Vila
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Catherine Takawira
- School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
| | | | - X Edward Guo
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Gerard A Ateshian
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA.,Department of Mechanical Engineering, Columbia University, New York, NY 10032, USA
| | - Mandi J Lopez
- School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Sidney B Eisig
- College of Dental Medicine, Columbia University, New York, NY 10032, USA
| | - Gordana Vunjak-Novakovic
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA. .,College of Dental Medicine, Columbia University, New York, NY 10032, USA.,Department of Medicine, Columbia University, New York, NY 10032, USA
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Abramowicz S, Crotts SJ, Hollister SJ, Goudy S. Tissue-engineered vascularized patient-specific temporomandibular joint reconstruction in a Yucatan pig model. Oral Surg Oral Med Oral Pathol Oral Radiol 2021; 132:145-152. [PMID: 33785329 DOI: 10.1016/j.oooo.2021.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 01/13/2021] [Accepted: 02/02/2021] [Indexed: 11/17/2022]
Abstract
PURPOSE Current pediatric temporomandibular joint (TMJ) reconstruction options are limited. The aim of this project was to develop a proof-of-principle porcine model for a load-bearing, customized, 3D-printed and bone morphogenic protein 2 (BMP-2)-coated scaffold implanted in a pedicled (temporal) flap as a regenerative approach to pediatric TMJ mandibular condyle reconstruction. MATERIALS AND METHODS Scaffolds were customized, 3D-printed based on porcine computed tomography, and coated with BMP-2. Two operations occurred: (1) implantation of the scaffold in temporalis muscle to establish vascularity and, (2) 6 weeks later, unilateral condylectomy and rotation of the vascularized scaffold (with preservation of superficial temporal artery) onto the defect. Six months later, pigs were sacrified. The experimental side (muscle-scaffold) and control side (unoperated condyle) were individually evaluated by clinical, mechanical, radiographic, and histologic methods. RESULTS Scaffolds maintained physical properties similar in appearance to unoperated condyles. Vascularized scaffolds had new bone formation. Condyle height on the reconstructed side was 68% and 78% of the control side. Reconstructed condyle stiffness was between 20% and 45% of the control side. CONCLUSION In our porcine model, customized 3D-printed TMJ scaffolds coated with BMP-2 and implanted in vascularized temporalis muscle have the ability to (1) reconstruct a TMJ, (2) maintain appropriate condylar height, and (3) generate new bone, without impacting functional outcomes.
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Affiliation(s)
- Shelly Abramowicz
- Division of Oral and Maxillofacial Surgery, Department of Surgery, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA.
| | - Sarah Jo Crotts
- Center for 3D Medical Fabrication, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
| | - Scott J Hollister
- Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
| | - Steve Goudy
- Pediatric Otolaryngology, Department of Otolaryngology, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA
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Talaat W, Aryal Ac S, Al Kawas S, Samsudin ABR, Kandile NG, Harding DRK, Ghoneim MM, Zeiada W, Jagal J, Aboelnaga A, Haider M. Nanoscale Thermosensitive Hydrogel Scaffolds Promote the Chondrogenic Differentiation of Dental Pulp Stem and Progenitor Cells: A Minimally Invasive Approach for Cartilage Regeneration. Int J Nanomedicine 2020; 15:7775-7789. [PMID: 33116500 PMCID: PMC7567564 DOI: 10.2147/ijn.s274418] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 09/16/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose Several scaffolds and cell sources are being investigated for cartilage regeneration. The aim of the study was to prepare nanocellulose-based thermosensitive injectable hydrogel scaffolds and assess their potential as 3D scaffolds allowing the chondrogenic differentiation of embedded human dental pulp stem and progenitor cells (hDPSCs). Materials and Methods The hydrogel-forming solutions were prepared by adding β-glycerophosphate (GP) to chitosan (CS) at different ratios. Nanocellulose (NC) suspension was produced from hemp hurd then added dropwise to the CS/GP mixture. In vitro characterization of the prepared hydrogels involved optimizing gelation and degradation time, mass-swelling ratio, and rheological properties. The hydrogel with optimal characteristics, NC-CS/GP-21, was selected for further investigation including assessment of biocompatibility. The chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel was investigated in vitro and compared to that of bone marrow-derived mesenchymal stem cells (BMSCs), then was confirmed in vivo in 12 adult Sprague Dawley rats. Results The selected hydrogel showed stability in culture media, had a gelation time of 2.8 minutes, showed a highly porous microstructure by scanning electron microscope, and was morphologically intact in vivo for 14 days after injection. Histological and immunohistochemical analyses and real-time PCR confirmed the chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel. Conclusion Our results suggest that nanocellulose–chitosan thermosensitive hydrogel is a biocompatible, injectable, mechanically stable and slowly degradable scaffold. hDPSCs embedded in NC-CS/GP-21 hydrogel is a promising, minimally invasive, stem cell-based strategy for cartilage regeneration.
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Affiliation(s)
- Wael Talaat
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.,Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suez Canal University, Ismaillia 41522, Egypt
| | - Smriti Aryal Ac
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Sausan Al Kawas
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - A B Rani Samsudin
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Nadia G Kandile
- Department of Chemistry, Faculty of Women, Ain Shams University, Heliopolis, Cairo 11757, Egypt
| | - David R K Harding
- School of Fundamental Sciences, Massey University, Palmerston North 4442, New Zealand
| | - Mohamed M Ghoneim
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Sinai University, Arish 45511, Egypt
| | - Waleed Zeiada
- Department of Civil and Environmental Engineering, College of Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates.,Public Works Engineering Department, College of Engineering, Mansoura University, Mansoura 35516, Egypt
| | - Jayalakshmi Jagal
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Ahmed Aboelnaga
- Department of Surgery, Faculty of Medicine, Suez Canal University, Ismaillia 41522, Egypt
| | - Mohamed Haider
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.,Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.,Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 71526, Egypt
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5
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Safari S, Mahdian A, Motamedian SR. Applications of stem cells in orthodontics and dentofacial orthopedics: Current trends and future perspectives. World J Stem Cells 2018; 10:66-77. [PMID: 29988866 PMCID: PMC6033713 DOI: 10.4252/wjsc.v10.i6.66] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/19/2018] [Accepted: 05/09/2018] [Indexed: 02/06/2023] Open
Abstract
A simple overview of daily orthodontic practice involves use of brackets, wires and elastomeric modules. However, investigating the underlying effect of orthodontic forces shows various molecular and cellular changes. Also, orthodontics is in close relation with dentofacial orthopedics which involves bone regeneration. In this review current and future applications of stem cells (SCs) in orthodontics and dentofacial orthopedics have been discussed. For craniofacial anomalies, SCs have been applied to regenerate hard tissue (such as treatment of alveolar cleft) and soft tissue (such as treatment of hemifacial macrosomia). Several attempts have been done to reconstruct impaired temporomandibular joint. Also, SCs with or without bone scaffolds and growth factors have been used to regenerate bone following distraction osteogenesis of mandibular bone or maxillary expansion. Current evidence shows that SCs also have potential to be used to regenerate infrabony alveolar defects and move the teeth into regenerated areas. Future application of SCs in orthodontics could involve accelerating tooth movement, regenerating resorbed roots and expanding tooth movement limitations. However, evidence supporting these roles is weak and further studies are required to evaluate the possibility of these ideas.
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Affiliation(s)
- Shiva Safari
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran
| | - Arezoo Mahdian
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran
| | - Saeed Reza Motamedian
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran.
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Van Bellinghen X, Idoux-Gillet Y, Pugliano M, Strub M, Bornert F, Clauss F, Schwinté P, Keller L, Benkirane-Jessel N, Kuchler-Bopp S, Lutz JC, Fioretti F. Temporomandibular Joint Regenerative Medicine. Int J Mol Sci 2018; 19:E446. [PMID: 29393880 PMCID: PMC5855668 DOI: 10.3390/ijms19020446] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 01/19/2018] [Accepted: 01/29/2018] [Indexed: 01/09/2023] Open
Abstract
The temporomandibular joint (TMJ) is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to increased interest in regenerative strategies combining stem cells, implantable scaffolds and well-targeting bioactive molecules. To succeed in functional and structural regeneration of TMJ is very challenging. Innovative strategies and biomaterials are absolutely crucial because TMJ can be considered as one of the most difficult tissues to regenerate due to its limited healing capacity, its unique histological and structural properties and the necessity for long-term prevention of its ossified or fibrous adhesions. The ideal approach for TMJ regeneration is a unique scaffold functionalized with an osteochondral molecular gradient containing a single stem cell population able to undergo osteogenic and chondrogenic differentiation such as BMSCs, ADSCs or DPSCs. The key for this complex regeneration is the functionalization with active molecules such as IGF-1, TGF-β1 or bFGF. This regeneration can be optimized by nano/micro-assisted functionalization and by spatiotemporal drug delivery systems orchestrating the 3D formation of TMJ tissues.
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Affiliation(s)
- Xavier Van Bellinghen
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
- Médecine et Chirurgie Bucco-Dentaires & Chirurgie Maxillo-Facial, Hôpitaux Universitaires de Strasbourg (HUS), 1 place de l'Hôpital, 67000 Strasbourg, France.
| | - Ysia Idoux-Gillet
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
| | - Marion Pugliano
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
| | - Marion Strub
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
- Médecine et Chirurgie Bucco-Dentaires & Chirurgie Maxillo-Facial, Hôpitaux Universitaires de Strasbourg (HUS), 1 place de l'Hôpital, 67000 Strasbourg, France.
| | - Fabien Bornert
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
- Médecine et Chirurgie Bucco-Dentaires & Chirurgie Maxillo-Facial, Hôpitaux Universitaires de Strasbourg (HUS), 1 place de l'Hôpital, 67000 Strasbourg, France.
| | - Francois Clauss
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
- Médecine et Chirurgie Bucco-Dentaires & Chirurgie Maxillo-Facial, Hôpitaux Universitaires de Strasbourg (HUS), 1 place de l'Hôpital, 67000 Strasbourg, France.
| | - Pascale Schwinté
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
| | - Laetitia Keller
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
| | - Nadia Benkirane-Jessel
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
| | - Sabine Kuchler-Bopp
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
| | - Jean Christophe Lutz
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Médecine et Chirurgie Bucco-Dentaires & Chirurgie Maxillo-Facial, Hôpitaux Universitaires de Strasbourg (HUS), 1 place de l'Hôpital, 67000 Strasbourg, France.
- Faculté de Médecine, Université de Strasbourg, 11 rue Humann, 67000 Strasbourg, France.
| | - Florence Fioretti
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 rue Humann, 67000 Strasbourg, France.
- Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Ste Elisabeth, 67000 Strasbourg, France.
- Médecine et Chirurgie Bucco-Dentaires & Chirurgie Maxillo-Facial, Hôpitaux Universitaires de Strasbourg (HUS), 1 place de l'Hôpital, 67000 Strasbourg, France.
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Ozawa T, Mickle DAG, Weisel RD, Matsubayashi K, Fujii T, Fedak PWM, Koyama N, Ikada Y, Li RK. Tissue-Engineered Grafts Matured in the Right Ventricular Outflow Tract. Cell Transplant 2017; 13:169-177. [DOI: 10.3727/000000004773301852] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Autologous smooth muscle cell (SMC)-seeded biodegradable scaffolds could be a suitable material to repair some pediatric right ventricular outflow tract (RVOT) cardiac anomalies. Adult syngenic Lewis rat SMCs (2 × 106) were seeded onto a new biodegradable copolymer sponge made of ∊-caprolactone-co-L-lactide reinforced with poly-L-lactide fabric (PCLA). Two weeks after seeding, the patch was used to repair a surgically created RVOT defect in an adult rat. At 8 weeks after implantation the spongy copolymer component was biodegraded, and SM tissue and extracellular matrices containing elastin fibers were present in the scaffolds. By 22 weeks more fibroblasts and collagen were present (p < 0.05). The number of capillaries in the grafts also increased (p < 0.001) between 8 and 22 weeks. The fibrous poly-L-lactide component of the PCLA scaffold remained. The 22-week grafts maintained their thickness and surface area in the RVOT. The SMCs prior to implantation were in a synthetic phenotype and developed in vivo into a more contractile phenotype. By 8 weeks the patches were endothelialized on their endocardial surfaces. Future work to increase the SM tissue and elastin content in the patch will be necessary before implantation into a pediatric large-animal model is tested.
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Affiliation(s)
- Tsukasa Ozawa
- Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada
| | - Donald A. G. Mickle
- Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada
| | - Richard D. Weisel
- Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada
| | - Keiji Matsubayashi
- Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada
| | - Takeshiro Fujii
- Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada
| | - Paul W. M. Fedak
- Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada
| | | | | | - Ren-Ke Li
- Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada
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8
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Aryaei A, Vapniarsky N, Hu JC, Athanasiou KA. Recent Tissue Engineering Advances for the Treatment of Temporomandibular Joint Disorders. Curr Osteoporos Rep 2016; 14:269-279. [PMID: 27704395 PMCID: PMC5106310 DOI: 10.1007/s11914-016-0327-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Temporomandibular disorders (TMDs) are among the most common maxillofacial complaints and a major cause of orofacial pain. Although current treatments provide short- and long-term relief, alternative tissue engineering solutions are in great demand. Particularly, the development of strategies, providing long-term resolution of TMD to help patients regain normal function, is a high priority. An absolute prerequisite of tissue engineering is to understand normal structure and function. The current knowledge of anatomical, mechanical, and biochemical characteristics of the temporomandibular joint (TMJ) and associated tissues will be discussed, followed by a brief description of current TMD treatments. The main focus is on recent tissue engineering developments for regenerating TMJ tissue components, with or without a scaffold. The expectation for effectively managing TMD is that tissue engineering will produce biomimetic TMJ tissues that recapitulate the normal structure and function of the TMJ.
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Affiliation(s)
- Ashkan Aryaei
- Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
| | - Natalia Vapniarsky
- Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
| | - Jerry C Hu
- Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
| | - Kyriacos A Athanasiou
- Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
- Department of Orthopedic Surgery, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA
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9
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Regenerative Engineering in Maxillofacial Reconstruction. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2016. [DOI: 10.1007/s40883-016-0009-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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10
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Mandibular Tissue Engineering: Past, Present, Future. J Oral Maxillofac Surg 2016; 73:S136-46. [PMID: 26608143 DOI: 10.1016/j.joms.2015.05.037] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Accepted: 05/27/2015] [Indexed: 12/19/2022]
Abstract
Almost 2 decades ago, the senior author's (M.T.J.) first article was with our mentor, Dr Leonard B. Kaban, a review article titled "Distraction Osteogenesis: Past, Present, Future." In 1998, many thought it would be impossible to have a remotely activated, small, curvilinear distractor that could be placed using endoscopic techniques. Currently, a U.S. patent for a curvilinear automated device and endoscopic techniques for minimally invasive access for jaw reconstruction exist. With minimally invasive access for jaw reconstruction, the burden to decrease donor site morbidity has increased. Distraction osteogenesis (DO) is an in vivo form of tissue engineering. The DO technique eliminates a donor site, is less invasive, requires a shorter operative time than usual procedures, and can be used for multiple reconstruction applications. Tissue engineering could further reduce morbidity and cost and increase treatment availability. The purpose of the present report was to review our experience with tissue engineering of bone: the past, present, and our vision for the future. The present report serves as a tribute to our mentor and acknowledges Dr Kaban for his incessant tutelage, guidance, wisdom, and boundless vision.
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12
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Gutierrez K, Dicks N, Glanzner WG, Agellon LB, Bordignon V. Efficacy of the porcine species in biomedical research. Front Genet 2015; 6:293. [PMID: 26442109 PMCID: PMC4584988 DOI: 10.3389/fgene.2015.00293] [Citation(s) in RCA: 133] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 09/04/2015] [Indexed: 01/02/2023] Open
Abstract
Since domestication, pigs have been used extensively in agriculture and kept as companion animals. More recently they have been used in biomedical research, given they share many physiological and anatomical similarities with humans. Recent technological advances in assisted reproduction, somatic cell cloning, stem cell culture, genome editing, and transgenesis now enable the creation of unique porcine models of human diseases. Here, we highlight the potential applications and advantages of using pigs, particularly minipigs, as indispensable large animal models in fundamental and clinical research, including the development of therapeutics for inherited and chronic disorders, and cancers.
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Affiliation(s)
- Karina Gutierrez
- Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue QC, Canada
| | - Naomi Dicks
- Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue QC, Canada
| | - Werner G Glanzner
- Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue QC, Canada
| | - Luis B Agellon
- School of Dietetics and Human Nutrition, McGill University, Sainte-Anne-de-Bellevue QC, Canada
| | - Vilceu Bordignon
- Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue QC, Canada
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Tissue-engineered bone with 3-dimensionally printed β-tricalcium phosphate and polycaprolactone scaffolds and early implantation: an in vivo pilot study in a porcine mandible model. J Oral Maxillofac Surg 2015; 73:1016.e1-1016.e11. [PMID: 25883004 DOI: 10.1016/j.joms.2015.01.021] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 01/25/2015] [Accepted: 01/26/2015] [Indexed: 11/22/2022]
Abstract
PURPOSE Deep bone penetration into implanted scaffolds remains a challenge in tissue engineering. The purpose of this study was to evaluate bone penetration depth within 3-dimensionally (3D) printed β-tricalcium phosphate (β-TCP) and polycaprolactone (PCL) scaffolds, seeded with porcine bone marrow progenitor cells (pBMPCs), and implanted early in vivo. MATERIALS AND METHODS Scaffolds were 3D printed with 50% β-TCP and 50% PCL. The pBMPCs were harvested, isolated, expanded, and differentiated into osteoblasts. Cells were seeded into the scaffolds and constructs were incubated in a rotational oxygen-permeable bioreactor system for 14 days. Six 2- × 2-cm defects were created in each mandible (N = 2 minipigs). In total, 6 constructs were placed within defects and 6 defects were used as controls (unseeded scaffolds, n = 3; empty defects, n = 3). Eight weeks after surgery, specimens were harvested and analyzed by hematoxylin and eosin (H&E), 4',6-diamidino-2-phenylindole (DAPI), and CD31 staining. Analysis included cell counts, bone penetration, and angiogenesis at the center of the specimens. RESULTS All specimens (N = 12) showed bone formation similar to native bone at the periphery. Of 6 constructs, 4 exhibited bone formation in the center. Histomorphometric analysis of the H&E-stained sections showed an average of 22.1% of bone in the center of the constructs group compared with 1.87% in the unseeded scaffolds (P < .05). The 2 remaining constructs, which did not display areas of mature bone in the center, showed massive cell penetration depth by DAPI staining, with an average of 2,109 cells/0.57 mm(2) in the center compared with 1,114 cells/0.57 mm(2) in the controls (P < .05). CD31 expression was greater in the center of the constructs compared with the unseeded scaffolds (P < .05). CONCLUSION 3D printed β-TCP and PCL scaffolds seeded with pBMPCs and implanted early into porcine mandibular defects display good bone penetration depth. Further study with a larger sample and larger bone defects should be performed before human applications.
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Abstract
Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling which has a great influence on cell proliferation, differentiation, and biology. Recently, application of scaffolds and MSCs is being utilized in obtaining more homogenous population of MSCs with higher cell proliferation rate and greater differentiation potential, which are crucial factors in regenerative medicine. In this review, the definition, biology, source, characterization, and isolation of MSCs and current report of application of nanofibers in regenerative medicine in different lesions are discussed.
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Shi D, Tatu R, Liu Q, Hosseinkhani H. Stem Cell-Based Tissue Engineering for Regenerative Medicine. ACTA ACUST UNITED AC 2014. [DOI: 10.1142/s1793984414300015] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The applications of stem cells in tissue engineering will show great promise in generating tailor-made tissue/organs for clinical applications. This paper gives a review on a broad spectrum of areas in stem cell-based tissue engineering including neuron repair, cardiac patches, skin regeneration, gene therapy and cartilage tissue engineering. This paper is intended to serve as an informative tutorial for scientists and physicians from fields other than stem cells and tissue engineering. It will shed light on various strategies of target tissue/organ repair involving stem cells.
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Affiliation(s)
- Donglu Shi
- Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200120, P. R. China
- The Materials Science and Engineering Program, Department of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221-0072, USA
| | - Rigwed Tatu
- The Materials Science and Engineering Program, Department of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221-0072, USA
| | - Qing Liu
- Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200120, P. R. China
| | - Hossein Hosseinkhani
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
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Shibazaki-Yorozuya R, Yamada A, Nagata S, Ueda K, Miller AJ, Maki K. Three-dimensional longitudinal changes in craniofacial growth in untreated hemifacial microsomia patients with cone-beam computed tomography. Am J Orthod Dentofacial Orthop 2014; 145:579-94. [PMID: 24785922 DOI: 10.1016/j.ajodo.2013.09.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Revised: 09/01/2013] [Accepted: 09/01/2013] [Indexed: 10/25/2022]
Abstract
INTRODUCTION The purpose of this study was to evaluate the concept that the affected and contralateral sides do not grow at the same rate in patients with hemifacial microsomia. Changes in the cranial base, maxilla, mandible, and occlusal plane were evaluated on 3-dimensional images from cone-beam computed tomography data in untreated patients. METHODS Six patients were classified as having mandibular Pruzansky/Kaban type I, IIA, or IIB hemifacial microsomia. Cone-beam computed tomography (MercuRay; Hitachi, Tokyo, Japan) scans were taken before orthodontic treatment during both growth and postpuberty periods. RESULTS The cranial base as defined by the position of the mastoid process was in a different position between the affected and contralateral control sides. The nasomaxillary length or height was shorter on the affected side for all 6 patients with hemifacial microsomia regardless of its severity, and it grew less than on the contralateral control side in 5 of the 6 patients. The occlusal plane angle became more inclined in 4 of the 6 patients. The mandibular ramus was shorter on the affected side in all patients and grew less on the affected side in 5 of the 6 patients. The mandibular body grew slower, the same, or faster than on the control side. CONCLUSIONS The cranial base, position of the condyle, lengths of the condyle and ramus, and positions of the gonial angle and condyle can vary between the affected and contralateral control sides of patients with hemifacial microsomia, with the ramus and nasomaxillary length usually growing slower than they grow on the control side. These results suggest that many factors affect the growth rate of the craniofacial region and, specifically, the mandible in patients with hemifacial microsomia.
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Affiliation(s)
- Reiko Shibazaki-Yorozuya
- Assistant professor, Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
| | - Akira Yamada
- Lecturer, Department of Plastic and Reconstructive Surgery, Osaka Medical School, Osaka, Japan; visiting professor, World Craniofacial Foundation, Dallas, Tex
| | - Satoru Nagata
- Director, Nagata Microtia and Reconstructive Plastic Surgery Clinic, Saitama, Japan; visiting professor, Department of Plastic and Reconstructive Surgery, University of California Irvine School of Medicine, Irvine, Calif
| | - Kouichi Ueda
- Professor and chair, Department of Plastic and Reconstructive Surgery, Osaka Medical School, Osaka, Japan
| | - Arthur J Miller
- Professor, Division of Orthodontics, Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, Calif
| | - Koutaro Maki
- Professor and chair, Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan
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Mehrotra D. TMJ Bioengineering: A review. J Oral Biol Craniofac Res 2013; 3:140-5. [PMID: 25737903 PMCID: PMC3941445 DOI: 10.1016/j.jobcr.2013.07.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 07/30/2013] [Indexed: 01/09/2023] Open
Abstract
Regeneration using scaffolds, growth factors, and stem cells is being investigated worldwide. Pubmed search for scaffolds for condyle resulted in 102 articles, of which 24 analyzed Temporomandibular joint (TMJ) scaffolds and only 6 evaluated hydroxyapatite scaffolds. 17 articles report studies on TMJ disc regeneration. The ideal bone construct for repair should be able to replicate the lost structure, restore function, be harmless, reliable and biodegradable. Scaffolds act as carriers for mesenchymal stem cells and/or growth factors and are useful for cell adhesion, migration, proliferation, and differentiation. Gene therapy has also led to the accelerated effective bone regeneration. The major materials used as scaffolds are natural or synthetic polymers, ceramics, composite materials, and electrospun nanofibers. Mesenchymal stem cells are responsible for the formation of virtually all dental, oral, and craniofacial structures. Tissue-engineered bone can possess the customized shape and dimensions. It has the potential for the biological replacement of craniofacial bones.
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Affiliation(s)
- Divya Mehrotra
- Professor, Department of Oral & Maxillofacial Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India
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Petrovic V, Zivkovic P, Petrovic D, Stefanovic V. Craniofacial bone tissue engineering. Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 114:e1-9. [PMID: 22862985 DOI: 10.1016/j.oooo.2012.02.030] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Revised: 01/18/2012] [Accepted: 02/29/2012] [Indexed: 12/17/2022]
Abstract
There are numerous conditions, such as trauma, cancer, congenital malformations, and progressive deforming skeletal diseases, that can compromise the function and architectonics of bones of craniofacial region. The need to develop new approaches for treatment of these disorders arises from the fact that conventional therapeutic strategies face many obstacles and limitations. The use of tissue engineering in regeneration of craniofacial bone structures is a very promising possibility and a great challenge for researchers and practitioners. Developments in stem cell biology and engineering have led to the discovery of different stem cell populations and biodegradable materials with suitable properties. This review summarizes the current achievements in tissue engineering of craniofacial bone, temporomandibular joint, and periodontal ligament.
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Affiliation(s)
- Vladimir Petrovic
- Department of Histology, Stem Cells Laboratory, University School of Medicine, Nis, Serbia
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Patil AS, Merchant Y, Nagarajan P. Tissue Engineering of Craniofacial Tissues – A Review. ACTA ACUST UNITED AC 2013. [DOI: 10.7243/2050-1218-2-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Pandit N, Malik R, Philips D. Tissue engineering: A new vista in periodontal regeneration. J Indian Soc Periodontol 2012; 15:328-37. [PMID: 22368355 PMCID: PMC3283928 DOI: 10.4103/0972-124x.92564] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Accepted: 11/28/2011] [Indexed: 01/14/2023] Open
Abstract
Tissue engineering is a highly promising field of reconstructive biology that draws on recent advances in medicine, surgery, molecular and cellular biology, polymer chemistry, and physiology. The objective of using tissue engineering as therapeutic application has been to harness its ability to exploit selected and primed cells together with an appropriate mix of regulatory factors, to allow growth and specialization of cells and matrix. The authors reviewed controlled clinical trials which also included histological studies that evaluated the potential of tissue engineering as a clinical tool in regeneration. PubMed/MEDLINE databases were searched for studies up to and including June 2010 to identify appropriate articles. A comprehensive search was designed, and the articles were independently screened for eligibility. Articles with authentic controls and proper randomization and pertaining specifically to their role in periodontal regeneration were included. Studies demonstrated that the periodontal regeneration with the use of combination of tissue engineered products with an osteoconductive matrix improve the beneficial effect of these materials by accelerating cellular in growth and revascularization of the wound site. Studies have suggested the use of rh Platelet-derived growth factor + beta tricalcium phosphate for regeneration of the periodontal attachment apparatus in combination with collagen membranes as an acceptable alternative to connective tissue graft for covering gingival recession defects. The studies concluded that growth factors promote true regeneration of the periodontal attachment apparatus and the use of combination protein therapeutics which is commercially available can provide more predictable, faster, less invasive, less traumatic, and efficient outcome for the patient.
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Affiliation(s)
- Nymphea Pandit
- Department of Periodontics and Oral Implantology, D.A.V (C) Dental College and Hospital, Yamuna Nagar, Haryana, India
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Lohberger B, Payer M, Rinner B, Kaltenegger H, Wolf E, Schallmoser K, Strunk D, Rohde E, Berghold A, Pekovits K, Wildburger A, Leithner A, Windhager R, Jakse N. Tri-lineage potential of intraoral tissue-derived mesenchymal stromal cells. J Craniomaxillofac Surg 2012; 41:110-8. [PMID: 22898339 DOI: 10.1016/j.jcms.2012.06.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 06/01/2012] [Accepted: 06/01/2012] [Indexed: 12/24/2022] Open
Abstract
The purpose of this study was to analyse the potential of intraoral tissues as a source of mesenchymal stromal and progenitor cells (MSPCs) for usage in future cell-based therapy models. Cells were isolated from four different tissues harvested during oral surgery intervention: (1) bone explants from the posterior maxilla, (2) bone explants from the oblique line, (3) from the mandibular periosteum, and (4) from the dental pulp. Donor sites and tissues were evaluated in terms of their accessibility, donor-site morbidity and average time period until appearance of MSPC colonies. Cell characterization was performed by flow cytometry and evaluation of in vitro osteogenic, adipogenic and chondrogenic differentiation potential. Adherent cell colonies were isolated from tissues from all sites after 4-8 days. The cells showed characteristics of MSPCs, so they were expanded up to clinical scales and demonstrated multipotency. The lowest donor-site morbidity was observed in the posterior maxilla harvests, while the highest donor-site morbidity was associated with harvests from mandibular sites. All sites seem to be potential sources of mesenchymal stromal and progenitor cells for tissue engineering approaches. Therefore, harvest morbidity and patient acceptance should affect the choice of the appropriate site.
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Affiliation(s)
- Birgit Lohberger
- Department of Orthopedic Surgery, Medical University of Graz, Graz, Austria.
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Abstract
Dental tissue injury and regeneration affects the daily lives of almost everyone. Tissue engineering is emerging as a promising therapy to regenerate missing teeth and dental tissues. The aim of regenerative dental therapies is to restore patients to full oral health. This means restoring normal function to missing or damaged tissue. Regeneration approaches use a combination of scaffolds, stem cells, growth factors, tissue engineering, organ tissue culture, transplantation, and tissue grafting. There are 8 key elements to create and use tissue constructs for tissue regeneration. These will be described in detail in this article.
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Affiliation(s)
- Peter E Murray
- Department of Endodontics, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328-2018, USA.
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Rosa V, Bona AD, Cavalcanti BN, Nör JE. Tissue engineering: from research to dental clinics. Dent Mater 2012; 28:341-8. [PMID: 22240278 PMCID: PMC3727423 DOI: 10.1016/j.dental.2011.11.025] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2010] [Revised: 08/23/2011] [Accepted: 11/29/2011] [Indexed: 01/09/2023]
Abstract
UNLABELLED Tissue engineering is an interdisciplinary field that combines the principles of engineering, material and biological sciences toward the development of therapeutic strategies and biological substitutes that restore, maintain, replace or improve biological functions. The association of biomaterials, stem cells, growth and differentiation factors has yielded the development of new treatment opportunities in most of the biomedical areas, including Dentistry. The objective of this paper is to present the principles underlying tissue engineering and the current scenario, the challenges and the perspectives of this area in Dentistry. SIGNIFICANCE The growth of tissue engineering as a research field has provided a novel set of therapeutic strategies for biomedical applications. Indeed, tissue engineering may lead to new strategies for the clinical management of patients with dental and craniofacial needs in the future.
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Affiliation(s)
- Vinicius Rosa
- Post-graduate Program in Dentistry, Dental School, University of Passo Fundo, Brasil
| | - Alvaro Della Bona
- Post-graduate Program in Dentistry, Dental School, University of Passo Fundo, Brasil
| | | | - Jacques Eduardo Nör
- Angiogenesis Research Laboratory, Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, USA
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Porto G, Vasconcelos B, Fraga S, Castro C, Andrade E. Development of temporomandibular joint ankylosis in rats using stem cells and bone graft. Int J Oral Maxillofac Surg 2011; 40:1414-20. [DOI: 10.1016/j.ijom.2011.07.910] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2011] [Revised: 06/13/2011] [Accepted: 07/28/2011] [Indexed: 11/24/2022]
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Jhaveri-Desai H, Khetarpal S. Tissue Engineering in Regenerative Dental Therapy. JOURNAL OF HEALTHCARE ENGINEERING 2011. [DOI: 10.1260/2040-2295.2.4.405] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Sharaf B, Faris CB, Abukawa H, Susarla SM, Vacanti JP, Kaban LB, Troulis MJ. Three-dimensionally printed polycaprolactone and β-tricalcium phosphate scaffolds for bone tissue engineering: an in vitro study. J Oral Maxillofac Surg 2011; 70:647-56. [PMID: 22079064 DOI: 10.1016/j.joms.2011.07.029] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2011] [Revised: 07/17/2011] [Accepted: 07/26/2011] [Indexed: 11/30/2022]
Abstract
PURPOSE The purpose of this study was to evaluate porcine bone marrow-derived progenitor cell (pBMPC) proliferation and penetration into a novel 3-dimensionally printed scaffold. MATERIALS AND METHODS Four different tissue engineering scaffolds to evaluate pBMPC proliferation and penetration were examined. Scaffolds were fabricated from polycaprolactone (PCL) or the combination of β-tricalcium phosphate (β-TCP) and PCL (50:50), with 2 separate channel sizes (1 mm [small (S)] vs 2 mm [large (L)]). Scaffolds were fabricated into 20 × 20 × 7-mm blocks by use of a TheriForm machine (Integra Life Sciences, Akron, OH). Four groups of scaffolds were examined for pBMPC proliferation and penetration: group 1, β-TCP/PCL S; group 2, β-TCP/PCL L; group 3, PCL S; and group 4, PCL L. Nonparametric mean (Kruskal-Wallis) and multiple comparisons tests were used to compare the 4 groups. RESULTS No shrinkage or deformation was noted in any of the scaffold groups after 2 weeks of culture. Mean surface cell counts ranged from 13.4 to 87.8 cells/0.57 mm(2), with group 1 (β-TCP/PCL S) having statistically significantly higher counts than the other groups (P < .001). Mean interior cell counts ranged from 10.9 to 75.6 cells/0.57 mm(2), with group 1 having the greatest interior cell count (P < .001). Total collagen formation ranged from 0.2% to 86%, with group 1 having the highest collagen formation (P < .001). CONCLUSIONS The 3-dimensionally printed scaffold (β-TCP/PCL) with 1-mm channels showed greater cellular proliferation, penetration, and collagen formation after a 2-week in vitro culture than the other scaffolds evaluated. β-TCP/PCL S scaffolds warrant further evaluation for bone tissue engineering in vivo.
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Affiliation(s)
- Basel Sharaf
- Department of Surgery, Buffalo General Hospital, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA
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Dormer NH, Busaidy K, Berkland CJ, Detamore MS. Osteochondral interface regeneration of rabbit mandibular condyle with bioactive signal gradients. J Oral Maxillofac Surg 2011; 69:e50-7. [PMID: 21470747 PMCID: PMC3101307 DOI: 10.1016/j.joms.2010.12.049] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2010] [Accepted: 12/28/2010] [Indexed: 12/22/2022]
Abstract
PURPOSE Tissue engineering solutions focused on the temporomandibular joint (TMJ) have expanded in number and variety during the past decade to address the treatment of TMJ disorders. The existing data on approaches for healing small defects in the TMJ condylar cartilage and subchondral bone, however, are sparse. The purpose of the present study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the rabbit mandibular condyle. MATERIALS AND METHODS Miniature bioactive plugs for regeneration of small mandibular condylar defects in New Zealand white rabbits were fabricated. The plugs were constructed from poly(D,L-lactic-co-glycolic acid) microspheres with a gradient transition between cartilage-promoting and bone-promoting growth factors. RESULTS At 6 weeks of healing, the results suggested that the implants provided support for the neosynthesized tissue as evidenced by the histologic and 9.4 T magnetic resonance imaging findings. CONCLUSION The inclusion of bioactive factors in a gradient-based scaffolding design is a promising new treatment strategy for focal defect repair in the TMJ.
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Affiliation(s)
- Nathan H. Dormer
- Bioengineering Program, University of Kansas, Lawrence, KS 66045
| | - Kamal Busaidy
- Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center, Houston, TX, 77030
| | - Cory J. Berkland
- Bioengineering Program, University of Kansas, Lawrence, KS 66045
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66045
- Department of Chemical & Petroleum Engineering, Lawrence, KS, 66045
| | - Michael S. Detamore
- Bioengineering Program, University of Kansas, Lawrence, KS 66045
- Department of Chemical & Petroleum Engineering, Lawrence, KS, 66045
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Zheng YH, Su K, Jian YT, Kuang SJ, Zhang ZG. Basic fibroblast growth factor enhances osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells in coral scaffold constructs. J Tissue Eng Regen Med 2010; 5:540-50. [PMID: 21695795 DOI: 10.1002/term.346] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Accepted: 07/08/2010] [Indexed: 11/08/2022]
Abstract
Temporomandibular joint (TMJ) disorders are commonly occurring degenerative joint diseases that require surgical replacement of the mandibular condyle in severe cases. Transplantation of tissue-engineered mandibular condyle constructs may solve some of the current surgical limitations to TMJ repair. We evaluated the feasibility of mandibular condyle constructs engineered from human bone marrow-derived mesenchymal cells (BMSCs). Specifically, human BMSCs were transfected with basic FGF (bFGF) gene-encoding plasmids and induced to differentiate into osteoblasts and chondroblasts. The cells were seeded onto mandibular condyle-shaped porous coral scaffolds and evaluated for osteogenic/chondrogenic differentiation, cell proliferation, collagen deposition and tissue vascularization. Transfected human BMSCs expressed bFGF and were highly proliferative. Osteogenesis was irregular, showing neovascularization around new bone tissue. There was no evidence of bilayered osteochondral tissue present in normal articulating surfaces. Collagen deposition, characteristic of bone and cartilage, was observed. Subcutaneous transplantation of seeded coral/hydrogel hyaluran constructs into nude mice resulted in bone formation and collagen type I and type II deposition. Neovascularization was observed around newly formed bone tissue; bFGF expression was detected in implanted constructs seeded with bFGF expressing hBMSCs. This report demonstrates that engineered porous coral constructs using bFGF gene-transfected human BMSCs may be a feasible option for surgical transplantation in TMJ repair.
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Affiliation(s)
- You-Hua Zheng
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China
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Payer M, Lohberger B, Stadelmeyer E, Bartmann C, Windhager R, Jakse N. Behaviour of multipotent maxillary bone-derived cells on beta-tricalcium phosphate and highly porous bovine bone mineral. Clin Oral Implants Res 2010; 21:699-708. [PMID: 20412093 DOI: 10.1111/j.1600-0501.2009.01856.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVES The aim of this study was to test the applicability of multipotent maxillary cells (MMC) for cell therapy concepts and to evaluate their in vitro behaviour on two different bone substitutes. MATERIAL AND METHODS Cells isolated from maxillary bone from 10 donors were expanded using media containing human platelet lysate (HPL) replacing foetal bovine serum and differentiated towards both the osteogenic and the adipogenic lineage. Surface markers were determined by fluorescence-activated cell sorting analysis. Calcium deposits, alkaline phosphatase (ALP) and osteocalcin (OC) were used as biomarkers of osteogenic differentiation. Oil Red O was used to verify adipogenic differentiation. The osteogenic lineage and undifferentiated controls were further cultured on natural bone mineral of bovine origin (BioOss) and beta-tricalcium phosphate (Vitoss) scaffolds. Scaffold efficacy and cell migration were evaluated with live cell imaging. RESULTS Isolated cells presented characteristics of bone marrow (BM)-stromal cells and could easily be expanded to clinical scales. Cells expressed osteogenic and adipogenic markers when cultured with inductive media. There were no obvious differences in cell migration and growth behaviour between the two bone substitutes, but significantly higher OC expression was observed on BioOss scaffolds. Both osteogenically differentiated and undifferentiated cell lines expressed ALP activity on the scaffolds. CONCLUSION Isolated maxillary cells demonstrate multipotent in vitro characteristics comparable with those of BM-stromal cells. HPL can predictably be used for clinical-scale expansion of MMCs. Both grafting materials provide potential carrier characteristics when loaded with MMCs.
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Affiliation(s)
- Michael Payer
- Department of Oral Surgery and Radiology, Dental School, Medical University of Graz, Graz, Austria
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Zilkens C, Lögters T, Bittersohl B, Krauspe R, Lensing-Höhn S, Jäger M. Spinning around or stagnation - what do osteoblasts and chondroblasts really like? Eur J Med Res 2010; 15:35-43. [PMID: 20159670 PMCID: PMC3351846 DOI: 10.1186/2047-783x-15-1-35] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective The influcence of cytomechanical forces in cellular migration, proliferation and differentation of mesenchymal stem cells (MSCs) is still poorly understood in detail. Methods Human MSCs were isolated and cultivated onto the surface of a 3 × 3 mm porcine collagen I/III carrier. After incubation, cell cultures were transfered to the different cutures systems: regular static tissue flasks (group I), spinner flasks (group II) and rotating wall vessels (group III). Following standard protocols cells were stimulated lineage specific towards the osteogenic and chondrogenic lines. To evaluate the effects of applied cytomechanical forces towards cellular differentiation distinct parameters were measured (morphology, antigen and antigen expression) after a total cultivation period of 21 days in vitro. Results Depending on the cultivation technique we found significant differences in both gen and protein expression. Conclusion Cytomechanical forces with rotational components strongly influence the osteogenic and chondrogenic differentiation.
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Affiliation(s)
- C Zilkens
- Department of Orthopaedics, Heinrich-Heine University of Duesseldorf, 40225 Duesseldorf, Germany
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Gallego L, Junquera L, García E, García V, Álvarez-Viejo M, Costilla S, Fresno MF, Meana Á. Repair of Rat Mandibular Bone Defects by Alveolar Osteoblasts in a Novel Plasma-Derived Albumin Scaffold. Tissue Eng Part A 2010; 16:1179-87. [DOI: 10.1089/ten.tea.2009.0517] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Lorena Gallego
- Department of Oral and Maxillofacial Surgery, Cabueñes Hospital, Gijón, Spain
| | - Luis Junquera
- Department of Oral and Maxillofacial Surgery, University Central Hospital, Oviedo, Spain
- University of Medicine, Oviedo, Spain
| | - Eva García
- Tissue Engineering Research Unit, Centro Comunitario de Sangre y Tejidos de Asturias, Oviedo, Spain
| | | | - María Álvarez-Viejo
- Tissue Engineering Research Unit, Centro Comunitario de Sangre y Tejidos de Asturias, Oviedo, Spain
- Transplant and Cell Therapy Unit, Central University Hospital, Oviedo, Spain
| | - Serafín Costilla
- University of Medicine, Oviedo, Spain
- Department of Radiology, Central University Hospital, Oviedo, Spain
| | - Manuel F. Fresno
- University of Medicine, Oviedo, Spain
- Department of Pathology, Central University Hospital, Oviedo, Spain
| | - Álvaro Meana
- Tissue Engineering Research Unit, Centro Comunitario de Sangre y Tejidos de Asturias, Oviedo, Spain
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Kokemueller H, Spalthoff S, Nolff M, Tavassol F, Essig H, Stuehmer C, Bormann KH, Rücker M, Gellrich NC. Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application. Int J Oral Maxillofac Surg 2010; 39:379-87. [PMID: 20167453 DOI: 10.1016/j.ijom.2010.01.010] [Citation(s) in RCA: 97] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2009] [Accepted: 01/20/2010] [Indexed: 01/09/2023]
Abstract
The key elements for bioartificial bone formation in 3D matrices are large numbers of osteogenic cells and supplies of oxygen and nutrition. Vascularization becomes more important with the increasing size and complexity of seeded scaffolds required for clinical application in reconstructive craniomaxillofacial surgery. Prefabrication of vascularized bioartificial bone grafts in vivo might be an alternative to in vitro tissue engineering techniques. Two cylindrical beta-TCP-scaffolds (25 mm long) were intraoperatively filled with autogenous bone marrow from the iliac crest for cell loading and implanted into the latissimus dorsi muscle in 12 sheep. To determine the effect of axial perfusion, one scaffold in each sheep was surgically supplied with a central vascular bundle. Sheep were killed 3 months after surgery. Histomorphometric analysis showed autogenous bone marrow from the iliac crest was an effective source of osteogenic cells and growth factors, inducing considerable ectopic bone growth in all implanted scaffolds. Bone growth, ceramic resorption and angiogenesis increased significantly with axial perfusion. The results encourage the application of prefabricated bioartificial bone for segmental mandibular reconstruction in man. In clinical practice, vascularized bioartificial bone grafts could change the principles of bone transplantation with minimal donor site morbidity and no shape or volume limitations.
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Affiliation(s)
- H Kokemueller
- Department for Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany.
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Zou D, Zhao J, Ding W, Xia L, Jang X, Huang Y. Wisdom teeth: Mankind’s future third vice-teeth? Med Hypotheses 2010; 74:52-5. [DOI: 10.1016/j.mehy.2009.08.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2009] [Accepted: 08/06/2009] [Indexed: 11/25/2022]
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Effect of ibuprofen on osteoblast differentiation of porcine bone marrow-derived progenitor cells. J Oral Maxillofac Surg 2009; 67:2412-7. [PMID: 19837310 DOI: 10.1016/j.joms.2009.05.434] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2008] [Accepted: 05/29/2009] [Indexed: 11/20/2022]
Abstract
PURPOSE Nonsteroidal anti-inflammatory drugs are commonly prescribed to reduce inflammation and pain. However, little is known about the direct effect of these drugs on the differentiation of bone marrow-derived progenitor cells into osteoblasts. The purpose of this study was to determine the effect of ibuprofen on osteoblast differentiation and proliferation in a minipig model. MATERIALS AND METHODS Bone marrow was aspirated from the minipig ilium, and porcine bone marrow-derived progenitor cells (pBMPCs) were isolated and expanded in standard culture medium. The pBMPCs were replated and differentiated into osteoblasts by use of osteogenic supplements (OS). Five groups were studied: negative control--pBMPCs in standard medium only; positive control--pBMPCs, standard culture medium, and OS; and 3 experimental groups--pBMPCs, standard culture medium, OS, and ibuprofen added in doses of 0.1, 1.0, and 3.0 mmol/L. Cell cultures were evaluated quantitatively by alkaline phosphatase (ALP) stain, von Kossa stain, and deoxyribonucleic acid (DNA) content. RESULTS pBMPCs cultured with OS and low-dose ibuprofen (0.1 mmol/L) showed ALP stain, von Kossa stain, and DNA content similar to pBMPCs cultured in OS (positive control). pBMPCs cultured in higher doses of ibuprofen (1.0 and 3.0 mmol/L) produced significantly less positive staining of ALP and von Kossa and decreased DNA content. CONCLUSION The results indicate that high-dose ibuprofen has a deleterious effect on pBMPC differentiation into osteoblasts whereas low-dose ibuprofen does not. The low dose of 0.1 mmol/L is the typical serum level when prescribed for clinical use.
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Oliveira JM, Silva SS, Malafaya PB, Rodrigues MT, Kotobuki N, Hirose M, Gomes ME, Mano JF, Ohgushi H, Reis RL. Macroporous hydroxyapatite scaffolds for bone tissue engineering applications: physicochemical characterization and assessment of rat bone marrow stromal cell viability. J Biomed Mater Res A 2009; 91:175-86. [PMID: 18780358 DOI: 10.1002/jbm.a.32213] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
In this work, a new methodology is reported for developing hydroxyapatite (HA) scaffolds using an organic sacrifice template. The novelty of work consists of possibility of obtaining porous and highly interconnected scaffolds mimicking the sacrificial component. Our purpose consisted of evaluating the physicochemical properties of the HA scaffolds by means of Fourier transform infra-red spectroscopy, X-ray diffraction analysis, and scanning electron microscopy (SEM) attached with an X-ray detector. The HA scaffolds obtained possess a porosity of approximately 70%, and macropores diameter in the range of 50-600 microm. In contrast, results regarding the microcomputed tomography analysis have demonstrated both high pore uniformity and interconnectivity across the scaffolds. The compressive strength of the HA scaffolds was found to be 30.2 +/- 6.0 MPa. Bioactivity of the HA scaffolds was assessed by immersion into a simulated body fluid solution, in vitro. SEM observations have showed a deposition of apatite on the surface of the HA scaffolds, with a "cauliflower-like" morphology after 1 day, and tend to be more pronounced with the immersion time. The changes in calcium and phosphorus concentration were monitored by inductively-coupled plasma optical emission spectrometry. Cytotoxicity of the HA scaffolds was preliminarily investigated by carrying direct observation of mouse fibroblasts cells (L929 cell-line) death in the inverted microscope, and then cell viability was determined by means of carrying out a MTS assay. Complementarily, a luminescent cell viability assay based on the quantification of adenosine triphosphate was performed using rat bone marrow stromal cells (RBMSCs). A LIVE/DEAD assay and SEM analysis allowed the visualization of the RBMSCs adhesion and proliferation on the surface of the HA scaffolds. According to the results obtained from 3D architecture, mechanical properties, biocompatibility, and adhesion tests, it is suggested that HA scaffolds has potential to find applications in bone tissue engineering scaffolding.
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Affiliation(s)
- Joaquim M Oliveira
- Department of Polymer Engineering, 3B's Research Group-Biomaterials, Biodegradables, and Biomimetics, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal.
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Stiehler M, Bünger C, Baatrup A, Lind M, Kassem M, Mygind T. Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells. J Biomed Mater Res A 2009; 89:96-107. [PMID: 18431785 DOI: 10.1002/jbm.a.31967] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ex vivo engineering of autologous bone tissue as an alternative to bone grafting is a major clinical need. In the present study, we evaluated the effect of 3-D dynamic spinner flask culture on the proliferation, distribution, and differentiation of human mesenchymal stem cells (MSCs). Immortalized human MSCs were cultured on porous 75:25 PLGA scaffolds for up to 3 weeks. Dynamically cultured cell/scaffold constructs demonstrated a 20% increase in DNA content (21 days), enhanced ALP specific activity (7 days and 21 days), a more than tenfold higher Ca2+ content (21 days), and significantly increased transcript levels of early osteogenesis markers (e.g., COL1A1, BMP2, RUNX-2) as compared with static culture. Despite the formation of a dense superficial cell layer, markedly increased cell ingrowth was observed by fluorescence microscopy on day 21. Furthermore, increased extracellular matrix deposition was visualized by scanning electron microscopy after 1 and 3 weeks of dynamic culture. The observed increased ingrowth and osteogenic differentiation of 3-D dynamically cultured human MSCs can be explained by generation of fluid shear stress and enhanced mass transport to the interior of the scaffold mimicking the native microenvironment of bone cells. This study provides evidence for the effectiveness of dynamic culture of human MSCs during the initial phase of ex vivo osteogenesis.
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Affiliation(s)
- Maik Stiehler
- Orthopedic Research Laboratory, Clinical Institute, Aarhus University Hospital, Aarhus, Denmark.
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Wang L, Lazebnik M, Detamore MS. Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application. Osteoarthritis Cartilage 2009; 17:346-53. [PMID: 18760638 DOI: 10.1016/j.joca.2008.07.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2008] [Accepted: 07/03/2008] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To compare temporomandibular joint (TMJ) condylar cartilage cells in vitro to hyaline cartilage cells cultured in a three-dimensional (3D) environment for tissue engineering of mandibular condylar cartilage. DESIGN Mandibular condylar cartilage and hyaline cartilage cells were harvested from pigs and cultured for 6 weeks in polyglycolic acid (PGA) scaffolds. Both types of cells were treated with glucosamine sulfate (0.4 mM), insulin-like growth factor-I (IGF-I) (100 ng/ml) and their combination. At weeks 0 and 6, cell number, glycosaminoglycan (GAG) and collagen content were determined, types I and II collagen were visualized by immunohistochemistry and GAGs were visualized by histology. RESULTS Hyaline cartilage cells produced from half an order to a full order of magnitude more GAGs and collagen than mandibular condylar cartilage cells in 3D culture. IGF-I was a highly effective signal for biosynthesis with hyaline cartilage cells, while glucosamine sulfate decreased cell proliferation and biosynthesis with both types of cells. In vitro culture of TMJ condylar cartilage cells produced a fibrous tissue with predominantly type I collagen, while hyaline cartilage cells formed a fibrocartilage-like tissue with types I and II collagen. The combination of IGF and glucosamine had a synergistic effect on maintaining the phenotype of TMJ condylar cells to generate both types I and II collagen. CONCLUSION Given the superior biosynthetic activity by hyaline cartilage cells and the practical surgical limitations of harvesting cells from the TMJ of a patient requiring TMJ reconstruction, cartilage cells from elsewhere in the body may be a potentially better alternative to cells harvested from the TMJ for TMJ tissue engineering. This finding may also apply to other fibrocartilages such as the intervertebral disc and knee meniscus in applications where a mature cartilage cell source is desired.
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Affiliation(s)
- L Wang
- Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS 66045, United States
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Zhang W, Abukawa H, Troulis MJ, Kaban LB, Vacanti JP, Yelick PC. Tissue engineered hybrid tooth–bone constructs. Methods 2009; 47:122-8. [PMID: 18845257 DOI: 10.1016/j.ymeth.2008.09.004] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2008] [Revised: 09/03/2008] [Accepted: 09/05/2008] [Indexed: 01/09/2023] Open
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Abukawa H, Zhang W, Young CS, Asrican R, Vacanti JP, Kaban LB, Troulis MJ, Yelick PC. Reconstructing mandibular defects using autologous tissue-engineered tooth and bone constructs. J Oral Maxillofac Surg 2009; 67:335-47. [PMID: 19138608 DOI: 10.1016/j.joms.2008.09.002] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2008] [Accepted: 09/05/2008] [Indexed: 11/29/2022]
Abstract
PURPOSE Current strategies for jaw reconstruction require multiple operations to replace bone and teeth. To improve on these methods, we investigated simultaneous mandibular and tooth reconstruction, using a Yucatan minipig model. MATERIALS AND METHODS Tooth and bone constructs were prepared from third molar tooth tissue and iliac-crest bone marrow-derived osteoblasts isolated from, and implanted back into, the same pig as an autologous reconstruction. Implants were harvested after 12 and 20 weeks and evaluated by x-ray, ultrahigh-resolution volume computed tomographic (VCT), histological, and immunohistochemical analyses. RESULTS Small tooth structures were identified, and consisted of organized dentin, enamel, pulp, and periodontal ligament tissues, surrounded by new bone. No dental tissues formed in implants without tooth-bud cells, and bone regeneration was observed to a limited extent. Immunohistochemical analyses using tooth-specific and bone-specific antibodies confirmed the identity of regenerated tissues. CONCLUSIONS This pilot study supports the feasibility of tissue-engineering approaches for coordinated autologous tooth and mandible reconstruction, and provides a basis for future improvement of this technique for eventual clinical use in humans.
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Affiliation(s)
- Harutsugi Abukawa
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA
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Athanasiou KA, Almarza AJ, Detamore MS, Kalpakci KN. Tissue Engineering of Temporomandibular Joint Cartilage. ACTA ACUST UNITED AC 2009. [DOI: 10.2200/s00198ed1v01y200906tis002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Nesti LJ, Li WJ, Shanti RM, Jiang YJ, Jackson W, Freedman BA, Kuklo TR, Giuliani JR, Tuan RS. Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. Tissue Eng Part A 2008; 14:1527-37. [PMID: 18707229 PMCID: PMC2676103 DOI: 10.1089/ten.tea.2008.0215] [Citation(s) in RCA: 126] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2008] [Accepted: 06/04/2008] [Indexed: 01/08/2023] Open
Abstract
Degeneration of the intervertebral disc (IVD) represents a significant musculoskeletal disease burden. Although spinal fusion has some efficacy in pain management, spine biomechanics is ultimately compromised. In addition, there is inherent limitation of hardware-based IVD replacement prostheses, which underscores the importance of biological approaches to disc repair. In this study, we have seeded multipotent, adult human mesenchymal stem cells (MSCs) into a novel biomaterial amalgam to develop a biphasic construct that consisted of electrospun, biodegradable nanofibrous scaffold (NFS) enveloping a hyaluronic acid (HA) hydrogel center. The seeded MSCs were induced to undergo chondrogenesis in vitro in the presence of transforming growth factor-beta for up to 28 days. The cartilaginous hyaluronic acid-nanofibrous scaffold (HANFS) construct architecturally resembled a native IVD, with an outer annulus fibrosus-like region and inner nucleus pulposus-like region. Histological and biochemical analyses, immunohistochemistry, and gene expression profiling revealed the time-dependent development of chondrocytic phenotype of the seeded cells. The cells also maintain the microarchitecture of a native IVD. Taken together, these findings suggest the prototypic potential of MSC-seeded HANFS constructs for the tissue engineering of biological replacements of degenerated IVD.
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Affiliation(s)
- Leon J. Nesti
- Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
- Department of Orthopaedics and Rehabilitation, Walter Reed Army Medical Center, Washington, D.C
| | - Wan-Ju Li
- Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
| | - Rabie M. Shanti
- Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
- Howard Hughes Medical Institute–National Institutes of Health Research Scholars Program, Bethesda, Maryland
| | - Yi Jen Jiang
- Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
| | - Wesley Jackson
- Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
| | - Brett A. Freedman
- Department of Orthopaedics and Rehabilitation, Walter Reed Army Medical Center, Washington, D.C
| | - Timothy R. Kuklo
- Department of Orthopaedics and Rehabilitation, Walter Reed Army Medical Center, Washington, D.C
| | - Jeffrey R. Giuliani
- Department of Orthopaedics and Rehabilitation, Walter Reed Army Medical Center, Washington, D.C
| | - Rocky S. Tuan
- Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
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Urkmez AS, Clark SG, Wheeler MB, Goldwasser MS, Jamison RD. Evaluation of Chitosan/Biphasic Calcium Phosphate Scaffolds for Maxillofacial Bone Tissue Engineering. ACTA ACUST UNITED AC 2008. [DOI: 10.1002/masy.200850912] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Hui TY, Cheung KMC, Cheung WL, Chan D, Chan BP. In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: influence of cell seeding density and collagen concentration. Biomaterials 2008; 29:3201-12. [PMID: 18462789 DOI: 10.1016/j.biomaterials.2008.04.001] [Citation(s) in RCA: 155] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2008] [Accepted: 04/01/2008] [Indexed: 10/22/2022]
Abstract
Given the inadequacies of existing repair strategies for cartilage injuries, tissue engineering approach using biomaterials and stem cells offers new hope for better treatments. Recently, we have fabricated injectable collagen-human mesenchymal stem cell (hMSC) microspheres using microencapsulation. Apart from providing a protective matrix for cell delivery, the collagen microspheres may also act as a bio-mimetic matrix facilitating the functional remodeling of hMSCs. In this study, whether the encapsulated hMSCs can be pre-differentiated into chondrogenic phenotype prior to implantation has been investigated. The effects of cell seeding density and collagen concentration on the chondrogenic differentiation potential of hMSCs have been studied. An in vivo implantation study has also been conducted. Fabrication of cartilage-like tissue micro-masses was demonstrated by positive immunohistochemical staining for cartilage-specific extracellular matrix components including type II collagen and aggrecan. The meshwork of collagen fibers was remodeled into a highly ordered microstructure, characterized by thick and parallel bundles, upon differentiation. Higher cell seeding density and higher collagen concentration favored the chondrogenic differentiation of hMSCs, yielding increased matrix production and mechanical strength of the micro-masses. These micro-masses were also demonstrated to integrate well with the host tissue in NOD/SCID mice.
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Affiliation(s)
- T Y Hui
- Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China
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Tanaka E, Detamore M, Mercuri L. Degenerative Disorders of the Temporomandibular Joint: Etiology, Diagnosis, and Treatment. J Dent Res 2008; 87:296-307. [DOI: 10.1177/154405910808700406] [Citation(s) in RCA: 470] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Temporomandibular joint (TMJ) disorders have complex and sometimes controversial etiologies. Also, under similar circumstances, one person’s TMJ may appear to deteriorate, while another’s does not. However, once degenerative changes start in the TMJ, this pathology can be crippling, leading to a variety of morphological and functional deformities. Primarily, TMJ disorders have a non-inflammatory origin. The pathological process is characterized by deterioration and abrasion of articular cartilage and local thickening. These changes are accompanied by the superimposition of secondary inflammatory changes. Therefore, appreciating the pathophysiology of the TMJ degenerative disorders is important to an understanding of the etiology, diagnosis, and treatment of internal derangement and osteoarthrosis of the TMJ. The degenerative changes in the TMJ are believed to result from dysfunctional remodeling, due to a decreased host-adaptive capacity of the articulating surfaces and/or functional overloading of the joint that exceeds the normal adaptive capacity. This paper reviews etiologies that involve biomechanical and biochemical factors associated with functional overloading of the joint and the clinical, radiographic, and biochemical findings important in the diagnosis of TMJ-osteoarthrosis. In addition, non-invasive and invasive modalities utilized in TMJ-osteoarthrosis management, and the possibility of tissue engineering, are discussed.
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Affiliation(s)
- E. Tanaka
- Department of Orthodontics and Dentofacial Orthopedics, The University of Tokushima Graduate School of Oral Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
- Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS, USA; and
- Department of Surgery, Division of Oral and Maxillofacial Surgery, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA
| | - M.S. Detamore
- Department of Orthodontics and Dentofacial Orthopedics, The University of Tokushima Graduate School of Oral Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
- Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS, USA; and
- Department of Surgery, Division of Oral and Maxillofacial Surgery, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA
| | - L.G. Mercuri
- Department of Orthodontics and Dentofacial Orthopedics, The University of Tokushima Graduate School of Oral Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
- Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS, USA; and
- Department of Surgery, Division of Oral and Maxillofacial Surgery, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA
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Meurer MI, Meurer E, Silva JVLD, Bárbara AS, Nobre LF, Oliveira MGD, Silva DN. Aquisição e manipulação de imagens por tomografia computadorizada da região maxilofacial visando à obtenção de protótipos biomédicos. Radiol Bras 2008. [DOI: 10.1590/s0100-39842008000100013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
O processo de construção de protótipos biomédicos surgiu da união das tecnologias de prototipagem rápida e do diagnóstico por imagens. No entanto, este processo é complexo, em função da necessária interação entre as ciências biomédicas e a engenharia. Para que bons resultados sejam obtidos, especial atenção deve ser dispensada à aquisição das imagens por tomografia computadorizada e à manipulação dessas imagens em softwares específicos. Este artigo apresenta a experiência multidisciplinar de um grupo de pesquisadores com a aquisição e a manipulação de imagens por tomografia computadorizada do complexo maxilofacial, visando à construção de protótipos biomédicos com finalidade cirúrgica.
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Shin M, Abukawa H, Troulis MJ, Vacanti JP. Development of a biodegradable scaffold with interconnected pores by heat fusion and its application to bone tissue engineering. J Biomed Mater Res A 2008; 84:702-9. [PMID: 17635029 DOI: 10.1002/jbm.a.31392] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Tissue engineering has been proposed as an approach to alleviate the shortage of donor tissue and organs by combining cells and a biodegradable scaffold as a temporary extracellular matrix. While numerous scaffold fabrication methods have been proposed, tissue formation is typically limited to the surface of the scaffolds in bone tissue engineering applications due to early calcification on the surface. To improve tissue formation, a novel scaffold with a hierarchical interconnected pore structure on two distinct length scales has been developed. Here we present the fabrication process and the application of the scaffold to bone tissue engineering. Porous poly(lactide-co-glycolide) (PLGA) scaffolds were made by combining solvent casting/particulate leaching with heat fusion. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were differentiated into osteoblasts and cultured on these scaffolds in vitro for 2, 4, and 6 weeks. Subsequently, the constructs were assessed using histology and scanning electron microscopy. The bone marrow-derived osteoblasts attached well on these scaffolds. Cells were observed throughout the scaffolds. These initial results show promise for this scaffold to aid in the regeneration of bone.
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Affiliation(s)
- Michael Shin
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
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47
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Tanaka E, Detamore MS, Tanimoto K, Kawai N. Lubrication of the temporomandibular joint. Ann Biomed Eng 2007; 36:14-29. [PMID: 17985243 DOI: 10.1007/s10439-007-9401-z] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2007] [Accepted: 10/26/2007] [Indexed: 10/22/2022]
Abstract
Although tissue engineering of the temporomandibular joint (TMJ) structures is in its infancy, tissue engineering provides the revolutionary possibility for treatment of temporomandibular disorders (TMDs). Recently, several reviews have provided a summary of knowledge of TMJ structure and function at the biochemical, cellular, or mechanical level for tissue engineering of mandibular cartilage, bone and the TMJ disc. As the TMJ enables large relative movements, joint lubrication can be considered of great importance for an understanding of the dynamics of the TMJ. The tribological characteristics of the TMJ are essential for reconstruction and tissue engineering of the joint. The purpose of this review is to provide a summary of advances relevant to the tribological characteristics of the TMJ and to serve as a reference for future research in this field. This review consists of four parts. Part 1 is a brief review of the anatomy and function of the TMJ articular components. In Part 2, the biomechanical and biochemical factors associated with joint lubrication are described: the articular surface topology with microscopic surface roughness and the biomechanical loading during jaw movements. Part 3 includes lubrication theories and possible mechanisms for breakdown of joint lubrication. Finally, in Part 4, the requirement and possibility of tissue engineering for treatment of TMDs with degenerative changes as a future treatment regimen will be discussed in a tribological context.
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Affiliation(s)
- Eiji Tanaka
- Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
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48
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Bailey MM, Wang L, Bode CJ, Mitchell KE, Detamore MS. A comparison of human umbilical cord matrix stem cells and temporomandibular joint condylar chondrocytes for tissue engineering temporomandibular joint condylar cartilage. ACTA ACUST UNITED AC 2007; 13:2003-10. [PMID: 17518722 DOI: 10.1089/ten.2006.0150] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The temporomandibular joint (TMJ) presents many problems in modern musculoskeletal medicine. Patients who suffer from TMJ disorders often experience a major loss in quality of life due to the debilitating effects that TMJ disorders can have on everyday activities. Cartilage tissue engineering can lead to replacement tissues that could be used to treat TMJ disorders. In this study, a spinner flask was used for a period of 6 days to seed polyglycolic acid (PGA) scaffolds with either TMJ condylar chondrocytes or mesenchymal-like stem cells derived from human umbilical cord matrix (HUCM). Samples were then statically cultured for 4 weeks either in growth medium containing chondrogenic factors or in control medium. Immunohistochemical staining of HUCM constructs after 4 weeks revealed a strong presence of collagen I and minute amounts of collagen II, whereas TMJ constructs revealed little collagen I and no collagen II. The HUCM constructs were shown to contain more GAGs than the TMJ constructs quantitatively at week 0 and histologically at week 4. Moreover, the cellularity of HUCM constructs was 55% higher at week 0 and nearly twice as high after 4 weeks, despite being seeded at the same density. The increased level of biosynthesis and higher cellularity of HUCM constructs clearly demonstrates that the HUCM stem cells outperformed the TMJ condylar cartilage cells under the prescribed conditions. HUCM stem cells may therefore be an attractive alternative to condylar cartilage cells for TMJ tissue engineering applications. Further, given the availability and ease of obtaining HUCM stem cells, these findings may have far-reaching implications, leading to novel developments in both craniofacial and orthopaedic tissue replacement therapies.
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Affiliation(s)
- Mark M Bailey
- Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence KS 66045-7609, USA
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Shanti RM, Li WJ, Nesti LJ, Wang X, Tuan RS. Adult mesenchymal stem cells: biological properties, characteristics, and applications in maxillofacial surgery. J Oral Maxillofac Surg 2007; 65:1640-7. [PMID: 17656295 DOI: 10.1016/j.joms.2007.04.008] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2006] [Revised: 12/15/2006] [Accepted: 04/05/2007] [Indexed: 12/14/2022]
Affiliation(s)
- Rabie M Shanti
- Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
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50
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Chen F, Feng X, Wu W, Ouyang H, Gao Z, Cheng X, Hou R, Mao T. Segmental bone tissue engineering by seeding osteoblast precursor cells into titanium mesh-coral composite scaffolds. Int J Oral Maxillofac Surg 2007; 36:822-7. [PMID: 17804199 DOI: 10.1016/j.ijom.2007.06.019] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2006] [Revised: 01/16/2007] [Accepted: 06/25/2007] [Indexed: 11/19/2022]
Abstract
The size and specific shape of bone grafts are important for jaw reconstruction. In this experiment, segmental bone grafts were engineered in a predetermined shape via seeding osteoblast precursor cells into titanium mesh-coral composite scaffolds. Titanium meshes were moulded into the shape of a column with length 12 mm and diameter 8mm. The column was filled with natural coral granules and the complex acted as a cell-seeding scaffold. About 4 x 10(7) osteoblast precursor cells in 200 microl cell-culture medium were seeded into each of six scaffolds and incubated in vitro for 2 days. Then, the composites were implanted subcutaneously into the backs of nude mice and incubated in vivo. Two months after implantation, the animals were killed and new bone formed in the scaffolds was investigated by gross inspection, X-ray examination, histological observation and mechanical testing. The results showed that newly formed tissue was red and presented the gross appearance of bone, and kept the original shape of the column. Titanium mesh was situated on the surface of the bone graft. An X-ray blocking shadow was observed in and around the titanium scaffolds; most of the coral granules had been absorbed. Histological observation demonstrated a large amount of new bone formed and integrated well with titanium mesh. Mechanical testing showed that new bone improved the mechanical property of the graft significantly. In conclusion, a titanium mesh-coral composite scaffold with osteoblast precursor cells is an efficient means to engineer segmental bone, possessing the desired shape and mechanical strength.
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Affiliation(s)
- F Chen
- Xi'da-RegeMed Lab of Tissue Engineering, Faculty of Life Science, Northwest University, Xi'an 710069, PR China.
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