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Marian D, Toro G, D’Amico G, Trotta MC, D’Amico M, Petre A, Lile I, Hermenean A, Fratila A. Challenges and Innovations in Alveolar Bone Regeneration: A Narrative Review on Materials, Techniques, Clinical Outcomes, and Future Directions. MEDICINA (KAUNAS, LITHUANIA) 2024; 61:20. [PMID: 39859003 PMCID: PMC11766548 DOI: 10.3390/medicina61010020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/11/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025]
Abstract
This review explores the recent advancements and ongoing challenges in regenerating alveolar bone, which is essential for dental implants and periodontal health. It examines traditional techniques like guided bone regeneration and bone grafting, alongside newer methods such as stem cell therapy, gene therapy, and 3D bioprinting. Each approach is considered for its strengths in supporting bone growth and integration, especially in cases where complex bone defects make regeneration difficult. This review also looks at different biomaterials, from bioactive scaffolds to nanomaterials, assessing how well they encourage cell growth and healing. Personalized treatments, like customized 3D-printed scaffolds, show promise in enhancing bone formation and tissue compatibility. Additionally, signaling molecules, like bone morphogenetic proteins, play a crucial role in guiding the process of bone formation and remodeling. Despite these advances, challenges remain-particularly with severe bone loss and with refining biomaterials for more reliable, long-term outcomes. This review proposes combining advanced materials, regenerative technologies, and personalized approaches to achieve more effective and consistent outcomes in oral and maxillofacial surgery.
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Affiliation(s)
- Diana Marian
- Department of Dentistry, Faculty of Dentistry, “Vasile Goldiș” Western University of Arad, 94-96 Revolutiei Blvd., 310025 Arad, Romania;
| | - Giuseppe Toro
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | | | - Maria Consiglia Trotta
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.T.); (M.D.)
| | - Michele D’Amico
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.T.); (M.D.)
| | - Alexandru Petre
- Department of Prosthodontics, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Ioana Lile
- Department of Dentistry, Faculty of Dentistry, “Vasile Goldiș” Western University of Arad, 94-96 Revolutiei Blvd., 310025 Arad, Romania;
| | - Anca Hermenean
- “Aurel Ardelean” Institute of Life Sciences, “Vasile Goldiș” Western University of Arad, 310025 Arad, Romania;
| | - Anca Fratila
- Department of Dental Medicine and Nursing, Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550169 Sibiu, Romania;
- Military Clinical Emergency Hospital of Sibiu, 550024 Sibiu, Romania
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2
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Nikhil A, Gugjoo MB, Das A, Ahmad SM, Kumar A. 3D-Printed-Cryogel-Impregnated Functionalized Scaffold Augments Bone Regeneration in Critical Tibia Fracture in Goat. Adv Healthc Mater 2024; 13:e2402619. [PMID: 39350449 DOI: 10.1002/adhm.202402619] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/10/2024] [Indexed: 12/28/2024]
Abstract
Critical-size bone trauma injuries present a significant clinical challenge because of the limited availability of autografts. In this study, a photocurable composite comprising of polycaprolactone, polypropylene fumarate, and nano-hydroxyapatite (nHAP) (P─P─H) is printed, which shows good osteoconduction in a rat model. A cryogel composed of gelatin-nHAP (GH) is developed to incorporate osteogenic components, specifically bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA), termed as GH+B+Z, which is investigated for osteoinductive property in a rat model. Further, a 3D-printed P─P─H scaffold impregnated with GH+B+Z is designed and implanted in a critical-size defect (25 × 10 × 5 mm) in goat tibia. After 4 months, the scaffold is well-integrated with adjacent native bone, with osteoinduction observed in the cryogel-filled region and osteoconduction over the printed scaffold. X-ray radiography and micro-CT analysis showed bone in-growth in the treatment group with 45 ± 1.4% bone volume/tissue volume (BV/TV), while the defect remained unhealed in the control group with BV/TV of 10.5 ± 0.5%. Histology showed significant cell infiltration and matrix deposition over the printed P─P─H scaffold and within the GH cryogel site in the treatment group. Immunohistochemical staining depicted significantly higher normalized collagen I intensity in the treatment group (34.45 ± 2.61%) compared to the control group (4.22 ± 0.78).
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Affiliation(s)
- Aman Nikhil
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P., 208016, India
| | - Mudasir B Gugjoo
- Division of Veterinary Clinical Complex, SKUAST-Kashmir, Srinagar, J&K, 190006, India
| | - Ankita Das
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P., 208016, India
| | - Syed M Ahmad
- Division of Animal Biotechnology, SKUAST-Kashmir, Srinagar, J&K, 190006, India
| | - Ashok Kumar
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P., 208016, India
- Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur, U.P., 208016, India
- The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur, U.P., 208016, India
- Centre of Excellence for Materials in Medicine, Gangwal School of Medical Sciences and Technology, Indian Institute of Technology Kanpur, Kanpur, U.P., 208016, India
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Ferraz MP. An Overview on the Big Players in Bone Tissue Engineering: Biomaterials, Scaffolds and Cells. Int J Mol Sci 2024; 25:3836. [PMID: 38612646 PMCID: PMC11012232 DOI: 10.3390/ijms25073836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/18/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
Presently, millions worldwide suffer from degenerative and inflammatory bone and joint issues, comprising roughly half of chronic ailments in those over 50, leading to prolonged discomfort and physical limitations. These conditions become more prevalent with age and lifestyle factors, escalating due to the growing elderly populace. Addressing these challenges often entails surgical interventions utilizing implants or bone grafts, though these treatments may entail complications such as pain and tissue death at donor sites for grafts, along with immune rejection. To surmount these challenges, tissue engineering has emerged as a promising avenue for bone injury repair and reconstruction. It involves the use of different biomaterials and the development of three-dimensional porous matrices and scaffolds, alongside osteoprogenitor cells and growth factors to stimulate natural tissue regeneration. This review compiles methodologies that can be used to develop biomaterials that are important in bone tissue replacement and regeneration. Biomaterials for orthopedic implants, several scaffold types and production methods, as well as techniques to assess biomaterials' suitability for human use-both in laboratory settings and within living organisms-are discussed. Even though researchers have had some success, there is still room for improvements in their processing techniques, especially the ones that make scaffolds mechanically stronger without weakening their biological characteristics. Bone tissue engineering is therefore a promising area due to the rise in bone-related injuries.
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Affiliation(s)
- Maria Pia Ferraz
- Departamento de Engenharia Metalúrgica e de Materiais, Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal;
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4099-002 Porto, Portugal
- INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4099-002 Porto, Portugal
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Buck HV, Stains JP. Osteocyte-mediated mechanical response controls osteoblast differentiation and function. Front Physiol 2024; 15:1364694. [PMID: 38529481 PMCID: PMC10961341 DOI: 10.3389/fphys.2024.1364694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 02/29/2024] [Indexed: 03/27/2024] Open
Abstract
Low bone mass is a pervasive global health concern, with implications for osteoporosis, frailty, disability, and mortality. Lifestyle factors, including sedentary habits, metabolic dysfunction, and an aging population, contribute to the escalating prevalence of osteopenia and osteoporosis. The application of mechanical load to bone through physical activity and exercise prevents bone loss, while sufficient mechanical load stimulates new bone mass acquisition. Osteocytes, cells embedded within the bone, receive mechanical signals and translate these mechanical cues into biological signals, termed mechano-transduction. Mechano-transduction signals regulate other bone resident cells, such as osteoblasts and osteoclasts, to orchestrate changes in bone mass. This review explores the mechanisms through which osteocyte-mediated response to mechanical loading regulates osteoblast differentiation and bone formation. An overview of bone cell biology and the impact of mechanical load will be provided, with emphasis on the mechanical cues, mechano-transduction pathways, and factors that direct progenitor cells toward the osteoblast lineage. While there are a wide range of clinically available treatments for osteoporosis, the majority act through manipulation of the osteoclast and may have significant disadvantages. Despite the central role of osteoblasts to the deposition of new bone, few therapies directly target osteoblasts for the preservation of bone mass. Improved understanding of the mechanisms leading to osteoblastogenesis may reveal novel targets for translational investigation.
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Affiliation(s)
| | - Joseph Paul Stains
- School of Medicine, University of Maryland, Baltimore, MD, United States
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Yaja K, Aungsuchawan S, Narakornsak S, Pothacharoen P, Pantan R, Tancharoen W. Combination of human platelet lysate and 3D gelatin scaffolds to enhance osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells. Heliyon 2023; 9:e18599. [PMID: 37576189 PMCID: PMC10413082 DOI: 10.1016/j.heliyon.2023.e18599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 07/14/2023] [Accepted: 07/21/2023] [Indexed: 08/15/2023] Open
Abstract
Bone disorders are major health issues requiring specialized care; however, the traditional bone grafting method had several limitations. Thus, bone tissue engineering has become a potential alternative. In therapeutic treatments, using fetal bovine serum (FBS) as a culture supplement may result in the risk of contamination and host immunological response; therefore, human platelet lysate (hPL) has been considered a viable alternative source. This study attempted to compare the effectiveness and safety of different culture supplements, either FBS or hPL, on the osteoblastic differentiation potential of mesenchymal stem cells derived from human amniotic fluid (hAF-MSCs) under a three-dimensional gelatin scaffold. The results indicate that hAF-MSCs have the potential to be used in clinical applications as they meet the criteria for mesenchymal stem cells based on their morphology, the expression of a particular surface antigen, their proliferation ability, and their capacity for multipotent differentiation. After evaluation by MTT and Alamar blue proliferation assay, 10% of hPL was selected. The osteogenic differentiation of hAF-MSCs under three-dimensional gelatin scaffold using osteogenic-induced media supplemented with hPL was achievable and markedly stimulated osteoblast differentiation. Moreover, the expressions of osteoblastogenic related genes, including OCN, ALP, and COL1A1, exhibited the highest degree of expression under hPL-supplemented circumstances when compared with the control and the FBS-supplemented group. The induced cells under hPL-supplemented conditions also presented the highest ALP activity level and the greatest degree of calcium accumulation. These outcomes would indicate that hPL is a suitable substitute for animal derived serum. Importantly, osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells using hPL-supplemented media and three-dimensional scaffolds may open the door to developing an alternative construct for repairing bone defects.
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Affiliation(s)
- Kantirat Yaja
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sirinda Aungsuchawan
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Suteera Narakornsak
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Peraphan Pothacharoen
- Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand
| | - Rungusa Pantan
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Waleephan Tancharoen
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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6
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Shineh G, Patel K, Mobaraki M, Tayebi L. Functional Approaches in Promoting Vascularization and Angiogenesis in Bone Critical-Sized Defects via Delivery of Cells, Growth Factors, Drugs, and Particles. J Funct Biomater 2023; 14:99. [PMID: 36826899 PMCID: PMC9960138 DOI: 10.3390/jfb14020099] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/06/2023] [Accepted: 02/09/2023] [Indexed: 02/16/2023] Open
Abstract
Critical-sized bone defects, or CSDs, are defined as bone defects that cannot be regenerated by themselves and require surgical intervention via employing specific biomaterials and a certain regenerative strategy. Although a variety of approaches can be used to treat CSDs, poor angiogenesis and vascularization remain an obstacle in these methods. The complex biological healing of bone defects depends directly on the function of blood flow to provide sufficient oxygen and nutrients and the removal of waste products from the defect site. The absence of vascularization can lead to non-union and delayed-union defect development. To overcome this challenge, angiogenic agents can be delivered to the site of injury to stimulate vessel formation. This review begins by introducing the treatment methods for CSDs. The importance of vascularization in CSDs is subsequently highlighted. Delivering angiogenesis agents, including relevant growth factors, cells, drugs, particles, cell secretion substances, their combination, and co-delivery to CSDs are fully explored. Moreover, the effects of such agents on new bone formation, followed by vessel formation in defect areas, are evaluated.
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Affiliation(s)
- Ghazal Shineh
- School of Biomedical Engineering, University of Sydney, Sydney, NSW 2006, Australia
| | - Kishan Patel
- School of Dentistry, Marquette University, Milwaukee, WI 53207, USA
| | - Mohammadmahdi Mobaraki
- Biomaterial Group, Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran 15916-34311, Iran
| | - Lobat Tayebi
- School of Dentistry, Marquette University, Milwaukee, WI 53207, USA
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The Localized Ionic Microenvironment in Bone Modelling/Remodelling: A Potential Guide for the Design of Biomaterials for Bone Tissue Engineering. J Funct Biomater 2023; 14:jfb14020056. [PMID: 36826855 PMCID: PMC9959312 DOI: 10.3390/jfb14020056] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 01/11/2023] [Accepted: 01/14/2023] [Indexed: 01/20/2023] Open
Abstract
Bone is capable of adjusting size, shape, and quality to maintain its strength, toughness, and stiffness and to meet different needs of the body through continuous remodeling. The balance of bone homeostasis is orchestrated by interactions among different types of cells (mainly osteoblasts and osteoclasts), extracellular matrix, the surrounding biological milieus, and waste products from cell metabolisms. Inorganic ions liberated into the localized microenvironment during bone matrix degradation not only form apatite crystals as components or enter blood circulation to meet other bodily needs but also alter cellular activities as molecular modulators. The osteoinductive potential of inorganic motifs of bone has been gradually understood since the last century. Still, few have considered the naturally generated ionic microenvironment's biological roles in bone remodeling. It is believed that a better understanding of the naturally balanced ionic microenvironment during bone remodeling can facilitate future biomaterial design for bone tissue engineering in terms of the modulatory roles of the ionic environment in the regenerative process.
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8
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Jörg DJ, Fuertinger DH, Cherif A, Bushinsky DA, Mermelstein A, Raimann JG, Kotanko P. Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types. eLife 2022; 11:76228. [PMID: 35942681 PMCID: PMC9363122 DOI: 10.7554/elife.76228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 06/26/2022] [Indexed: 11/13/2022] Open
Abstract
For the treatment of postmenopausal osteoporosis, several drug classes with different mechanisms of action are available. Since only a limited set of dosing regimens and drug combinations can be tested in clinical trials, it is currently unclear whether common medication strategies achieve optimal bone mineral density gains or are outperformed by alternative dosing schemes and combination therapies that have not been explored so far. Here, we develop a mathematical framework of drug interventions for postmenopausal osteoporosis that unifies fundamental mechanisms of bone remodeling and the mechanisms of action of four drug classes: bisphosphonates, parathyroid hormone analogs, sclerostin inhibitors, and receptor activator of NF-κB ligand inhibitors. Using data from several clinical trials, we calibrate and validate the model, demonstrating its predictive capacity for complex medication scenarios, including sequential and parallel drug combinations. Via simulations, we reveal that there is a large potential to improve gains in bone mineral density by exploiting synergistic interactions between different drug classes, without increasing the total amount of drug administered.
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Affiliation(s)
- David J Jörg
- Biomedical Modeling and Simulation Group, Global Research and Development, Fresenius Medical Care Germany, Bad Homburg, Germany
| | - Doris H Fuertinger
- Biomedical Modeling and Simulation Group, Global Research and Development, Fresenius Medical Care Germany, Bad Homburg, Germany
| | | | - David A Bushinsky
- Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, United States
| | | | | | - Peter Kotanko
- Renal Research Institute, New York, United States.,Icahn School of Medicine at Mount Sinai, New York, United States
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9
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Singh YP, Dasgupta S. Gelatin-based electrospun and lyophilized scaffolds with nano scale feature for bone tissue engineering application: review. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2022; 33:1704-1758. [PMID: 35443894 DOI: 10.1080/09205063.2022.2068943] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The rebuilding of the normal functioning of the damaged human body bone tissue is one of the main objectives of bone tissue engineering (BTE). Fabricated scaffolds are mostly treated as artificial supports and as materials for regeneration of neo bone tissues and must closely biomimetic the native extracellular matrix of bone. The materials used for developing scaffolds should be biodegradable, nontoxic, and biocompatible. For the resurrection of bone disorder, specifically natural and synthetic polymers such as chitosan, PCL, gelatin, PGA, PLA, PLGA, etc. meet the requirements for serving their functions as artificial bone substitute materials. Gelatin is one of the potential candidates which could be blended with other polymers or composites to improve its physicochemical, mechanical, and biological performances as a bone graft. Scaffolds are produced by several methods including electrospinning, self-assembly, freeze-drying, phase separation, fiber drawing, template synthesis, etc. Among them, freeze-drying and electrospinning are among the popular, simplest, versatile, and cost-effective techniques. The design and preparation of freeze-dried and electrospun scaffolds are of intense research over the last two decades. Freeze-dried and electrospun scaffolds offer a distinctive architecture at the micro to nano range with desired porosity and pore interconnectivity for selective movement of small biomolecules and play its role as an appropriate matrix very similar to the natural bone extracellular matrix. This review focuses on the properties and functionalization of gelatin-based polymer and its composite in the form of bone scaffolds fabricated primarily using lyophilization and electrospinning technique and their applications in BTE.
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Affiliation(s)
- Yogendra Pratap Singh
- Department of Ceramic Engineering, National Institute of Technology Rourkela, Rourkela, Odisha, India
| | - Sudip Dasgupta
- Department of Ceramic Engineering, National Institute of Technology Rourkela, Rourkela, Odisha, India
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10
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Wani TU, Khan RS, Rather AH, Beigh MA, Sheikh FA. Local dual delivery therapeutic strategies: Using biomaterials for advanced bone tissue regeneration. J Control Release 2021; 339:143-155. [PMID: 34563589 DOI: 10.1016/j.jconrel.2021.09.029] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/18/2021] [Accepted: 09/21/2021] [Indexed: 01/18/2023]
Abstract
Bone development is a complex process involving a vast number of growth factors and chemical substances. These factors include transforming growth factor-beta, platelet-derived growth factor, insulin-like growth factor, and most importantly, the bone morphogenetic protein, which exhibits excellent therapeutic value in bone repair. However, the spatial-temporal relationship in the expression of these factors during bone formation makes the bone repair a more complicated process to address. Thus, using a single therapeutic agent to address bone formation does not seem to provide a clinically effective option. Conversely, a dual delivery approach facilitating the co-delivery of agents has proved to be a dynamic alternative since such a strategy can provide more efficient spatial-temporal action. Such delivery systems can smartly target more than one pathway or differentiation lineage and thus offer more efficient bone regeneration. This review discusses various dual delivery strategies reported in the literature employed to achieve improved bone regeneration. These include concurrent use of different therapeutic agents (including growth factors and drugs), enhancing bone formation and cell recruitment, and improving the efficiency of bone healing.
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Affiliation(s)
- Taha Umair Wani
- Department of Nanotechnology, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India
| | - Rumysa Saleem Khan
- Department of Nanotechnology, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India
| | - Anjum Hamid Rather
- Department of Nanotechnology, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India
| | - Mushtaq A Beigh
- Department of Nanotechnology, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India
| | - Faheem A Sheikh
- Department of Nanotechnology, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India.
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11
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Gillman CE, Jayasuriya AC. FDA-approved bone grafts and bone graft substitute devices in bone regeneration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 130:112466. [PMID: 34702541 PMCID: PMC8555702 DOI: 10.1016/j.msec.2021.112466] [Citation(s) in RCA: 181] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 07/26/2021] [Accepted: 09/24/2021] [Indexed: 12/28/2022]
Abstract
To induce bone regeneration there is a complex cascade of growth factors. Growth factors such as recombinant BMP-2, BMP-7, and PDGF are FDA-approved therapies in bone regeneration. Although, BMP shows promising results as being an alternative to autograft, it also has its own downfalls. BMP-2 has many adverse effects such as inflammatory complications such as massive soft-tissue swelling that can compromise a patient's airway, ectopic bone formation, and tumor formation. BMP-2 may also be advantageous for patients not willing to give up smoking as it shows bone regeneration success with smokers. BMP-7 is no longer an option for bone regeneration as it has withdrawn off the market. PDGF-BB grafts in studies have shown PDGF had similar fusion rates to autologous grafts and fewer adverse effects. There is also an FDA-approved bioactive molecule for bone regeneration, a peptide P-15. P-15 was found to be effective, safe, and have similar outcomes to autograft at 2 years post-op for cervical radiculopathy due to cervical degenerative disc disease. Growth factors and bioactive molecules show some promising results in bone regeneration, although more research is needed to avoid their adverse effects and learn about the long-term effects of these therapies. There is a need of a bone regeneration method of similar quality of an autograft that is osteoconductive, osteoinductive, and osteogenic. This review covers all FDA-approved bone regeneration therapies such as the "gold standard" autografts, allografts, synthetic bone grafts, and the newer growth factors/bioactive molecules. It also covers international bone grafts not yet approved in the United States and upcoming technologies in bone grafts.
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Affiliation(s)
- Cassidy E Gillman
- The Doctor of Medicine (M.D.) Program, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH 43614, USA
| | - Ambalangodage C Jayasuriya
- Department of Orthopaedic Surgery, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH 43614, USA.
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12
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Nørregaard KS, Jürgensen HJ, Gårdsvoll H, Engelholm LH, Behrendt N, Søe K. Osteosarcoma and Metastasis Associated Bone Degradation-A Tale of Osteoclast and Malignant Cell Cooperativity. Int J Mol Sci 2021; 22:ijms22136865. [PMID: 34202300 PMCID: PMC8269025 DOI: 10.3390/ijms22136865] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 12/28/2022] Open
Abstract
Cancer-induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer-dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast-mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast-mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer-associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer-associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.
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Affiliation(s)
- Kirstine Sandal Nørregaard
- Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; (H.J.J.); (H.G.); (L.H.E.); (N.B.)
- Correspondence: ; Tel.: +45-3545-6030
| | - Henrik Jessen Jürgensen
- Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; (H.J.J.); (H.G.); (L.H.E.); (N.B.)
| | - Henrik Gårdsvoll
- Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; (H.J.J.); (H.G.); (L.H.E.); (N.B.)
| | - Lars Henning Engelholm
- Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; (H.J.J.); (H.G.); (L.H.E.); (N.B.)
| | - Niels Behrendt
- Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; (H.J.J.); (H.G.); (L.H.E.); (N.B.)
| | - Kent Søe
- Clinical Cell Biology, Pathology Research Unit, Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark;
- Clinical Cell Biology, Department of Pathology, Odense University Hospital, 5000 Odense, Denmark
- Department of Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark
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13
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Accelerated Bone Induction of Adult Rat Compact Bone Plate Scratched by Ultrasonic Scaler Using Acidic Electrolyzed Water. MATERIALS 2021; 14:ma14123347. [PMID: 34204338 PMCID: PMC8234999 DOI: 10.3390/ma14123347] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/10/2021] [Accepted: 06/10/2021] [Indexed: 11/16/2022]
Abstract
Fresh compact bone, the candidate graft material for bone regeneration, is usually grafted for horizontal bone augmentation. However, the dense calcified structure inhibits the release of growth factors and limits cellular and vascular perfusion. We aimed to create mechano-chemically altered dense skull bone by ultrasonic treatment, along with partial demineralization using commercially available acidic electrolyzed water (AEW). The parietal skull bone of an 11-month-old Wistar rat was exposed and continuously treated with a piezoelectric ultrasonic scaler tip for 1 min, using AEW (pH 2.3) or distilled water (DW, pH 5.6) as irrigants. Treated parietal bone was removed, cut into plates (5 × 5 × 1 mm3), grafted into the back subcutaneous tissues of syngeneic rats, and explanted at 1, 2, and 3 weeks. AEW bone showed an irregular surface, deep nano-microcracks, and decalcified areas. SEM-EDS revealed small amounts of residual calcium content in the AEW bone (0.03%) compared to the DW bone (0.86%). In the animal assay, the AEW bone induced bone at 2 weeks. Histomorphometric analysis showed that the area of new bone in the AEW bone at 2 and 3 weeks was significantly larger. This new combination technique of AEW-demineralization with ultrasonic treatment will improve the surface area and three-dimensional (3D) architecture of dense bone and accelerate new bone synthesis.
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14
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Lupi SM, Torchia M, Rizzo S. Biochemical Modification of Titanium Oral Implants: Evidence from In Vivo Studies. MATERIALS (BASEL, SWITZERLAND) 2021; 14:2798. [PMID: 34074006 PMCID: PMC8197372 DOI: 10.3390/ma14112798] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 05/02/2021] [Accepted: 05/19/2021] [Indexed: 12/29/2022]
Abstract
The discovery of osseointegration of titanium implants revolutionized the dental prosthesis field. Traditionally, implants have a surface that is processed by additive or subtractive techniques, which have positive effects on the osseointegration process by altering the topography. In the last decade, innovative implant surfaces have been developed, on which biologically active molecules have been immobilized with the aim of increasing stimulation at the implant-biological tissue interface, thus favoring the quality of osseointegration. Among these molecules, some are normally present in the human body, and the techniques for the immobilization of these molecules on the implant surface have been called Biochemical Modification of Titanium Surfaces (BMTiS). Different techniques have been described in order to immobilize those biomolecules on titanium implant surfaces. The aim of the present paper is to present evidence, available from in vivo studies, about the effects of biochemical modification of titanium oral implants on osseointegration.
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15
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Midavaine É, Côté J, Sarret P. The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers. Cancer Metastasis Rev 2021; 40:427-445. [PMID: 33973098 DOI: 10.1007/s10555-021-09974-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 04/30/2021] [Indexed: 02/06/2023]
Abstract
Breast and prostate cancers have a great propensity to metastasize to long bones. The development of bone metastases is life-threatening, incurable, and drastically reduces patients' quality of life. The chemokines CCL2 and CXCL12 and their respective receptors, CCR2 and CXCR4, are central instigators involved in all stages leading to cancer cell dissemination and secondary tumor formation in distant target organs. They orchestrate tumor cell survival, growth and migration, tumor invasion and angiogenesis, and the formation of micrometastases in the bone marrow. The bone niche is of particular importance in metastasis formation, as it expresses high levels of CCL2 and CXCL12, which attract tumor cells and contribute to malignancy. The limited number of available effective treatment strategies highlights the need to better understand the pathophysiology of bone metastases and reduce the skeletal tumor burden in patients diagnosed with metastatic bone disease. This review focuses on the involvement of the CCL2/CCR2 and CXCL12/CXCR4 chemokine axes in the formation and development of bone metastases, as well as on therapeutic perspectives aimed at targeting these chemokine-receptor pairs.
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Affiliation(s)
- Élora Midavaine
- Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada. .,Centre de recherche du Centre hospitalier universitaire de Sherbrooke, CIUSSS de l'Estrie - CHUS, Sherbrooke, QC, Canada.
| | - Jérôme Côté
- Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada.,Centre de recherche du Centre hospitalier universitaire de Sherbrooke, CIUSSS de l'Estrie - CHUS, Sherbrooke, QC, Canada
| | - Philippe Sarret
- Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada.,Centre de recherche du Centre hospitalier universitaire de Sherbrooke, CIUSSS de l'Estrie - CHUS, Sherbrooke, QC, Canada
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16
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Dindelegan GC, Caziuc A, Brie I, Soritau O, Dindelegan MG, Bintintan V, Pascalau V, Mihu C, Popa C. Multilayered Porous Titanium-Based 3rd Generation Biomaterial Designed for Endosseous Implants. MATERIALS (BASEL, SWITZERLAND) 2021; 14:1727. [PMID: 33807480 PMCID: PMC8036277 DOI: 10.3390/ma14071727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/18/2021] [Accepted: 03/26/2021] [Indexed: 11/17/2022]
Abstract
This work proposes a novel complex multi-layered material consisting of porous titanium as a substrate and a complex coating consisting of a chitosan film engulfing microsphere loaded with growth factors such as BMP2 (bone morphogenic protein 2) and IGF1 (insulin-like growth factor-1). The microspheres were obtained through deposition of dual layers of calcium cross linked pectin-chitosan/pectin polyelectrolyte onto a BSA (bovine serum albumin) gel core. The multilayer was conceived to behave like a 3rd generation biomaterial, by slow delivery of viable growth factors around implants, and to assist the healing of implantation wound and the development of new vital bone. The biologic effect of the delivery of growth factors was studied in vitro, on MSC-CD1 mesenchymal stem cells, and in vivo, on CD1 mice. Proliferation and differentiation of cells were accelerated by growth factors, especially IGF1 for proliferation and BMP2 for differentiation. In vivo tests analyzed histologically and by MicroCT show a more structured tissue around BMP2 samples. The present concept will give the best clinical results if both growth factors are delivered together by a coating film that contains a double population of microcarriers.
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Affiliation(s)
- George Calin Dindelegan
- Surgical Department, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; (G.C.D.); (V.B.)
| | - Alexandra Caziuc
- Surgical Department, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; (G.C.D.); (V.B.)
| | - Ioana Brie
- Radiobiology and Tumor Biology Department, Oncologic Institute Ion Chiricuta, 400015 Cluj-Napoca, Romania; (I.B.); (O.S.)
| | - Olga Soritau
- Radiobiology and Tumor Biology Department, Oncologic Institute Ion Chiricuta, 400015 Cluj-Napoca, Romania; (I.B.); (O.S.)
| | | | - Vasile Bintintan
- Surgical Department, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; (G.C.D.); (V.B.)
| | - Violeta Pascalau
- Department of Science and Technology, Faculty of Materials and Environmental Engineering, Technical University of Cluj-Napoca, 400114 Cluj-Napoca, Romania; (V.P.); (C.P.)
| | - Carmen Mihu
- Histology Department, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania;
| | - Catalin Popa
- Department of Science and Technology, Faculty of Materials and Environmental Engineering, Technical University of Cluj-Napoca, 400114 Cluj-Napoca, Romania; (V.P.); (C.P.)
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17
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Wu K, Chen YC, Lin SM, Chang CH. In vitro and in vivo effectiveness of a novel injectable calcitonin-loaded collagen/ceramic bone substitute. J Biomater Appl 2021; 35:1355-1365. [PMID: 33522363 DOI: 10.1177/0885328221989984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
This study aimed to evaluate the effectiveness of a novel calcitonin-loaded calcium phosphate composite bone cement in vitro and in vivo. The novel composite bone cements were composed of NuROs injectable bone graft substitute, type I collagen, and/or salmon calcitonin. The setting time, porosity, wettability, compressive strength, compressive modulus, and crystallographic structures of cement specimens were determined. Degradation rate, calcitonin release rate, and osteoinductivity were assessed in vitro. In addition, osteogenic effect was examined in a rabbit model of femoral defect. The results revealed that addition of collagen/calcitonin did not substantially alter physical properties and degradation rate of bone cement specimens. Calcitonin was released into culture medium in a two-phase manner. Osteogenic effect of conditioned medium derived from calcitonin containing bone cement was observed. Finally, de novo bone growth and bone mineralization across the bone defect area were observed in rabbits after implantation of composite bone cement specimens. In conclusion, this novel calcitonin-loaded composite calcium phosphate bone cement exhibits biocompatibility, bioresorbability, osteoinductivity, and osteoconductivity, which may be suitable for clinical use.
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Affiliation(s)
- Karl Wu
- Department of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Department of Materials and Textiles, Oriental Institute of Technology, New Taipei City, Taiwan
| | - Yu-Chun Chen
- Department of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,College of General Studies, Yuan Ze University, Taoyuan City, Taiwan
| | - Shang M Lin
- Department of Materials and Textiles, Oriental Institute of Technology, New Taipei City, Taiwan
| | - Chih-Hung Chang
- Department of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan City, Taiwan
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18
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Shrestha S, Shrestha BK, Ko SW, Kandel R, Park CH, Kim CS. Engineered cellular microenvironments from functionalized multiwalled carbon nanotubes integrating Zein/Chitosan @Polyurethane for bone cell regeneration. Carbohydr Polym 2021; 251:117035. [DOI: 10.1016/j.carbpol.2020.117035] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 08/20/2020] [Accepted: 08/30/2020] [Indexed: 01/15/2023]
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19
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Licini C, Montalbano G, Ciapetti G, Cerqueni G, Vitale-Brovarone C, Mattioli-Belmonte M. Analysis of multiple protein detection methods in human osteoporotic bone extracellular matrix: From literature to practice. Bone 2020; 137:115363. [PMID: 32298836 DOI: 10.1016/j.bone.2020.115363] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 04/02/2020] [Accepted: 04/07/2020] [Indexed: 11/15/2022]
Abstract
The punctual analysis of bone Extracellular Matrix (ECM) proteins represents a pivotal point for medical research in bone diseases like osteoporosis. Studies in this field, historically done to appreciate bone biology, were mainly conducted on animal samples and, up to today, only a few studies on protein detection in human bone are present. The challenges in bone ECM protein extraction and quantitation protocols are related to both the separation of proteins from the mineral content (i.e. hydroxyapatite) and the difficulty of avoiding protein denaturation during the extraction processes. The aim of the present work was to define appropriate protocol(s) for bone ECM protein extraction that could be applied to investigate both normal and pathological conditions. We compared and optimised some of the most used protocols present in the literature, modifying the protein precipitation method, the buffer used for resuspension and/or the volume of reagent used. Bradford and BCA assays and Western Blotting were used to evaluate the variations in the total protein recovery and the amount of selected proteins (Type I Collagen, TGF-β, IGF-1, Decorin, Osteopontin, Bone Sialoprotein-2 and Osteocalcin). Collectively, we were capable to draw-up two single-extract protocols with optimal recovery and ideal protein content, that can be used for a detailed analysis of ECM proteins in pathological bone samples. Time-consuming multi-extract procedures, optimised in their precipitation methods, are however crucial for a precise detection of specific proteins, like osteocalcin. As the matter of fact, also the demineralization processes, commonly suggested and performed in several protocols, could hinder an accurate protein detection, thus inherently affecting the study of a pathological bone ECM. This study represents a starting point for the definition of appropriate strategies in the study of bone extracellular matrix proteins involved in the onset and maintenance of bone diseases, as well as a tool for the development of customized scaffolds capable to modulate a proper feedback loop in bone remodelling, altered in case of diseases like osteoporosis.
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Affiliation(s)
- Caterina Licini
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy; Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/A, 60126 Ancona, Italy
| | - Giorgia Montalbano
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy
| | - Gabriela Ciapetti
- Laboratorio di Fisiopatologia Ortopedica e Medicina Rigenerativa, Istituto Ortopedico Rizzoli, IRCCS, Via di Barbiano 1/10, 40136 Bologna, Italy
| | - Giorgia Cerqueni
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/A, 60126 Ancona, Italy
| | - Chiara Vitale-Brovarone
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
| | - Monica Mattioli-Belmonte
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/A, 60126 Ancona, Italy
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20
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Tanaka M, Aoki K, Haniu H, Kamanaka T, Takizawa T, Sobajima A, Yoshida K, Okamoto M, Kato H, Saito N. Applications of Carbon Nanotubes in Bone Regenerative Medicine. NANOMATERIALS (BASEL, SWITZERLAND) 2020; 10:E659. [PMID: 32252244 PMCID: PMC7221610 DOI: 10.3390/nano10040659] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 03/28/2020] [Accepted: 03/29/2020] [Indexed: 01/02/2023]
Abstract
Scaffolds are essential for bone regeneration due to their ability to maintain a sustained release of growth factors and to provide a place where cells that form new bone can enter and proliferate. In recent years, scaffolds made of various materials have been developed and evaluated. Functionally effective scaffolds require excellent cell affinity, chemical properties, mechanical properties, and safety. Carbon nanotubes (CNTs) are fibrous nanoparticles with a nano-size diameter and have excellent strength and chemical stability. In the industrial field, they are used as fillers to improve the performance of materials. Because of their excellent physicochemical properties, CNTs are studied for their promising clinical applications as biomaterials. In this review article, we focused on the results of our research on CNT scaffolds for bone regeneration, introduced the promising properties of scaffolds for bone regeneration, and described the potential of CNT scaffolds.
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Affiliation(s)
- Manabu Tanaka
- Department of Orthopaedic Surgery, Okaya City Hospital, 4-11-33 Honcho, Okaya, Nagano 394-8512, Japan
| | - Kaoru Aoki
- Physical Therapy Division, School of Health Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;
| | - Hisao Haniu
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (H.H.); (N.S.)
- Department of Biomedical Engineering, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Takayuki Kamanaka
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (T.K.); (T.T.); (K.Y.); (M.O.); (H.K.)
| | - Takashi Takizawa
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (T.K.); (T.T.); (K.Y.); (M.O.); (H.K.)
| | - Atsushi Sobajima
- Department of Orthopaedic Surgery, Marunouchi Hospital, 1-7-45 Nagisa, Matsumoto, Nagano 390-8601, Japan;
| | - Kazushige Yoshida
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (T.K.); (T.T.); (K.Y.); (M.O.); (H.K.)
| | - Masanori Okamoto
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (T.K.); (T.T.); (K.Y.); (M.O.); (H.K.)
| | - Hiroyuki Kato
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (T.K.); (T.T.); (K.Y.); (M.O.); (H.K.)
| | - Naoto Saito
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (H.H.); (N.S.)
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21
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Udomluck N, Koh WG, Lim DJ, Park H. Recent Developments in Nanofiber Fabrication and Modification for Bone Tissue Engineering. Int J Mol Sci 2019; 21:E99. [PMID: 31877799 PMCID: PMC6981959 DOI: 10.3390/ijms21010099] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 12/02/2019] [Accepted: 12/19/2019] [Indexed: 01/22/2023] Open
Abstract
Bone tissue engineering is an alternative therapeutic intervention to repair or regenerate lost bone. This technique requires three essential components: stem cells that can differentiate into bone cells, growth factors that stimulate cell behavior for bone formation, and scaffolds that mimic the extracellular matrix. Among the various kinds of scaffolds, highly porous nanofibrous scaffolds are a potential candidate for supporting cell functions, such as adhesion, delivering growth factors, and forming new tissue. Various fabricating techniques for nanofibrous scaffolds have been investigated, including electrospinning, multi-axial electrospinning, and melt writing electrospinning. Although electrospun fiber fabrication has been possible for a decade, these fibers have gained attention in tissue regeneration owing to the possibility of further modifications of their chemical, biological, and mechanical properties. Recent reports suggest that post-modification after spinning make it possible to modify a nanofiber's chemical and physical characteristics for regenerating specific target tissues. The objectives of this review are to describe the details of recently developed fabrication and post-modification techniques and discuss the advanced applications and impact of the integrated system of nanofiber-based scaffolds in the field of bone tissue engineering. This review highlights the importance of nanofibrous scaffolds for bone tissue engineering.
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Affiliation(s)
- Nopphadol Udomluck
- School of Integrative Engineering, College of Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea;
| | - Won-Gun Koh
- Department of Chemical and Biomolecular Engineering, YONSEI University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea;
| | - Dong-Jin Lim
- Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Hansoo Park
- School of Integrative Engineering, College of Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea;
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22
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Yau A, Sands I, Chen Y. Nano-Scale Surface Modifications to Advance Current Treatment Options for Cervical Degenerative Disc Disease (CDDD). JOURNAL OF ORTHOPEDIC RESEARCH AND THERAPY 2019; 4:1147. [PMID: 33709068 PMCID: PMC7946151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Degenerative Disc Disease (DDD) causes a nagging to severe back pain as well as numbing sensation to the extremities leading to loss of overall patients' height and weakness to leg muscles. Degenerative disc disease is often observed in aging patients as well as patients who have suffered from a back injury. Cervical Degenerative Disc Disease (CDDD) is a progressive condition that leads to the degeneration of the intervertebral discs supporting the cervical vertebral column. Anterior Cervical Interbody Fusion (ACIF) has been the longstanding treatment option for severe degenerative disc disease; however, ACIF presents various novel complications, necessitating numerous comparative device studies to reduce the negative effects of spinal fusion. Cervical disc arthroplasty, the recent focus of clinical attention, was one of the alternatives studied to mitigate the complications associated with vertebral fusion but presents its own disadvantages. These complications prompted further investigation and modifications that can be introduced into these devices. We will be discussing the nano-scale interactions between the implant and extracellular matrix play a crucial role in device integration and efficacy, providing an additional approach towards a device's overall success.
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Affiliation(s)
- Anne Yau
- Corresponding author: Yupeng Chen, Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Unit 3247, Storrs, CT 06269-3247, USA. Tel: +1-8604867911; Fax: +1-8604862500;
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23
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Effect of growth hormone and somatomedin-C axis on fracture healing. JOURNAL OF SURGERY AND MEDICINE 2019. [DOI: 10.28982/josam.617669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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24
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Wagner DR, Karnik S, Gunderson ZJ, Nielsen JJ, Fennimore A, Promer HJ, Lowery JW, Loghmani MT, Low PS, McKinley TO, Kacena MA, Clauss M, Li J. Dysfunctional stem and progenitor cells impair fracture healing with age. World J Stem Cells 2019; 11:281-296. [PMID: 31293713 PMCID: PMC6600851 DOI: 10.4252/wjsc.v11.i6.281] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/26/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023] Open
Abstract
Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.
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Affiliation(s)
- Diane R Wagner
- Department of Mechanical and Energy Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States
| | - Sonali Karnik
- Department of Mechanical and Energy Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States
| | - Zachary J Gunderson
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Jeffery J Nielsen
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, United States
| | - Alanna Fennimore
- Department of Physical Therapy, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States
| | - Hunter J Promer
- Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN 46222, United States
| | - Jonathan W Lowery
- Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN 46222, United States
| | - M Terry Loghmani
- Department of Physical Therapy, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States
| | - Philip S Low
- Department of Chemistry, Purdue University, West Lafayette, IN 47907 United States
| | - Todd O McKinley
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Melissa A Kacena
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, United States
- Richard L. Roudebush VA Medical Center, Indianapolis, IN 46202, United States
| | - Matthias Clauss
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Jiliang Li
- Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States
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25
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Effects of dynamic loading on fracture healing under different locking compression plate configurations: A finite element study. J Mech Behav Biomed Mater 2019; 94:74-85. [DOI: 10.1016/j.jmbbm.2019.03.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 02/04/2019] [Accepted: 03/05/2019] [Indexed: 12/30/2022]
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26
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Nune KC, Misra RDK, Bai Y, Li S, Yang R. Interplay of topographical and biochemical cues in regulating osteoblast cellular activity in BMP-2 eluting three-dimensional cellular titanium alloy mesh structures. J Biomed Mater Res A 2018; 107:49-60. [DOI: 10.1002/jbm.a.36520] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 06/22/2018] [Accepted: 07/31/2018] [Indexed: 01/05/2023]
Affiliation(s)
- Krishna Chaitanya Nune
- Biomaterials and Biomedical Engineering Research Laboratory, Department of Metallurgical, Materials, and Biomedical Engineering; The University of Texas at El Paso; 500 W. University Avenue, El Paso, Texas, 79968
| | - R. Devesh Kumar Misra
- Biomaterials and Biomedical Engineering Research Laboratory, Department of Metallurgical, Materials, and Biomedical Engineering; The University of Texas at El Paso; 500 W. University Avenue, El Paso, Texas, 79968
| | - Yun Bai
- Shenyang National Laboratory for Materials Science; Institute of Metal Research, Chinese Academy of Sciences; 72 Wenhua Road, Shenyang, 110016 China
| | - Shujun Li
- Shenyang National Laboratory for Materials Science; Institute of Metal Research, Chinese Academy of Sciences; 72 Wenhua Road, Shenyang, 110016 China
| | - Rui Yang
- Shenyang National Laboratory for Materials Science; Institute of Metal Research, Chinese Academy of Sciences; 72 Wenhua Road, Shenyang, 110016 China
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Ghimire S, Miramini S, Richardson M, Mendis P, Zhang L. Role of Dynamic Loading on Early Stage of Bone Fracture Healing. Ann Biomed Eng 2018; 46:1768-1784. [DOI: 10.1007/s10439-018-2083-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 06/23/2018] [Indexed: 12/14/2022]
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Best one hundred papers of International Orthopaedics: a bibliometric analysis. INTERNATIONAL ORTHOPAEDICS 2017; 41:689-697. [DOI: 10.1007/s00264-016-3376-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 12/11/2016] [Indexed: 01/05/2023]
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Abstract
Experimental studies have shown a great potential for periodontal regeneration. The limitations of periodontal regeneration largely depend on the regenerative potential at the root surface. Cellular intrinsic fiber cementum (CIFC), so-called bone-like tissue, may form instead of the desired acellular extrinsic fiber cementum (AEFC), and the interfacial tissue bonding may be weak. The periodontal ligament harbors progenitor cells that can differentiate into periodontal ligament fibroblasts, osteoblasts, and cementoblasts, but their precise location is unknown. It is also not known whether osteoblasts and cementoblasts arise from a common precursor cell line, or whether distinct precursor cell lines exist. Thus, there is limited knowledge about how cell diversity evolves in the space between the developing root and the alveolar bone. This review supports the hypothesis that AEFC is a unique tissue, while CIFC and bone share some similarities. Morphologically, functionally, and biochemically, however, CIFC is distinctly different from any bone type. There are several lines of evidence to propose that cementoblasts that produce both AEFC and CIFC are unique phenotypes that are unrelated to osteoblasts. Cementum attachment protein appears to be cementum-specific, and the expression of two proteoglycans, fibromodulin and lumican, appears to be stronger in CIFC than in bone. A theory is presented that may help explain how cell diversity evolves in the periodontal ligament. It proposes that Hertwig’s epithelial root sheath and cells derived from it play an essential role in the development and maintenance of the periodontium. The role of enamel matrix proteins in cementoblast and osteoblast differentiation and their potential use for tissue engineering are discussed.
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Affiliation(s)
- D D Bosshardt
- Department of Periodontology and Fixed Prosthodontics, School of Dental Medicine, University of Berne, Freiburgstrasse 7, CH-3010 Berne, Switzerland.
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Atluri K, Lee J, Seabold D, Elangovan S, Salem AK. Gene-Activated Titanium Surfaces Promote In Vitro Osteogenesis. Int J Oral Maxillofac Implants 2016; 32:e83–e96. [PMID: 27706263 DOI: 10.11607/jomi.5026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
PURPOSE Commercially pure titanium (CpTi) and its alloys possess favorable mechanical and biologic properties for use as implants in orthopedics and dentistry. However, failures in osseointegration still exist and are common in select individuals with risk factors such as smoking. Therefore, in this study, a proposal was made to enhance the potential for osseointegration of CpTi discs by coating their surfaces with nanoplexes comprising polyethylenimine (PEI) and plasmid DNA (pDNA) encoding bone morphogenetic protein-2 (pBMP-2). MATERIALS AND METHODS The nanoplexes were characterized for size and surface charge with a range of N/P ratios (the molar ratio of amine groups of PEI to phosphate groups in pDNA backbone). CpTi discs were surface characterized for morphology and composition before and after nanoplex coating using scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRD). The cytotoxicity and transfection ability of CpTi discs coated with nanoplexes of varying N/P ratios in human bone marrow-derived mesenchymal stem cells (BMSCs) was measured via MTS assays and flow cytometry, respectively. RESULTS The CpTi discs coated with nanoplexes prepared at an N/P ratio of 10 (N/P-10) were considered optimal, resulting in 75% cell viability and 14% transfection efficiency. Enzyme-linked immunosorbent assay results demonstrated a significant enhancement in BMP-2 protein secretion by BMSCs 7 days posttreatment with PEI/pBMP-2 nanoplexes (N/P-10) compared to the controls, and real-time PCR data demonstrated that the BMSCs treated with PEI/pBMP-2 nanoplex-coated CpTi discs resulted in an enhancement of Runx-2, alkaline phosphatase, and osteocalcin gene expressions on day 7 posttreatment. In addition, these BMSCs demonstrated enhanced calcium deposition on day 30 posttreatment as determined by qualitative (alizarin red staining) and quantitative (atomic absorption spectroscopy) assays. CONCLUSION It can be concluded that PEI/pBMP-2 nanoplex (N/P-10)-coated CpTi discs have the potential to induce osteogenesis and enhance osseointegration.
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31
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Kim YD, Pofali P, Park TE, Singh B, Cho K, Maharjan S, Dandekar P, Jain R, Choi YJ, Arote R, Cho CS. Gene therapy for bone tissue engineering. Tissue Eng Regen Med 2016; 13:111-125. [PMID: 30603391 PMCID: PMC6170855 DOI: 10.1007/s13770-016-9063-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 09/24/2015] [Accepted: 09/29/2015] [Indexed: 02/06/2023] Open
Abstract
Gene therapy holds a great promise and has been extensively investigated to improve bone formation and regeneration therapies in bone tissue engineering. A variety of osteogenic genes can be delivered by combining different vectors (viral or non-viral), scaffolds and delivery methodologies. Ex vivo & in vivo gene enhanced tissue engineering approaches have led to successful osteogenic differentiation and bone formation. In this article, we review recent advances of gene therapy-based bone tissue engineering discussing strengths and weaknesses of various strategies as well as general overview of gene therapy.
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Affiliation(s)
- Young-Dong Kim
- Department of Molecular Genetics, School of Dentistry, Seoul National University, Seoul, Korea
| | - Prasad Pofali
- Department of Chemical Engineering, Institute of Chemical Technology, Mumbai, India
| | - Tae-Eun Park
- Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea
| | - Bijay Singh
- Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea
| | - Kihyun Cho
- Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea
| | - Sushila Maharjan
- Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea
| | - Prajakta Dandekar
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India
| | - Ratnesh Jain
- Department of Chemical Engineering, Institute of Chemical Technology, Mumbai, India
| | - Yun-Jaie Choi
- Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea
| | - Rohidas Arote
- Department of Molecular Genetics, School of Dentistry, Seoul National University, Seoul, Korea
| | - Chong-Su Cho
- Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea
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32
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Nune KC, Kumar A, Murr LE, Misra RDK. Interplay between self-assembled structure of bone morphogenetic protein-2 (BMP-2) and osteoblast functions in three-dimensional titanium alloy scaffolds: Stimulation of osteogenic activity. J Biomed Mater Res A 2015; 104:517-32. [PMID: 26475990 DOI: 10.1002/jbm.a.35592] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 10/09/2015] [Accepted: 10/15/2015] [Indexed: 12/18/2022]
Abstract
Three-dimensional cellular scaffolds are receiving significant attention in bone tissue engineering to treat segmental bone defects. However, there are indications of lack of significant osteoinductive ability of three-dimensional cellular scaffolds. In this regard, the objective of the study is to elucidate the interplay between bone morphogenetic protein (BMP-2) and osteoblast functions on 3D mesh structures with different porosities and pore size that were fabricated by electron beam melting. Self-assembled dendritic microstructure with interconnected cellular-type morphology of BMP-2 on 3D scaffolds stimulated osteoblast functions including adhesion, proliferation, and mineralization, with prominent effect on 2-mm mesh. Furthermore, immunofluorescence studies demonstrated higher density and viability of osteoblasts on lower porosity mesh structure (2 mm) as compared to 3- and 4-mm mesh structures. Enhanced filopodia cellular extensions with extensive cell spreading was observed on BMP-2 treated mesh structures, a behavior that is attributed to the unique self-assembled structure of BMP-2 that effectively communicates with the cells. The study underscores the potential of BMP-2 in imparting osteoinductive capability to the 3D printed scaffolds.
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Affiliation(s)
- K C Nune
- Biomaterials and Biomedical Engineering Research Laboratory, Department of Metallurgical, Materials, and Biomedical Engineering, University of Texas at El Paso, 500 W. University Avenue, El Paso, Texas, 79968
| | - A Kumar
- Biomaterials and Biomedical Engineering Research Laboratory, Department of Metallurgical, Materials, and Biomedical Engineering, University of Texas at El Paso, 500 W. University Avenue, El Paso, Texas, 79968
| | - L E Murr
- Biomaterials and Biomedical Engineering Research Laboratory, Department of Metallurgical, Materials, and Biomedical Engineering, University of Texas at El Paso, 500 W. University Avenue, El Paso, Texas, 79968
| | - R D K Misra
- Biomaterials and Biomedical Engineering Research Laboratory, Department of Metallurgical, Materials, and Biomedical Engineering, University of Texas at El Paso, 500 W. University Avenue, El Paso, Texas, 79968
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Wei Q, Pohl TLM, Seckinger A, Spatz JP, Cavalcanti-Adam EA. Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation. Beilstein J Org Chem 2015; 11:773-83. [PMID: 26124879 PMCID: PMC4464188 DOI: 10.3762/bjoc.11.87] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 05/07/2015] [Indexed: 12/21/2022] Open
Abstract
Stem cells respond to the microenvironment (niche) they are located in. Under natural conditions, the extracellular matrix (ECM) is the essential component the in stem cell niche, in which both integrin ligands and growth factors are important regulators to directly or indirectly modulate the cell behavior. In this review, we summarize the current knowledge about the potential of integrin ligands and growth factors to induce osteogenic differentiation of stem cells, and discuss the signaling pathways that are initiated by both individual and cooperative parameters. The joint effect of integrin ligands and growth factors is highlighted as the multivalent interactions for bone therapy.
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Affiliation(s)
- Qiang Wei
- Department of Biophysical Chemistry, Institute for Physical Chemistry, University of Heidelberg, INF 253, 69120 Heidelberg, Germany ; Department of New Materials and Biosystems, Max-Planck Institute for Intelligent Systems, Stuttgart, Germany
| | - Theresa L M Pohl
- Department of Biophysical Chemistry, Institute for Physical Chemistry, University of Heidelberg, INF 253, 69120 Heidelberg, Germany ; Department of New Materials and Biosystems, Max-Planck Institute for Intelligent Systems, Stuttgart, Germany
| | - Anja Seckinger
- Department of Internal Medicine V, Oncology, Hematology, and Rheumatology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Joachim P Spatz
- Department of Biophysical Chemistry, Institute for Physical Chemistry, University of Heidelberg, INF 253, 69120 Heidelberg, Germany ; Department of New Materials and Biosystems, Max-Planck Institute for Intelligent Systems, Stuttgart, Germany
| | - Elisabetta A Cavalcanti-Adam
- Department of Biophysical Chemistry, Institute for Physical Chemistry, University of Heidelberg, INF 253, 69120 Heidelberg, Germany ; Department of New Materials and Biosystems, Max-Planck Institute for Intelligent Systems, Stuttgart, Germany
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Abstract
Angiogenesis is a vital component of bone healing. The formation of the new blood vessels at the fracture site restores the hypoxia and nutrient deprivation found at the early stages after fracture whilst at a later stage facilitates osteogenesis by the activity of the osteoprogenitor cells. Emerging evidence suggests that there are certain molecules and gene therapies that could promote new blood vessel formation and as a consequence enhance the local bone healing response. This article summarizes the current in vivo evidence on therapeutic approaches aiming at the augmentation of the angiogenic signalling during bone repair.
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Romagnoli C, Brandi ML. Adipose mesenchymal stem cells in the field of bone tissue engineering. World J Stem Cells 2014; 6:144-152. [PMID: 24772241 PMCID: PMC3999772 DOI: 10.4252/wjsc.v6.i2.144] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 12/19/2013] [Accepted: 03/04/2014] [Indexed: 02/06/2023] Open
Abstract
Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians. Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility, biodegradability and osteoinductivity. Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells (MSCs). In particular, a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue. These adipose stem cells (ASCs) can be obtained in large quantities with little donor site morbidity or patient discomfort, in contrast to the invasive and painful isolation of bone marrow MSCs. The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models, with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients. Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration, the lack of standardization in applied techniques makes the comparison between studies difficult. Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns, which must be resolved to permit application in regenerative medicine.
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Ulanova LS, Isapour G, Maleki A, Fanaian S, Zhu K, Hoenen A, Xu C, Evensen Ø, Griffiths G, Nyström B. Development of methods for encapsulation of viruses into polymeric nano- and microparticles for aquaculture vaccines. J Appl Polym Sci 2014. [DOI: 10.1002/app.40714] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Lilia S. Ulanova
- Department of Molecular Biosciences; University of Oslo; N-0316 Oslo Norway
| | - Golnaz Isapour
- Department of Chemistry; University of Oslo; N-0315 Oslo Norway
| | - Atoosa Maleki
- Department of Chemistry; University of Oslo; N-0315 Oslo Norway
| | - Shirin Fanaian
- Department of Chemistry; University of Oslo; N-0315 Oslo Norway
| | - Kaizheng Zhu
- Department of Chemistry; University of Oslo; N-0315 Oslo Norway
| | - Antje Hoenen
- Department of Molecular Biosciences; University of Oslo; N-0316 Oslo Norway
| | - Cheng Xu
- Department of Basic Sciences and Aquatic Medicine; Norwegian School of Veterinary Science; Oslo Norway
| | - Øystein Evensen
- Department of Basic Sciences and Aquatic Medicine; Norwegian School of Veterinary Science; Oslo Norway
| | - Gareth Griffiths
- Department of Molecular Biosciences; University of Oslo; N-0316 Oslo Norway
| | - Bo Nyström
- Department of Chemistry; University of Oslo; N-0315 Oslo Norway
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Ultrastructure of Intervertebral Disc and Vertebra-Disc Junctions Zones as a Link in Etiopathogenesis of Idiopathic Scoliosis. ACTA ACUST UNITED AC 2014. [DOI: 10.1155/2014/850594] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Background Context. There is no general accepted theory on the etiology of idiopathic scoliosis (IS). An important role of the vertebrae endplate physes (VEPh) and intervertebral discs (IVD) in spinal curve progression is acknowledged, but ultrastructural mechanisms are not well understood. Purpose. To analyze the current literature on ultrastructural characteristics of VEPh and IVD in the context of IS etiology. Study Design/Setting. A literature review. Results. There is strong evidence for multifactorial etiology of IS. Early wedging of vertebra bodies is likely due to laterally directed appositional bone growth at the concave side, caused by a combination of increased cell proliferation at the vertebrae endplate and altered mechanical properties of the outer annulus fibrosus of the adjacent IVD. Genetic defects in bending proteins necessary for IVD lamellar organization underlie altered mechanical properties. Asymmetrical ligaments, muscular stretch, and spine instability may also play roles in curve formation. Conclusions. Development of a reliable, cost effective method for identifying patients at high risk for curve progression is needed and could lead to a paradigm shift in treatment options. Unnecessary anxiety, bracing, and radiation could potentially be minimized and high risk patient could receive surgery earlier, rendering better outcomes with fewer fused segments needed to mitigate curve progression.
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Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep. Eur J Pharm Biopharm 2014; 85:99-106. [PMID: 23958321 DOI: 10.1016/j.ejpb.2013.03.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Revised: 03/11/2013] [Accepted: 03/12/2013] [Indexed: 11/20/2022]
Abstract
Spatiotemporal release of growth factors from a delivery device can profoundly affect the efficacy of bone growth induction. Here, we report on a delivery platform based on the encapsulation of insulin-like growth factor I (IGF-I) in different poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I release profiles generally exhibited an initial burst (14-36% of total IGF-I content), which was followed by a more or less pronounced dormant phase with little release (2 to 34 days), and finally, a third phase of re-increased IGF-I release. The osteoinductive potential of these different IGF-I PL(G)A MS formulations was tested in studies using 8-mm metaphyseal drill hole bone defects in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that new bone formation was improved in the defects locally treated with IGF-I PL(G)A MS (n=5) as compared to defects filled with IGF-I-free PL(G)A MS (n=4). The extent of new bone formation was affected by the particular release kinetics, although a definitive relationship was not evident. Local administration of IGF-I resulted in down-regulation of inflammatory marker genes in all IGF-I treated defects. The over-expression of growth factor genes in response to IGF-I delivery was restricted to formulations that produced osteogenic responses. These experiments demonstrate the osteoinductive potential of sustained IGF-I delivery and show the importance of delivery kinetics for successful IGF-I-based therapies.
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Giovanini AF, Deliberador TM, Tannuri Nemeth JE, Crivellaro VR, Portela GS, de Oliveira Filho MA, de Araujo MR, Zielak JC, Gonzaga CC. Leukocyte-platelet-rich plasma (L-PRP) impairs the osteoconductive capacity of the autograft associated to changes in the immunolocalization of TGF-β1 and its co-expression with Wnt10b and CD34 cells. J Craniomaxillofac Surg 2013; 41:e180-6. [DOI: 10.1016/j.jcms.2013.01.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Revised: 01/02/2013] [Accepted: 01/03/2013] [Indexed: 12/25/2022] Open
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Romagnoli C, D’Asta F, Brandi ML. Drug delivery using composite scaffolds in the context of bone tissue engineering. CLINICAL CASES IN MINERAL AND BONE METABOLISM : THE OFFICIAL JOURNAL OF THE ITALIAN SOCIETY OF OSTEOPOROSIS, MINERAL METABOLISM, AND SKELETAL DISEASES 2013; 10:155-161. [PMID: 24554923 PMCID: PMC3917575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
INTRODUCTION Due to the disadvantages of the current bone autograft and allograft in many clinical condition in which bone regeneration is required in large quantity, engineered biomaterials combined with growth factors, such as bone morphogenetic protein-2 (BMP-2), have been demonstrated to be an effective approach in bone tissue engineering, since they can act both as a scaffold and as a drug delivery system to promote bone repair and regeneration. AREA COVERED Recent advantages in the field of engineered scaffolds have been obtained from the investigation of composite scaffolds designed by the combination of bioceramics, especially hydroxyapatite (HA), and biodegradable polymers, such as poly (D,L-lactide-co-glycolide) (PLGA) and chitosan, in order to realize osteoconductive structures that can mimic the natural properties of bone tissue. Herein it is demonstrated that the incorporation of BMP-2 into different composite scaffolds, by encapsulation, absorption or entrapment, could be advantageous in terms of osteoinduction for new bone tissue engineered scaffolds as drug delivery systems and some of them should be further analyzed to optimized the drug release for future therapeutic applications. EXPERT OPINION New design concepts and fabrication techniques represent novel challenges for further investigations about the development of scaffolds as a drug delivery system for bone tissue regeneration.
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Affiliation(s)
- Cecilia Romagnoli
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Federica D’Asta
- Department of Neurosciences, Psychology, Drug Area and Child Health, University of Florence, Florence, Italy
| | - Maria Luisa Brandi
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
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Kobayashi D, Kawai N, Sato S, Naiki T, Yamada K, Yasui T, Tozawa K, Kobayashi T, Takahashi S, Kohri K. Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model. Prostate 2013; 73:913-22. [PMID: 23334935 DOI: 10.1002/pros.22637] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Accepted: 12/07/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND Bone metastasis is a serious problem for individuals with prostate cancer, and the effects of the anticancer drug docetaxel (DTX) are insufficient. We therefore examined the therapeutic potential of magnetic cationic liposomes (MCL) in a novel rat model that allows the evaluation of tumor immunity. The effects of MCL thermotherapy were compared with those of DTX as a conventional therapy for the treatment of bone metastatic prostate cancer. METHODS Prostate tumor tissues were transplanted into the femurs of model rats divided into four groups: control, MCL, DTX, and MCL + DTX. Tumors were injected with MCL, and alternating magnetic field (AMF) irradiation was performed three times a week. Tumor proliferation and bone destruction were evaluated by proliferating cell nuclear antigen positivity, computed tomography, and CD68-positive cell number, while tumor immunity was evaluated by heat shock protein (HSP) 70 expression and CD8-positive lymphocyte number. RESULTS We successfully established a novel femur metastasis model of prostate cancer, and demonstrated that tumor proliferation and bone destruction in the MCL and MCL + DTX groups were significantly suppressed compared with control and DTX groups. MCL thermotherapy concurrently induced necrosis and apoptosis. The expression of HSP70 in the MCL and MCL + DTX groups was also significantly increased, and tumor immunity was enhanced through the induction of CD8-positive lymphocytes. CONCLUSION MCL thermotherapy was clearly more effective than DTX in treating bone metastatic prostate cancer. A combination of MCL thermotherapy and DTX therefore deserves consideration as a novel treatment for this disease.
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Affiliation(s)
- Daichi Kobayashi
- Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
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Smad3 is the key to transforming growth factor-β1-induced osteoclast differentiation in giant cell tumor of bone. Med Oncol 2013; 30:606. [DOI: 10.1007/s12032-013-0606-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 05/09/2013] [Indexed: 01/29/2023]
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Hutton DL, Moore EM, Gimble JM, Grayson WL. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells. Tissue Eng Part A 2013; 19:2076-86. [PMID: 23582144 DOI: 10.1089/ten.tea.2012.0752] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Vasculature is essential to the functional integration of a tissue-engineered bone graft to enable sufficient nutrient delivery and viability after implantation. Native bone and vasculature develop through intimately coupled, tightly regulated spatiotemporal cell-cell signaling. The complexity of these developmental processes has been a challenge for tissue engineers to recapitulate, resulting in poor codevelopment of both bone and vasculature within a unified graft. To address this, we cultured adipose-derived stromal/stem cells (ASCs), a clinically relevant, single cell source that has been previously investigated for its ability to give rise to vascularized bone grafts, and studied the effects of initial spatial organization of cells, the temporal addition of growth factors, and the presence of exogenous platelet-derived growth factor-BB (PDGF-BB) on the codevelopment of bone and vascular tissue structures. Human ASCs were aggregated into multicellular spheroids via the hanging drop method before encapsulation and subsequent outgrowth in fibrin gels. Cellular aggregation substantially increased vascular network density, interconnectivity, and pericyte coverage compared to monodispersed cultures. To form robust vessel networks, it was essential to culture ASCs in a purely vasculogenic medium for at least 8 days before the addition of osteogenic cues. Physiologically relevant concentrations of exogenous PDGF-BB (20 ng/mL) substantially enhanced both vascular network stability and osteogenic differentiation. Comparisons with the bone morphogenetic protein-2, another pro-osteogenic and proangiogenic growth factor, indicated that this potential to couple the formation of both lineages might be unique to PDGF-BB. Furthermore, the resulting tissue structure demonstrated the close association of mineral deposits with pre-existing vascular structures that have been described for developing tissues. This combination of a single cell source with a potent induction factor used at physiological concentrations can provide a clinically relevant approach to engineering highly vascularized bone grafts.
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Affiliation(s)
- Daphne L Hutton
- Department of Biomedical Engineering, Translational Tissue Engineering Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA
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MATTAR TIAGO, FRIEDRICH PATRICIAF, BISHOP ALLENT. Effect of rhBMP-2 and VEGF in a vascularized bone allotransplant experimental model based on surgical neoangiogenesis. J Orthop Res 2013. [PMID: 23192572 PMCID: PMC3972920 DOI: 10.1002/jor.22277] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We have demonstrated survival of living allogeneic bone without long-term immunosuppression using short-term immunosuppression and simultaneous creation of an autogenous neoagiogenic circulation. In this study, bone morphogenic protein-2 (rhBMP-2), and/or vascular endothelial growth factor (VEGF), were used to augment this process. Femoral diaphyseal bone was transplanted heterotopically from 46 Dark Agouti to 46 Lewis rats. Microvascular repair of the allotransplant nutrient pedicle was combined with intra-medullary implantation of an autogenous saphenous arteriovenous (AV) bundle and biodegradable microspheres containing buffer (control), rhBMP-2 or rhBMP-2 + VEGF. FK-506 given daily for 14 days maintained nutrient pedicle flow during angiogenesis. After an 18 weeks survival period, we measured angiogenesis (capillary density) from the AV bundle and cortical bone blood flow. Both measures were greater in the combined (rhBMP-2 + VEGF) group than rhBMP-2 and control groups (p < 0.05). Osteoblast counts were also higher in the rhBMP-2 + VEGF group (p < 0.05). A trend towards greater bone formation was seen in both rhBMP2 + VGF and rhBMP2 groups as compared to controls (p = 0.059). Local administration of VEGF and rhBMP-2 augments angiogenesis, osteoblastic activity and bone blood flow from implanted blood vessels of donor origin in vascularized bone allografts.
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Affiliation(s)
- TIAGO MATTAR
- Department of Orthopedics, University of São Paulo, Rua Dr Ovídio Pires de Campos, 333, Cerqueira Cesar, São Paulo, SP, 05403-010, Brazil
| | - PATRICIA F. FRIEDRICH
- Microvascular Research Laboratory, Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
| | - ALLEN T. BISHOP
- Microvascular Research Laboratory, Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, Corresponding author: Allen T. Bishop Telephone: 507-284-4149 Fax: 507-284- 5539
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Bone Healing in Critical-Size Defects Treated With Immediate Transplant of Fragmented Autogenous White Adipose Tissue. J Craniofac Surg 2012; 23:1239-44. [DOI: 10.1097/scs.0b013e31825da9d9] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Relevance of deep decortication and vascularization in a case of post-traumatic femoral non-union treated with grafts, platelet gel and bone marrow stromal cells. Knee Surg Sports Traumatol Arthrosc 2012; 20:1834-8. [PMID: 22113222 DOI: 10.1007/s00167-011-1790-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2011] [Accepted: 11/14/2011] [Indexed: 10/15/2022]
Abstract
PURPOSE A male patient suffering from non-union of the femoral diaphysis after a traumatic fracture was treated with deep decortication and grafted with lyophilized bone, platelet gel (PG) and autologous bone marrow stromal cells (BMSCs). After 40 days from surgery, he was re-operated, due to fracture secondary displacement, caused by inappropriate load during sports activity. In addition to radiographs, two bone biopsies were retrieved: this allowed for a histological evaluation of the early response of host bone to the graft. To our knowledge, there is no report describing such early tissue response. METHODS A clinical-radiographic evaluation of the patient and a histomorphometric analysis of the bone biopsies were performed. RESULTS An early reparative bone formation was observed adjacent to the osteointegrated graft. Non-resorbed bone chips and large islands of non-vital bone particles, surrounded by fibrous tissue, were observed in a zone of sclerotic diaphyseal bone, that is the process was delayed despite decortication. CONCLUSIONS These findings support the concept, until now evidenced only by imaging, that bone chips added with PG and BMSCs are effective in shortening the healing time in fracture non-union. The clinical relevance of deep decortication and vascularization is emphasized. LEVEL OF EVIDENCE Therapeutic studies-investigating the results of treatment, Level V.
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Abstract
BACKGROUND The morbidity and socioeconomic costs associated with long bone healing are considerable. Platelet-rich therapies are autologous blood products with a greater concentration of platelets than physiological whole blood. Despite promising results from a number of in-vitro animal studies, clinical evidence to support the use of platelet-rich therapy in long bone healing is unclear. OBJECTIVES To assess the effects (benefits or harms) of platelet-rich therapies for treating long bone osteotomies, acute fractures, un-united fractures and defects in adults. SEARCH METHODS We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (8 November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 4), MEDLINE (1948 to November Week 1 2011) and EMBASE (1980 to Week 44 2011). Trial registers and reference lists of articles were also searched. SELECTION CRITERIA Randomised and quasi-randomised controlled clinical trials evaluating any type of platelet-rich therapy compared with either no additional treatment or a placebo in the management of long bone osteotomies, acute fractures, un-united fractures and defects in adults. Studies including participants over 18 years of age; reporting functional outcomes, time to union, non-union, secondary procedures such as for fixation failure or delayed or non-union, adverse effects, pain or costs were included. DATA COLLECTION AND ANALYSIS Two authors independently selected the studies for inclusion in the review. Studies were assessed for the risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. Treatment effects for dichotomous outcomes were expressed with risk ratios (RR) and continuous measures with mean differences, together with 95% confidence intervals (CI). MAIN RESULTS Only one eligible study, involving 21 participants, was included. The study compared platelet-rich therapy and allogenic bone graft with allogenic bone graft alone in patients undergoing corrective osteotomy for medial compartment osteoarthrosis of the knee. The risk of bias associated with this study was substantial. There was no significant difference in patient-reported or clinician-assessed functional outcome scores between groups at one year. There was a statistically significant benefit from platelet-rich therapy in the proportion of bones that were united at one year (8/9 versus 3/9; RR 2.67; 95% CI 1.03 to 6.91). This benefit, however, was not maintained when assuming poor outcomes for participants who were lost to follow-up (8/11 versus 3/10; RR 2.42; 95% CI 0.88 to 6.68). One adverse event was reported in a participant receiving platelet-rich therapy.One other eligible study involving hip fracture patients is currently underway. AUTHORS' CONCLUSIONS While a potential benefit of platelet-rich therapies to augment long bone healing in adults cannot be ruled out, the currently available evidence from a single trial is insufficient to support the routine use of this intervention in clinical practice. Future trials should focus on reporting patient-reported functional outcomes from all trial participants for a minimum follow-up of one year.
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Affiliation(s)
- Xavier L Griffin
- Warwick Orthopaedics,WarwickMedical School, University ofWarwick, Coventry UK.
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Kasten P, Beverungen M, Lorenz H, Wieland J, Fehr M, Geiger F. Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect. Cells Tissues Organs 2012; 196:523-33. [PMID: 22796828 DOI: 10.1159/000337490] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/13/2012] [Indexed: 12/27/2022] Open
Abstract
Both platelet-rich plasma (PRP) and vascular endothelial growth factor (VEGF) can promote regeneration. The aim of this study was to compare the effects of these two elements on bone formation and vascularization in combination with bone marrow stromal cells (BMSC) in a critical-size bone defect in rabbits. The critical-size defects of the radius were filled with: (1) a calcium-deficient hydroxyapatite (CDHA) scaffold + phVEGF(165)-transfected BMSC (VEGF group), (2) CDHA and PRP, or (3) CDHA, autogenous BMSC, and PRP. As controls served: (4) the CDHA scaffold alone and (5) the CDHA scaffold and autogenous BMSC. The volume of new bone was measured by means of micro-CT scans, and vascularization was assessed in histology after 16 weeks. Bone formation was higher in the PRP + CDHA, BMSC + CDHA, and PRP + BMSC + CDHA groups than in the VEGF group (p < 0.05). VEGF transfection significantly promoted vascularization of the scaffolds in contrast to BMSC and PRP (p < 0.05), but was similar to the result of the CDHA + PRP + BMSC group. The results show that VEGF-transfected BMSC as well as the combination of PRP and BMSC improve vascularization, but bone healing was better with the combination of BMSC and PRP than with VEGF-transfected BMSC. Expression of VEGF in BMSC as a single growth factor does not seem to be as effective for bone formation as expanded BMSC alone or PRP which contains a mixture of growth factors.
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Affiliation(s)
- P Kasten
- Division of Experimental Orthopaedics, Orthopaedic University Hospital of Heidelberg, Heidelberg, Germany
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Surface Engineering for Bone Implants: A Trend from Passive to Active Surfaces. COATINGS 2012. [DOI: 10.3390/coatings2030095] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Griffin XL, Wallace D, Parsons N, Costa ML. Platelet rich therapies for long bone healing in adults. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2011. [DOI: 10.1002/14651858.cd009496] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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