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Li Y, Ge Z, Liu Z, Li L, Song J, Wang H, Tian F, Lei P, Li L, Xue J. Integrating electrospun aligned fiber scaffolds with bovine serum albumin-basic fibroblast growth factor nanoparticles to promote tendon regeneration. J Nanobiotechnology 2024; 22:799. [PMID: 39731092 DOI: 10.1186/s12951-024-03022-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 11/14/2024] [Indexed: 12/29/2024] Open
Abstract
BACKGROUND Electrospun nanofiber scaffolds have been widely used in tissue engineering because they can mimic extracellular matrix-like structures and offer advantages including high porosity, large specific surface area, and customizable structure. In this study, we prepared scaffolds composed of aligned and random electrospun polycaprolactone (PCL) nanofibers capable of delivering basic fibroblast growth factor (bFGF) in a sustained manner for repairing damaged tendons. RESULTS Aligned and random PCL fiber scaffolds containing bFGF-loaded bovine serum albumin (BSA) nanoparticles (BSA-bFGF NPs, diameter 146 ± 32 nm) were fabricated, respectively. To validate the viability of bFGF-loaded aligned PCL nanofiber scaffold (aPCL + bFGF group) in tendon tissue engineering, we assessed the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage and the in vivo regeneration of tendons using a rat Achilles tendon defect model. The encapsulated bFGF could be delivered in a sustained manner in vitro. The aPCL + bFGF scaffold promoted the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage. In the repair of a rat Achilles tendon defect model, the aPCL + bFGF group showed a better repair effect. The scaffold offers a promising substrate for the regeneration of tendon tissue. CONCLUSIONS The aligned and random PCL fiber scaffolds containing bFGF nanoparticles were successfully prepared, and their physical and chemical properties were characterized. The aPCL + bFGF scaffold could promote the expression of the related genes and proteins of tendon-forming, facilitating tendon differentiation. In the rat Achilles tendon defect experiments, the aPCL + bFGF exhibited excellent tendon regeneration effects.
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Affiliation(s)
- Yuwan Li
- Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
| | - Zhen Ge
- Department of Orthopaedics, Haining People's Hospital, Haining, 314400, Zhejiang, China
- Department of Orthopaedics, the First Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Ziming Liu
- Beijing Key Laboratory of Sports Injuries, Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, China
| | - Longfei Li
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Jian Song
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Hongde Wang
- Beijing Key Laboratory of Sports Injuries, Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, China
| | - Feng Tian
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Pengfei Lei
- Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.
| | - Long Li
- College of Materials and Metallurgy, Guizhou University, Guiyang, 550025, Guizhou, China.
| | - Jiajia Xue
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.
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Goker M, Derici US, Gokyer S, Parmaksiz MG, Kaya B, Can A, Yilgor P. Spatial Growth Factor Delivery for 3D Bioprinting of Vascularized Bone with Adipose-Derived Stem/Stromal Cells as a Single Cell Source. ACS Biomater Sci Eng 2024; 10:1607-1619. [PMID: 38416687 PMCID: PMC10934245 DOI: 10.1021/acsbiomaterials.3c01222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 02/18/2024] [Accepted: 02/20/2024] [Indexed: 03/01/2024]
Abstract
Encapsulating multiple growth factors within a scaffold enhances the regenerative capacity of engineered bone grafts through their localization and controls the spatiotemporal release profile. In this study, we bioprinted hybrid bone grafts with an inherent built-in controlled growth factor delivery system, which would contribute to vascularized bone formation using a single stem cell source, human adipose-derived stem/stromal cells (ASCs) in vitro. The strategy was to provide precise control over the ASC-derived osteogenesis and angiogenesis at certain regions of the graft through the activity of spatially positioned microencapsulated BMP-2 and VEGF within the osteogenic and angiogenic bioink during bioprinting. The 3D-bioprinted vascularized bone grafts were cultured in a perfusion bioreactor. Results proved localized expression of osteopontin and CD31 by the ASCs, which was made possible through the localized delivery activity of the built-in delivery system. In conclusion, this approach provided a methodology for generating off-the-shelf constructs for vascularized bone regeneration and has the potential to enable single-step, in situ bioprinting procedures for creating vascularized bone implants when applied to bone defects.
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Affiliation(s)
- Meric Goker
- Department
of Biomedical Engineering, Ankara University
Faculty of Engineering, Ankara 06830, Turkey
- Department
of Anatomy and Regenerative Medicine, Royal
College of Surgeons in Ireland, Dublin D02 YN77, Ireland
| | - Utku Serhat Derici
- Department
of Biomedical Engineering, Ankara University
Faculty of Engineering, Ankara 06830, Turkey
| | - Seyda Gokyer
- Department
of Biomedical Engineering, Ankara University
Faculty of Engineering, Ankara 06830, Turkey
| | - Mehmet Goktug Parmaksiz
- Department
of Biomedical Engineering, Ankara University
Faculty of Engineering, Ankara 06830, Turkey
| | - Burak Kaya
- Department
of Plastic, Reconstructive and Aesthetic Surgery, Ankara University Faculty of Medicine, Ankara 06620, Turkey
- Ankara
University Medical Design Research and Application Center, MEDITAM, Ankara 06520, Turkey
| | - Alp Can
- Department
of Histology and Embryology, Ankara University
Faculty of Medicine, Ankara 06230, Turkey
| | - Pinar Yilgor
- Department
of Biomedical Engineering, Ankara University
Faculty of Engineering, Ankara 06830, Turkey
- Ankara
University Medical Design Research and Application Center, MEDITAM, Ankara 06520, Turkey
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Arias-Betancur A, Badilla-Wenzel N, Astete-Sanhueza Á, Farfán-Beltrán N, Dias FJ. Carrier systems for bone morphogenetic proteins: An overview of biomaterials used for dentoalveolar and maxillofacial bone regeneration. JAPANESE DENTAL SCIENCE REVIEW 2022; 58:316-327. [PMID: 36281233 PMCID: PMC9587372 DOI: 10.1016/j.jdsr.2022.10.001] [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: 02/12/2022] [Revised: 09/14/2022] [Accepted: 10/11/2022] [Indexed: 11/27/2022] Open
Abstract
Different types of biomaterials have been used to fabricate carriers to deliver bone morphogenetic proteins (BMPs) in both dentoalveolar and maxillofacial bone regeneration procedures. Despite that absorbable collagen sponge (ACS) is considered the gold standard for BMP delivery, there is still some concerns regarding its use mainly due to its poor mechanical properties. To overcome this, novel systems are being developed, however, due to the wide variety of biomaterial combination, the heterogeneous assessment of newly formed tissue, and the intended clinical applications, there is still no consensus regarding which is more efficient in a particular clinical scenario. The combination of two or more biomaterials in different topological configurations has allowed specific controlled-release patterns for BMPs, improving their biological and mechanical properties compared with classical single-material carriers. However, more basic research is needed. Since the BMPs can be used in multiple clinical scenarios having different biological and mechanical needs, novel carriers should be developed in a context-specific manner. Thus, the purpose of this review is to gather current knowledge about biomaterials used to fabricate delivery systems for BMPs in both dentoalveolar and maxillofacial contexts. Aspects related with the biological, physical and mechanical characteristics of each biomaterial are also presented and discussed.
Strategies for bone formation and regeneration are a major concern in dentistry. Topical delivery of bone morphogenetic proteins (BMPs) allows rapid bone formation. BMPs requires proper carrier system to allow controlled and sustained release. Carrier should also fulfill mechanical requirements of bone defect sites. By using complex composites, it would be possible to develop new carriers for BMPs.
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Affiliation(s)
- Alain Arias-Betancur
- Department of Integral Adult Dentistry, Research Centre for Dental Sciences (CICO-UFRO), Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile
| | - Nicolás Badilla-Wenzel
- Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile
| | - Álvaro Astete-Sanhueza
- Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile
| | - Nicole Farfán-Beltrán
- Department of Integral Adult Dentistry, Research Centre for Dental Sciences (CICO-UFRO), Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile.,Universidad Adventista de Chile, Chillán 3780000, Chile
| | - Fernando José Dias
- Department of Integral Adult Dentistry, Oral Biology Research Centre (CIBO-UFRO), Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile
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V. K. AD, Ray S, Arora U, Mitra S, Sionkowska A, Jaiswal AK. Dual drug delivery platforms for bone tissue engineering. Front Bioeng Biotechnol 2022; 10:969843. [PMID: 36172012 PMCID: PMC9511792 DOI: 10.3389/fbioe.2022.969843] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 08/23/2022] [Indexed: 11/22/2022] Open
Abstract
The dual delivery platforms used in bone tissue engineering provide supplementary bioactive compounds that include distinct medicines and growth factors thereby aiding enhanced bone regeneration. The delivery of these compounds can be adjusted for a short or prolonged time based on the requirement by altering various parameters of the carrier platform. The platforms thus used are fabricated to mimic the niche of the bone microenvironment, either in the form of porous 3D structures, microspheres, or films. Thus, this review article focuses on the concept of dual drug delivery platform and its importance, classification of various platforms for dual drug delivery specific to bone tissue engineering, and finally highlights the foresight into the future direction of these techniques for better clinical applications.
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Affiliation(s)
- Anupama Devi V. K.
- Tissue Engineering Group, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore, India
- School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, India
| | - Sarbajit Ray
- School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, India
| | - Udita Arora
- School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, India
| | - Sunrito Mitra
- School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, India
| | | | - Amit Kumar Jaiswal
- Tissue Engineering Group, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore, India
- *Correspondence: Amit Kumar Jaiswal,
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Kilian D, Cometta S, Bernhardt A, Taymour R, Golde J, Ahlfeld T, Emmermacher J, Gelinsky M, Lode A. Core-shell bioprinting as a strategy to apply differentiation factors in a spatially defined manner inside osteochondral tissue substitutes. Biofabrication 2021; 14. [PMID: 34933296 DOI: 10.1088/1758-5090/ac457b] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/21/2021] [Indexed: 11/12/2022]
Abstract
One of the key challenges in osteochondral tissue engineering is to define specified zones with varying material properties, cell types and biochemical factors supporting locally adjusted differentiation into the osteogenic and chondrogenic lineage, respectively. Herein, extrusion-based core-shell bioprinting is introduced as a potent tool allowing a spatially defined delivery of cell types and differentiation factors TGF-β3 and BMP-2 in separated compartments of hydrogel strands, and, therefore, a local supply of matching factors for chondrocytes and osteoblasts. Ink development was based on blends of alginate and methylcellulose, in combination with varying concentrations of the nanoclay Laponite whose high affinity binding capacity for various molecules was exploited. Release kinetics of model molecules was successfully tuned by Laponite addition. Core-shell bioprinting was proven to generate well-oriented compartments within one strand as monitored by optical coherence tomography in a non-invasive manner. Chondrocytes and osteoblasts were applied each in the shell while the respective differentiation factors (TGF-β3, BMP-2) were provided by a Laponite-supported core serving as central factor depot within the strand, allowing directed differentiation of cells in close contact to the core. Experiments with bi-zonal constructs, comprising an osteogenic and a chondrogenic zone, revealed that the local delivery of the factors from the core reduces effects of these factors on the cells in the other scaffold zone. These observations prove the general suitability of the suggested system for co-differentiation of different cell types within a zonal construct.
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Affiliation(s)
- David Kilian
- Centre for Translational Bone, Joint and Soft Tissue Research, Technische Universitaet Dresden, Fetscherstrasse 74, Dresden, 01307, GERMANY
| | - Silvia Cometta
- Dresden University of Technology, Fetscherstrasse 74, Dresden, Sachsen, 01307, GERMANY
| | - Anne Bernhardt
- Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine, Dresden University of Technology, Fetscherstrasse 74, Dresden, Sachsen, 01307, GERMANY
| | - Rania Taymour
- Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine, Dresden University of Technology, Fetscherstrasse 74, Dresden, Sachsen, 01307, GERMANY
| | - Jonas Golde
- Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Dresden University of Technology, Fetscherstrasse 74, Dresden, Sachsen, 01307, GERMANY
| | - Tilman Ahlfeld
- Centre for Translational Bone, Joint and Soft Tissue Research, Technische Universitaet Dresden, Fetscherstrasse 74, Dresden, 01307, GERMANY
| | - Julia Emmermacher
- Centre for translational bone, joint and soft tissue research, Technische Universitat Dresden, Fetscherstrasse 74, Dresden, 01307, GERMANY
| | - Michael Gelinsky
- Centre for Translational Bone, Joint and Soft Tissue Research, Technische Universitaet Dresden, Fetscherstr. 74, Dresden, 01307, GERMANY
| | - Anja Lode
- Centre for Translational Bone, Joint and Soft Tissue Research, Technische Universitaet Dresden, Fetscherstrasse 74, Dresden, 01307, GERMANY
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Roy S, Mukherjee P, Das PK, Ghosh PR, Datta P, Kundu B, Nandi SK. Local delivery systems of morphogens/biomolecules in orthopedic surgical challenges. MATERIALS TODAY COMMUNICATIONS 2021; 27:102424. [DOI: 10.1016/j.mtcomm.2021.102424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Mainardi VL, Arrigoni C, Bianchi E, Talò G, Delcogliano M, Candrian C, Dubini G, Levi M, Moretti M. Improving cell seeding efficiency through modification of fiber geometry in 3D printed scaffolds. Biofabrication 2021; 13. [PMID: 33578401 DOI: 10.1088/1758-5090/abe5b4] [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] [Received: 07/02/2020] [Accepted: 02/12/2021] [Indexed: 11/11/2022]
Abstract
Cell seeding on 3D scaffolds is a very delicate step in tissue engineering applications, influencing the outcome of the subsequent culture phase, and determining the results of the entire experiment. Thus, it is crucial to maximize its efficiency. To this purpose, a detailed study of the influence of the geometry of the scaffold fibers on dynamic seeding efficiency is presented. 3D printing technology was used to realize PLA porous scaffolds, formed by fibers with a non-circular cross-sectional geometry, named multilobed to highlight the presence of niches and ridges. An oscillating perfusion bioreactor was used to perform bidirectional dynamic seeding of MG63 cells. The fiber shape influences the fluid dynamic parameters of the flow, affecting values of fluid velocity and wall shear stress. The path followed by cells through the scaffold fibers is also affected and results in a larger number of adhered cells in multilobed scaffolds compared to scaffolds with standard pseudo cylindrical fibers. Geometrical and fluid dynamic features can also have an influence on the morphology of adhered cells. The obtained results suggest that the reciprocal influence of geometrical and fluid dynamic features and their combined effect on cell trajectories should be considered to improve the dynamic seeding efficiency when designing scaffold architecture.
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Affiliation(s)
- Valerio Luca Mainardi
- Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale, Via Tesserete, 46, Lugano, 6900, SWITZERLAND
| | - Chiara Arrigoni
- Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale, Via Tesserete, 46, Lugano, 6900, SWITZERLAND
| | - Elena Bianchi
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Piazza Leonardo da Vinci, 32, Milano, 20133, ITALY
| | - Giuseppe Talò
- Cell and Tissue Engineering Lab, IRCCS Istituto Ortopedico Galeazzi, Via Riccardo Galeazzi, 4, Milano, 20161, ITALY
| | - Marco Delcogliano
- Unità di Traumatologia e Ortopedia, Ente Ospedaliero Cantonale, Via Tesserete, 46, Lugano, 6900, SWITZERLAND
| | - Christian Candrian
- Unità di Traumatologia e Ortopedia, Ente Ospedaliero Cantonale, Via Tesserete, 46, Lugano, 6900, SWITZERLAND
| | - Gabriele Dubini
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Piazza Leonardo da Vinci, 32, Milano, 20133, ITALY
| | - Marinella Levi
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Piazza Leonardo da Vinci, 32, Milano, 20133, ITALY
| | - Matteo Moretti
- Regenerative Medicine Technologies Laboratory, Ente Ospedaliero Cantonale, Via Tesserete, 46, Lugano, 6900, SWITZERLAND
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Jing X, Xie B, Li X, Dai Y, Nie L, Li C. Peptide decorated demineralized dentin matrix with enhanced bioactivity, osteogenic differentiation via carboxymethyl chitosan. Dent Mater 2020; 37:19-29. [PMID: 33257086 DOI: 10.1016/j.dental.2020.09.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 07/06/2020] [Accepted: 09/30/2020] [Indexed: 12/31/2022]
Abstract
OBJECTIVES To improve the biocompatibility and osteogenic activity of demineralized dentin matrix (DDM) by grafting peptides on its surface. METHODS DDM was obtained by pulverizing extracted human teeth that had been systematically demineralized and dried. Four groups of materials were evaluated: DDM, DDM/carboxymethyl chitosan (CMC), DDM/CMC/bone forming peptide-1 (BFP-1), and blank. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and fluorescence localization were used to characterize the surface of the DDM materials. Cell viability was assessed using a CCK8 assay, scanning electron microscopy (SEM) and in vitro osteogenesis was analyzed using real-time RT-PCR (RT-qPCR) and Alizarin red and alkaline phosphatase staining. Three different materials were implanted into mandibular bone defects in rats. After 8 weeks, bone regeneration was assessed by histomorphometry of HE-stained slides. RESULTS FT-IR, XPS, and fluorescence microscopy demonstrated that the DDM surfaces were successfully modified with BFP-1. The CCK8 assay indicated that the proliferation of cells is higher on the DDM/CMC/BFP-1 material than on DDM or DDM/CMC (P < 0.05). Cells were more likely to adhere to DDM/CMC/BFP-1, as observed by SEM. Greater in vitro osteogenesis was observed in the DDM/CMC/BFP-1 group which displayed stronger alkaline phosphatase activity, more alizarin red-stained nodules, and higher target gene expression, as detected by RT-qPCR (P<0.05). HE staining of in vivo explants indicated that greater quantities of new bone had formed in the DDM/CMC/BFP-1 group. SIGNIFICANCE Compared with DDM, DDM/CMC/BFP-1 exhibited superior biocompatibility and osteogenesis, using a method of surface modification that has great potential for future clinical use.
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Affiliation(s)
- Xueqin Jing
- Stomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Bingwu Xie
- Stomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
| | - Xinyue Li
- Stomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Youli Dai
- Stomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Li Nie
- Stomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Conghua Li
- Stomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
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Wu R, Gao G, Xu Y. Electrospun Fibers Immobilized with BMP-2 Mediated by Polydopamine Combined with Autogenous Tendon to Repair Developmental Dysplasia of the Hip in a Porcine Model. Int J Nanomedicine 2020; 15:6563-6577. [PMID: 32982218 PMCID: PMC7490068 DOI: 10.2147/ijn.s259028] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 08/10/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose Developmental dysplasia of the hip (DDH) can increase the pressure between the joints, which causes secondary hip osteoarthritis. The aim of the present study was to fabricate poly(D, L-lactic acid)-poly(ethylene glycol)-poly(D, L-lactic acid) (PELA) electrospun fibrous scaffolds, immobilized with bone morphogenetic protein-2 (BMP-2), to repair the acetabulum defects. Methods The characteristics of PELA electrospun were analyzed using scanning electron microscopy, the release kinetics of BMP-2 in vitro were analyzed using enzyme-linked immunosorbent assays. Human mesenchymal stem cells (hMSCs) were used for in vitro experiments, the biocompatibility of the electrospinning materials was investigated using a cell counting kit-8 (CCK-8) kit, and osteogenic differentiation was tested via alkaline phosphatase (ALP) activity and relative gene expression. Eighteen miniature pig animal models were used in the in vivo experiment. The pigs were sacrificed at 24 weeks after surgery, and the reconstructed acetabulum was evaluated using histological sections. Results Structural analysis revealed that the diameter of the PELA electrospun fiber was 0.8195 ± 0.16 μm. The PELA electrospun fiber materials showed good hydrophilicity and biocompatibility and could continuously release BMP-2 within 27 days: 16.07 ± 0.11 ng of BMP-2 was released from the scaffold. A total of sixteen implants fully filled the defects, and hematoxylin and eosin staining and Goldner's trichrome staining showed that the simple tendon group (T group) was mostly fibrous tissues, lots of fibroblasts and small amounts of chondrocytes were observed in the polydopamine-coated electrospun fiber group (DP group). The DP plus BMP-2 (DPB) group showed a large number of chondrocytes and partial new bone tissues. Conclusion PELA electrospun fibrous scaffolds are good sustained-release carriers, which can not only induce implant differentiation into cartilage and bone but also are completely degraded without toxicity. Therefore, the material can be used for bone and cartilage regeneration.
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Affiliation(s)
- Ruiqi Wu
- Department of Sports Medicine, Peking University Third Hospital, Beijing, People's Republic of China
| | - Guanying Gao
- Department of Sports Medicine, Peking University Third Hospital, Beijing, People's Republic of China
| | - Yan Xu
- Department of Sports Medicine, Peking University Third Hospital, Beijing, People's Republic of China
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Vácz G, Major B, Gaál D, Petrik L, Horváthy DB, Han W, Holczer T, Simon M, Muir JM, Hornyák I, Lacza Z. Hyperacute serum has markedly better regenerative efficacy than platelet-rich plasma in a human bone oxygen-glucose deprivation model. Regen Med 2018; 13:531-543. [PMID: 30132395 DOI: 10.2217/rme-2017-0141] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
AIM Platelet-rich plasma (PRP) and hyperacute serum (HAS) were compared in a novel human model of ex vivo bone damage induced by oxygen-glucose deprivation (OGD). MATERIALS & METHODS Osteoarthritic subchondral bone pieces were harvested from discarded femoral heads during hip replacement surgery and subjected to transient OGD. RESULTS Proteome profiling revealed that PRP is more angiopoietic, whereas HAS is more antiangiopoietic in composition. However, treatment of OGD-exposed bone with multiple PRP preparations had no effect on cell counts, whereas HAS restored cell proliferation capacity and rescued viable cell number following OGD. CONCLUSION A similar pro-proliferation effect was observed with recombinant growth factors, indicating that HAS may be an alternative agent for enhancing the regeneration of damaged bone cells.
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Affiliation(s)
- Gabriella Vácz
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Bálint Major
- Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Orthopaedic Department, Frankel Leo u. 54., Budapest, Hungary, 1023
| | - Dorottya Gaál
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Laura Petrik
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Dénes Balázs Horváthy
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Weiping Han
- Bioimaging Consortium, A-STAR, Singapore, Helios, Biopolis Way 11
| | - Tünde Holczer
- Department of Laboratory Medicine, Semmelweis University, Nagyvárad t. 4, Budapest, Hungary, 1089
| | - Melinda Simon
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Jeffrey M Muir
- Motion Research, 3-35 Stone Church Rd, Suite 215, Ancaster, Ontario, L9K 3S9 Canada
| | - István Hornyák
- OrthoSera GmbH, Dr. Karl-Dorrek-Straße 23-29, 3500 Krems an der Donau, Austria
| | - Zsombor Lacza
- OrthoSera GmbH, Dr. Karl-Dorrek-Straße 23-29, 3500 Krems an der Donau, Austria.,University of Physical Education, Alkotás u. 44, Budapest, Hungary 1123
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Aragón J, Salerno S, De Bartolo L, Irusta S, Mendoza G. Polymeric electrospun scaffolds for bone morphogenetic protein 2 delivery in bone tissue engineering. J Colloid Interface Sci 2018; 531:126-137. [PMID: 30029031 DOI: 10.1016/j.jcis.2018.07.029] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 07/08/2018] [Accepted: 07/09/2018] [Indexed: 01/05/2023]
Abstract
HYPOTHESIS The development of novel scaffolds based on biocompatible polymers is of great interest in the field of bone repair for fabrication of biodegradable scaffolds that mimic the extracellular matrix and have osteoconductive and osteoinductive properties for enhanced bone regeneration. EXPERIMENTS Polycaprolactone (PCL) and polycaprolactone/polyvinyl acetate (PCL/PVAc) core-shell fibers were synthesised and decorated with poly(lactic-co-glycolic acid) [PLGA] particles loaded with bone morphogenetic protein 2 (BMP2) by simultaneous electrospinning and electrospraying. Hydroxyapatite nanorods (HAn) were loaded into the core of fibers. The obtained scaffolds were characterised by scanning and transmission electron microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The in vitro potential of these materials for bone regeneration was assessed in biodegradation assays, osteoblast viability assays, and analyses of expression of specific bone markers, such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). FINDINGS PLGA particles were homogeneously distributed in the entire fibre mat. The growth factor load was 1.2-1.7 μg/g of the scaffold whereas the HAn load was in the 8.8-12.6 wt% range. These scaffolds were able to support and enhance cell growth and proliferation facilitating the expression of osteogenic and osteoconductive markers (OCN and OPN). These observations underline the great importance of the presence of BMP2 in scaffolds for bone remodelling as well as the good potential of the newly developed scaffolds for clinical use in tissue engineering.
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Affiliation(s)
- Javier Aragón
- Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza, Campus Rio Ebro-Edificio I+D, C/Mariano Esquillor S/N, 50018 Zaragoza, Spain; Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain.
| | - Simona Salerno
- Institute for Membrane Technology, National Research Council of Italy, ITM-CNR c/o University of Calabria, Via P. Bucci cubo 17/C, I-87036 Rende, Italy.
| | - Loredana De Bartolo
- Institute for Membrane Technology, National Research Council of Italy, ITM-CNR c/o University of Calabria, Via P. Bucci cubo 17/C, I-87036 Rende, Italy.
| | - Silvia Irusta
- Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza, Campus Rio Ebro-Edificio I+D, C/Mariano Esquillor S/N, 50018 Zaragoza, Spain; Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; Networking Research Center for Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029 Madrid, Spain.
| | - Gracia Mendoza
- Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza, Campus Rio Ebro-Edificio I+D, C/Mariano Esquillor S/N, 50018 Zaragoza, Spain; Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain.
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Nguyen MK, Jeon O, Dang PN, Huynh CT, Varghai D, Riazi H, McMillan A, Herberg S, Alsberg E. RNA interfering molecule delivery from in situ forming biodegradable hydrogels for enhancement of bone formation in rat calvarial bone defects. Acta Biomater 2018; 75:105-114. [PMID: 29885529 PMCID: PMC6119505 DOI: 10.1016/j.actbio.2018.06.007] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 06/01/2018] [Accepted: 06/04/2018] [Indexed: 11/22/2022]
Abstract
RNA interference (RNAi) may be an effective and valuable tool for promoting the growth of functional tissue, as short interfering RNA (siRNA) and microRNA (miRNA) can block the expression of genes that have negative effects on tissue regeneration. Our group has recently reported that the localized and sustained presentation of siRNA against noggin (siNoggin) and miRNA-20a from in situ forming poly(ethylene glycol) (PEG) hydrogels enhanced osteogenic differentiation of encapsulated human bone marrow-derived mesenchymal stem cells (hMSCs). Here, the capacity of the hydrogel system to accelerate bone formation in a rat calvarial bone defect model is presented. After 12 weeks post-implantation, the hydrogels containing encapsulated hMSCs and miRNA-20a resulted in more bone formation in the defects than the hydrogels containing hMSCs without siRNA or with negative control siRNA. This localized and sustained RNA interfering molecule delivery system may provide an excellent platform for healing bony defects and other tissues. STATEMENT OF SIGNIFICANCE Delivery of RNAi molecules may be a valuable strategy to guide cell behavior for tissue engineering applications, but to date there have been no reports of a biomaterial system capable of both encapsulation of cells and controlled delivery of incorporated RNA. Here, we present PEG hydrogels that form in situ via Michael type reaction, and that permit encapsulation of hMSCs and the concomitant controlled delivery of siNoggin and/or miRNA-20a. These RNAs were chosen to suppress noggin, a BMP-2 antagonist, and/or PPAR-γ, a negative regulator of BMP-2-mediated osteogenesis, and therefore promote osteogenic differentiation of hMSCs and subsequent bone repair in critical-sized rat calvarial defects. Simultaneous delivery of hMSCs and miRNA-20a enhanced repair of these defects compared to hydrogels containing hMSCs without siRNA or with negative control siRNA. This in situ forming PEG hydrogel system offers an exciting platform for healing critical-sized bone defects by localized, controlled delivery of RNAi molecules to encapsulated hMSCs and surrounding cells.
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Affiliation(s)
- Minh K Nguyen
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Oju Jeon
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Phuong N Dang
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Cong T Huynh
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Davood Varghai
- Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Hooman Riazi
- Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Alexandra McMillan
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Samuel Herberg
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States
| | - Eben Alsberg
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Orthopaedic Surgery, Case Western Reserve University, Cleveland, OH 44106, United States.
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Lukasova V, Buzgo M, Sovkova V, Dankova J, Rampichova M, Amler E. Osteogenic differentiation of 3D cultured mesenchymal stem cells induced by bioactive peptides. Cell Prolif 2017; 50. [PMID: 28714176 DOI: 10.1111/cpr.12357] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 05/10/2017] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVES Bioactive peptides derived from receptor binding motifs of native proteins are a potent source of bioactive molecules that can induce signalling pathways. These peptides could substitute for osteogenesis promoting supplements. The work presented here compares three kinds of bioactive peptides derived from collagen III, bone morphogenetic protein 7 (BMP-7) and BMP-2 with their potential osteogenic activity on the model of porcine mesenchymal stem cells (pMSCs). MATERIALS AND METHODS pMSCs were cultured on electrospun polycaprolactone nanofibrous scaffolds with different concentrations of the bioactive peptides without addition of any osteogenic supplement. Analysis of pMSCs cultures included measurement of the metabolic activity and proliferation, immunofluorescence staining and also qPCR. RESULTS Results showed no detrimental effect of the bioactive peptides to cultured pMSCs. Based on qPCR analysis, the bioactive peptides are specific for osteogenic differentiation with no detectable expression of collagen II. Our results further indicate that peptide derived from BMP-2 protein promoted the expression of mRNA for osteocalcin (OCN) and collagen I significantly compared to control groups and also supported deposition of OCN as observed by immunostaining method. CONCLUSION The data suggest that bioactive peptide with an amino acid sequence of KIPKASSVPTELSAISTLYL derived from BMP-2 protein was the most potent for triggering osteogenic differentiation of pMSCs.
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Affiliation(s)
- Vera Lukasova
- Faculty of Science, Charles University in Prague, Prague, Czech Republic.,Laboratory of Tissue Engineering, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
| | - Matej Buzgo
- Institute of Biophysics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.,University Center for Energy Efficient Buildings, Czech Technical University in Prague, Bustehrad, Czech Republic
| | - Vera Sovkova
- Laboratory of Tissue Engineering, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.,Institute of Biophysics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
| | - Jana Dankova
- Laboratory of Tissue Engineering, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.,Institute of Biophysics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
| | - Michala Rampichova
- Laboratory of Tissue Engineering, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.,University Center for Energy Efficient Buildings, Czech Technical University in Prague, Bustehrad, Czech Republic
| | - Evzen Amler
- Laboratory of Tissue Engineering, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.,Institute of Biophysics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.,University Center for Energy Efficient Buildings, Czech Technical University in Prague, Bustehrad, Czech Republic
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Akkineni AR, Ahlfeld T, Lode A, Gelinsky M. A versatile method for combining different biopolymers in a core/shell fashion by 3D plotting to achieve mechanically robust constructs. Biofabrication 2016; 8:045001. [DOI: 10.1088/1758-5090/8/4/045001] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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15
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Wang D, Tabassum A, Wu G, Deng L, Wismeijer D, Liu Y. Bone regeneration in critical-sized bone defect enhanced by introducing osteoinductivity to biphasic calcium phosphate granules. Clin Oral Implants Res 2016; 28:251-260. [PMID: 26970206 DOI: 10.1111/clr.12791] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2016] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Biphasic calcium phosphate (BCP) is frequently used as bone substitute and often needs to be combined with autologous bone to gain an osteoinductive property for guided bone regeneration in implant dentistry. Given the limitations of using autologous bone, bone morphogenetic protein-2 (BMP2)-coprecipitated, layer-by-layer assembled biomimetic calcium phosphate particles (BMP2-cop.BioCaP) have been developed as a potential osteoinducer. In this study, we hypothesized that BMP2-cop.BioCaP could introduce osteoinductivity to BCP and so could function as effectively as autologous bone for the repair of a critical-sized bone defect. MATERIALS AND METHODS We prepared BMP2-cop.BioCaP and monitored the loading and release kinetics of BMP2 from it in vitro. Seven groups (n = 6 animals/group) were established: (i) Empty defect; (ii) BCP; (iii) BCP mixed with biomimetic calcium phosphate particles (BioCaP); (iv) BCP mixed with BMP2-cop.BioCaP; (v) BioCaP; (vi) BMP2-cop.BioCaP; (vii) BCP mixed with autologous bone. They were implanted into 8-mm-diameter rat cranial critical-sized bone defects for an in vivo evaluation. Autologous bone served as a positive control. The osteoinductive efficacy and degradability of materials were evaluated using micro-CT, histology and histomorphometry. RESULTS The combined application of BCP and BMP2-cop.BioCaP resulted in significantly more new bone formation than BCP alone. The osteoinductive efficacy of BMP2-cop.BioCaP was comparable to the golden standard use of autologous bone. Compared with BCP alone, significantly more BCP degradation was found when mixed with BMP2-cop.BioCaP. CONCLUSION The combination of BCP and BMP2-cop.BioCaP showed a promising potential for guided bone regeneration clinically in the future.
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Affiliation(s)
- D Wang
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam, the Netherlands
| | - A Tabassum
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam, the Netherlands
| | - G Wu
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam, the Netherlands
| | - L Deng
- School of Stomatology, Zhejiang Chinese Medical University, Hangzhou, China
| | - D Wismeijer
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam, the Netherlands
| | - Y Liu
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam, the Netherlands
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Modified chitosan scaffolds: Proliferative, cytotoxic, apoptotic, and necrotic effects on Saos-2 cells and antimicrobial effect on Escherichia coli. J BIOACT COMPAT POL 2016. [DOI: 10.1177/0883911515627471] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Scaffolds used in tissue engineering applications should have high biocompatibility with minimum allergic, toxic, apoptotic, or necrotic effects on the growing cells and newly forming tissue and, if possible, have antimicrobial property to prevent infection at the host site. In this study, novel micro-fibrous chitosan scaffolds, having mineralized bioactive surface to enhance cell adhesion and a model antibiotic (gentamicin) to prevent bacterial attack, were prepared. The effects of the scaffolds on proliferation, viability, apoptosis, and necrosis of Saos-2 cells are reported for the first time. Wet spinning technique was used in the scaffold preparation and biomineralization was achieved by incubating them in five-time concentrated simulated body fluid for 2, 7, or 14 days (coded as CH-BM/2, CH-BM/7, and CH-BM/14, respectively). Gentamicin, an effectively used antibiotic in bone treatments, was loaded by vacuum-pressure cycle. Energy-dispersive X-ray results demonstrated that Ca/P ratio of the mineral phase varies depending on the incubation period. When the scaffolds were cultured with Saos-2 cells, cell adhesion and extracellular matrix formation occurred on all types of scaffolds. Alamar Blue cytotoxicity tests showed correlation among mineral concentration and cytotoxicity where CH-BM/2 had significantly more favorable properties. For all types of scaffolds, apoptosis and necrosis were less than 10%, meaning the samples are biocompatible. Gentamicin-loaded scaffolds showed high antimicrobial efficacy against Escherichia coli. The presence of mineral phase enhanced the adhesive capacity of cells and entrapment efficiency of antibiotic. These results suggest that the bioactive and antimicrobial scaffolds prepared in this study can act as promising matrices in bone tissue engineering applications.
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17
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Farokhi M, Mottaghitalab F, Shokrgozar MA, Ou KL, Mao C, Hosseinkhani H. Importance of dual delivery systems for bone tissue engineering. J Control Release 2016; 225:152-69. [PMID: 26805518 DOI: 10.1016/j.jconrel.2016.01.033] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 01/18/2016] [Accepted: 01/19/2016] [Indexed: 02/07/2023]
Abstract
Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering.
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Affiliation(s)
- Mehdi Farokhi
- National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
| | - Fatemeh Mottaghitalab
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Keng-Liang Ou
- Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, Taipei Medical University - Shuang Ho Hospital, New Taipei city, Taiwan
| | - Chuanbin Mao
- Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK 73019, USA
| | - Hossein Hosseinkhani
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
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De la Paz Orozco A, Vega FJ, Martel-Estrada SA, Aguilar AH, Mendoza-Duarte ME, Chavarría-Gaytán MC, Rodríguez-González CA, Olivas-Armendáriz I. Development of Chitosan/Poly(L-Lactide)/Multiwalled Carbon Nanotubes Scaffolds for Bone Tissue Engineering. ACTA ACUST UNITED AC 2016. [DOI: 10.4236/ojrm.2016.51002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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19
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Kim YH, Tabata Y. Dual-controlled release system of drugs for bone regeneration. Adv Drug Deliv Rev 2015; 94:28-40. [PMID: 26079284 DOI: 10.1016/j.addr.2015.06.003] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 05/23/2015] [Accepted: 06/08/2015] [Indexed: 02/08/2023]
Abstract
Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials.
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20
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Controlled release of drugs in electrosprayed nanoparticles for bone tissue engineering. Adv Drug Deliv Rev 2015; 94:77-95. [PMID: 26415888 DOI: 10.1016/j.addr.2015.09.007] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Revised: 08/28/2015] [Accepted: 09/18/2015] [Indexed: 12/17/2022]
Abstract
Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration.
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Monteiro N, Martins A, Reis RL, Neves NM. Nanoparticle-based bioactive agent release systems for bone and cartilage tissue engineering. Regen Ther 2015; 1:109-118. [PMID: 31245450 PMCID: PMC6581799 DOI: 10.1016/j.reth.2015.05.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 04/07/2015] [Accepted: 05/25/2015] [Indexed: 11/22/2022] Open
Abstract
The inability to deliver bioactive agents locally in a transient but sustained manner is one of the challenges on the development of bio-functionalized scaffolds for tissue engineering (TE) and regenerative medicine. The mode of release is especially relevant when the bioactive agent is a growth factor (GF), because the dose and the spatiotemporal release of such agents at the site of injury are crucial to achieve a successful outcome. Strategies that combine scaffolds and drug delivery systems have the potential to provide more effective tissue regeneration relative to current therapies. Nanoparticles (NPs) can protect the bioactive agents, control its profile, decrease the occurrence and severity of side effects and deliver the bioactive agent to the target cells maximizing its effect. Scaffolds containing NPs loaded with bioactive agents can be used for their local delivery, enabling site-specific pharmacological effects such as the induction of cell proliferation and differentiation, and, consequently, neo-tissue formation. This review aims to describe the concept of combining NPs with scaffolds, and the current efforts aiming to develop highly multi-functional bioactive agent release systems, with the emphasis on their application in TE of connective tissues.
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Affiliation(s)
- Nelson Monteiro
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Albino Martins
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L. Reis
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Nuno M. Neves
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
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Motamedian SR, Hosseinpour S, Ahsaie MG, Khojasteh A. Smart scaffolds in bone tissue engineering: A systematic review of literature. World J Stem Cells 2015; 7:657-668. [PMID: 25914772 PMCID: PMC4404400 DOI: 10.4252/wjsc.v7.i3.657] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 12/10/2014] [Accepted: 12/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To improve osteogenic differentiation and attachment of cells. METHODS An electronic search was conducted in PubMed from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold (cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors (group I-11 studies), extracellular matrix-like molecules (group II-13 studies) and nanoparticles (nano-HA) (group III-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone (PCL). In group II, collagen 1 in combination with PCL, hydroxyapatite (HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable. CONCLUSION Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.
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Affiliation(s)
- Saeed Reza Motamedian
- Saeed Reza Motamedian, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran PO Box 19839, Iran
| | - Sepanta Hosseinpour
- Saeed Reza Motamedian, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran PO Box 19839, Iran
| | - Mitra Ghazizadeh Ahsaie
- Saeed Reza Motamedian, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran PO Box 19839, Iran
| | - Arash Khojasteh
- Saeed Reza Motamedian, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran PO Box 19839, Iran
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Makhdom AM, Nayef L, Tabrizian M, Hamdy RC. The potential roles of nanobiomaterials in distraction osteogenesis. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2015; 11:1-18. [PMID: 24965757 DOI: 10.1016/j.nano.2014.05.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2014] [Revised: 04/25/2014] [Accepted: 05/16/2014] [Indexed: 10/25/2022]
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Siddiqui N, Pramanik K. Development of fibrin conjugated chitosan/nano β-TCP composite scaffolds with improved cell supportive property for bone tissue regeneration. J Appl Polym Sci 2014. [DOI: 10.1002/app.41534] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Nadeem Siddiqui
- Department of Biotechnology and Medical Engineering; National Institute of Technology; Rourkela India 769008
| | - Krishna Pramanik
- Department of Biotechnology and Medical Engineering; National Institute of Technology; Rourkela India 769008
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25
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Oryan A, Alidadi S, Moshiri A, Bigham-Sadegh A. Bone morphogenetic proteins: a powerful osteoinductive compound with non-negligible side effects and limitations. Biofactors 2014; 40:459-81. [PMID: 25283434 DOI: 10.1002/biof.1177] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2014] [Revised: 07/21/2014] [Accepted: 07/26/2014] [Indexed: 12/29/2022]
Abstract
Healing and regeneration of large bone defects leading to non-unions is a great concern in orthopedic surgery. Since auto- and allografts have limitations, bone tissue engineering and regenerative medicine (TERM) has attempted to solve this issue. In TERM, healing promotive factors are necessary to regulate the several important events during healing. An ideal treatment strategy should provide osteoconduction, osteoinduction, osteogenesis, and osteointegration of the graft or biomaterials within the healing bone. Since many materials have osteoconductive properties, only a few biomaterials have osteoinductive properties which are important for osteogenesis and osteointegration. Bone morphogenetic proteins (BMPs) are potent inductors of the osteogenic and angiogenic activities during bone repair. The BMPs can regulate the production and activity of some growth factors which are necessary for the osteogenesis. Since the introduction of BMP, it has added a valuable tool to the surgeon's possibilities and is most commonly used in bone defects. Despite significant evidences suggesting their potential benefit on bone healing, there are some evidences showing their side effects such as ectopic bone formation, osteolysis and problems related to cost effectiveness. Bone tissue engineering may create a local environment, using the delivery systems, which enables BMPs to carry out their activities and to lower cost and complication rate associated with BMPs. This review represented the most important concepts and evidences regarding the role of BMPs on bone healing and regeneration from basic to clinical application. The major advantages and disadvantages of such biologic compounds together with the BMPs substitutes are also discussed.
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Affiliation(s)
- Ahmad Oryan
- Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
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Dai F, Yang S, Zhang F, Shi D, Zhang Z, Wu J, Xu J. hTERT- and hCTLA4Ig-expressing human bone marrow-derived mesenchymal stem cells: in vitro and in vivo characterization and osteogenic differentiation. J Tissue Eng Regen Med 2014; 11:400-411. [PMID: 25047146 DOI: 10.1002/term.1924] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Revised: 02/21/2014] [Accepted: 04/25/2014] [Indexed: 01/01/2023]
Abstract
Multipotent mesenchymal stem cells (MSCs) are commonly used as seed cells in studies of tissue engineering and regenerative medicine but their clinical application is limited, due to insufficient numbers of autogeneic MSCs, immune rejection of allogeneic MSCs and replicative senescence. We constructed two gene expression vectors for transfection of the human telomerase reverse transcriptase (hTERT) and cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4Ig) genes into human bone marrow-derived stem cells (hBMSCs). Successful transfection of both genes generated hTERT-CTLA4Ig hBMSCs that expressed both telomerase (shown by immunohistochemistry and a TRAPeze assay) and CTLA4Ig (demonstrated by immunocytochemistry and western blotting) without apparent mutual interference. Both hTERT BMSCs (92 population doublings) and hTERT-CTLA4Ig hBMSCs (60 population doublings) had an extended lifespan compared with hBMSCs (18 population doublings). Cell cycle analysis revealed that, compared with hBMSCs, a lower proportion of hTERT hBMSCs were in G0 /G1 phase but a higher proportion were in S phase; compared with hTERT hBMSCs, a higher proportion of hTERT-CTLA4Ig hBMSCs were in G0 /G1 phase, while a lower proportion were in S and G2 /M phases. hTERT-CTLA4Ig hBMSCs retained their capacity for osteogenic differentiation in vitro, shown by the detection of hydroxyapatite mineral deposition (labelled tetracycline fluorescence staining), calcareous nodules (alizarin red S staining), alkaline phosphatase (calcium-cobalt method) and osteocalcin (immunocytochemistry). Furthermore, subcutaneous transplantation of hTERT-CTLA4Ig hBMSCs in a rat xenotransplantation model resulted in the successful generation of bone-like tissue, confirmed using radiography and histological assessment. We propose that allogeneic hTERT-CTLA4Ig hBMSCs may be ideal seed cells for bone tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.
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Affiliation(s)
- Fei Dai
- National and Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Sisi Yang
- Institute of Burns Research, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Fei Zhang
- National and Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Dongwen Shi
- Institute of Burns Research, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Zehua Zhang
- National and Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Jun Wu
- Institute of Burns Research, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Jianzhong Xu
- National and Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
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Siddiqui N, Pramanik K. Effects of micro and nano β-TCP fillers in freeze-gelled chitosan scaffolds for bone tissue engineering. J Appl Polym Sci 2014. [DOI: 10.1002/app.41025] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Nadeem Siddiqui
- Department of Biotechnology and Medical Engineering; National Institute of Technology; Rourkela Odisha 769008 India
| | - Krishna Pramanik
- Department of Biotechnology and Medical Engineering; National Institute of Technology; Rourkela Odisha 769008 India
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28
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Huang CL, Lee WL, Loo JS. Drug-eluting scaffolds for bone and cartilage regeneration. Drug Discov Today 2014; 19:714-24. [DOI: 10.1016/j.drudis.2013.11.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Revised: 10/16/2013] [Accepted: 11/06/2013] [Indexed: 12/19/2022]
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Draenert ME, Hickel R, Draenert Y. ε-Caprolactone in micro-chambered ceramic beads--a new carrier for gentamicin. Chemotherapy 2014; 59:239-46. [PMID: 24401180 DOI: 10.1159/000354986] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Accepted: 08/12/2013] [Indexed: 11/19/2022]
Abstract
PURPOSE The purpose of this preliminary and descriptive study was to evaluate a biodegradable drug delivery system in combination with an innovative ceramic implant. METHODS The delivery of gentamicin of standardized samples was measured in the laboratory using ultra-high-performance liquid chromatography. Biocompatibility and biodegradation of the materials was investigated in an animal experiment in sheep up to 14 months. As carrier ε-caprolactone, 1:1 mixed with gentamicin, intruded into micro-chambered β-tricalcium-phosphate beads (MCB®) was studied. RESULTS AND DISCUSSION Gentamicin was released in calculable concentrations during the first 30 days. The release from ε-caprolactone was higher than that from polymethylmethacrylate and more predictable. The caprolactone carrier was reabsorbed by osteoclasts.
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Affiliation(s)
- Miriam E Draenert
- Clinic for Restorative Dentistry and Periodontology, Ludwig-Maximilian University of Munich, Germany
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Kiziltay A, Marcos-Fernandez A, San Roman J, Sousa RA, Reis RL, Hasirci V, Hasirci N. Poly(ester-urethane) scaffolds: effect of structure on properties and osteogenic activity of stem cells. J Tissue Eng Regen Med 2013; 9:930-42. [DOI: 10.1002/term.1848] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2012] [Revised: 06/13/2013] [Accepted: 10/07/2013] [Indexed: 12/28/2022]
Affiliation(s)
- Aysel Kiziltay
- BIOMATEN-Centre of Excellence in Biomaterials and Tissue Engineering; Middle East Technical University (METU); Ankara Turkey
- Graduate Department of Biotechnology; Middle East Technical University (METU); Ankara Turkey
- Central Laboratory; Middle East Technical University (METU); Ankara Turkey
| | | | - Julio San Roman
- Instituto de Ciencia y Tecnología de Polímeros (CSIC); Madrid Spain
| | - Rui A. Sousa
- 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics; Universidade do Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine; Taipas Guimarães Portugal
- ICVS/3Bs PT Government Associated Laboratory; Braga Guimarães Portugal
| | - Rui L. Reis
- 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics; Universidade do Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine; Taipas Guimarães Portugal
- ICVS/3Bs PT Government Associated Laboratory; Braga Guimarães Portugal
| | - Vasif Hasirci
- BIOMATEN-Centre of Excellence in Biomaterials and Tissue Engineering; Middle East Technical University (METU); Ankara Turkey
- Graduate Department of Biotechnology; Middle East Technical University (METU); Ankara Turkey
- Department of Biological Sciences; Middle East Technical University (METU); Ankara Turkey
| | - Nesrin Hasirci
- BIOMATEN-Centre of Excellence in Biomaterials and Tissue Engineering; Middle East Technical University (METU); Ankara Turkey
- Graduate Department of Biotechnology; Middle East Technical University (METU); Ankara Turkey
- Department of Chemistry; Middle East Technical University (METU); Ankara Turkey
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Poly(ε-caprolactone) composite scaffolds loaded with gentamicin-containing β-tricalcium phosphate/gelatin microspheres for bone tissue engineering applications. J Appl Polym Sci 2013. [DOI: 10.1002/app.40110] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine. Ann Biomed Eng 2013; 42:1557-72. [PMID: 24170072 DOI: 10.1007/s10439-013-0932-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2013] [Accepted: 10/21/2013] [Indexed: 12/19/2022]
Abstract
To realize the potential of regenerative medicine, controlling the delivery of biomolecules in the cellular microenvironment is important as these factors control cell fate. Controlled delivery for tissue engineering and regenerative medicine often requires bioengineered materials and cells capable of spatiotemporal modulation of biomolecule release and presentation. This review discusses biomolecule delivery from the outside of the cell inwards through the delivery of soluble and insoluble biomolecules as well as from the inside of the cell outwards through gene transfer. Ex vivo and in vivo therapeutic strategies are discussed, as well as combination delivery of biomolecules, scaffolds, and cells. Various applications in regenerative medicine are highlighted including bone tissue engineering and wound healing.
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Ucar S, Yilgor P, Hasirci V, Hasirci N. Chitosan-based wet-spun scaffolds for bioactive agent delivery. J Appl Polym Sci 2013. [DOI: 10.1002/app.39629] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
| | - Pinar Yilgor
- Department of Biomedical Engineering; Faculty of Engineering and Architecture; Cukurova University; 01330; Adana; Turkey
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34
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Yilgor Huri P, Huri G, Yasar U, Ucar Y, Dikmen N, Hasirci N, Hasirci V. A biomimetic growth factor delivery strategy for enhanced regeneration of iliac crest defects. Biomed Mater 2013; 8:045009. [DOI: 10.1088/1748-6041/8/4/045009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Sun Y, Deng Y, Ye Z, Liang S, Tang Z, Wei S. Peptide decorated nano-hydroxyapatite with enhanced bioactivity and osteogenic differentiation via polydopamine coating. Colloids Surf B Biointerfaces 2013; 111:107-16. [PMID: 23792546 DOI: 10.1016/j.colsurfb.2013.05.037] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2013] [Revised: 05/11/2013] [Accepted: 05/25/2013] [Indexed: 01/03/2023]
Abstract
To be better used as implant materials in bone graft substitutes, bioactivity and osteogenesis of nano-hydroxyapatite (nano-HA) need to be further enhanced. Inspired by adhesive proteins in mussels, here we developed a novel bone forming peptide decorated nano-HA material. In this study, nano-HA was coated by one-step pH-induced polymerization of dopamine, and then the peptide was grafted onto polydopamine (pDA) coated nano-HA (HA-pDA) through catechol chemistry. Our results demonstrated that the peptide-conjugated nano-HA crystals could induce the adhesion and proliferation of MG-63 cells. Moreover, the highly alkaline phosphatase activity of the functionalized nano-HA indicated that the grafted peptide could maintain its biological activity after immobilization onto the surface of HA-pDA, especially at the concentration of 100μg/mL. These modified nano-HA crystals with better bioactivity and osteogenic differentiation hold great potential to be applied as bioactive materials in bone repairing, bone regeneration and bio-implant coating applications.
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Affiliation(s)
- Yuhua Sun
- Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081, China
| | - Yi Deng
- Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081, China; Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
| | - Ziyou Ye
- Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; School of Biology and Basic Medical Sciences, Medical College, Soochow University, Jiangsu 215123, China
| | - Shanshan Liang
- Department of Oral and Maxillofacial Surgery, School of Stomatology, Hainan Medical College, Hainan 571199, China
| | - Zhihui Tang
- 2nd Dental Center, School and Hospital of Stomatology, Peking University, Beijing 100081, China.
| | - Shicheng Wei
- Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081, China; Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; 2nd Dental Center, School and Hospital of Stomatology, Peking University, Beijing 100081, China.
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36
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Santo VE, Gomes ME, Mano JF, Reis RL. Controlled release strategies for bone, cartilage, and osteochondral engineering--Part II: challenges on the evolution from single to multiple bioactive factor delivery. TISSUE ENGINEERING PART B-REVIEWS 2013; 19:327-52. [PMID: 23249320 DOI: 10.1089/ten.teb.2012.0727] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors.
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Affiliation(s)
- Vítor E Santo
- 3Bs Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
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Chien KB, Makridakis E, Shah RN. Three-dimensional printing of soy protein scaffolds for tissue regeneration. Tissue Eng Part C Methods 2012; 19:417-26. [PMID: 23102234 DOI: 10.1089/ten.tec.2012.0383] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Fabricating three-dimensional (3D) porous scaffolds with controlled structure and geometry is crucial for tissue regeneration. To date, exploration in printing 3D natural protein scaffolds is limited. In this study, soy protein slurry was successfully printed using the 3D Bioplotter to form scaffolds. A method to verify the structural integrity of resulting scaffolds during printing was developed. This process involved measuring the mass extrusion flow rate of the slurry from the instrument, which was directly affected by the extrusion pressure and the soy protein slurry properties. The optimal mass flow rate for printing soy slurry at 27°C was 0.0072±0.0002 g/s. The addition of dithiothreitol to soy slurries demonstrated the importance of disulfide bonds in forming solid structures upon printing. Resulting Bioplotted soy protein scaffolds were cured using 95% ethanol and post-treated using dehydrothermal treatment (DHT), a combination of freeze-drying and DHT, and chemical crosslinking using 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (EDC) chemistry. Surface morphologies of the different treatment groups were characterized using scanning electron microscopy. Scaffold properties, including relative crosslink density, mass loss upon rinsing, and compressive modulus revealed that EDC crosslinked scaffolds were the most robust with moduli of approximately 4 kPa. Scaffold geometry (45° and 90° layer rotations) affected the mechanical properties for DHT and EDC crosslinked scaffolds. Seeding efficiency of human mesenchymal stem cells (hMSC) was highest for nontreated and thermally treated scaffolds, and all scaffolds supported hMSC viability over time.
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Affiliation(s)
- Karen B Chien
- Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois, USA
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Valente J, Valente T, Alves P, Ferreira P, Silva A, Correia I. Alginate based scaffolds for bone tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2012. [DOI: 10.1016/j.msec.2012.08.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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39
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Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7. Biomaterials 2012; 33:7057-63. [DOI: 10.1016/j.biomaterials.2012.06.036] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 06/22/2012] [Indexed: 11/18/2022]
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40
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Balmert SC, Little SR. Biomimetic delivery with micro- and nanoparticles. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2012; 24:3757-78. [PMID: 22528985 PMCID: PMC3627374 DOI: 10.1002/adma.201200224] [Citation(s) in RCA: 96] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Indexed: 05/16/2023]
Abstract
The nascent field of biomimetic delivery with micro- and nanoparticles (MNP) has advanced considerably in recent years. Drawing inspiration from the ways that cells communicate in the body, several different modes of "delivery" (i.e., temporospatial presentation of biological signals) have been investigated in a number of therapeutic contexts. In particular, this review focuses on (1) controlled release formulations that deliver natural soluble factors with physiologically relevant temporal context, (2) presentation of surface-bound ligands to cells, with spatial organization of ligands ranging from isotropic to dynamically anisotropic, and (3) physical properties of particles, including size, shape and mechanical stiffness, which mimic those of natural cells. Importantly, the context provided by multimodal, or multifactor delivery represents a key element of most biomimetic MNP systems, a concept illustrated by an analogy to human interpersonal communication. Regulatory implications of increasingly sophisticated and "cell-like" biomimetic MNP systems are also discussed.
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Affiliation(s)
- Stephen C Balmert
- Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261 USA
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41
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Vardar E, Vert M, Coudane J, Hasirci V, Hasirci N. Porous Agarose-Based Semi-IPN Hydrogels: Characterization and Cell Affinity Studies. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012; 23:2273-86. [DOI: 10.1163/156856211x614770] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- E. Vardar
- a Department of Biomedical Engineering , Middle East Technical University (METU) , 06531 , Ankara , Turkey
| | - Michel Vert
- b Department of Pharmacy , Universite de Montpellier I , 15 avenue Charles Flahault, BP 14491 34093 , Montpellier , France
| | - Jean Coudane
- b Department of Pharmacy , Universite de Montpellier I , 15 avenue Charles Flahault, BP 14491 34093 , Montpellier , France
| | - V. Hasirci
- a Department of Biomedical Engineering , Middle East Technical University (METU) , 06531 , Ankara , Turkey
- c Department of Biological Sciences , Middle East Technical University (METU) , 06531 , Ankara , Turkey
- d European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark, Zona Industrial da Gandra, S. Claudio do Barco, 4806-909 , Caldas das Taipas — Guimaraes , Portugal
- e METU, BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering , Ankara , Turkey
| | - N. Hasirci
- a Department of Biomedical Engineering , Middle East Technical University (METU) , 06531 , Ankara , Turkey
- d European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark, Zona Industrial da Gandra, S. Claudio do Barco, 4806-909 , Caldas das Taipas — Guimaraes , Portugal
- e METU, BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering , Ankara , Turkey
- f Department of Chemistry , Middle East Technical University (METU) , 06531 , Ankara , Turkey
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Zhang Q, He QF, Zhang TH, Yu XL, Liu Q, Deng FL. Improvement in the delivery system of bone morphogenetic protein-2: a new approach to promote bone formation. Biomed Mater 2012; 7:045002. [PMID: 22556155 DOI: 10.1088/1748-6041/7/4/045002] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Much research has been focused on developing bone morphogenetic protein-2(BMP-2) delivery systems to enhance bone formation in bone defect repair and bone tissue engineering. However, many of these current systems have several drawbacks associated with low loading efficiencies and reduced biological activities after release. Collagen scaffolds can be used as in delivery systems because of their biocompatibility. However, growth factors have naturally low affinity to collagen, which is disadvantageous for maintaining a sufficient growth factor concentration at the delivery sites. To enhance BMP-2 binding to collagen scaffolds, we chose a porous collagen scaffold that was chemically modified using Traut's reagent. The modified collagen scaffold allows cross-linking of the collagen fibers and is able to immobilize more BMP-2 after treatment with Sulfo-SMCC. We demonstrated that cross-linking led to a slower release rate of BMP-2, but did not reduce its biological activity. Moreover, more ectopic bone formation was induced by subcutaneous implants of cross-linked collagen treated with BMP-2. We concluded that collagen scaffolds chemically conjugated with BMP-2 using Traut's reagent and Sulfo-SMCC was an effective delivery system for use in bone defect repair and in bone tissue engineering.
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Affiliation(s)
- Quan Zhang
- Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, People's Republic of China
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Lavin DM, Stefani RM, Zhang L, Furtado S, Hopkins RA, Mathiowitz E. Multifunctional polymeric microfibers with prolonged drug delivery and structural support capabilities. Acta Biomater 2012; 8:1891-900. [PMID: 22326788 DOI: 10.1016/j.actbio.2012.01.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Revised: 01/17/2012] [Accepted: 01/17/2012] [Indexed: 11/25/2022]
Abstract
The strength and stability of hybrid fiber delivery systems, ones that perform a mechanical function and simultaneously deliver drug, are critical in the design of surgically implantable constructs. We report the fabrication of drug-eluting microfibers where drug loading and processing conditions alone increase microfiber strength and stability partially due to solvent-induced crystallization. Poly(L-lactic acid) microfibers of 64±7 μm diameter were wet spun by phase inversion. Encapsulation of a model hydrophobic anti-inflammatory drug, dexamethasone, at high loading provided stability to microfibers which maintained linear cumulative release kinetics up to 8 weeks in vitro. In our wet spinning process, all microfibers had increased crystallinity (13-17%) in comparison to unprocessed polymer without any mechanical stretching. Moreover, microfibers with the highest drug loading retained 97% of initial tensile strength and were statistically stronger than all other microfiber formulations, including control fibers without drug. Results indicate that the encapsulation of small hydrophobic molecules (<400 Da) may increase the mechanical integrity of microfilaments whose crystallinity is also increased as a result of the process. Multifunctional drug-eluting microfibers can provide an exciting new opportunity to design novel biomaterials with mechanical stability and controlled release of a variety of therapeutics with micron-scale accuracy.
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Yilgor P, Yilmaz G, Onal MB, Solmaz I, Gundogdu S, Keskil S, Sousa RA, Reis RL, Hasirci N, Hasirci V. Anin vivostudy on the effect of scaffold geometry and growth factor release on the healing of bone defects. J Tissue Eng Regen Med 2012; 7:687-96. [DOI: 10.1002/term.1456] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2011] [Revised: 11/01/2011] [Accepted: 11/24/2011] [Indexed: 01/09/2023]
Affiliation(s)
| | - G. Yilmaz
- Department of Pathology; Gazi University Faculty of Medicine; Ankara; Turkey
| | - M. B. Onal
- Department of Neurosurgery; Gulhane Military Medical Academy; Ankara; Turkey
| | - I. Solmaz
- Department of Neurosurgery; Gulhane Military Medical Academy; Ankara; Turkey
| | - S. Gundogdu
- Department of Radiology; Ufuk University Faculty of Medicine; Ankara; Turkey
| | - S. Keskil
- Department of Neurosurgery; Bayindir Medical Centre; Kavaklidere; Ankara; Turkey
| | - R. A. Sousa
- 3Bs Research Group; University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine; Guimarães; Portugal
| | - R. L. Reis
- 3Bs Research Group; University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine; Guimarães; Portugal
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Kim JE, Lee EJ, Kim HE, Koh YH, Jang JH. The impact of immobilization of BMP-2 on PDO membrane for bone regeneration. J Biomed Mater Res A 2012; 100:1488-93. [PMID: 22396132 DOI: 10.1002/jbm.a.34089] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2011] [Revised: 11/23/2011] [Accepted: 12/22/2011] [Indexed: 12/24/2022]
Abstract
Poly(dioxanone) (PDO) is colorless, crystalline, a biodegradable synthetic polymers that is used for biomedical applications, such as surgical sutures, cardiovascular applications, orthopedics, and plastic surgery. Recently, bone morphogenetic protein-2 (BMP-2) is widely used for bone tissue engineering. For the first time we report here on the in vitro performance of an electrospun PDO membrane immobilized with BMP-2. Immobilized BMP-2 on PDO membrane enhanced ALPase activity, the osteogenic differentiation gene expressions as well as cell attachment, except cell proliferation when compared to that of PDO membrane alone. These results suggest that PDO membrane with BMP-2 is helpful to promote bone healing and regeneration.
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Affiliation(s)
- Ji-Eun Kim
- Department of Biochemistry, School of Medicine, Inha University, Incheon 400-712, Republic of Korea
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Gurkan UA, Tasoglu S, Kavaz D, Demirel MC, Demirci U. Emerging technologies for assembly of microscale hydrogels. Adv Healthc Mater 2012; 1:149-158. [PMID: 23184717 PMCID: PMC3774531 DOI: 10.1002/adhm.201200011] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2012] [Revised: 02/08/2012] [Indexed: 01/30/2023]
Abstract
Assembly of cell encapsulating building blocks (i.e., microscale hydrogels) has significant applications in areas including regenerative medicine, tissue engineering, and cell-based in vitro assays for pharmaceutical research and drug discovery. Inspired by the repeating functional units observed in native tissues and biological systems (e.g., the lobule in liver, the nephron in kidney), assembly technologies aim to generate complex tissue structures by organizing microscale building blocks. Novel assembly technologies enable fabrication of engineered tissue constructs with controlled properties including tunable microarchitectural and predefined compositional features. Recent advances in micro- and nano-scale technologies have enabled engineering of microgel based three dimensional (3D) constructs. There is a need for high-throughput and scalable methods to assemble microscale units with a complex 3D micro-architecture. Emerging assembly methods include novel technologies based on microfluidics, acoustic and magnetic fields, nanotextured surfaces, and surface tension. In this review, we survey emerging microscale hydrogel assembly methods offering rapid, scalable microgel assembly in 3D, and provide future perspectives and discuss potential applications.
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Affiliation(s)
- Umut Atakan Gurkan
- Bio-Acoustic MEMS in Medicine (BAMM) Laboratory Center for Bioengineering Brigham and Women's Hospital Harvard Medical School Boston, MA 02115, USA
| | - Savas Tasoglu
- Bio-Acoustic MEMS in Medicine (BAMM) Laboratory Center for Bioengineering Brigham and Women's Hospital Harvard Medical School Boston, MA 02115, USA
| | - Doga Kavaz
- Bio-Acoustic MEMS in Medicine (BAMM) Laboratory Center for Bioengineering Brigham and Women's Hospital Harvard Medical School Boston, MA 02115, USA
| | - Melik C Demirel
- Materials Research Institute Pennsylvania State University University Park, PA 16802, USA
| | - Utkan Demirci
- Bio-Acoustic MEMS in Medicine (BAMM) Laboratory Center for Bioengineering Brigham and Women's Hospital Harvard Medical School Boston, MA 02115, USA
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PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 2012; 161:505-22. [PMID: 22353619 DOI: 10.1016/j.jconrel.2012.01.043] [Citation(s) in RCA: 2386] [Impact Index Per Article: 183.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 01/27/2012] [Accepted: 01/30/2012] [Indexed: 02/06/2023]
Abstract
Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully developed biodegradable polymers. Among the different polymers developed to formulate polymeric nanoparticles, PLGA has attracted considerable attention due to its attractive properties: (i) biodegradability and biocompatibility, (ii) FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, (iii) well described formulations and methods of production adapted to various types of drugs e.g. hydrophilic or hydrophobic small molecules or macromolecules, (iv) protection of drug from degradation, (v) possibility of sustained release, (vi) possibility to modify surface properties to provide stealthness and/or better interaction with biological materials and (vii) possibility to target nanoparticles to specific organs or cells. This review presents why PLGA has been chosen to design nanoparticles as drug delivery systems in various biomedical applications such as vaccination, cancer, inflammation and other diseases. This review focuses on the understanding of specific characteristics exploited by PLGA-based nanoparticles to target a specific organ or tissue or specific cells.
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Zou Y, Brooks JL, Talwalkar V, Milbrandt TA, Puleo DA. Development of an injectable two-phase drug delivery system for sequential release of antiresorptive and osteogenic drugs. J Biomed Mater Res B Appl Biomater 2011; 100:155-62. [DOI: 10.1002/jbm.b.31933] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2011] [Revised: 05/25/2011] [Accepted: 06/25/2011] [Indexed: 01/06/2023]
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Henson F, Getgood A. The use of scaffolds in musculoskeletal tissue engineering. Open Orthop J 2011; 5 Suppl 2:261-6. [PMID: 21886690 PMCID: PMC3149868 DOI: 10.2174/1874325001105010261] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Revised: 04/16/2011] [Accepted: 04/24/2011] [Indexed: 12/19/2022] Open
Abstract
The use of bioengineering scaffolds remains an integral part of the tissue engineering concept. A significant amount of basic science and clinical research has been focused on the regeneration of musculoskeletal tissues including bone, articular cartilage, meniscus, ligament and tendon. This review aims to provide the reader with a summary of the principals of using material scaffolds in musculoskeletal tissue engineering applications and how these materials may eventually come to be incorporated in clinical practice.
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Affiliation(s)
- Frances Henson
- Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, UK
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