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Ehlen Q, Costello JP, Mirsky NA, Slavin BV, Parra M, Ptashnik A, Nayak VV, Coelho PG, Witek L. Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review. ACS Biomater Sci Eng 2024; 10:7314-7336. [PMID: 39527574 PMCID: PMC11632667 DOI: 10.1021/acsbiomaterials.4c01279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 10/18/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024]
Abstract
Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.
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Affiliation(s)
- Quinn
T. Ehlen
- University
of Miami Miller School of Medicine, Miami, Florida 33136, United States
| | - Joseph P. Costello
- University
of Miami Miller School of Medicine, Miami, Florida 33136, United States
| | - Nicholas A. Mirsky
- University
of Miami Miller School of Medicine, Miami, Florida 33136, United States
| | - Blaire V. Slavin
- University
of Miami Miller School of Medicine, Miami, Florida 33136, United States
| | - Marcelo Parra
- Center
of Excellence in Morphological and Surgical Studies (CEMyQ), Faculty
of Medicine, Universidad de La Frontera, Temuco 4811230, Chile
- Department
of Comprehensive Adult Dentistry, Faculty of Dentistry, Universidad de La Frontera, Temuco 4811230, Chile
| | - Albert Ptashnik
- Biomaterials
Division, NYU Dentistry, New York, New York 10010, United States
| | - Vasudev Vivekanand Nayak
- Department
of Biochemistry and Molecular Biology, University
of Miami Miller School of Medicine, Miami, Florida 33136, United States
| | - Paulo G. Coelho
- Department
of Biochemistry and Molecular Biology, University
of Miami Miller School of Medicine, Miami, Florida 33136, United States
- Division
of Plastic Surgery, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, United States
| | - Lukasz Witek
- Biomaterials
Division, NYU Dentistry, New York, New York 10010, United States
- Department
of Biomedical Engineering, NYU Tandon School
of Engineering, Brooklyn, New York 11201, United States
- Hansjörg
Wyss Department of Plastic Surgery, NYU
Grossman School of Medicine, New
York, New York 10016, United States
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Ali M, Bathaei MJ, Istif E, Karimi SNH, Beker L. Biodegradable Piezoelectric Polymers: Recent Advancements in Materials and Applications. Adv Healthc Mater 2023; 12:e2300318. [PMID: 37235849 PMCID: PMC11469082 DOI: 10.1002/adhm.202300318] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 05/21/2023] [Indexed: 05/28/2023]
Abstract
Recent materials, microfabrication, and biotechnology improvements have introduced numerous exciting bioelectronic devices based on piezoelectric materials. There is an intriguing evolution from conventional unrecyclable materials to biodegradable, green, and biocompatible functional materials. As a fundamental electromechanical coupling material in numerous applications, novel piezoelectric materials with a feature of degradability and desired electrical and mechanical properties are being developed for future wearable and implantable bioelectronics. These bioelectronics can be easily integrated with biological systems for applications, including sensing physiological signals, diagnosing medical problems, opening the blood-brain barrier, and stimulating healing or tissue growth. Therefore, the generation of piezoelectricity from natural and synthetic bioresorbable polymers has drawn great attention in the research field. Herein, the significant and recent advancements in biodegradable piezoelectric materials, including natural and synthetic polymers, their principles, advanced applications, and challenges for medical uses, are reviewed thoroughly. The degradation methods of these piezoelectric materials through in vitro and in vivo studies are also investigated. These improvements in biodegradable piezoelectric materials and microsystems could enable new applications in the biomedical field. In the end, potential research opportunities regarding the practical applications are pointed out that might be significant for new materials research.
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Affiliation(s)
- Mohsin Ali
- Department of Biomedical Sciences and EngineeringKoç UniversityRumelifeneri YoluSarıyerIstanbul34450Turkey
| | - Mohammad Javad Bathaei
- Department of Biomedical Sciences and EngineeringKoç UniversityRumelifeneri YoluSarıyerIstanbul34450Turkey
| | - Emin Istif
- Department of Mechanical EngineeringKoç UniversityRumelifeneri YoluSarıyerIstanbul34450Turkey
- Faculty of Engineering and Natural SciencesKadir Has UniversityCibaliIstanbul34083Turkey
| | - Seyed Nasir Hosseini Karimi
- Koç University Research Center for Translational Research (KUTTAM)Rumelifeneri YoluSarıyerIstanbul34450Turkey
| | - Levent Beker
- Department of Biomedical Sciences and EngineeringKoç UniversityRumelifeneri YoluSarıyerIstanbul34450Turkey
- Department of Mechanical EngineeringKoç UniversityRumelifeneri YoluSarıyerIstanbul34450Turkey
- Koç University Research Center for Translational Research (KUTTAM)Rumelifeneri YoluSarıyerIstanbul34450Turkey
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3
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Milazzo M, Fitzpatrick V, Owens CE, Carraretto IM, McKinley GH, Kaplan DL, Buehler MJ. 3D Printability of Silk/Hydroxyapatite Composites for Microprosthetic Applications. ACS Biomater Sci Eng 2023; 9:1285-1295. [PMID: 36857509 DOI: 10.1021/acsbiomaterials.2c01357] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
Micro-prosthetics requires the fabrication of mechanically robust and personalized components with sub-millimetric feature accuracy. Three-dimensional (3D) printing technologies have had a major impact on manufacturing such miniaturized devices for biomedical applications; however, biocompatibility requirements greatly constrain the choice of usable materials. Hydroxyapatite (HA) and its composites have been widely employed to fabricate bone-like structures, especially at the macroscale. In this work, we investigate the rheology, printability, and prosthetic mechanical properties of HA and HA-silk protein composites, focusing on the roles of composition and water content. We correlate key linear and nonlinear shear rheological parameters to geometric outcomes of printing and explain how silk compensates for the inherent brittleness of printed HA components. By increasing ink ductility, the inclusion of silk improves the quality of printed items through two mechanisms: (1) reducing underextrusion by lowering the required elastic modulus and, (2) reducing slumping by increasing the ink yield stress proportional to the modulus. We demonstrate that the elastic modulus and compressive strength of parts fabricated from silk-HA inks are higher than those for rheologically comparable pure-HA inks. We construct a printing map to guide the manufacturing of HA-based inks with excellent final properties, especially for use in biomedical applications for which sub-millimetric features are required.
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Affiliation(s)
- Mario Milazzo
- Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), Massachusetts Avenue 77, Cambridge, Massachusetts 02139, United States
- Department of Civil and Industrial Engineering, University of Pisa, Largo L. Lazzarino 2, 56122 Pisa, Italy
| | - Vincent Fitzpatrick
- Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States
| | - Crystal E Owens
- Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
| | - Igor M Carraretto
- Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
- Department of Energy, Politecnico di Milano, via Lambruschini 4a, 20156 Milano, MI, Italy
| | - Gareth H McKinley
- Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
| | - David L Kaplan
- Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States
| | - Markus J Buehler
- Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), Massachusetts Avenue 77, Cambridge, Massachusetts 02139, United States
- Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
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4
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Holanda FH, Ribeiro AN, Sánchez-Ortiz BL, de Souza GC, Borges SF, Ferreira AM, Florentino AC, Yoshioka SA, Moraes LS, Carvalho JCT, Ferreira IM. Anti-inflammatory potential of baicalein combined with silk fibroin protein in a zebrafish model (Danio rerio). Biotechnol Lett 2023; 45:235-253. [PMID: 36550336 PMCID: PMC9778464 DOI: 10.1007/s10529-022-03334-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/19/2022] [Accepted: 11/17/2022] [Indexed: 12/24/2022]
Abstract
Baicalein (BA) is a flavonoid with wide-ranging pharmacological activity. However, its biological evaluation is hampered by its low solubility in aqueous medium, making forms of incorporation that improve its solubility necessary. In the present study, BA was combined with a solution of silk fibroin protein (SF), a biomaterial used too as a drug carrier, to evaluate the anti-inflammatory potential of this combination, in vivo, in an experimental model, zebrafish (Danio rerio). Baicalein-silk fibroin (BASF) improved the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging rate (95%) in comparison with BA in solution. The acute toxicity study and histopathological analysis in zebrafish showed that BASF has low cytotoxic potential, except for the maxim dose of 2000 mg/kg. The use of BA in combination with SF enhanced the anti-inflammatory effect of flavonoids by inducing inflammatory peritoneal edema through carrageenan and achieved 77.6% inhibition of abdominal edema at a dose of 75 mg/kg. The results showed that the BASF, significantly increases the bioavailability and therapeutic effect of flavonoids and several results observed in this study may help in the development of new drugs.
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Affiliation(s)
- Fabrício H Holanda
- Biocatalysis and Applied Organic Synthesis Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Arlefe N Ribeiro
- Biocatalysis and Applied Organic Synthesis Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Brenda L Sánchez-Ortiz
- Drug Research Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Gisele C de Souza
- Drug Research Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Swanny F Borges
- Drug Research Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Adriana M Ferreira
- Drug Research Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Alexandro C Florentino
- Laboratório de Ictio e Genotoxidade, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Sérgio A Yoshioka
- Biochemistry and Biomaterials Laboratory, Institute of Chemistry of São Carlos, University of São Paulo, Universidade de São Paulo, São Carlos, SP, Brazil
| | - Lienne S Moraes
- Biocatalysis and Applied Organic Synthesis Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - José Carlos T Carvalho
- Drug Research Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil
| | - Irlon M Ferreira
- Biocatalysis and Applied Organic Synthesis Laboratory, Federal University of Amapá, Campus Universitário Marco Zero do Equador, Macapá, AP, Brazil.
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Nie K, Zhou S, Li H, Tian J, Shen W, Huang W. Advanced silk materials for musculoskeletal tissue regeneration. Front Bioeng Biotechnol 2023; 11:1199507. [PMID: 37200844 PMCID: PMC10185897 DOI: 10.3389/fbioe.2023.1199507] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 04/19/2023] [Indexed: 05/20/2023] Open
Abstract
Musculoskeletal diseases are the leading causes of chronic pain and physical disability, affecting millions of individuals worldwide. Over the past two decades, significant progress has been made in the field of bone and cartilage tissue engineering to combat the limitations of conventional treatments. Among various materials used in musculoskeletal tissue regeneration, silk biomaterials exhibit unique mechanical robustness, versatility, favorable biocompatibility, and tunable biodegradation rate. As silk is an easy-to-process biopolymer, silks have been reformed into various materials formats using advanced bio-fabrication technology for the design of cell niches. Silk proteins also offer active sites for chemical modifications to facilitate musculoskeletal system regeneration. With the emergence of genetic engineering techniques, silk proteins have been further optimized from the molecular level with other functional motifs to introduce new advantageous biological properties. In this review, we highlight the frontiers in engineering natural and recombinant silk biomaterials, as well as recent progress in the applications of these new silks in the field of bone and cartilage regeneration. The future potentials and challenges of silk biomaterials in musculoskeletal tissue engineering are also discussed. This review brings together perspectives from different fields and provides insight into improved musculoskeletal engineering.
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Affiliation(s)
- Kexin Nie
- Centre for Regeneration and Cell Therapy, The Zhejiang University—University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Sicheng Zhou
- Department of Orthopedics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Hu Li
- Centre for Regeneration and Cell Therapy, The Zhejiang University—University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Jingyi Tian
- Centre for Regeneration and Cell Therapy, The Zhejiang University—University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Weiliang Shen
- Department of Orthopedics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Wenwen Huang
- Centre for Regeneration and Cell Therapy, The Zhejiang University—University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
- Department of Orthopedics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Wenwen Huang,
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6
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Liu X, Yang Y, Yu H, Wang L, Sheng Y, Huang Z, Yang J, Ni Z, Shen D. Instant and Tough Adhesives for Rapid Gastric Perforation and Traumatic Pneumothorax Sealing. Adv Healthc Mater 2022; 11:e2201798. [PMID: 36148602 DOI: 10.1002/adhm.202201798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/13/2022] [Indexed: 01/28/2023]
Abstract
Hydrogel adhesives are hot spots due to their ubiquity and practical relevance. However, achieving a robust wet adhesion is still a challenge due to the preferential formation of hydrogen bonds between interfacial fluids and bulk hydrogel, as well as targeted substrates. Herein, a half-dry adhesive consisting of a silk fibroin (SF) semi-interpenetrating network and poly(acrylic acid) covalent network, which can allow a rapid liquid adsorption and repulsion process encountering a wet tissue, is reported. The remaining water enables excellent hydrogel flexibility to a dynamic surface, while the β-sheet fold endows its tough bulk strength under the peeling-off process. Notably, the wet adhesion energy versus porcine skin is 1440 J m-2 due to the combination of hydrogen bonds, electrostatic interactions, and chain entanglement derived from SF. In particular, both in vitro and in vivo outcomes indicate excellent hemostatic effects and result in incision closure of skin, artery, gastric perforation, and lung. After the first-stage closure, polyacrylic-silk fibroin adhesive (PSA) sealants can detach from the lung surface, fitting well to the healing period. By virtue of the reliable adhesion and good noncytotoxicity, PSA may be a prospective candidate for tissue sealant and drug carrier applications.
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Affiliation(s)
- Xiaowei Liu
- State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China
| | - Ying Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P. R. China
| | - Haojie Yu
- State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China
| | - Li Wang
- State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China
| | - Yan Sheng
- Department of Ophthalmology, the First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310030, P. R. China
| | - Zhikun Huang
- State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China
| | - Jian Yang
- State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China
| | - Zhipeng Ni
- State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China
| | - Di Shen
- State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China
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7
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Bucciarelli A, Motta A. Use of Bombyx mori silk fibroin in tissue engineering: From cocoons to medical devices, challenges, and future perspectives. BIOMATERIALS ADVANCES 2022; 139:212982. [PMID: 35882138 DOI: 10.1016/j.bioadv.2022.212982] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 05/26/2023]
Abstract
Silk fibroin has become a prominent material in tissue engineering (TE) over the last 20 years with almost 10,000 published works spanning in all the TE applications, from skeleton to neuronal regeneration. Fibroin is an extremely versatile biopolymer that, due to its ease of processing, has enabled the development of an entire plethora of materials whose properties and architectures can be tailored to suit target applications. Although the research and development of fibroin TE materials and devices is mature, apart from sutures, only a few medical products made of fibroin are used in the clinical routines. <40 clinical trials of Bombyx mori silk-related products have been reported by the FDA and few of them resulted in a commercialized device. In this review, after explaining the structure and properties of silk fibroin, we provide an overview of both fibroin constructs existing in the literature and fibroin devices used in clinic. Through the comparison of these two categories, we identified the burning issues faced by fibroin products during their translation to the market. Two main aspects will be considered. The first is the standardization of production processes, which leads both to the standardization of the characteristics of the issued device and the correct assessment of its failure. The second is the FDA regulations, which allow new devices to be marketed through the 510(k) clearance by demonstrating their equivalence to a commercialized medical product. The history of some fibroin medical devices will be taken as a case study. Finally, we will outline a roadmap outlining what actions we believe are needed to bring fibroin products to the market.
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Affiliation(s)
- Alessio Bucciarelli
- CNR nanotech, National Council of Research, University Campus Ecotekne, Via Monteroni, 73100 Lecce, Italy.
| | - Antonella Motta
- BIOtech research centre and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Department of Industrial Engineering, University of Trento, Via delle Regole 101, 38123 Trento, Italy.
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Tan XH, Liu L, Mitryashkin A, Wang Y, Goh JCH. Silk Fibroin as a Bioink - A Thematic Review of Functionalization Strategies for Bioprinting Applications. ACS Biomater Sci Eng 2022; 8:3242-3270. [PMID: 35786841 DOI: 10.1021/acsbiomaterials.2c00313] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Bioprinting is an emerging tissue engineering technique that has attracted the attention of researchers around the world, for its ability to create tissue constructs that recapitulate physiological function. While the technique has been receiving hype, there are still limitations to the use of bioprinting in practical applications, much of which is due to inappropriate bioink design that is unable to recapitulate complex tissue architecture. Silk fibroin (SF) is an exciting and promising bioink candidate that has been increasingly popular in bioprinting applications because of its processability, biodegradability, and biocompatibility properties. However, due to its lack of optimum gelation properties, functionalization strategies need to be employed so that SF can be effectively used in bioprinting applications. These functionalization strategies are processing methods which allow SF to be compatible with specific bioprinting techniques. Previous literature reviews of SF as a bioink mainly focus on discussing different methods to functionalize SF as a bioink, while a comprehensive review on categorizing SF functional methods according to their potential applications is missing. This paper seeks to discuss and compartmentalize the different strategies used to functionalize SF for bioprinting and categorize the strategies for each bioprinting method (namely, inkjet, extrusion, and light-based bioprinting). By compartmentalizing the various strategies for each printing method, the paper illustrates how each strategy is better suited for a target tissue application. The paper will also discuss applications of SF bioinks in regenerating various tissue types and the challenges and future trends that SF can take in its role as a bioink material.
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Affiliation(s)
- Xuan Hao Tan
- Department of Biomedical Engineering, College of Engineering and Design, National University of Singapore, 15 Kent Ridge Crescent, E7-06-03, Singapore 119276, Singapore.,Integrative Sciences and Engineering Programme, National University of Singapore, University Hall, Tan Chin Tuan Wing, #05-03, 21 Lower Kent Ridge Road, Singapore 119077, Singapore
| | - Ling Liu
- Department of Biomedical Engineering, College of Engineering and Design, National University of Singapore, 15 Kent Ridge Crescent, E7-06-03, Singapore 119276, Singapore
| | - Alexander Mitryashkin
- Department of Biomedical Engineering, College of Engineering and Design, National University of Singapore, 15 Kent Ridge Crescent, E7-06-03, Singapore 119276, Singapore
| | - Yunyun Wang
- Department of Biomedical Engineering, College of Engineering and Design, National University of Singapore, 15 Kent Ridge Crescent, E7-06-03, Singapore 119276, Singapore
| | - James Cho Hong Goh
- Department of Biomedical Engineering, College of Engineering and Design, National University of Singapore, 15 Kent Ridge Crescent, E7-06-03, Singapore 119276, Singapore.,Integrative Sciences and Engineering Programme, National University of Singapore, University Hall, Tan Chin Tuan Wing, #05-03, 21 Lower Kent Ridge Road, Singapore 119077, Singapore.,Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore 119288, Singapore
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9
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Maltseva ES, Nikolaeva VO, Savin AM, Dobryakov MY, Koshel EI, Krivoshapkin PV, Krivoshapkina EF. Fluorescent Hybrid Material Based on Natural Spider Silk and Carbon Dots for Bioapplication. ACS Biomater Sci Eng 2022; 8:3310-3319. [PMID: 35763797 DOI: 10.1021/acsbiomaterials.2c00322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Since the outcome of an operation largely depends on the quality of wound healing, it is one of the most challenging stages in surgery. Today, wound closure is mostly undertaken by means of a surgical suture. Good surgical sutures are biocompatible and biodegradable and possess excellent mechanical properties. Preferably, these sutures demonstrate optical activity for bacteria detection as there is a risk of surgical site infections. In this study, a solution, which fulfills all the requirements for manufacturing a multifunctional hybrid material, is proposed. In this work, a method for the in situ modification of spider silk with fluorescent carbon dots has been developed. The basic concept is the use of silk fibers as both the main framework for tissue regeneration and a carbon source during carbon dot synthesis. The resulting hybrid material exhibits strong photoluminescence in the red region of the spectrum (590 nm) when irradiated with blue light (480 nm). The proposed approach potentially allows for simultaneous wound closure and pathogen detection.
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Affiliation(s)
- Elizaveta S Maltseva
- Institute of Solution Chemistry of Advanced Materials and Technologies, ITMO University, Lomonosova Street 9, Saint Petersburg 191002, Russia
| | - Valeria O Nikolaeva
- Institute of Solution Chemistry of Advanced Materials and Technologies, ITMO University, Lomonosova Street 9, Saint Petersburg 191002, Russia
| | - Artemii M Savin
- Institute of Solution Chemistry of Advanced Materials and Technologies, ITMO University, Lomonosova Street 9, Saint Petersburg 191002, Russia
| | - Mikhail Y Dobryakov
- Institute of Solution Chemistry of Advanced Materials and Technologies, ITMO University, Lomonosova Street 9, Saint Petersburg 191002, Russia
| | - Elena I Koshel
- Institute of Solution Chemistry of Advanced Materials and Technologies, ITMO University, Lomonosova Street 9, Saint Petersburg 191002, Russia
| | - Pavel V Krivoshapkin
- Institute of Solution Chemistry of Advanced Materials and Technologies, ITMO University, Lomonosova Street 9, Saint Petersburg 191002, Russia
| | - Elena F Krivoshapkina
- Institute of Solution Chemistry of Advanced Materials and Technologies, ITMO University, Lomonosova Street 9, Saint Petersburg 191002, Russia
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10
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Bibliometric Analysis of Trends in Mulberry and Silkworm Research on the Production of Silk and Its By-Products. INSECTS 2022; 13:insects13070568. [PMID: 35886744 PMCID: PMC9317361 DOI: 10.3390/insects13070568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 02/05/2023]
Abstract
Simple Summary Over the past two decades scientific research on sericulture, the agricultural activity of silk production, generated a great number of outputs in the form of articles reported and classified by one of the most well-known and used database dealing with scientific literature. This occurrence demonstrates an increasing interest in this sector especially starting from 2000s; results presented in relevant papers showed their applicability even in fields apparently not related to silk production as commonly meant, like medicine, cosmetics, and engineering. To understand how sericulture has been transcending its usual boundaries, which are its current “hotspots”, and links with other fields of study, the authors propose a text-mining based analysis of the outputs of scientific research on sericulture and silk; the final goal is to establish “quantitative” indicators for researchers, entrepreneurs, and scholars. Abstract Traditionally, sericulture is meant as the agricultural activity of silk production, from mulberry (Morus sp.pl.) cultivation to silkworm (Bombyx mori L.) rearing. The aim of the present work is to analyze the trends and outputs of scientific research on sericulture-related topics during the last two decades, from 2000 to 2020. In this work the authors propose a text-mining analysis of the titles, abstracts and keywords of scientific articles focused on sericulture and available in the SCOPUS database considering the above-mentioned period of time; from this article collection, the 100 most recurrent terms were extracted and studied in detail. The number of publications per year in sericulture-related topics increased from 87 in 2000 to 363 in 2020 (+317%). The 100 most recurrent terms were then aggregated in clusters. The analysis shows how in the last period scientific research, besides the traditional themes of sericulture, also focused on alternative products obtainable from the sericultural practice, as fruits of mulberry trees (increment of +134% of the occurrences in the last five years) and chemical compounds as antioxidants (+233% of occurrences), phenolics (+330% of occurrences) and flavonoids (+274% of occurrences). From these considerations, the authors can state how sericulture is an active and multidisciplinary research field.
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Hixon KR, Miller AN. Animal models of impaired long bone healing and tissue engineering- and cell-based in vivo interventions. J Orthop Res 2022; 40:767-778. [PMID: 35072292 DOI: 10.1002/jor.25277] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 12/05/2021] [Accepted: 01/16/2022] [Indexed: 02/04/2023]
Abstract
Bone healing after injury typically follows a systematic process and occurs spontaneously under appropriate physiological conditions. However, impaired long bone healing is still quite common and may require surgical intervention. Various complications can result in different forms of impaired bone healing including nonunion, critical-size defects, or stress fractures. While a nonunion may occur due to impaired biological signaling and/or mechanical instability, a critical-size defect exhibits extensive bone loss that will not spontaneously heal. Comparatively, a stress fracture occurs from repetitive forces and results in a non-healing crack or break in the bone. Clinical standards of treatment vary between these bone defects due to their pathological differences. The use of appropriate animal models for modeling healing defects is critical to improve current treatment methods and develop novel rescue therapies. This review provides an overview of these clinical bone healing impairments and current animal models available to study the defects in vivo. The techniques used to create these models are compared, along with the outcomes, to clarify limitations and future objectives. Finally, rescue techniques focused on tissue engineering and cell-based therapies currently applied in animal models are specifically discussed to analyze their ability to initiate healing at the defect site, providing information regarding potential future therapies. In summary, this review focuses on the current animal models of nonunion, critical-size defects, and stress fractures, as well as interventions that have been tested in vivo to provide an overview of the clinical potential and future directions for improving bone healing.
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Affiliation(s)
- Katherine R Hixon
- Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri, USA.,Thayer School of Engineering, Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA
| | - Anna N Miller
- Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri, USA
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12
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Brebels J, Mignon A. Polymer-Based Constructs for Flexor Tendon Repair: A Review. Polymers (Basel) 2022; 14:867. [PMID: 35267690 PMCID: PMC8912457 DOI: 10.3390/polym14050867] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/15/2022] [Accepted: 02/20/2022] [Indexed: 02/04/2023] Open
Abstract
A flexor tendon injury is acquired fast and is common for athletes, construction workers, and military personnel among others, treated in the emergency department. However, the healing of injured flexor tendons is stretched over a long period of up to 12 weeks, therefore, remaining a significant clinical problem. Postoperative complications, arising after traditional tendon repair strategies, include adhesion and tendon scar tissue formation, insufficient mechanical strength for early active mobilization, and infections. Various researchers have tried to develop innovative strategies for developing a polymer-based construct that minimalizes these postoperative complications, yet none are routinely used in clinical practice. Understanding the role such constructs play in tendon repair should enable a more targeted approach. This review mainly describes the polymer-based constructs that show promising results in solving these complications, in the hope that one day these will be used as a routine practice in flexor tendon repair, increasing the well-being of the patients. In addition, the review also focuses on the incorporation of active compounds in these constructs, to provide an enhanced healing environment for the flexor tendon.
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Affiliation(s)
| | - Arn Mignon
- Surface and Interface Engineered Materials, Campus Group T, KU Leuven, Andreas Vesaliusstraat 13, 3000 Leuven, Belgium;
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13
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Hussain A, Rafeeq H, Afsheen N, Jabeen Z, Bilal M, Iqbal HMN. Urease-Based Biocatalytic Platforms―A Modern View of a Classic Enzyme with Applied Perspectives. Catal Letters 2022; 152:414-437. [DOI: 10.1007/s10562-021-03647-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/02/2021] [Indexed: 02/08/2023]
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Guo L, Liang Z, Yang L, Du W, Yu T, Tang H, Li C, Qiu H. The role of natural polymers in bone tissue engineering. J Control Release 2021; 338:571-582. [PMID: 34481026 DOI: 10.1016/j.jconrel.2021.08.055] [Citation(s) in RCA: 171] [Impact Index Per Article: 42.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 12/31/2022]
Abstract
Bone is a dynamic self-healing organ and a continuous remodeling ensures the restoration of the bone structure and function over time. However, bone remodeling is not able to repair large traumatic injuries. Therefore, surgical interventions and bone substitutes are required. The aim of bone tissue engineering is to repair and regenerate tissues and engineered a bone graft as a bone substitute. To met this goal, several natural or synthetic polymers have been used to develop a biocompatible and biodegradable polymeric construct. Among the polymers, natural polymers have higher biocompatibility, excellent biodegradability, and no toxicity. So far, collagen, chitosan, gelatin, silk fibroin, alginate, cellulose, and starch, alone or in combination, have been widely used in bone tissue engineering. These polymers have been used as scaffolds, hydrogels, and micro-nanospheres. The functionalization of the polymer with growth factors and bioactive glasses increases the potential use of polymers for bone regeneration. As bone is a dynamic highly vascularized tissue, the vascularization of the polymeric scaffolds is vital for successful bone regeneration. Several in vivo and in vitro strategies have been used to vascularize the polymeric scaffolds. In this review, the application of the most commonly used natural polymers is discussed.
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Affiliation(s)
- Linqi Guo
- Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, China
| | - Zhihui Liang
- Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154000, China
| | - Liang Yang
- Department of Orthopaedics, The People's Hospital of Daqing, Daqing 163000, China
| | - Wenyan Du
- Department of Orthopaedics, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, China
| | - Tao Yu
- Department of Orthopaedics, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, China
| | - Huayu Tang
- Department of Orthopaedics, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, China
| | - Changde Li
- Department of Orthopaedics, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, China
| | - Hongbin Qiu
- Department of Public Health, Jiamusi University, Jiamusi, 154000, China.
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15
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Troy E, Tilbury MA, Power AM, Wall JG. Nature-Based Biomaterials and Their Application in Biomedicine. Polymers (Basel) 2021; 13:3321. [PMID: 34641137 PMCID: PMC8513057 DOI: 10.3390/polym13193321] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/09/2021] [Accepted: 09/17/2021] [Indexed: 02/07/2023] Open
Abstract
Natural polymers, based on proteins or polysaccharides, have attracted increasing interest in recent years due to their broad potential uses in biomedicine. The chemical stability, structural versatility, biocompatibility and high availability of these materials lend them to diverse applications in areas such as tissue engineering, drug delivery and wound healing. Biomaterials purified from animal or plant sources have also been engineered to improve their structural properties or promote interactions with surrounding cells and tissues for improved in vivo performance, leading to novel applications as implantable devices, in controlled drug release and as surface coatings. This review describes biomaterials derived from and inspired by natural proteins and polysaccharides and highlights their promise across diverse biomedical fields. We outline current therapeutic applications of these nature-based materials and consider expected future developments in identifying and utilising innovative biomaterials in new biomedical applications.
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Affiliation(s)
- Eoin Troy
- Microbiology, College of Science and Engineering, National University of Ireland, NUI Galway, H91 TK33 Galway, Ireland; (E.T.); (M.A.T.)
| | - Maura A. Tilbury
- Microbiology, College of Science and Engineering, National University of Ireland, NUI Galway, H91 TK33 Galway, Ireland; (E.T.); (M.A.T.)
- SFI Centre for Medical Devices (CÚRAM), NUI Galway, H91 TK33 Galway, Ireland
| | - Anne Marie Power
- Zoology, School of Natural Sciences, NUI Galway, H91 TK33 Galway, Ireland;
| | - J. Gerard Wall
- Microbiology, College of Science and Engineering, National University of Ireland, NUI Galway, H91 TK33 Galway, Ireland; (E.T.); (M.A.T.)
- SFI Centre for Medical Devices (CÚRAM), NUI Galway, H91 TK33 Galway, Ireland
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Fitzpatrick V, Martín-Moldes Z, Deck A, Torres-Sanchez R, Valat A, Cairns D, Li C, Kaplan DL. Functionalized 3D-printed silk-hydroxyapatite scaffolds for enhanced bone regeneration with innervation and vascularization. Biomaterials 2021; 276:120995. [PMID: 34256231 PMCID: PMC8408341 DOI: 10.1016/j.biomaterials.2021.120995] [Citation(s) in RCA: 105] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 06/20/2021] [Accepted: 06/24/2021] [Indexed: 02/07/2023]
Abstract
Our goal was to generate functionalized 3D-printed scaffolds for bone regeneration using silk-hydroxyapatite bone cements and osteoinductive, proangiogenic and neurotrophic growth factors or morphogens for accelerated bone formation. 3D printing was utilized to generate macroporous scaffolds with controlled geometries and architectures that promote osseointegration. We build on the knowledge that the osteoinductive factor Bone Morphogenetic Protein-2 (BMP2) can also positively impact vascularization, Vascular Endothelial Growth Factor (VEGF) can impact osteoblastic differentiation, and that Neural Growth Factor (NGF)-mediated signaling can influence bone regeneration. We assessed functions on the 3D printed construct via the osteogenic differentiation of human mesenchymal stem cells; migration and proliferation of human umbilical vein endothelial cells; and proliferation of human induced neural stem cells. The scaffolds provided mechanical properties suitable for bone and the materials were cytocompatible, osteoconductive and maintained the activity of the morphogens and cytokines. Synergistic outcomes between BMP-2, VEGF and NGF in terms of osteoblastic differentiation in vitro were identified, based on the upregulation of genes associated with osteoblastic differentiation (Runt-related transcription factor-2, Osteopontin, Bone Sialoprotein). Additional studies will be required to assess these scaffold designs in vivo. These results are expected to have a strong impact in bone regeneration in dental, oral and maxillofacial surgery.
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Affiliation(s)
- Vincent Fitzpatrick
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Zaira Martín-Moldes
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Anna Deck
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | | | - Anne Valat
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Dana Cairns
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Chunmei Li
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - David L Kaplan
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
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Li W, Sheng K, Ran Y, Zhang J, Li B, Zhu Y, Chen J, He Q, Chen X, Wang J, Jiang T, Yu X, Ye Z. Transformation of acellular dermis matrix with dicalcium phosphate into 3D porous scaffold for bone regeneration. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2021; 32:2071-2087. [PMID: 34266365 DOI: 10.1080/09205063.2021.1955817] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Animal derived biomaterials have attracted much attentions in treating large size bone defect due to their excellent biocompatibility and potent bioactivities offered by the biomacromolecules and growth factors contained in these materials. Dermis-derived matrix (ADM) has been used as skin grafts and wound dressings for decades, however its application in bone tissue engineering has been largely limited as ADM possesses a dense structure which does not support bone tissue ingrowth. Recently, we have successfully fabricated porous scaffold structure using an ADM with the aid of micronization technique. When integrated with inorganic components such as calcium phosphate, ADM could be transformed to bone graft substitutes with desirable osteogenic properties. While purified and chemically cross-linked collagen has lost its natural structure, our ADM successfully preserved natural tropocollagen structure, as well as other bioactive components. A composite scaffold was fabricated by incorporating dicalcium phosphate (DCP) microparticles into ADM microfibers and freeze-dried to form a highly porous structure. Unlike conventional ADM materials, this scaffold possesses high porosity with interconnected pores. More importantly, our evaluation data demonstrated that it performed much more effective in treating critical bone defects in comparison with best commercial product on the market. In a head-to-head comparison with a commercial bone graft material Bongold®, the ADM/DCP scaffold showed superior osteogenic capacity by filling the defect with well-organized new bone tissue in a rabbit radius segmental defect model. Put together, our results exhibited a novel bone graft substitute was developed by circumventing processing barriers associated with natural ADM, which offers another novel bone graft substitute for bone regeneration.
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Affiliation(s)
- Weixu Li
- Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Orthopedics Research Institute, Zhejiang University, Hangzhou, Zhejiang, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, PR China
| | - Kunkun Sheng
- Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Orthopedics Research Institute, Zhejiang University, Hangzhou, Zhejiang, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, PR China
| | - Yongfeng Ran
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Jingyi Zhang
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Bo Li
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Yuqing Zhu
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Jiayu Chen
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Qianhong He
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Xin Chen
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Jianwei Wang
- Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Orthopedics Research Institute, Zhejiang University, Hangzhou, Zhejiang, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, PR China
| | - Tao Jiang
- Hangzhou Huamai Medical Device Co., Ltd., Hangzhou, Zhejiang, PR China
| | - Xiaohua Yu
- Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Orthopedics Research Institute, Zhejiang University, Hangzhou, Zhejiang, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, PR China
| | - Zhaoming Ye
- Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Orthopedics Research Institute, Zhejiang University, Hangzhou, Zhejiang, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, PR China
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18
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Wehrle E, Tourolle Né Betts DC, Kuhn GA, Floreani E, Nambiar MH, Schroeder BJ, Hofmann S, Müller R. Spatio-temporal characterization of fracture healing patterns and assessment of biomaterials by time-lapsed in vivo micro-computed tomography. Sci Rep 2021; 11:8660. [PMID: 33883593 PMCID: PMC8060377 DOI: 10.1038/s41598-021-87788-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 03/30/2021] [Indexed: 01/29/2023] Open
Abstract
Thorough preclinical evaluation of functionalized biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of functionalized biomaterials using collagen and bone morphogenetic protein (BMP-2). Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of functionalized biomaterials. This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of functionalized biomaterials.
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Affiliation(s)
- Esther Wehrle
- Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland
| | | | - Gisela A Kuhn
- Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland
| | - Erica Floreani
- Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland
| | - Malavika H Nambiar
- Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland
| | - Bryant J Schroeder
- Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland
| | - Sandra Hofmann
- Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland
- Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands
| | - Ralph Müller
- Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland.
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Barik A, Ray SK, Byram PK, Sinha R, Chakravorty N. Extensive early mineralization of pre-osteoblasts, inhibition of osteoclastogenesis and faster peri-implant bone healing in osteoporotic rat model: principle effectiveness of bone-specific delivery of Tibolone as evaluated in vitro and in vivo. ACTA ACUST UNITED AC 2020; 15:064102. [PMID: 33226007 DOI: 10.1088/1748-605x/abb12b] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.
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Affiliation(s)
- Anwesha Barik
- School of Medical science and Technology, IIT Kharagpur, Kharagpur, West Bengal Pin code-721302, India
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Silk fibroin as a natural polymeric based bio-material for tissue engineering and drug delivery systems-A review. Int J Biol Macromol 2020; 163:2145-2161. [DOI: 10.1016/j.ijbiomac.2020.09.057] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/06/2020] [Accepted: 09/09/2020] [Indexed: 12/13/2022]
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Li H, Zhang J, Liu S, Yan Y, Li X. Consecutive dephosphorylation by alkaline phosphatase-directed in situ formation of porous hydrogels of SF with nanocrystalline calcium phosphate ceramics for bone regeneration. J Mater Chem B 2020; 8:9043-9051. [PMID: 32955073 DOI: 10.1039/d0tb01777a] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Alkaline phosphatase, as an enzyme involved in the process of bone mineralization and regeneration, was incorporated into a solution of SF to induce its gelation and mineralization through consecutive dephosphorylation actions on different substrates. In these processes, alkaline phosphatase firstly worked on a small peptide of NapGFFYp by removing its hydrophilic phosphate group. The resulted NapGFFY performed supramolecular assembly in the solution of SF and synergistically induced the conformation transition of SF from random coil to β-sheet structures, leading to the formation of a stable SF hydrogel under physiological conditions. And then, the entrapped ALP within the SF-NY gel network retained its catalytic activity, released phosphate ions from glycerophosphate, and catalysed the formation of calcium phosphate minerals within the porous gel. Because of the mild conditions of these processes and good biocompatibility of the scaffold, the mineralized SF gel can work as a biomimetic scaffold to promote the osteogenic differentiation of rBMSCs and stimulate femoral defect regeneration in a rat model.
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Affiliation(s)
- Hang Li
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.
| | - Jikun Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.
| | - Shengnan Liu
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.
| | - Yufei Yan
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. and Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China
| | - Xinming Li
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.
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22
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Tandon S, Kandasubramanian B, Ibrahim SM. Silk-Based Composite Scaffolds for Tissue Engineering Applications. Ind Eng Chem Res 2020. [DOI: 10.1021/acs.iecr.0c02195] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Saloni Tandon
- Biotechnology Lab, Center for Converging Technologies, University of Rajasthan, JLN Marg, Jaipur-302004, Rajasthan, India
| | - Balasubramanian Kandasubramanian
- Nano Surface Texturing Lab, Department of Metallurgical and Materials Engineering, Defence Institute of Advanced Technology (DU), Girinagar, Pune-411025, Maharashtra, India
| | - Sobhy M. Ibrahim
- Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
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23
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Wang S, Zhang L, Chen W, Jin H, Zhang Y, Wu L, Shao H, Fang Z, He X, Zheng S, Cao CY, Wong HM, Li Q. Rapid regeneration of enamel-like-oriented inorganic crystals by using rotary evaporation. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 115:111141. [PMID: 32600729 DOI: 10.1016/j.msec.2020.111141] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 05/20/2020] [Accepted: 05/28/2020] [Indexed: 10/24/2022]
Abstract
Enamel, the hardest tissue in the human body, has excellent mechanical properties, mainly due to its highly ordered spatial structure. Fabricating enamel-like structure is still a challenge today. In this work, a simple and highly efficient method was introduced, using the silk fibroin as a template to regulate calcium- and phosphate- supersaturated solution to regenerate enamel-like hydroxyapatite crystals on various substrates (enamel, dentin, titanium, and polyethylene) under rotary evaporation. The enamel-like zinc oxide nanorod array structure was also successfully synthesized using the aforementioned method. This strategy provides a new approach to design and fabricate mineral crystals with particular orientation coatings for materials.
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Affiliation(s)
- Shengrui Wang
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Le Zhang
- Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, The Prince Philip Dental Hospital, Hong Kong 999077, China
| | - Wendy Chen
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Huimin Jin
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Ya Zhang
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Leping Wu
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Hui Shao
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Zehui Fang
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Xiaoxue He
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Shunli Zheng
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Chris Ying Cao
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China
| | - Hai Ming Wong
- Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, The Prince Philip Dental Hospital, Hong Kong 999077, China.
| | - Quanli Li
- Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei 230032, China.
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24
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Hydrogen sulfide-releasing silk fibroin scaffold for bone tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 102:471-482. [DOI: 10.1016/j.msec.2019.04.039] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 03/20/2019] [Accepted: 04/12/2019] [Indexed: 02/07/2023]
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25
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Silk: A Promising Biomaterial Opening New Vistas Towards Affordable Healthcare Solutions. J Indian Inst Sci 2019. [DOI: 10.1007/s41745-019-00114-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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26
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Eswaramoorthy SD, Dhiman N, Korra G, Oranges CM, Schaefer DJ, Rath SN, Madduri S. Isogenic-induced endothelial cells enhance osteogenic differentiation of mesenchymal stem cells on silk fibroin scaffold. Regen Med 2019; 14:647-661. [DOI: 10.2217/rme-2018-0166] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aim: We investigated the role of induced endothelial cells (iECs) in mesenchymal stem cells (MSCs)/iECs co-culture and assessed their osteogenic ability on silk fibroin nanofiber scaffolds. Methods: The osteogenic differentiation was assessed by the ALP assay, calcium assay and gene expression studies. Results: The osteogenic differentiation of the iECs co-cultures was found to be higher than the MSCs group and proximal to endothelial cells (ECs) co-cultures. Furthermore, the usage of isogenic iECs for co-culture increased the osteogenic and endothelial gene expression. Conclusion: These findings suggest that iECs mimic endothelial cells when co-cultured with MSCs and that one MSCs source can be used to give rise to both MSCs and iECs. The isogenic MSCs/iECs co-culture provides a new option for bone tissue engineering applications.
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Affiliation(s)
- Sindhuja D Eswaramoorthy
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, 502285 Telangana, India
| | - Nandini Dhiman
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, 502285 Telangana, India
| | - Gayathri Korra
- Sri Sai Krishna Multi Specialty Hospital, Department of Obstetrics and Gynecology, Sangareddy 502001, Medak, Telangana, India
| | - Carlo M Oranges
- Department of Plastic, Reconstructive, Aesthetic & Hand Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Dirk J Schaefer
- Department of Plastic, Reconstructive, Aesthetic & Hand Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Subha N Rath
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, 502285 Telangana, India
| | - Srinivas Madduri
- Department of Plastic, Reconstructive, Aesthetic & Hand Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
- Department of Biomedicine, University of Basel, CH-4031 Basel, Switzerland
- Department of Biomedical Engineering, University of Basel, CH-4123 Allschwil, Switzerland
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27
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Eswaramoorthy SD, Ramakrishna S, Rath SN. Recent advances in three-dimensional bioprinting of stem cells. J Tissue Eng Regen Med 2019; 13:908-924. [PMID: 30866145 DOI: 10.1002/term.2839] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 02/01/2019] [Accepted: 02/21/2019] [Indexed: 12/29/2022]
Abstract
In spite of being a new field, three-dimensional (3D) bioprinting has undergone rapid growth in the recent years. Bioprinting methods offer a unique opportunity for stem cell distribution, positioning, and differentiation at the microscale to make the differentiated architecture of any tissue while maintaining precision and control over the cellular microenvironment. Bioprinting introduces a wide array of approaches to modify stem cell fate. This review discusses these methodologies of 3D bioprinting stem cells. Fabricating a fully operational tissue or organ construct with a long life will be the most significant challenge of 3D bioprinting. Once this is achieved, a whole human organ can be fabricated for the defect place at the site of surgery.
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Affiliation(s)
- Sindhuja D Eswaramoorthy
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad (IITH), Sangareddy, Telangana, India
| | - Seeram Ramakrishna
- Centre for Nanofibers & Nanotechnology, NUS Nanoscience & Nanotechnology Initiative, Singapore
| | - Subha N Rath
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad (IITH), Sangareddy, Telangana, India
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28
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Hang Y, Ma J, Li S, Zhang X, Liu B, Ding Z, Lu Q, Chen H, Kaplan DL. Structure–Chemical Modification Relationships with Silk Materials. ACS Biomater Sci Eng 2019; 5:2762-2768. [DOI: 10.1021/acsbiomaterials.9b00369] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Yingjie Hang
- College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People’s Republic of China
| | - Jie Ma
- Department of Burns, Gansu Provincial Hospital, Lanzhou 730000, People’s Republic of China
| | - Siyuan Li
- College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People’s Republic of China
| | - Xiaoyi Zhang
- National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, People’s Republic of China
| | - Bing Liu
- College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People’s Republic of China
| | - Zhaozhao Ding
- National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, People’s Republic of China
| | - Qiang Lu
- College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People’s Republic of China
- National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, People’s Republic of China
| | - Hong Chen
- College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People’s Republic of China
| | - David L Kaplan
- Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States
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29
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Chorsi MT, Curry EJ, Chorsi HT, Das R, Baroody J, Purohit PK, Ilies H, Nguyen TD. Piezoelectric Biomaterials for Sensors and Actuators. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2019; 31:e1802084. [PMID: 30294947 DOI: 10.1002/adma.201802084] [Citation(s) in RCA: 290] [Impact Index Per Article: 48.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 07/01/2018] [Indexed: 05/20/2023]
Abstract
Recent advances in materials, manufacturing, biotechnology, and microelectromechanical systems (MEMS) have fostered many exciting biosensors and bioactuators that are based on biocompatible piezoelectric materials. These biodevices can be safely integrated with biological systems for applications such as sensing biological forces, stimulating tissue growth and healing, as well as diagnosing medical problems. Herein, the principles, applications, future opportunities, and challenges of piezoelectric biomaterials for medical uses are reviewed thoroughly. Modern piezoelectric biosensors/bioactuators are developed with new materials and advanced methods in microfabrication/encapsulation to avoid the toxicity of conventional lead-based piezoelectric materials. Intriguingly, some piezoelectric materials are biodegradable in nature, which eliminates the need for invasive implant extraction. Together, these advancements in the field of piezoelectric materials and microsystems can spark a new age in the field of medicine.
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Affiliation(s)
- Meysam T Chorsi
- Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA
| | - Eli J Curry
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA
| | - Hamid T Chorsi
- Department of Electrical & Computer Engineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA
| | - Ritopa Das
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA
| | - Jeffrey Baroody
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA
| | - Prashant K Purohit
- Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Horea Ilies
- Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA
| | - Thanh D Nguyen
- Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA
- Institute of Materials Science, University of Connecticut, Storrs, CT, 06269, USA
- Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT, 06030, USA
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30
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Rufaihah AJ, Cheyyatraivendran S, Mazlan MDM, Lim K, Chong MSK, Mattar CNZ, Chan JKY, Kofidis T, Seliktar D. The Effect of Scaffold Modulus on the Morphology and Remodeling of Fetal Mesenchymal Stem Cells. Front Physiol 2018; 9:1555. [PMID: 30622472 PMCID: PMC6308149 DOI: 10.3389/fphys.2018.01555] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 10/17/2018] [Indexed: 12/17/2022] Open
Abstract
Hydrogel materials have been successfully used as matrices to explore the role of biophysical and biochemical stimuli in directing stem cell behavior. Here, we present our findings on the role of modulus in guiding bone marrow fetal mesenchymal stem cell (BMfMSC) fate determination using semi-synthetic hydrogels made from PEG-fibrinogen (PF). The BMfMSCs were cultivated in the PF for up to 2 weeks to study the influence of matrix modulus (i.e., cross-linking density of the PF) on BMfMSC survival, morphology and integrin expression. Both two-dimensional (2D) and three-dimensional (3D) culture conditions were employed to examine the BMfMSCs as single cells or as cell spheroids. The hydrogel modulus affected the rate of BMfMSC metabolic activity, the integrin expression levels and the cell morphology, both as single cells and as spheroids. The cell seeding density was also found to be an important parameter of the system in that high densities were favorable in facilitating more cell-to-cell contacts that favored higher metabolic activity. Our findings provide important insight about design of a hydrogel scaffold that can be used to optimize the biological response of BMfMSCs for various tissue engineering applications.
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Affiliation(s)
- Abdul Jalil Rufaihah
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Suganya Cheyyatraivendran
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Muhammad Danial Mohd Mazlan
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kenrich Lim
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Mark Seow Khoon Chong
- Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore
| | | | - Jerry Kok Yen Chan
- Department of Obstretics and Gynaecology, National University of Singapore, Singapore, Singapore
| | - Theodoros Kofidis
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Cardiac, Thoracic and Vascular Surgery, National University Heart Centre Singapore, National University Health System, Singapore, Singapore
| | - Dror Seliktar
- Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore, Singapore.,Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
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31
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Wang Q, Zhao G, Xing Z, Zhan J, Ma J. Comparative evaluation of the osteogenic capacity of human mesenchymal stem cells from bone marrow and umbilical cord tissue. Exp Ther Med 2018; 17:764-772. [PMID: 30651861 DOI: 10.3892/etm.2018.6975] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 09/27/2018] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have been extensively investigated in the field of regenerative medicine. Human bone MSCs (BMSCs) have become a common type of seed cell for bone tissue engineering. However, the viability and cell number of BMSCs are negatively correlated with donor age, and as the extraction process is painful, this method has not been widely used. As human umbilical cord MSCs (UCMSCs) may be harvested inexpensively and inexhaustibly, the present study evaluated and compared the regenerative potential of UCMSCs and BMSCs to determine whether UCMSCs may be used as a novel cell type for bone regeneration. In the present study, the proliferation and osteogenic capacity of BMSCs and UCMSCs was compared in vitro. BMSCs and UCMSCs were respectively combined with biofunctionalized macroporous calcium phosphate cement, and their bone regenerative potentials were determined by investigating their capacity for ectopic bone formation in a nude mouse model as well as their efficacy in a rat model of tibia bone defect. The extent of bone regeneration was examined by X-ray, histological and immunohistochemical analyses. The results revealed that UCMSCs exhibited a good osteogenic differentiation potential, similarly to that of BMSCs, and that UCMSCs were able to contribute to the regeneration of bone and blood vessels. Furthermore, no significant differences were identified between BMSCs and UCMSCs in terms of their bone regenerative effect.
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Affiliation(s)
- Qian Wang
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Gang Zhao
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Zijun Xing
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Juming Zhan
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Jie Ma
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
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32
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Bhattarai DP, Aguilar LE, Park CH, Kim CS. A Review on Properties of Natural and Synthetic Based Electrospun Fibrous Materials for Bone Tissue Engineering. MEMBRANES 2018; 8:E62. [PMID: 30110968 PMCID: PMC6160934 DOI: 10.3390/membranes8030062] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 07/27/2018] [Accepted: 08/09/2018] [Indexed: 12/17/2022]
Abstract
Bone tissue engineering is an interdisciplinary field where the principles of engineering are applied on bone-related biochemical reactions. Scaffolds, cells, growth factors, and their interrelation in microenvironment are the major concerns in bone tissue engineering. Among many alternatives, electrospinning is a promising and versatile technique that is used to fabricate polymer fibrous scaffolds for bone tissue engineering applications. Copolymerization and polymer blending is a promising strategic way in purpose of getting synergistic and additive effect achieved from either polymer. In this review, we summarize the basic chemistry of bone, principle of electrospinning, and polymers that are used in bone tissue engineering. Particular attention will be given on biomechanical properties and biological activities of these electrospun fibers. This review will cover the fundamental basis of cell adhesion, differentiation, and proliferation of the electrospun fibers in bone tissue scaffolds. In the last section, we offer the current development and future perspectives on the use of electrospun mats in bone tissue engineering.
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Affiliation(s)
- Deval Prasad Bhattarai
- Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756, Korea.
- Department of Chemistry, Amrit Campus, Tribhuvan University, Kathmandu 44613, Nepal.
| | - Ludwig Erik Aguilar
- Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756, Korea.
| | - Chan Hee Park
- Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756, Korea.
- Division of Mechanical Design Engineering, Chonbuk National University, Jeonju 561-756, Korea.
| | - Cheol Sang Kim
- Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756, Korea.
- Division of Mechanical Design Engineering, Chonbuk National University, Jeonju 561-756, Korea.
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33
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Midha S, Kumar S, Sharma A, Kaur K, Shi X, Naruphontjirakul P, Jones JR, Ghosh S. Silk fibroin-bioactive glass based advanced biomaterials: towards patient-specific bone grafts. Biomed Mater 2018; 13:055012. [DOI: 10.1088/1748-605x/aad2a9] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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34
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Ma D, Wang Y, Dai W. Silk fibroin-based biomaterials for musculoskeletal tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2018; 89:456-469. [DOI: 10.1016/j.msec.2018.04.062] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 02/22/2018] [Accepted: 04/19/2018] [Indexed: 12/16/2022]
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35
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Choi JH, Jeon H, Song JE, Oliveira JM, Reis RL, Khang G. Biofunctionalized Lysophosphatidic Acid/Silk Fibroin Film for Cornea Endothelial Cell Regeneration. NANOMATERIALS 2018; 8:nano8050290. [PMID: 29710848 PMCID: PMC5977304 DOI: 10.3390/nano8050290] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/25/2018] [Accepted: 04/25/2018] [Indexed: 11/25/2022]
Abstract
Cornea endothelial cells (CEnCs) tissue engineering is a great challenge to repair diseased or damaged CEnCs and require an appropriate biomaterial to support cell proliferation and differentiation. Biomaterials for CEnCs tissue engineering require biocompatibility, tunable biodegradability, transparency, and suitable mechanical properties. Silk fibroin-based film (SF) is known to meet these factors, but construction of functionalized graft for bioengineering of cornea is still a challenge. Herein, lysophosphatidic acid (LPA) is used to maintain and increase the specific function of CEnCs. The LPA and SF composite film (LPA/SF) was fabricated in this study. Mechanical properties and in vitro studies were performed using a rabbit model to demonstrate the characters of LPA/SF. ATR-FTIR was characterized to identify chemical composition of the films. The morphological and physical properties were performed by SEM, AFM, transparency, and contact angle. Initial cell density and MTT were performed for adhesion and cell viability in the SF and LPA/SF film. Reverse transcription polymerase chain reactions (RT-PCR) and immunofluorescence were performed to examine gene and protein expression. The results showed that films were designed appropriately for CEnCs delivery. Compared to pristine SF, LPA/SF showed higher biocompatibility, cell viability, and expression of CEnCs specific genes and proteins. These indicate that LPA/SF, a new biomaterial, offers potential benefits for CEnCs tissue engineering for regeneration.
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Affiliation(s)
- Joo Hee Choi
- Department of BIN Convergence Technology, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
- Department of Polymer Nano Science & Technology and Polymer BIN Research Center, Chonbuk National University, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
| | - Hayan Jeon
- Department of BIN Convergence Technology, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
- Department of Polymer Nano Science & Technology and Polymer BIN Research Center, Chonbuk National University, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
| | - Jeong Eun Song
- Department of BIN Convergence Technology, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
- Department of Polymer Nano Science & Technology and Polymer BIN Research Center, Chonbuk National University, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
| | - Joaquim Miguel Oliveira
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark-Parque de Ciência e Tecnologia, Zona Industrial de Gandra, 4805-017 Barco, Guimarães, Portugal.
- ICVS/3B's-PT Government Associated Laboratory, Braga/Guimarães, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal.
| | - Rui Luis Reis
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark-Parque de Ciência e Tecnologia, Zona Industrial de Gandra, 4805-017 Barco, Guimarães, Portugal.
- ICVS/3B's-PT Government Associated Laboratory, Braga/Guimarães, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal.
| | - Gilson Khang
- Department of BIN Convergence Technology, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
- Department of Polymer Nano Science & Technology and Polymer BIN Research Center, Chonbuk National University, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
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36
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Cheng B, Yan Y, Qi J, Deng L, Shao ZW, Zhang KQ, Li B, Sun Z, Li X. Cooperative Assembly of a Peptide Gelator and Silk Fibroin Afford an Injectable Hydrogel for Tissue Engineering. ACS APPLIED MATERIALS & INTERFACES 2018; 10:12474-12484. [PMID: 29584396 DOI: 10.1021/acsami.8b01725] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Silk fibroin (SF) from Bombyx mori has received increasing interest in biomedical fields, because of its slow biodegradability, good biocompatibility, and low immunogenicity. Although SF-based hydrogels have been studied intensively as a potential matrix for tissue engineering, weak gelation performance and low mechanical strength are major limitations that hamper their widespread applicability. Therefore, searching for new strategies to improve the SF gelation property is highly desirable in tissue engineering research. Herein, we report a facile approach to induce rapid gelation of SF by a small peptide gelator (e.g., NapFF). Following the simple mixing of SF and NapFF in water, a stable hydrogel of SF was obtained in a short time period at physiological pH, and the minimum gelation concentration of SF can reach as low as 0.1%. In this process of gelation, NapFF not only can behave itself as a gelator for supramolecular self-assembly, but also can trigger the conformational transition of the SF molecule from random coil to β-sheet structure via hydrophobic and hydrogen-bonding interactions. More importantly, for the generation of a scaffold with favorable cell-surface interactions, a new peptide gelator (NapFFRGD) with Arg-Gly-Asp (RGD) domain was applied to functionalize SF hydrogel with improved bioactivity for cell adhesion and growth. Following encapsulating the vascular endothelial growth factor (VEGF), the SF gel was subcutaneously injected in mice, and served as an effective matrix to trigger the generation of new blood capillaries in vivo.
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Affiliation(s)
- Baochang Cheng
- College of Chemistry, Chemical Engineering and Materials Science , Soochow University , Suzhou 215123 , China
| | - Yufei Yan
- Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital , Shanghai Jiaotong University, School of Medicine , Shanghai 200025 , China
| | - Jingjing Qi
- College of Chemistry, Chemical Engineering and Materials Science , Soochow University , Suzhou 215123 , China
| | - Lianfu Deng
- Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital , Shanghai Jiaotong University, School of Medicine , Shanghai 200025 , China
| | - Zeng-Wu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical School , Huazhong University of Science and Technology , Wuhan 430022 , China
| | - Ke-Qin Zhang
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering , Soochow University , Suzhou 215123 , China
| | - Bin Li
- Department of Orthopaedics, The First Affiliated Hospital, Orthopaedic Institute , Soochow University , Suzhou 215006 , China
| | - Ziling Sun
- School of Biology and Basic Medical Science , Soochow University , Suzhou 215123 , China
| | - Xinming Li
- College of Chemistry, Chemical Engineering and Materials Science , Soochow University , Suzhou 215123 , China
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37
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Matsiko A, Thompson EM, Lloyd-Griffith C, Cunniffe GM, Vinardell T, Gleeson JP, Kelly DJ, O'Brien FJ. An endochondral ossification approach to early stage bone repair: Use of tissue-engineered hypertrophic cartilage constructs as primordial templates for weight-bearing bone repair. J Tissue Eng Regen Med 2018; 12:e2147-e2150. [PMID: 29327428 DOI: 10.1002/term.2638] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Revised: 11/18/2017] [Accepted: 01/02/2018] [Indexed: 12/20/2022]
Abstract
Mimicking endochondral ossification to engineer constructs offers a novel solution to overcoming the problems associated with poor vascularisation in bone repair. This can be achieved by harnessing the angiogenic potency of hypertrophic cartilage. In this study, we demonstrate that tissue-engineered hypertrophically primed cartilage constructs can be developed from collagen-based scaffolds cultured with mesenchymal stem cells. These constructs were subsequently implanted into femoral defects in rats. It was evident that the constructs could support enhanced early stage healing at 4 weeks of these weight-bearing femoral bone defects compared to untreated defects. This study demonstrates the value of combining knowledge of development biology and tissue engineering in a developmental engineering inspired approach to tissue repair.
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Affiliation(s)
- Amos Matsiko
- Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.,Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland
| | - Emmet M Thompson
- Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.,Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland
| | - Cai Lloyd-Griffith
- Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.,Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland
| | - Gráinne M Cunniffe
- Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland.,Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin (TCD), Dublin 2, Ireland
| | - Tatiana Vinardell
- Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland.,Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin (TCD), Dublin 2, Ireland
| | - John P Gleeson
- Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland.,SurgaColl Technologies Ltd, Invent Centre, Glasnevin, Dublin 9, Ireland
| | - Daniel J Kelly
- Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.,Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland.,Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin (TCD), Dublin 2, Ireland
| | - Fergal J O'Brien
- Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.,Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), Dublin 2, Ireland.,Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity College Dublin, Dublin 2, Ireland.,Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin (TCD), Dublin 2, Ireland
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Binsalah MA, Ramalingam S, Alkindi M, Nooh N, Al-Hezaimi K. Guided Bone Regeneration of Femoral Segmental Defects using Equine Bone Graft: An In-Vivo Micro-Computed Tomographic Study in Rats. J INVEST SURG 2018; 32:456-466. [DOI: 10.1080/08941939.2018.1441343] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Mohammed Awadh Binsalah
- Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Sundar Ramalingam
- Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alkindi
- Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Nasser Nooh
- Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Khalid Al-Hezaimi
- American Board of Periodontology & Endodontics, Riyadh Elm University, Riyadh, Saudi Arabia
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39
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Silk Fibroin-Based Scaffold for Bone Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1077:371-387. [PMID: 30357699 DOI: 10.1007/978-981-13-0947-2_20] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Regeneration of diseased or damaged skeletal tissues is one of the challenge that needs to be solved. Although there have been many bone tissue engineering developed, scaffold-based tissue engineering complement the conventional treatment for large bone by completing biological and functional environment. Among many materials, silk fibroin (SF) is one of the favorable material for applications in bone tissue engineering scaffolding. SF is a fibrous protein mainly extracted from Bombyx mori. and spiders. SF has been used as a biomaterial for bone graft by its unique mechanical properties, controllable biodegradation rate and high biocompatibility. Moreover, SF can be processed using conventional and advanced biofabrication methods to form various scaffold types such as sponges, mats, hydrogels and films. This review discusses about recent application and advancement of SF as a biomaterial.
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40
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Advances in Nanotechnologies for the Fabrication of Silk Fibroin-Based Scaffolds for Tissue Regeneration. EXTRACELLULAR MATRIX FOR TISSUE ENGINEERING AND BIOMATERIALS 2018. [DOI: 10.1007/978-3-319-77023-9_6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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41
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Bhattacharjee P, Kundu B, Naskar D, Kim HW, Maiti TK, Bhattacharya D, Kundu SC. Silk scaffolds in bone tissue engineering: An overview. Acta Biomater 2017; 63:1-17. [PMID: 28941652 DOI: 10.1016/j.actbio.2017.09.027] [Citation(s) in RCA: 187] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 08/26/2017] [Accepted: 09/19/2017] [Indexed: 12/17/2022]
Abstract
Bone tissue plays multiple roles in our day-to-day functionality. The frequency of accidental bone damage and disorder is increasing worldwide. Moreover, as the world population continues to grow, the percentage of the elderly population continues to grow, which results in an increased number of bone degenerative diseases. This increased elderly population pushes the need for artificial bone implants that specifically employ biocompatible materials. A vast body of literature is available on the use of silk in bone tissue engineering. The current work presents an overview of this literature from materials and fabrication perspective. As silk is an easy-to-process biopolymer; this allows silk-based biomaterials to be molded into diverse forms and architectures, which further affects the degradability. This makes silk-based scaffolds suitable for treating a variety of bone reconstruction and regeneration objectives. Silk surfaces offer active sites that aid the mineralization and/or bonding of bioactive molecules that facilitate bone regeneration. Silk has also been blended with a variety of polymers and minerals to enhance its advantageous properties or introduce new ones. Several successful works, both in vitro and in vivo, have been reported using silk-based scaffolds to regenerate bone tissues or other parts of the skeletal system such as cartilage and ligament. A growing trend is observed toward the use of mineralized and nanofibrous scaffolds along with the development of technology that allows to control scaffold architecture, its biodegradability and the sustained releasing property of scaffolds. Further development of silk-based scaffolds for bone tissue engineering, taking them up to and beyond the stage of human trials, is hoped to be achieved in the near future through a cross-disciplinary coalition of tissue engineers, material scientists and manufacturing engineers. STATEMENT OF SIGNIFICANCE The state-of-art of silk biomaterials in bone tissue engineering, covering their wide applications as cell scaffolding matrices to micro-nano carriers for delivering bone growth factors and therapeutic molecules to diseased or damaged sites to facilitate bone regeneration, is emphasized here. The review rationalizes that the choice of silk protein as a biomaterial is not only because of its natural polymeric nature, mechanical robustness, flexibility and wide range of cell compatibility but also because of its ability to template the growth of hydroxyapatite, the chief inorganic component of bone mineral matrix, resulting in improved osteointegration. The discussion extends to the role of inorganic ions such as Si and Ca as matrix components in combination with silk to influence bone regrowth. The effect of ions or growth factor-loaded vehicle incorporation into regenerative matrix, nanotopography is also considered.
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Dual growth factor loaded nonmulberry silk fibroin/carbon nanofiber composite 3D scaffolds for in vitro and in vivo bone regeneration. Biomaterials 2017; 136:67-85. [DOI: 10.1016/j.biomaterials.2017.05.014] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 04/24/2017] [Accepted: 05/07/2017] [Indexed: 12/19/2022]
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Panda D, Konar S, Bajpai SK, Arockiarajan A. Synthesis and viscoelastic characterization of microstructurally aligned Silk fibroin sponges. J Mech Behav Biomed Mater 2017; 71:362-371. [DOI: 10.1016/j.jmbbm.2017.03.029] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Revised: 03/24/2017] [Accepted: 03/26/2017] [Indexed: 10/19/2022]
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Lim PN, Feng J, Wang Z, Chong M, Konishi T, Tan LG, Chan J, Thian ES. In-vivo evaluation of subcutaneously implanted cell-loaded apatite microcarriers for osteogenic potency. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2017; 28:86. [PMID: 28470444 DOI: 10.1007/s10856-017-5897-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 04/22/2017] [Indexed: 06/07/2023]
Abstract
Cell-loaded apatite microcarriers present as potential scaffolds for direct in-vivo delivery of cells post-expansion to promote bone regeneration. The objective of this study was to evaluate the osteogenic potency of human foetal mesenchymal stem cells (hfMSC)-loaded apatite microcarriers when implanted subcutaneously in a mouse model. This was done by examining for ectopic bone formation at 2 weeks, 1 month and 2 months, which were intended to coincide with the inflammation, healing and remodelling phases, respectively. Three histological examinations including haematoxylin and eosin staining to examine general tissue morphology, Masson's trichrome staining to identify tissue type, and Von Kossa staining to examine extent of tissue mineralisation were performed. In addition, immunohistochemistry assay of osteopontin was conducted to confirm active bone formation by the seeded hfMSCs. Results showed a high level of tissue organisation and new bone formation, with active bone remodelling being observed at the end of 2 months, and an increase in tissue density, organisation, and mineralisation could also be observed for hfMSC-loaded apatite microcarriers. Various cell morphology resembling that of osteoblasts and osteoclasts could be seen on the surfaces of the hfMSC-loaded apatite microcarriers, with presence of woven bone tissue formation being observed at the intergranular space. These observations were consistent with evidence of ectopic bone formation, which were absent in group containing apatite microcarriers only. Overall, results suggested that hfMSC-loaded apatite microcarriers retained their osteogenic potency after implantation, and provided an effective platform for bone tissue regeneration.
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Affiliation(s)
- Poon Nian Lim
- Department of Mechanical Engineering, National University of Singapore, Singapore, 117 576, Singapore
| | - Jason Feng
- Department of Mechanical Engineering, National University of Singapore, Singapore, 117 576, Singapore
| | - Zuyong Wang
- Department of Mechanical Engineering, National University of Singapore, Singapore, 117 576, Singapore
- College of Materials Science and Engineering, Hunan University, Changsha, 410 082, China
| | - Mark Chong
- Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637 459, Singapore
| | - Toshiisa Konishi
- Department of Mechanical Engineering, National University of Singapore, Singapore, 117 576, Singapore
- Graduate School of Natural Science and Technology, Okayama University, Okayama, 700 8530, Japan
| | - Lay Geok Tan
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119 228, Singapore
| | - Jerry Chan
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119 228, Singapore
- Department of Reproductive Medicine, Division of Obstetrics & Gynaecology, KK Women's and Children's Hospital, Singapore, 229 899, Singapore
| | - Eng San Thian
- Department of Mechanical Engineering, National University of Singapore, Singapore, 117 576, Singapore.
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45
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Parekh N, Hushye C, Warunkar S, Sen Gupta S, Nisal A. In vitro study of novel microparticle based silk fibroin scaffold with osteoblast-like cells for load-bearing osteo-regenerative applications. RSC Adv 2017. [DOI: 10.1039/c7ra03288a] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Silk Fibroin microparticle scaffolds show promise in bone tissue engineering applications.
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Affiliation(s)
- Nimisha Parekh
- Polymer Science and Engineering Dept
- National Chemical Laboratory
- Pune – 411008
- India
| | | | | | - Sayam Sen Gupta
- Department of Chemical Sciences
- Indian Institute of Science and Educational Research
- Kolkata
- India
| | - Anuya Nisal
- Polymer Science and Engineering Dept
- National Chemical Laboratory
- Pune – 411008
- India
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46
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Maisani M, Pezzoli D, Chassande O, Mantovani D. Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment? J Tissue Eng 2017; 8:2041731417712073. [PMID: 28634532 PMCID: PMC5467968 DOI: 10.1177/2041731417712073] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Accepted: 04/26/2017] [Indexed: 12/16/2022] Open
Abstract
Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.
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Affiliation(s)
- Mathieu Maisani
- Laboratory for Biomaterials & Bioengineering (CRC-I), Department Min-Met-Materials Engineering & Research Center CHU de Québec, Laval University, Québec City, QC, Canada
- Laboratoire BioTis, Inserm U1026, Université de Bordeaux, Bordeaux, France
| | - Daniele Pezzoli
- Laboratory for Biomaterials & Bioengineering (CRC-I), Department Min-Met-Materials Engineering & Research Center CHU de Québec, Laval University, Québec City, QC, Canada
| | - Olivier Chassande
- Laboratoire BioTis, Inserm U1026, Université de Bordeaux, Bordeaux, France
| | - Diego Mantovani
- Laboratory for Biomaterials & Bioengineering (CRC-I), Department Min-Met-Materials Engineering & Research Center CHU de Québec, Laval University, Québec City, QC, Canada
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Tseng LF, Wang J, Baker RM, Wang G, Mather PT, Henderson JH. Osteogenic Capacity of Human Adipose-Derived Stem Cells is Preserved Following Triggering of Shape Memory Scaffolds. Tissue Eng Part A 2016; 22:1026-35. [PMID: 27401991 DOI: 10.1089/ten.tea.2016.0095] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Recent advances in shape memory polymers have enabled the study of programmable, shape-changing, cytocompatible tissue engineering scaffolds. For treatment of bone defects, scaffolds with shape memory functionality have been studied for their potential for minimally invasive delivery, conformal fitting to defect margins, and defect stabilization. However, the extent to which the osteogenic differentiation capacity of stem cells resident in shape memory scaffolds is preserved following programmed shape change has not yet been determined. As a result, the feasibility of shape memory polymer scaffolds being employed in stem cell-based treatment strategies remains unclear. To test the hypothesis that stem cell osteogenic differentiation can be preserved during and following triggering of programmed architectural changes in shape memory polymer scaffolds, human adipose-derived stem cells were seeded in shape memory polymer foam scaffolds or in shape memory polymer fibrous scaffolds programmed to expand or contract, respectively, when warmed to body temperature. Osteogenic differentiation in shape-changing and control scaffolds was compared using mineral deposition, protein production, and gene expression assays. For both shape-changing and control scaffolds, qualitatively and quantitatively comparable amounts of mineral deposition were observed; comparable levels of alkaline phosphatase activity were measured; and no significant differences in the expression of genetic markers of osteogenesis were detected. These findings support the feasibility of employing shape memory in scaffolds for stem cell-based therapies for bone repair.
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Affiliation(s)
- Ling-Fang Tseng
- 1 Department of Biomedical and Chemical Engineering, Syracuse University , Syracuse, New York.,2 Syracuse Biomaterials Institute, Syracuse University , Syracuse, New York
| | - Jing Wang
- 1 Department of Biomedical and Chemical Engineering, Syracuse University , Syracuse, New York.,2 Syracuse Biomaterials Institute, Syracuse University , Syracuse, New York
| | - Richard M Baker
- 1 Department of Biomedical and Chemical Engineering, Syracuse University , Syracuse, New York.,2 Syracuse Biomaterials Institute, Syracuse University , Syracuse, New York
| | - Guirong Wang
- 3 Department of Surgery, SUNY Upstate Medical University , Syracuse, New York
| | - Patrick T Mather
- 1 Department of Biomedical and Chemical Engineering, Syracuse University , Syracuse, New York.,2 Syracuse Biomaterials Institute, Syracuse University , Syracuse, New York
| | - James H Henderson
- 1 Department of Biomedical and Chemical Engineering, Syracuse University , Syracuse, New York.,2 Syracuse Biomaterials Institute, Syracuse University , Syracuse, New York
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48
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Osteogenic signaling on silk-based matrices. Biomaterials 2016; 97:133-53. [DOI: 10.1016/j.biomaterials.2016.04.020] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 03/25/2016] [Accepted: 04/20/2016] [Indexed: 12/11/2022]
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49
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Sun W, Motta A, Shi Y, Seekamp A, Schmidt H, Gorb SN, Migliaresi C, Fuchs S. Co-culture of outgrowth endothelial cells with human mesenchymal stem cells in silk fibroin hydrogels promotes angiogenesis. ACTA ACUST UNITED AC 2016; 11:035009. [PMID: 27271291 DOI: 10.1088/1748-6041/11/3/035009] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Sufficient vascularization of the implant construct is required for tissue regeneration to ensure the supply of oxygen and nutrients. In our previous work, we established sonication-induced silk fibroin hydrogel to load neural stem cells for brain tissue engineering applications. In this study, we explored the application of silk fibroin as an injectable hydrogel for vascularization of soft tissues. We investigated the ability of outgrowth endothelial cells (OECs) in mono-culture or in co-culture with human bone marrow-derived mesenchymal stem cells (BM-MSCs) to form capillary networks in silk fibroin hydrogels. Furthermore, the silk fibroin hydrogel was modified with IKVAV peptide revealing a sequence derived from the extracellular matrix component laminin-1 to test its effects on angiogenesis, using unmodified and VVIAK modified silk fibroin hydrogel as controls. In monocultures of OECs, no angiogenic structures were observed in silk fibroin hydrogels. In contrast, vascular structures were abundant and increased in co-culture, as confirmed by immunocytochemistry and scanning electron microscopy (SEM) over 10 d of culture in silk fibroin-based hydrogels. Although no significant differences in angiogenic activity seem to be caused by the IKVAV peptide in our experimental settings, these results indicate that sonication-induced silk fibroin-based hydrogels support the formation of functional endothelial tubes and vascularization networks in the presence of mesenchymal cells supporting the vascular sprouting of endothelial cells.
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Affiliation(s)
- Wei Sun
- Department of Industrial Engineering and Biotech Research Center, University of Trento, via Mesiano 77, 38123 Trento, Italy. European Institute of Excellence on Tissue Engineering and Regenerative medicine, Trento, Italy
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50
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Pullulan microcarriers for bone tissue regeneration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2016; 63:439-49. [DOI: 10.1016/j.msec.2016.03.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 02/02/2016] [Accepted: 03/01/2016] [Indexed: 11/21/2022]
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