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      Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

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          Abstract

          Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage. However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering (TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.

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          The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder.

          A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.
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            Electrospun Nanofibers: New Concepts, Materials, and Applications

            Electrospinning is a simple and versatile technique that relies on the electrostatic repulsion between surface charges to continuously draw nanofibers from a viscoelastic fluid. It has been applied to successfully produce nanofibers, with diameters down to tens of nanometers, from a rich variety of materials, including polymers, ceramics, small molecules, and their combinations. In addition to solid nanofibers with a smooth surface, electrospinning has also been adapted to generate nanofibers with a number of secondary structures, including those characterized by a porous, hollow, or core-sheath structure. The surface and/or interior of such nanofibers can be further functionalized with molecular species or nanoparticles during or after an electrospinning process. In addition, electrospun nanofibers can be assembled into ordered arrays or hierarchical structures by manipulation of their alignment, stacking, and/or folding. All of these attributes make electrospun nanofibers well-suited for a broad spectrum of applications, including those related to air filtration, water purification, heterogeneous catalysis, environmental protection, smart textiles, surface coating, energy harvesting/conversion/storage, encapsulation of bioactive species, drug delivery, tissue engineering, and regenerative medicine. Over the past 15 years, our group has extensively explored the use of electrospun nanofibers for a range of applications. Here we mainly focus on two examples: (i) use of ceramic nanofibers as catalytic supports for noble-metal nanoparticles and (ii) exploration of polymeric nanofibers as scaffolding materials for tissue regeneration. Because of their high porosity, high surface area to volume ratio, well-controlled composition, and good thermal stability, nonwoven membranes made of ceramic nanofibers are terrific supports for catalysts based on noble-metal nanoparticles. We have investigated the use of ceramic nanofibers made of various oxides, including SiO2, TiO2, SnO2, CeO2, and ZrO2, as supports for heterogeneous catalysts based on noble metals such as Au, Pt, Pd, and Rh. On the other hand, the diameter, composition, alignment, porosity, and surface properties of polymeric nanofibers can be engineered in a controllable fashion to mimic the hierarchical architecture of an extracellular matrix and help manipulate cell behaviors for tissue engineering and regenerative medicine. To this end, we can mimic the native structure and morphology of the extracellular matrix in tendon using uniaxially aligned nanofibers; we can use radially aligned nanofibers to direct the migration of cells from the periphery to the center in an effort to speed up wound healing; and we can also use uniaxially aligned nanofibers to guide and expedite the extension of neurites for peripheral nerve repair. Furthermore, we can replicate the anatomic structures at the tendon-to-bone insertion using nanofiber scaffolds with graded mineral coatings. In this Account, we aim to demonstrate the unique capabilities of electrospun nanofibers as porous supports for heterogeneous catalysis and as functional scaffolds for tissue regeneration by concentrating on some of the recent results.
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              Porous chitosan scaffolds for tissue engineering.

              The wide array of tissue engineering applications exacerbates the need for biodegradable materials with broad potential. Chitosan, the partially deacetylated derivative of chitin, may be one such material. In this study, we examined the use of chitosan for formation of porous scaffolds of controlled microstructure in several tissue-relevant geometries. Porous chitosan materials were prepared by controlled freezing and lyophilization of chitosan solutions and gels. The materials were characterized via light and scanning electron microscopy as well as tensile testing. The scaffolds formed included porous membranes, blocks, tubes and beads. Mean pore diameters could be controlled within the range 1-250 microm, by varying the freezing conditions. Freshly lyophilized chitosan scaffolds could be treated with glycosaminoglycans to form ionic complex materials which retained the original pore structure. Chitosan scaffolds could be rehydrated via an ethanol series to avoid the stiffening caused by rehydration in basic solutions. Hydrated porous chitosan membranes were at least twice as extensible as non-porous chitosan membranes, but their elastic moduli and tensile strengths were about tenfold lower than non-porous controls. The methods and structures described here provide a starting point for the design and fabrication of a family of polysaccharide based scaffold materials with potentially broad applicability.
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                Author and article information

                Contributors
                orthoyan@bjmu.edu.cn
                Journal
                Int J Oral Sci
                Int J Oral Sci
                International Journal of Oral Science
                Nature Publishing Group UK (London )
                1674-2818
                2049-3169
                6 February 2020
                6 February 2020
                2020
                : 12
                : 6
                Affiliations
                [1 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, , Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, ; Beijing, China
                [2 ]ISNI 0000 0004 0644 5174, GRID grid.411519.9, State Key Laboratory of Heavy Oil Processing, College of New Energy and Materials, Beijing Key Laboratory of Biogas Upgrading Utilization, , China University of Petroleum (Beijing), ; Beijing, China
                Author information
                http://orcid.org/0000-0002-8193-6729
                Article
                73
                10.1038/s41368-020-0073-y
                7002518
                31900382
                a39b9f99-91f8-497a-9f35-84deb692e79b
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 November 2019
                : 15 December 2019
                : 18 December 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81571815
                Award ID: 81871492
                Award ID: 51902344
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100004826, Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation);
                Award ID: L182005
                Award ID: 2184119
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100005090, Beijing Nova Program;
                Award ID: Z171100001117018
                Award Recipient :
                Funded by: Beijing Nova Programme Interdisciplinary Cooperation Project No. Z181100006218135
                Funded by: FundRef https://doi.org/10.13039/501100010244, Science Foundation of China University of Petroleum, Beijing;
                Award ID: 2462018BJB002
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2020

                Dentistry
                regeneration,mesenchymal stem cells,bioinspired materials,nanostructures
                Dentistry
                regeneration, mesenchymal stem cells, bioinspired materials, nanostructures

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