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      Advances in the design of macroporous polymer scaffolds for potential applications in dentistry

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          Abstract

          A paradigm shift is taking place in medicine and dentistry from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous three-dimensional (3D) material hydrogels integrated with cells and bioactive factors to regenerate tissues such as dental bone and other oral tissues. Hydrogels have been established as a biomaterial of choice for many years, as they offer diverse properties that make them ideal in regenerative medicine, including dental applications. Being highly biocompatible and similar to native extracellular matrix, hydrogels have emerged as ideal candidates in the design of 3D scaffolds for tissue regeneration and drug delivery applications. However, precise control over hydrogel properties, such as porosity, pore size, and pore interconnectivity, remains a challenge. Traditional techniques for creating conventional crosslinked polymers have demonstrated limited success in the formation of hydrogels with large pore size, thus limiting cellular infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the case of bone) of tissue-engineered constructs. Emerging technologies have demonstrated the ability to control microarchitectural features in hydrogels such as the creation of large pore size, porosity, and pore interconnectivity, thus allowing the creation of engineered hydrogel scaffolds with a structure and function closely mimicking native tissues. In this review, we explore the various technologies available for the preparation of macroporous scaffolds and their potential applications.

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          Most cited references 117

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          Porosity of 3D biomaterial scaffolds and osteogenesis.

          Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be approximately 100 microm due to cell size, migration requirements and transport. However, pore sizes >300 microm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vascularization, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs.
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            Electrospinning of polymeric nanofibers for tissue engineering applications: a review.

            Interest in electrospinning has recently escalated due to the ability to produce materials with nanoscale properties. Electrospun fibers have been investigated as promising tissue engineering scaffolds since they mimic the nanoscale properties of native extracellular matrix. In this review, we examine electrospinning by providing a brief description of the theory behind the process, examining the effect of changing the process parameters on fiber morphology, and discussing the potential applications and impacts of electrospinning on the field of tissue engineering.
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              Harnessing Traction-Mediated Manipulation of the Cell-Matrix Interface to Control Stem Cell Fate

              Stem cells sense and respond to the mechanical properties of the extracellular matrix. However, both the extent to which extracellular matrix mechanics affect stem cell fate in 3D micro-environments and the underlying biophysical mechanisms are unclear. We demonstrate that the commitment of mesenchymal stem cell (MSC) populations changes in response to the rigidity of 3D micro-environments, with osteogenesis occurring predominantly at 11–30 kPa. In contrast to previous 2D work, however, cell fate was not correlated with morphology. Instead, matrix stiffness regulated integrin binding as well as reorganization of adhesion ligands on the nanoscale, both of which were traction-dependent and correlated with osteogenic commitment of MSC populations. These findings suggest that cells interpret changes in the physical properties of adhesion substrates as changes in adhesion ligand presentation, and that cells themselves can be harnessed as tools to mechanically process materials into structures that feedback to manipulate their fate.
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                Author and article information

                Affiliations
                [1 ]School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
                [2 ]Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
                [3 ]Laboratory of Microsystems, STI-LMIS4, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
                Author notes
                Correspondence: Sidi A. Bencherif. School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. sidi@ 123456seas.harvard.edu , Tel: +1-617-495-1689, Fax: +1-617-495-8534
                Journal
                J Periodontal Implant Sci
                J Periodontal Implant Sci
                JPIS
                Journal of Periodontal & Implant Science
                Korean Academy of Periodontology
                2093-2278
                2093-2286
                December 2013
                31 December 2013
                : 43
                : 6
                : 251-261
                3891856
                10.5051/jpis.2013.43.6.251
                Copyright © 2013 Korean Academy of Periodontology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/).

                Categories
                Review Article

                Dentistry

                polymers, hydrogels, tissue engineering

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