The influence of elasticity and surface roughness on myogenic and osteogenic-differentiation of cells on silk-elastin biomaterials

Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Biomaterials (Impact Factor: 8.56). 08/2011; 32(34):8979-89. DOI: 10.1016/j.biomaterials.2011.08.037
Source: PubMed


The interactions of C2C12 myoblasts and human bone marrow stem cells (hMSCs) with silk-tropoelastin biomaterials, and the capacity of each to promote attachment, proliferation, and either myogenic- or osteogenic-differentiation were investigated. Temperature-controlled water vapor annealing was used to control beta-sheet crystal formation to generate insoluble silk-tropoelastin biomaterial matrices at defined ratios of the two proteins. These ratios controlled surface roughness and micro/nano-scale topological patterns, and elastic modulus, stiffness, yield stress, and tensile strength. A combination of low surface roughness and high stiffness in the silk-tropoelastin materials promoted proliferation and myogenic-differentiation of C2C12 cells. In contrast, high surface roughness with micro/nano-scale surface patterns was favored by hMSCs. Increasing the content of human tropoelastin in the silk-tropoelastin materials enhanced the proliferation and osteogenic-differentiation of hMSCs. We conclude that the silk-tropoelastin composition facilitates fine tuning of the growth and differentiation of these cells.

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Available from: Anthony S Weiss, Sep 30, 2015
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    • "More importantly, silk-based biomaterials can be tailored for diverse applications [19]; including morphological changes, structural control, and a range of material formats can be prepared such as sponges, hydrogels, fibers, films and other forms [19]. Bio-functional modification of silk materials, changes in elasticity, control of surface roughness [20], biomimetic coatings [21], and collagen incorporation [22] to direct stem cell behavior have all been explored. In total, silk is a useful material for artificial stem cell microenvironment fabrication to deliver seeded cells for bone regeneration, with porous silk scaffolds to facilitate cell survival, proliferation and migration in vitro [23]. "
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    ABSTRACT: Stem cell-based tissue engineering shows promise for bone regeneration and requires artificial microenvironments to enhance the survival, proliferation and differentiation of the seeded cells. Silk fibroin, as a natural protein polymer, has unique properties for tissue regeneration. The present study aimed to evaluate the influence of porous silk scaffolds on rat bone marrow stem cells (BMSCs) by lenti-GFP tracking both in vitro and in vivo in cranial bone defects. The number of cells seeded within silk scaffolds in rat cranial bone defects increased from 2 days to 2 weeks after implantation, followed by a decrease at eight weeks. Importantly, the implanted cells survived for 8 weeks in vivo and some of the cells might differentiate into endothelial cells and osteoblasts induced by the presence of VEGF and BMP-2 in the scaffolds to promote angiogenesis and osteogenesis. The results demonstrate that porous silk scaffolds provide a suitable niche to maintain long survival and function of the implanted cells for bone regeneration.
    PLoS ONE 07/2014; 9(7):e102371. DOI:10.1371/journal.pone.0102371 · 3.23 Impact Factor
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    • "Firstly, such studies have elucidated fundamental understanding of the mechanisms of a myriad of biological processes like cell adhesion, proliferation, migration and differentiation [5e8]. These and a multitude of cell responses are governed by complex chemical and physical cues from the surrounding environment encompassing different length scales, from nano to micro [9] [10], the mechanisms of which are poorly understood. "
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    ABSTRACT: Physicochemical features of a cell nanoenvironment exert important influence on stem cell behavior and include the influence of matrix elasticity and topography on differentiation processes. The presence of growth factors such as TGF-β and BMPs on these matrices provides chemical cues and thus plays vital role in directing eventual stem cell fate. Engineering of functional biomimetic scaffolds that present programmed spatio-temporal physical and chemical signals to stem cells holds great promise in stem cell therapy. Progress in this field requires tacit understanding of the mechanistic aspects of cell-environment nanointeractions, so that they can be manipulated and exploited for the design of sophisticated next generation biomaterials. In this review, we report and discuss the evolution of these processes and pathways in the context of matrix adhesion as they might relate to stemness and stem cell differentiation. Super-resolution microscopy and single-molecule methods for in vitro nano-manipulation are helping to identify and characterize the molecules and mechanics of structural transitions within stem cells and matrices. All these advances facilitate research toward understanding of stem cell niche and consequently to developing new class of biomaterials helping the “used biomaterials” for applications in tissue engineering and regenerative medicine.
    Biomaterials 07/2014; 35(20):5278–5293. DOI:10.1016/j.biomaterials.2014.03.044 · 8.56 Impact Factor
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    • "Though physically crosslinked silicate polymer hydrogels have shown attractive biological properties, their applications as scaffold structures for bone regeneration are limited because of their insufficient mechanical properties [29] [30]. On the contrary, silk fibroin protein is rather stable and mechanically robust, but the utilization of silk is restrained from elastomeric biomaterial applications because of its inherent tendency to form stiff materials (>1 MPa) as a result of the beta sheet crystal formation [13]. Hence, the development of a 3-D material that can mimic the physiological ECM allows the investigation of cell responses to substrate mechanics, which are independent of both biochemical and transport properties would be a major breakthrough in tissue engineering. "
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    ABSTRACT: Cells respond to various chemical signals as well as environmental aspects of the extracellular matrix (ECM) that may alter cellular structures and functions. Hence, better understanding of the mechanical stimuli of the matrix is essential for creating an adjuvant material that mimics the physiological environment to support cell growth and differentiation, and control the release of the growth factor. In this study, we utilized the property of transglutaminase cross-linked gelatin (TG-Gel), where modification of the mechanical properties of TG-Gel can be easily achieved by tuning the concentration of gelatin. Modifying one or more of the material parameters will result in changes of the cellular responses, including different phenotype-specific gene expressions and functional differentiations. In this study, stiffer TG-Gels itself facilitated focal contact formation and osteogenic differentiation while soft TG-Gel promoted cell proliferation. We also evaluated the interactions between a stimulating factor (i.e. BMP-2) and matrix rigidity on osteogenesis both in vitro and in vivo. The results presented in this study suggest that the interactions of chemical and physical factors in ECM scaffolds may work synergistically to enhance bone regeneration.
    Biomaterials 04/2014; 35(20). DOI:10.1016/j.biomaterials.2014.02.040 · 8.56 Impact Factor
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