Optimization strategies for electrospun silk fibroin tissue engineering scaffolds

Institute of Pharmaceutical Sciences, ETH Zurich, Department for Chemistry and Applied Biosciences, HCI J 390.1, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Biomaterials (Impact Factor: 8.56). 03/2009; 30(17):3058-67. DOI: 10.1016/j.biomaterials.2009.01.054
Source: PubMed


As a contribution to the functionality of scaffolds in tissue engineering, here we report on advanced scaffold design through introduction and evaluation of topographical, mechanical and chemical cues. For scaffolding, we used silk fibroin (SF), a well-established biomaterial. Biomimetic alignment of fibers was achieved as a function of the rotational speed of the cylindrical target during electrospinning of a SF solution blended with polyethylene oxide. Seeding fibrous SF scaffolds with human mesenchymal stem cells (hMSCs) demonstrated that fiber alignment could guide hMSC morphology and orientation demonstrating the impact of scaffold topography on the engineering of oriented tissues. Beyond currently established methodologies to measure bulk properties, we assessed the mechanical properties of the fibers by conducting extension at breakage experiments on the level of single fibers. Chemical modification of the scaffolds was tested using donor/acceptor fluorophore labeled fibronectin. Fluorescence resonance energy transfer imaging allowed to assess the conformation of fibronectin when adsorbed on the SF scaffolds, and demonstrated an intermediate extension level of its subunits. Biological assays based on hMSCs showed enhanced cellular adhesion and spreading as a result of fibronectin adsorbed on the scaffolds. Our studies demonstrate the versatility of SF as a biomaterial to engineer modified fibrous scaffolds and underscore the use of biofunctionally relevant analytical assays to optimize fibrous biomaterial scaffolds.

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Available from: Hans P Merkle, Feb 28, 2014
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    • "These experimental difficulties arising from the use of aqueousbased dopes might be due to the particular combination of high surface tension, low net charge density and low vapor pressure of water [44]. Previous studies evidenced the need to use polymer blends (e.g. with PEO) [27] [36], rather high SF concentrations (28–30 wt%) [24] [35] and/or addition of salts to the dope solution [23] in order to stabilize the aqueous electrospinning process. In our work, the jet became very stable when 5–10 wt% FA was added to aqueous solutions of 10–20 wt% SF and when they were electrospun at voltages below 15 kV. "
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    ABSTRACT: Regenerated silk fibroin solutions from Bombyx mori were tested for electrospinning. Simple and reproducible tensile tests were performed on threads of aligned fibers to obtain information about their mechanical performance at the fiber level. The binary solvent formic acid/chloroform (10:1, v/v) rendered unbeaded thinner fibers with increased extensibility before failure when compared with pure formic acid. A remarkable improvement in strength was induced by immersing length-restricted fibers into ethanol for 5 min. Conformational changes of the protein chains were studied by solid-state NMR.
    European Polymer Journal 11/2014; 60:123–134. DOI:10.1016/j.eurpolymj.2014.08.030 · 3.01 Impact Factor
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    • "A vision of in situ guided tissue regeneration strategies has been developed, where smart materials delivering peptide or small molecules with and without regenerative cells can be applied with minimally invasive techniques to enhance endogenous regeneration respecting (stem) cell biology and developmental processes (Gilbert and Blau 2011; Lutolf et al. 2009; Uebersax et al. 2009). Exciting developments in material science are capable of perfectly matching these scenarios using intelligent and functional materials, which can also be designed for perfect timely release of factors involved in regeneration (Astachov et al. 2011; Chen et al. 2010; Di Maggio et al. 2011; Dvir et al. 2011; Gilbert and Blau 2011; Grafahrend et al. 2010; Klinkhammer et al. 2010; Lutolf et al. 2009; Meinel et al. 2009; Votteler et al. 2010). Cellular and organismal aging phenomena in an elderly and diseased target population for regenerative strategies may be serious obstacles for successful treatment regimens. "
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    ABSTRACT: In situ guided tissue regeneration, also addressed as in situ tissue engineering or endogenous regeneration, has a great potential for population-wide "minimal invasive" applications. During the last two decades, tissue engineering has been developed with remarkable in vitro and preclinical success but still the number of applications in clinical routine is extremely small. Moreover, the vision of population-wide applications of ex vivo tissue engineered constructs based on cells, growth and differentiation factors and scaffolds, must probably be deemed unrealistic for economic and regulation-related issues. Hence, the progress made in this respect will be mostly applicable to a fraction of post-traumatic or post-surgery situations such as big tissue defects due to tumor manifestation. Minimally invasive procedures would probably qualify for a broader application and ideally would only require off the shelf standardized products without cells. Such products should mimic the microenvironment of regenerating tissues and make use of the endogenous tissue regeneration capacities. Functionally, the chemotaxis of regenerative cells, their amplification as a transient amplifying pool and their concerted differentiation and remodeling should be addressed. This is especially important because the main target populations for such applications are the elderly and diseased. The quality of regenerative cells is impaired in such organisms and high levels of inhibitors also interfere with regeneration and healing. In metabolic bone diseases like osteoporosis, it is already known that antagonists for inhibitors such as activin and sclerostin enhance bone formation. Implementing such strategies into applications for in situ guided tissue regeneration should greatly enhance the efficacy of tailored procedures in the future.
    Cell and Tissue Research 10/2011; 347(3):725-35. DOI:10.1007/s00441-011-1237-z · 3.57 Impact Factor
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    • "Fibroin nanofiber scaffolds and regenerative medicine 28 Int J Burn Trauma 2011;1(1):27-33 tures were shown be deeply influenced by the treatments SF undergoes prior to and/or during electrospinning [4] [21] [25] [39] [40] [41]. Application of SF nanofiber scaffolds has been suggested for the engineering and regeneration of both soft tissues, like vascular grafts, nerves, skin wounds [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54], and hard tissues, like tendons, ligaments, bone and cartilage [16] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65], although in the latter instances SF was also used as microfiber or sponge and mixed with other biomaterials. "
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    ABSTRACT: Presently, some view silk fibroin-based biomaterials as obsolete, being outperformed by a host of newly discovered biomaterials. But several lines of evidence support the notion that silk fibroin proteins, especially those from B. mori and spiders and their recombinant forms, particularly in the form of electrospun nanofiber scaffolds, still represent promising tools for human tissue engineering/regeneration. Inevitably, the allure of recently reported biomaterials turns away many scientists and resources from the aim of more deeply elucidating the biological interactions of the various kinds of silk fibroin nanofiber scaffolds in vivo. But, even the biological features of newly reported biomaterials are not investigated in adequate depth. Hence, collaborative efforts among biomaterialists, biomedical experts, and private firms must be undertaken on a much greater scale than hitherto done to assess the real usefulness of silk fibroin proteins, thereby allowing or denying their useful introduction into the fields of Translational Regenerative Medicine.
    International Journal of Burns and Trauma 01/2011; 1(1):27-33.
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