Using Lessons from Cellular and Molecular Structures for Future Materials

LeDuc, Philip R.; Robinson, Douglas N.

doi:10.1002/adma.200701286

Cited by 40 publications

(36 citation statements)

References 76 publications

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“…However, current biomaterials used for scaffolding do not present a hierarchical structure as that found in natural materials and this could affect the cell behavior and differentiation. A rigorous understanding of collagen's scale and strain dependent stiffness may help in designing biomaterials with appropriate mechanical characteristics and thus addresses an immediate need for optimized matrix elasticity to foster differentiation and regeneration for regenerative medicine applications based on stem cell therapies such as cardiomyoplasty, muscular dystrophy, and neuroplasty [61][62][63]. To highlight the variation of Young's modulus and bending rigidity for a variety of biological and synthetic fibers we present a comparative analysis as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Gautieri

Vesentini²,

Redaelli³

et al. 2011

Nano Lett.

601

488

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Abstract:Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to connective tissues. Collagen is also the dominating material in the extracellular matrix (ECM) and is thus crucial for cell differentiation, growth and pathology. However, fundamental questions remain with respect to the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility and nonlinear mechanical response. By using x-ray diffraction data of a collagen fibril reported by Orgel et al.(Proceedings of the National Academy of Sciences USA, 2006) in combination with protein structure identification methods, here we present an experimentally validated model of the nanomechanics of a collagen microfibril that incorporates the full biochemical details of the amino acid sequence of the constituting molecules. We report the analysis of its mechanical properties under different levels of stress and solvent conditions, using a full-atomistic force field including explicit water solvent. Mechanical testing of hydrated collagen microfibrils yields a Young's modulus of ≈300 MPa at small and ≈1.2 GPa at larger deformation in excess of 10% strain, in excellent agreement with experimental data. Dehydrated, dry collagen microfibrils show a significantly increased Young's modulus of ≈1.8 to 2.25 GPa (or ≈6.75 times the modulus in the wet state) owing to a much tighter molecular packing, in good agreement with experimental measurements (where an increase of the modulus by ≈9 times was found). Our model demonstrates that the unique mechanical properties of collagen microfibrils can be explained based on their hierarchical structure, where deformation is mediated through mechanisms that operate at different hierarchical levels. Key mechanisms involve straightening of initially disordered and helically twisted molecules at small strains, followed by axial stretching of molecules, and eventual molecular uncoiling at extreme deformation. These mechanisms explain the striking difference of the modulus of collagen fibrils compared with single molecules, which is found in the range of 4.8±2 GPa or ≈10-20 times greater. These findings corroborate the notion that collagen tissue properties are highly scale dependent and nonlinear elastic, an issue that must be considered in the development of models that describe the interaction of cells with collagen in the extracellular matrix. A key impact the atomistic model of collagen microfibril mechanics reported here is that it enables the bottom-up elucidation of structure-property relationships in the broader class of collagen materials such as tendon or bone, including studies in the context of genetic disease where the incorporation of biochemical, genetic details in material models of connective tissue is essential.

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Section: Resultsmentioning

confidence: 99%

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Gautieri

Vesentini²,

Redaelli³

et al. 2011

Nano Lett.

601

488

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“…MG63 cells were grown in Alpha Minimum Essential Medium (a-MEM, Gibco) containing 10% fetal bovine serum (FBS), 2.5 mg mL À1 fungizone, 100 U mL À1 penicillin-streptomycin and 85 mg mL À1 gentamicin. 26 During routine propagation, the cells were maintained in 75 cm 2 Nunc Easy Flasks at 37 C in humidified atmosphere containing 5% CO 2 for 3-4 days. Then, the cells were removed by applying a trypsin-EDTA solution and seeded on the disk shaped composite samples at 1.5 Â 10 À5 cells mL À1 in 12-well polystyrene culture plates, using the same culture conditions.…”

Section: 25mentioning

confidence: 99%

Integrated biomimetic carbon nanotube composites for in vivo systems

et al. 2010

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As interest in using carbon nanotubes for developing biologically compatible systems continues to grow, biological inspiration is stimulating new directions for in vivo approaches. The ability to integrate nanotechnology-based systems in the body will provide greater successes if the implanted material is made to mimic elements of the biological milieu especially through tuning physical and chemical characteristics. Here, we demonstrate the highly successful capacity for in vivo implantation of a new carbon nanotube-based composite that is, itself, integrated with a hydroxyapatite-polymethyl methacrylate to create a nanocomposite. The success of this approach is grounded in finely tailoring the physical and chemical properties of this composite for the critical demands of biological integration. This is accomplished through controlling the surface modification scheme, which affects the interactions between carbon nanotubes and the hydroxyapatite-polymethyl methacrylate. Furthermore, we carefully examine cellular response with respect to adhesion and proliferation to examine in vitro compatibility capacity. Our results indicate that this new composite accelerates cell maturation through providing a mechanically competent bone matrix; this likely facilitates osteointegration in vivo. We believe that these results will have applications in a diversity of areas including carbon nanotube, regeneration, chemistry, and engineering research.

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“…Electrospun nanofibers are of interest in biomedical research, as they may closely mimic the nanofibrous structure of the native extracellular matrix. [1,2] Cell behaviors such as migration, orientation, and cytoskeletal arrangement can be greatly influenced by substrate topography alone without additional biochemical cues. [3] Furthermore, the scaffolds produced by electrospinning offer a high surface area to volume ratio, which would allow for increased cellular interaction with the material.…”

Section: Introductionmentioning

confidence: 99%

Electrospun Alginate Nanofibers with Controlled Cell Adhesion for Tissue Engineeringa

Jeong

Krebs

Bonino

et al. 2010

Macromolecular Bioscience

139

100

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Alginate, a natural polysaccharide that has shown great potential as a cell scaffold for the regeneration of many tissues, has only been nominally explored as an electrospun biomaterial due to cytotoxic chemicals that have typically been used during nanofiber formation and crosslinking. Alginate cannot be electrospun by itself and is often co-spun with poly(ethylene oxide) (PEO). In this work, a cell adhesive peptide (GRGDSP) modified alginate (RA) and unmodified alginate (UA) were blended with PEO at different concentrations and blending ratios, and then electrospun to prepare uniform nanofibers. The ability of electrospun RA scaffolds to support human dermal fibroblast cell attachment, spreading, and subsequent proliferation was greatly enhanced on the adhesion ligand-modified nanofibers, demonstrating the promise of this electrospun polysaccharide material with defined nanoscale architecture and cell adhesive properties for tissue regeneration applications.

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Using Lessons from Cellular and Molecular Structures for Future Materials

Cited by 40 publications

References 76 publications

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Integrated biomimetic carbon nanotube composites for in vivo systems

Electrospun Alginate Nanofibers with Controlled Cell Adhesion for Tissue Engineeringa

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