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Research Papers

Fabrication and Modeling of Dynamic Multipolymer Nanofibrous Scaffolds

[+] Author and Article Information
Brendon M. Baker, Dawn M. Elliott

Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, and Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104

Nandan L. Nerurkar

Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104

Jason A. Burdick

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104

Robert L. Mauck1

Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, and Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104lemauck@mail.med.upenn.edu

1

Corresponding author.

J Biomech Eng 131(10), 101012 (Sep 14, 2009) (10 pages) doi:10.1115/1.3192140 History: Received November 15, 2008; Revised June 02, 2009; Published September 14, 2009

Aligned nanofibrous scaffolds hold tremendous potential for the engineering of dense connective tissues. These biomimetic micropatterns direct organized cell-mediated matrix deposition and can be tuned to possess nonlinear and anisotropic mechanical properties. For these scaffolds to function in vivo, however, they must either recapitulate the full dynamic mechanical range of the native tissue upon implantation or must foster cell infiltration and matrix deposition so as to enable construct maturation to meet these criteria. In our recent studies, we noted that cell infiltration into dense aligned structures is limited but could be expedited via the inclusion of a distinct rapidly eroding sacrificial component. In the present study, we sought to further the fabrication of dynamic nanofibrous constructs by combining multiple-fiber populations, each with distinct mechanical characteristics, into a single composite nanofibrous scaffold. Toward this goal, we developed a novel method for the generation of aligned electrospun composites containing rapidly eroding (PEO), moderately degradable (PLGA and PCL/PLGA), and slowly degrading (PCL) fiber populations. We evaluated the mechanical properties of these composites upon formation and with degradation in a physiologic environment. Furthermore, we employed a hyperelastic constrained-mixture model to capture the nonlinear and time-dependent properties of these scaffolds when formed as single-fiber populations or in multipolymer composites. After validating this model, we demonstrated that by carefully selecting fiber populations with differing mechanical properties and altering the relative fraction of each, a wide range of mechanical properties (and degradation characteristics) can be achieved. This advance allows for the rational design of nanofibrous scaffolds to match native tissue properties and will significantly enhance our ability to fabricate replacements for load-bearing tissues of the musculoskeletal system.

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Copyright © 2009 by American Society of Mechanical Engineers
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Figures

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Figure 3

Study II: Single- and multiple-fiber population scaffold tensile behaviors are modulated by composition and degradation time. (a) Stress-strain curves of day 0 PCL, blend, and composite scaffolds tested in the fiber direction. Yield strain (b) and modulus (c) of samples tested in the fiber direction over 63 days (n=5/group per time point). (d) Modulus in the transverse direction as a function of time (n=5/group per time point). (e) Percent mass loss relative to dry, as-formed samples over the 63 day time course (n=5/group per time point). Note that composite scaffolds on day 0 lose ∼22% of their starting mass due to the removal of the PEO fiber population during hydration. *:p<0.01 versus day 0.

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Figure 4

Characterization of single-fiber population (PCL (solid) and blend (dashed)) scaffold tensile behavior with a hyperelastic fiber-reinforced constitutive model. Curve fit results (lines) on day 0 are shown along with experimental data (circles) for the transverse (a) and fiber (d) directions. From transverse direction testing, matrix parameters μ (b) and ν (c) were determined at each time point. These values, coupled with fits to fiber-direction data at each time point, were used to determine fiber parameters, γ (e) and ξ (f).

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Figure 5

Material parameters from single-component scaffolds successfully predict composite scaffold behavior. (a) Stress-strain curves for composites tested in the fiber direction. Stress-strain profiles diminished as degradation occurred over 63 days, due to the decreasing properties of the blend fiber population. Model predictions of composite stress response when tested in the fiber direction on days 0 (b), 7 (c), 21 (d), 42 (e), and 63 (f) showed good agreement with experimental measures. Each plot contains all five experimental curves (dotted lines) and the corresponding five model-generated predictions (solid lines).

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Figure 6

Simulation of composite scaffolds of any formulation. (a) Behavior of composites covering the full range of possible PCL/blend combinations (as indicated by the initial mass fraction of blend fibers, ∅B) was simulated for as-formed samples and with degradation over time. Modulus for each theoretical composite is denoted both by height as well as color. (b) Stress-strain behavior of composites of varying formulations on day 0.

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Figure 1

Composite nanofibrous scaffolds containing three distinct fiber populations were fabricated with a custom electrospinning device. (a) Schematic of the formation of electrospun scaffolds containing fast, medium, and slow-degrading fiber populations. (b) Diagram depicting the temporal evolution of porosity in composite scaffolds that lose fiber elements in a preprogramed fashion via differing degradation profiles. (c) Novel electrospinning device for forming single- and multipolymer fibrous scaffolds by co-electrospinning from up to three jets onto a common rotating mandrel. (d) Fiber morphology in composites imaged via SEM (scale bar: 10 μm). (e) Composites fabricated with fluorescently labeled fiber populations show the presence and interspersion of each element (scale bar: 10 μm).

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Figure 2

Study I: Electrospun PCL, PLGA, and PEO scaffolds have unique stress-strain profiles. When all three elements are combined, the composite scaffold stress-strain behavior shares characteristics of each constituent. (a) Stress-strain profiles of PCL, PEO, PLGA, and composite scaffolds extended in the fiber direction. Modulus (b) and yield strain (c) for each scaffold (n=5/group). (d) Samples from composite scaffolds removed along the length of the mandrel showed a range of behaviors, likely dependent on the relative fractions of PLGA or PCL fibers at each location.

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