The hyperelastic and failure behaviors of skin in relation to the dynamic application of microscopic penetrators in a murine model

Meliga, Stefano C., Coffey, Jacob W., Crichton, Michael L., Flaim, Christopher, Veidt, Martin and Kendall, Mark A. F. (2017) The hyperelastic and failure behaviors of skin in relation to the dynamic application of microscopic penetrators in a murine model. Acta Biomaterialia, 48 341-356. doi:10.1016/j.actbio.2016.10.021


Author Meliga, Stefano C.
Coffey, Jacob W.
Crichton, Michael L.
Flaim, Christopher
Veidt, Martin
Kendall, Mark A. F.
Title The hyperelastic and failure behaviors of skin in relation to the dynamic application of microscopic penetrators in a murine model
Journal name Acta Biomaterialia   Check publisher's open access policy
ISSN 1878-7568
1742-7061
Publication date 2017-01-15
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.actbio.2016.10.021
Open Access Status Not yet assessed
Volume 48
Start page 341
End page 356
Total pages 16
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Abstract In-depth understanding of skin elastic and rupture behavior is fundamental to enable next-generation biomedical devices to directly access areas rich in cells and biomolecules. However, the paucity of skin mechanical characterization and lack of established fracture models limits their rational design. We present an experimental and numerical study of skin mechanics during dynamic interaction with individual and arrays of micro-penetrators. Initially, micro-indentation of individual skin strata revealed hyperelastic moduli were dramatically rate-dependent, enabling extrapolation of stiffness properties at high velocity regimes (>1ms(-1)). A layered finite-element model satisfactorily predicted the penetration of micro-penetrators using characteristic fracture energies (∼10pJμm(-2)) significantly lower than previously reported (≫100pJμm(-2)). Interestingly, with our standard application conditions (∼2ms(-1), 35gpistonmass), ∼95% of the application kinetic energy was transferred to the backing support rather than the skin ∼5% (murine ear model). At higher velocities (∼10ms(-1)) strain energy accumulated in the top skin layers, initiating fracture before stress waves transmitted deformation to the backing material, increasing energy transfer efficiency to 55%. Thus, the tools developed provide guidelines to rationally engineer skin penetrators to increase depth targeting consistency and payload delivery across patients whilst minimizing penetration energy to control skin inflammation, tolerability and acceptability.

The mechanics of skin penetration by dynamically-applied microscopic tips is investigated using a combined experimental-computational approach. A FE model of skin is parameterized using indentation tests and a ductile-failure implementation validated against penetration assays. The simulations shed light on skin elastic and fracture properties, and elucidate the interaction with microprojection arrays for vaccine delivery allowing rational design of next-generation devices.
Formatted abstract
In-depth understanding of skin elastic and rupture behavior is fundamental to enable next-generation biomedical devices to directly access areas rich in cells and biomolecules. However, the paucity of skin mechanical characterization and lack of established fracture models limits their rational design. We present an experimental and numerical study of skin mechanics during dynamic interaction with individual and arrays of micro-penetrators. Initially, micro-indentation of individual skin strata revealed hyperelastic moduli were dramatically rate-dependent, enabling extrapolation of stiffness properties at high velocity regimes (>1 ms−1). A layered finite-element model satisfactorily predicted the penetration of micro-penetrators using characteristic fracture energies (∼10 pJ μm−2) significantly lower than previously reported (≫100 pJ μm−2). Interestingly, with our standard application conditions (∼2 ms−1, 35 g piston mass), ∼95% of the application kinetic energy was transferred to the backing support rather than the skin ∼5% (murine ear model). At higher velocities (∼10 ms−1) strain energy accumulated in the top skin layers, initiating fracture before stress waves transmitted deformation to the backing material, increasing energy transfer efficiency to 55%. Thus, the tools developed provide guidelines to rationally engineer skin penetrators to increase depth targeting consistency and payload delivery across patients whilst minimizing penetration energy to control skin inflammation, tolerability and acceptability.

Statement of Significance: The mechanics of skin penetration by dynamically-applied microscopic tips is investigated using a combined experimental-computational approach. A FE model of skin is parameterized using indentation tests and a ductile-failure implementation validated against penetration assays. The simulations shed light on skin elastic and fracture properties, and elucidate the interaction with microprojection arrays for vaccine delivery allowing rational design of next-generation devices.
Keyword Hyperelastic
Microprojection arrays
Nanopatch
Penetration
Skin
Strain-rate
Subcutaneous backing
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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