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

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• 作者：Stefano C. Meliga^a ; Jacob W. Coffey^a ; ^b ; Michael L. Crichton^a ; ^b ; Christopher Flaim^c ; Martin Veidt^d ; Mark A.F. Kendall^a ; ^b ; ^e ; ^{m.kendall@uq.edu.au}
• 关键词：Skin ; Penetration ; Microprojection arrays ; Nanopatch ; Subcutaneous backing ; Strain-rate ; Hyperelastic
• 刊名：Acta Biomaterialia
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：48
• 期：Complete
• 页码：341-356
• 全文大小：3708 K
• 卷排序：48

文摘

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 SignificanceThe 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.