title: The hyperelastic and failure behaviors of skin in relation to the dynamic application of microscopic penetrators in a murine model.
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.
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Stefano C
authors.initials: SC
authors.lastname: Meliga
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Coffey
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Crichton
authors.affiliation: Vaxxas Pty Ltd, TRI, 37 Kent St, Woolloongabba QLD 4102, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Flaim
authors.affiliation: School of Mechanical and Mining Engineering, Frank White Building 43, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Veidt
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia; The University of Queensland, Faculty of Medicine and Biomedical Sciences, Royal Brisbane and Women's Hospital, Herston, Queensland 4006, Australia. Electronic address: m.kendall@uq.edu.au.
authors.forename: Mark A F
authors.initials: MAF
authors.lastname: Kendall
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D004548:Elasticity; D005260:Female; D020342:Finite Element Analysis; D008807:Mice, Inbred BALB C; D008853:Microscopy / Q000379:methods*; D023421:Models, Animal; D008962:Models, Theoretical; D009716:Numerical Analysis, Computer-Assisted; D010539:Permeability; D015203:Reproducibility of Results; D012879:Skin Physiological Phenomena; D013314:Stress, Mechanical; D014783:Viscosity
keywords: Hyperelastic; Microprojection arrays; Nanopatch; Penetration; Skin; Strain-rate; Subcutaneous backing