Mechanical damage in porcine dermis: Micro-mechanical model and experimental characterization.

Skin is subjected to extreme mechanical loading during needle insertion and drug delivery to the subcutaneous space. There is a rich literature on the characterization of porcine skin biomechanics as the preeminent animal model for human skin, but the emphasis has been on the elastic response and specific anatomical locations such as the dorsal and the ventral regions. During drug delivery, however, energy dissipation in the form of damage, softening, and fracture, is expected. Similarly, reports on experimental characterization are complemented by modeling efforts, but with similar gaps in microstructure-driven modeling of dissipative mechanisms. Here we contribute to the bridging of these gaps by testing porcine skin from belly and breast regions, in two different orientation with respect to anatomical axes, and to progressively higher stretches in order to show damage accumulation and stiffness degradation. We complement the mechanical test with imaging of the collagen structure and a micro-mechanics modeling framework. We found that skin from the belly is stiffer with respect to the breast region when comparing the calf stiffness of the J-shaped stress-stretch response observed in most collagenous tissues. No significant direction dependent properties were found in either anatomical location. Both locations showed energy dissipation due to damage, evident though a softening of the stress-stretch response. The microstructure model was able to capture the elastic and damage progression with a small set of parameters, some of which were determined directly from imaging. We anticipate that data and model fits can help in predictive simulations for device design in situations where skin is subject to supra-physiological deformation such as in subcutaneous drug delivery.

Damage and Fracture Mechanics of Porcine Subcutaneous Tissue Under Tensile Loading.

Subcutaneous injection, which is a preferred delivery method for many drugs, causes deformation, damage, and fracture of the subcutaneous tissue. Yet, experimental data and constitutive modeling of these dissipation mechanisms in subcutaneous tissue remain limited. Here we show that subcutaneous tissue from the belly and breast anatomical regions in the swine show nonlinear stress-strain response with the characteristic J-shaped behavior of collagenous tissue. Additionally, subcutaneous tissue experiences damage, defined as a decrease in the strain energy capacity, as a function of the previously experienced maximum deformation. The elastic and damage response of the tissue are accurately described by a microstructure-driven constitutive model that relies on the convolution of a neo-Hookean material of individual fibers with a fiber orientation distribution and a fiber recruitment distribution. The model fit revealed that subcutaneous tissue can be treated as initially isotropic, and that changes in the fiber recruitment distribution with loading are enough to explain the dissipation of energy due to damage. When tested until failure, subcutaneous tissue that has undergone damage fails at the same peak stress as virgin samples, but at a much larger stretch, overall increasing the tissue toughness. Together with a finite element implementation, these data and constitutive model may enable improved drug delivery strategies and other applications for which subcutaneous tissue biomechanics are relevant.

Anisotropic damage model for collagenous tissues and its application to model fracture and needle insertion mechanics.

The analysis of tissue mechanics in biomedical applications demands nonlinear constitutive models able to capture the energy dissipation mechanisms, such as damage, that occur during tissue deformation. Furthermore, implementation of sophisticated material models in finite element models is essential to improve medical devices and diagnostic tools. Building on previous work toward microstructure-driven models of collagenous tissue, here we show a constitutive model based on fiber orientation and waviness distributions for skin that captures not only the anisotropic strain-stiffening response of this and other collagen-based tissues, but, additionally, accounts for tissue damage directly as a function of changes in the microstructure, in particular changes in the fiber waviness distribution. The implementation of this nonlinear constitutive model as a user subroutine in the popular finite element package Abaqus enables large-scale finite element simulations for biomedical applications. We showcase the performance of the model in fracture simulations during pure shear tests, as well as simulations of needle insertion into skin relevant to auto-injector design.

Biaxial mechanics of thermally denaturing skin - Part 2: Modeling.

Understanding the response of skin to superphysiological temperatures is critical to the diagnosis and prognosis of thermal injuries, and to the development of temperature-based medical therapeutics. Unfortunately, this understanding has been hindered by our incomplete knowledge about the nonlinear coupling between skin temperature and its mechanics. In Part I of this study we experimentally demonstrated a complex interdependence of time, temperature, direction, and load in skin's response to superphysiological temperatures. In Part II of our study, we test two different models of skin's thermo-mechanics to explain our observations. In both models we assume that skin's response to superphysiological temperatures is governed by the denaturation of its highly collageneous microstructure. Thus, we capture skin's native mechanics via a microstructurally-motivated strain energy function which includes probability distributions for collagen fiber orientation and waviness. In the first model, we capture skin's response to superphysiological temperatures as a transition between two states that link the kinetics of collagen fiber denaturation to fiber coiling and to the transformation of each fiber's constitutive behavior from purely elastic to viscoelastic. In the second model, we capture skin's response to superphysiological temperatures instead via three states in which a sequence of two reactions link the kinetics of collagen fiber denaturation to fiber coiling, followed by a state of fiber damage. Given the success of both models in qualitatively and quantitatively capturing our observations, we expect that our work will provide guidance for future experiments that could probe each model's assumptions toward a better understanding of skin's coupled thermo-mechanics and that our work will be used to guide the engineering design of heat treatment therapies. STATEMENT OF SIGNIFICANCE: Quantifying and modeling skin thermo-mechanics is critical to our understanding of skin physiology, pathophysiology, as well as heat-based treatments. This work addresses a lack of theoretical and computational models of the coupled thermo-mechanics of skin. Our model accounts for skin microstructure through modeling the probability of fiber orientation and fiber stress-free states. Denaturing induces changes in the stress-free configuration of collagen, as well as changes in fiber stiffness and viscoelastic properties. We propose two competing models that fit all of our experimental observations. These models will enable future developments of thermal-therapeutics, prevention and management of skin thermal injuries, and set a foundation for improved mechanistic models of skin thermo-mechanics.