Challenge of the Soft-tissue to Device Interface: A Rheology-based Approach to Biomaterial Development

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Challenge of the Soft-tissue to Device Interface: A Rheology-based Approach to Biomaterial Development
Holt, Brian M (creator)
Morgan, Jeffrey (Director)
Tripathi, Anubhav (Director)
Darling, Eric (Reader)
Mathiowitz, Edith (Reader)
Huang, Helen (Reader)
Brown University. Biomedical Engineering (sponsor)
Copyright Date
Percutaneous implants are a family of devices that penetrate the skin and suffer from infection-mediated device failure caused by lack of integration/adhesion at the skin/device interface. Mechanical discontinuities at the skin/device interface lead to stress concentrations and micro-trauma that chronically breaks any seal that forms. Minimizing stress concentrations may prevent epidermal regression mediated infection and device failure. This dissertation contained three chapters focused on: 1) the viscoelastic characterization of human skin and dermis-only under dynamic, low magnitude shear loading conditions; 2) a comprehensive rheology-based biomaterial design approach for the development of a novel, porous poly(2-hydroxyethyl methacrylate) [pHEMA]-based substrate intended to match the viscoelastic response of human skin; and 3) an interrogation of the in vitro cellular response to a mechanically matched porous pHEMA substrate. Using a stress-controlled rheometer, isothermal (37oC) frequency response experiments between 0.1 to 10Hz (0.628 to 75.39rad/s) were performed on whole skin and dermis-only samples. Step-stress experiments of 5 and 10Pa shear loads were also conducted. Both the frequency and step stress response data suggested the epidermis provides elastic rigidity and the dermis provides viscoelasticity to the whole skin. Viscoelastic response data of skin was used to design and optimize novel, porous pHEMA-based substrates. Physiologically relevant, isothermal (37oC) oscillatory strain, stress, and frequency response experiments, and temperature-dependent frequency response experiments were conducted. Independent of substrate composition, micro-porous pHEMA substrates were predominately elastic and exhibited stable linear viscoelastic behavior across a wide range of shear strains and stress; mimicking the response of human skin. To determine how cell growth might alter pHEMA substrates human dermal fibroblasts grown on them for fourteen days. As a result of cellular activity, the magnitude of G' and G" increased at low frequencies while also altering the degree of high frequency dependence. The emphasis of mechanically matching a biomaterial's rheological behavior to that of a soft-tissue for skin-related applications is unique. Consequently, this dissertation provided invaluable insight for minimizing the challenge presented by the skin to device interface of percutaneous medical devices, as well as establishing a new design criterion for addressing the obstacles presented by other soft-tissue related clinical and biomedical applications.
human skin
percutaneous device
Regression analysis
Thesis (Ph.D. -- Brown University (2011)
xxii, 176 p.


Holt, Brian M., "Challenge of the Soft-tissue to Device Interface: A Rheology-based Approach to Biomaterial Development" (2011). Biomedical Engineering Theses and Dissertations. Brown Digital Repository. Brown University Library.