Project History

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Our lab has a long history of work in this area, dating back to 1993, almost 30 years. Skin breakdown in prosthesis users is a debilitating problem. It is painful and frustrating. It typically prevents a person from using their prosthesis until the damaged tissue heals, limiting mobility and limiting the patient's quality of life.

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When first starting in this area, our initial focus was to figure out how skin adapts to mechanical stress on a microstructural level and then use that insight to design a non-invasive imaging modality to quantify those microstructural changes. In 1995, we published a literature review on research from the evolutionary and developmental adaptation, biomechanics, and rehabilitation fields, from which we gleaned useful clinical insight (1995.1).

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Dr. Dan Leotta, then a PhD student in Bioengineering, now a senior engineer at the Applied Physics Laboratory at the University of Washington, pursued the use of ultrasound to pick up the collagen fibril structural changes we expected to see based on our literature review (1993, 1994, 1995.2). Ultimately, that avenue of research was never funded thus we were unable to pursue it further. However, with Dan's help and much assistance from Rehabilitation Medicine Professor Barry Goldstein MD-PhD, we successfully developed an animal model (pig) (1998), a "skin scrubber" (a closed-loop biaxial force applicator) (1997), and image processing strategies (1999) to characterize skin adaptation to mechanical stress. Professor Joe Garbini in Mechanical Engineering and graduate students Jamie Leschen and Mike Strange were instrumental in engineering aspects of this endeavor. That work was very well received - Professor Sanders was awarded the Whitaker Young Investigator George W. Thorn Award for that work (1996.2). From that effort we found (1996.1, 1998) that skin adapted to mechanical stress by increasing its fibril diameter, decreasing its fibril density (fibrils/cross-sectional area), and maintaining a relatively consistent total volume of collagen (2001).

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With NIH funding, we extended the project to engineer an environmental system to execute the same mechanical loading strategy on an excised piece of skin, a skin explant from a pig. Using this system we found comparable results to the in vivo studies in terms of fibril diameter and fibril density changes in response to repetitive mechanical stress (2002). The finding is relevant because it suggests that the blood-borne inflammatory response cells, i.e., macrophages, are not involved in skin adaptation. We realized that skin adaptation is not so much an inflammatory response as a directed remodeling response. The blood likely triggered remodeling, but not through inflammatory cell cytokines like happens in wound healing. This changed how we thought skin adaptation happened. Postdoctoral fellow Dr. Yak-Nam Wang, now a principal research scientist/engineer at the Applied Physics Laboratory at the University of Washington, developed a hypothesis of how skin adapts to mechanical stress at a cellular and molecular level (2003), and put that effort into a more global perspective (2005). We conducted a preliminary study that suggested our adaptation hypothesis was at least partially correct. Our results in terms of cellular level response variables were consistent with the hypothesis. However, control samples also demonstrated meaningful changes, suggesting that part of the response was due to the transition to the in vitro cell culture environment. The molecular-based hypothesis needs to be tested and could lead to drug based therapies for skin adaptation in patients. However, this avenue of research at the molecular level is not within our lab's area of expertise.

We determined that we would contribute more effectively to enhanced clinical care by addressing the question, "How can we tell if a patient's skin is poorly adapted, and thus likely at risk of injury?" We reasoned that a key was to understand the bioprocess, what the body does to adapt properly. We knew from our studies so far that the collagen architecture remodeled without a meaningful gain in collagen volume, a very efficient process. We reasoned that a key indicator was the local transportation highway, i.e., the microvasculature in the skin. A group from the Netherlands led by Dr. Jan H. Meijer had done some related work on spinal cord injury patients using thermistors placed on the skin to try to predict early skin injury. We extended from that work using infrared imaging for assessment, first a handheld unit on the pig model (2000) and then a dynamic thermal imaging system on amputee participants (2007). In clinical studies, we asked prosthesis users to stand or walk in place, then quickly sit and doff their prosthesis and liner. We thermally imaged the residual limb for about 10 min. Qualitatively, results showed longer thermal recovery times in locations that within the next one to two months experienced clinical skin breakdown (2007).

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Though our efforts were successful and the remarkable infrared imaging results laid the foundation for a novel means to assess skin quality in prosthesis users, funding agencies did not continue to support this avenue of our research, despite our several attempts over the ensuing years. In the mid 2010's, PhD student Eric Swanson joined our lab and with help from Bioengineering Professor Ricky Wang PhD and Utku Baran, pursued the use of Optical Coherence Tomography for skin adaptation assessment (2018). Eric and the team, in collaboration with Rehabilitation Medicine Professor Janna Friedly MD, conducted  a series of investigations characterizing vascular microstructural response in skin adapting to repetitive mechanical stress. He also characterized skin subjected to a temporary thermal increase (2020, 2021.2). In addition, Dr Swanson compared the residual limb and contralateral limb of prosthesis users. Dr. Ty Youngblood, another PhD student in the lab, was at the time trying to understand how elevated vacuum affected skin physiology. He used Eric's OCT system on elevated vacuum users to characterize their vascular microstructural response to stress (2021.1).

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