This work focused on building interdisciplinary collaborations between engineers, scientists and clinicians to develop new flexible electronic solutions for clinical applications, initially focusing on new technologies and methods for wound healing. Through a vibrant, continuous and extremely productive collaboration between researchers and clinicians at the University of California, Berkeley and the University of California, San Francisco, a number of successful technologies were developed and transitioned from laboratory into early clinical tests. Several examples of the innovations that resulted from this funded effort are illustrated below.

A technology for monitoring and predicting pressure ulcers (Figure 1). When pressure is applied to a localized area of the body for an extended time, the resulting loss of blood flow and subsequent reperfusion to the tissue causes cell death and a pressure ulcer develops. Preventing pressure ulcers is challenging because the combination of pressure and time that results in tissue damage varies widely between patients, and the underlying damage is often severe by the time a surface wound becomes visible. Prior to our work, no method existed to detect early tissue damage and enable intervention. We demonstrated a flexible, electronic device that non-invasively mapped pressure-induced tissue damage, even when such damage cannot be visually observed. Our results demonstrated the feasibility of an automated, non-invasive ‘smart bandage’ for early detection of pressure ulcers. The technology was translated in a collaboration with Dr. David Young, M.D. at the University of California, San Francisco, who is now leading an effort to commercialize the technology.

Flexible technologies for medical devices (Figure 2). More broadly, bioelectronic interfaces require electrodes that are mechanically flexible and chemically inert. Flexibility allows pristine electrode contact to skin and tissue, and chemical inertness prevents electrodes from reacting with biological fluids and living tissues. Flexible gold electrodes are ideal for bioimpedance and biopotential measurements such as bioimpedance tomography, electrocardiography (ECG), electroencephalography (EEG), and electromyography (EMG). However, prior to this effort, a manufacturing process to fabricate gold electrode arrays on plastic substrates was elusive. Khan and colleagues demonstrated a fabrication and low-temperature sintering (≈200 °C) technique to fabricate gold electrodes. Overall, the fabrication process of an inkjet-printed gold electrode array that was electrically reproducible, mechanically robust, and promising for bioimpedance and biopotential measurements was demonstrated.

A Magnetic compression anastomosis (Magnamosis): from bench to trials (Figure 3,4). Intestinal anastomosis is fundamental to general surgery. Currently, most anastomoses are either hand-sewn or made with stapling devices, but a device that could automatically and consistently produce an optimal anastomosis could reduce morbidity and save significant operative time and resources. The concept of compression anastomosis is first credited to French physician Felix-Nicholas Denans in the early 19^th century. Magnetic compression anastomosis (“magnamosis”) is a modern iteration of this classic idea, which uses the force of magnetic attraction to form an intestinal anastomosis without sutures or staples.    As part of this work, researchers at the University of California, San Francisco pioneered new technologies which leveraged the magnamosis concept.  The MagnamosisÔ device (Magnamosis, Inc., San Francisco, CA) is a matched pair of self-centering, rare earth magnets encased in polycarbonate. The two rings self-align and self-center, and the mated rings compress the interposed tissue. The device produces a gradient of compressive forces on the bowel wall that causes transmural ischemia and necrosis centrally, but allows for remodeling of the intestine at the periphery, to gradually form a full-thickness anastomosis. In extensive pre-clinical testing, including animal trials in over 90 pigs and 10 monkeys, we have demonstrated the device’s ability to consistently create histologically well-formed anastomoses with burst strength comparable to or better than hand-sewn or stapled anastomoses.

Impedance spectroscopy for monitoring bone healing. Lastly, new and successful efforts have grown out of the work supported by these funds. One example, is multi-year, multi-investigator project focused on applying the impedance spectroscopy technology used to detect pressure ulcers to the healing of bones; this work is being performed by researchers in the Maharbiz lab at the University of California, Berkeley and researchers and clinicians at the University of California, San Francisco in the Center for Disruptive Musculoskeletal Innovations (CDMI). Accurate evaluation of fracture healing is important for clinical decisions on when to begin weight-bearing and when early intervention is necessary in cases of fracture nonunion. While the stages of healing have been well characterized, physicians typically track fracture healing by using subjective physical examinations and radiographic techniques that are only able to detect mineralized stages of bone healing. This exposes the need for a quantitative, reliable technique to monitor fracture healing. Recently, we showed that impedance spectroscopy not only can distinguish between cadaver tissues involved throughout fracture repair, but also correlates to fracture callus composition over the middle stages of healing. Work towards the development of implantable devices for monitoring bone healing is well underway.

Last Modified: 08/19/2017
Modified by: Michel M Maharbiz