Major Research Interests
The lab of Timothy King, M.D., Ph.D., focuses on the development of regenerative therapeutics for use in reconstructive plastic surgery. We are pursuing this goal through the investigation of cellular signaling pathways and the development of tissue engineered constructs for use in wound healing.
Why is wound healing research important?
Every year in the United States, more than 1.25 million people suffer from cutaneous burns, and 6.5 million have chronic skin ulcers related to other etiologies such as pressure, venous stasis disease and diabetes mellitus. An estimated excess of $25 billion is spent annually on treatment of chronic wounds, and an additional $12 billion is spent annually on the treatment of scars.
Cutaneous wound healing is a complex, dynamic series of events involving soluble mediators, extracellular matrix and multiple cell types. The ultimate goal of cutaneous healing is rapid wound closure, as well as a functional and aesthetically acceptable scar. If there is a delay in this process, patients will require long-term care of their wounds and are at increased risk of infection, fluid loss and, in severe cases, even death.
Notch and Wound Healing
Notch is a multi-functional transmembrane receptor that regulates cellular differentiation, development, proliferation and survival in multiple tissues in the body (see Figure 1). Notch has been shown to play an essential role in cutaneous wound healing. However, the role of Notch signaling in mammalian skin is not fully understood. Notch signaling has been shown to regulate epidermal development, and a loss of Notch in the skin leads to a “wound-like” environment. We believe that modulation of the Notch signaling in skin could improve wound healing. We are using skin-specific Notch knockout mice, as well as investigations utilizing 3D organotypic cell culture and ex vivo human tissue, to determine the role of Notch in cutaneous wound healing. We will then apply this understanding to the development of a “smart band-aid” that would increase the rate of wound closure.
Figure 1: 3D Organotypic keratinocyte cell culture shows similar architecture to normal skin on H&E (upper left). Involucrin (middle left) and Keratin-10 (lower left), differentiation markers of keratinocytes, are expressed in the superficial layers of the 3D organotypic cultures in a similar fashion to normal skin. All three Notch receptors (right) localize to the basal & suprabasal layers while Notch3 also localizes to the granular layer.
3-D Printing for Tissue Engineering
Current strategies for engineering tissues have yielded a variety of sophisticated tools for fabrication that may have application in future clinical use. Bioprinting technology allows fabrication of biomimetic and even anatomic 3D structures by using images obtained through medical imaging technologies (e.g., computer tomography and magnetic resonance imaging). Faculty in the UAB Department of Biomedical Engineering have designed and constructed a custom bioprinter (see Figure 2). This device is designed to print layers of cells, cell spheroids, and cell-laden bioinks rapidly to reduce fabrication time. King and Joel Berry, Ph.D., associate professor of biomedical engieneering, are currently applying this technology to the development of 3D printed skin for use in wound healing.
Figure 2: Custom designed 3D bioprinter currently in development. (Image courtesy of Dr. Berry, BME faculty)
Additional Research Activities
In addition to his active translational research laboratory, King has several clinical studies in plastic and reconstructive surgery. Some recent topics include disparities in the treatment of facial trauma, disparities in the treatment of upper extremity trauma and disparities in the treatment of lower extremity trauma.