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Research Papers

Implantable Sensors for Regenerative Medicine

[+] Author and Article Information
Brett S. Klosterhoff, Robert E. Guldberg

George W. Woodruff School
of Mechanical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332;
Parker H. Petit Institute for
Bioengineering and Bioscience,
Georgia Institute of Technology,
Atlanta, GA 30332

Melissa Tsang

School of Electrical and Computer Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332

Didi She

Department of Electrical and
Systems Engineering,
University of Pennsylvania,
Philadelphia, PA 19104

Keat Ghee Ong

Department of Biomedical Engineering,
Michigan Technological University,
Houghton, MI 49931

Mark G. Allen

School of Electrical and Computer Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332;
Department of Electrical and
Systems Engineering,
University of Pennsylvania,
Philadelphia, PA 19104

Nick J. Willett

Parker H. Petit Institute for
Bioengineering and Bioscience,
Georgia Institute of Technology,
Atlanta, GA 30332;
Department of Orthopaedics,
Emory University,
Atlanta, GA 30303;
Atlanta Veteran's Affairs Medical Center,
Decatur, GA 30033;
Wallace H. Coulter Department
of Biomedical Engineering,
Georgia Institute of Technology
and Emory University,
Atlanta, GA 30332

Manuscript received July 6, 2016; final manuscript received November 28, 2016; published online January 19, 2017. Assoc. Editor: Victor H. Barocas.

J Biomech Eng 139(2), 021009 (Jan 19, 2017) (11 pages) Paper No: BIO-16-1284; doi: 10.1115/1.4035436 History: Received July 06, 2016; Revised November 28, 2016

The translation of many tissue engineering/regenerative medicine (TE/RM) therapies that demonstrate promise in vitro are delayed or abandoned due to reduced and inconsistent efficacy when implemented in more complex and clinically relevant preclinical in vivo models. Determining mechanistic reasons for impaired treatment efficacy is challenging after a regenerative therapy is implanted due to technical limitations in longitudinally measuring the progression of key environmental cues in vivo. The ability to acquire real-time measurements of environmental parameters of interest including strain, pressure, pH, temperature, oxygen tension, and specific biomarkers within the regenerative niche in situ would significantly enhance the information available to tissue engineers to monitor and evaluate mechanisms of functional healing or lack thereof. Continued advancements in material and fabrication technologies utilized by microelectromechanical systems (MEMSs) and the unique physical characteristics of passive magnetoelastic sensor platforms have created an opportunity to implant small, flexible, low-power sensors into preclinical in vivo models, and quantitatively measure environmental cues throughout healing. In this perspective article, we discuss the need for longitudinal measurements in TE/RM research, technical progress in MEMS and magnetoelastic approaches to implantable sensors, the potential application of implantable sensors to benefit preclinical TE/RM research, and the future directions of collaborative efforts at the intersection of these two important fields.

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Figures

Grahic Jump Location
Fig. 1

Schematic outlining the temporal profile of bone regeneration, illustrating phases of healing, structural progression in the defect, and qualitative estimates of environmental parameter profiles. Nondestructive, quantitative measurements of these environmental cues would significantly enhance fundamental understanding of the temporal progression of the bone healing environment as well as many other diseases of interest, providing a better foundation to develop and evaluate effective regenerative therapies. Created using images from Servier Medical Art, CC-BY 3.0.

Grahic Jump Location
Fig. 2

Rendering of one approach which could be implemented to implant sensors in a rodent femoral defect model to measure oxygen tension and/or strain during bone regeneration. Animal injury models utilizing structural implants are particularly advantageous for implantable devices because they provide a stable foundation to anchor the sensor. Depending on the size constraints of the anatomical space under investigation, transceiver and circuitry components could be packaged within a single device or subcutaneous wires could be routed to a remote transceiver pack mounted either intraperitoneally or subcutaneously. Created using images from Servier Medical Art, CC-BY 3.0.

Grahic Jump Location
Fig. 3

Advancements in implantable sensors. Early iterations of implantable sensors featured materials and design approaches that were direct outgrowth from traditional CMOS processing, as denoted by the outward-oriented arrows. However, research developments at the materials-, device- and systems-level have paved the road toward more application-driven, physiologically motivated designs. The integration of these approaches, along with addressing physiological constraints and representative testing, will be necessary for the development of next-generation, implantable sensors for smart regenerative therapies and preclinical tools.

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