Microfluidic-Based 3D Tissue Model for
Infection-Preventing Biomaterials Research

Woo Lee
Stevens Institute of Technology

Infection is one of the leading causes of biomedical device failure today.  Infection occurs 
because of bacteria cells adhere to the abiotic surface of implanted devices, and form highly 
cooperative communities known as biofilms.  In sessile biofilm microenvironments, slow-growing 
or stationary bacteria cells are encapsulated by an extracellular matrix and exhibit extraordinary 
resistance to host defense and antibiotics.  Standard care today therefore is the removal of 
infected devices.  A promising solution to address the device-associated infection problem is the 
development of coatings that contain antimicrobial agents and/or antifouling materials.  However, 
demonstrating the efficacy of infection-preventing biomaterials has been difficult mainly 
because:  (1) in vitro and in vivo results are often contradictory and (2) clinical studies require 
large patient populations due to low infection rates and are therefore become rather costly.   
There is an important need to enhance the predictive capability of in vitro tools, which can 
complement animal and clinical studies, for rapid development and rational translation of new 
coating and surface formulation ideas to clinical practice.  

With recent advances in tissue regeneration and microfluidics, we can envision the possibility of 
modeling the complex and dynamic interplay involving: (1) the physiology of wound healing, (2) 
the pathogenesis of device infection, and (3) infection-preventing coating formulations.  For 
eukaryotic cell biology and tissue regeneration studies, microfluidic devices have been explored 
to understand and control biological phenomena occurring under various geometrical, fluid 
dynamic, and mass transport constraints of physiological microenvironments.  Soft lithography, 
based on polydimethylsiloxane (PDMS), is now routinely used as a simple yet versatile way of 
fabricating microfluidic devices with complex geometries and functions with attractive properties 
of PDMS as a biocompatible, transparent, and elastomeric material.  These new microfluidic-
based tools are being applied to advance the speed of our progress in understanding 
microenvironment factors such as soluble factors, cell-cell communication, physical forces, 
extracellular matrix (ECM), and 3-D architecture.  

This lecture will describe our long-term objectives and approach to develop a 3D tissue model 
with the ability to emulate three levels of tissue responses to bacteria inoculation with the 
following order of increasing complexity:  (1) healthy soft tissue with relevant 3D spatial 
organization, vascularization, and immune components; (2) progression of wound healing with a 
provisional ECM region adjacent to the healthy tissue to represent a wound site; and (3) 
development of poorly organized vascular capillaries during wound healing in the provisional 
ECM region between the healthy tissue and the biomaterials surface, due to the lack of 
interstitial flow perpendicular to the biomaterial surface.   I will share initial design concepts and 
building blocks for constructing the 3D tissue model based on our experience to date with 
microfluidic devices for:  (1) co-culturing eukaryotic cells and bacteria in the context of the well-
accepted "race for the surface" phenomenon, (2) creating and analyzing interstitial flow 
conditions with ECM-filled microchambers, and (3) integrating biomaterial surface into the 
microfluidic chamber while producing physiologically relevant flow conditions on the biomaterial 
surface.  The lecture is intended to invite many questions and criticisms about the realism 
behind building the desired tissue model as well as about the eventual utility of the tissue model 
for high-throughput evaluation of the efficacy of infection-preventing coatings and, more broadly, 
for screening new antibiotic compounds in this era of rapidly emerging antibiotic-resistant 
bacteria strains.