Kenneth H. Church

Tissue Engineering by Self-Assembly of Cells Printed into Topologically Defined Structures

Understanding the principles of biological self-assembly is indispensable for developing efficient strategies to build living tissues and organs. We exploit the self-organizing capacity of cells and tissues to construct functional living structures of prescribed shape. In our technology, multicellular spheroids (bio-ink particles) are placed into biocompatible environment (bio-paper) by the use of a three-dimensional delivery device (bio-printer). Our approach mimics early morphogenesis and is based on the realization that the genetic control of developmental patterning through self-assembly involves physical mechanisms. Three-dimensional tissue structures are formed through the postprinting fusion of the bio-ink particles, in analogy with early structure-forming processes in the embryo that utilize the apparent liquid-like behavior of tissues composed of motile and adhesive cells. We modeled the process of self-assembly by fusion of bio-ink particles, and employed this novel technology to print extended cellular structures of various shapes. Functionality was tested on cardiac constructs built from embryonic cardiac and endothelial cells. The postprinting self-assembly of bio-ink particles resulted in synchronously beating solid tissue blocks, showing signs of early vascularization, with the endothelial cells organized into vessel-like conduits.

Rapid prototyping of electronics via direct writing and laser processing

High-quality electronic circuit elements are being written directly onto substrates with relatively low temperature tolerances by means of a pen-dispensing process. Conductor, resistor, and dielectric paste formulations are deposited onto the substrate, then thermally treated with a laser to reach final form. The laser-treatment process is facilitated by using optical pyrometer temperature measurements as real-time feedback for laser power control. The paste deposition and laser processing technologies have been incorporated into the development of a machine tool for conducting rapid prototyping of electronic circuits deposited onto conformal substrates.High-quality electronic circuit elements are being written directly onto substrates with relatively low temperature tolerances by means of a pen-dispensing process. Conductor, resistor, and dielectric paste formulations are deposited onto the substrate, then thermally treated with a laser to reach final form. The laser-treatment process is facilitated by using optical pyrometer temperature measurements as real-time feedback for laser power control. The paste deposition and laser processing technologies have been incorporated into the development of a machine tool for conducting rapid prototyping of electronic circuits deposited onto conformal substrates.

Laser-machined microfluidic bioreactors with printed scaffolds and integrated optical waveguides

Laser micromachining combined with digital printing allows rapid prototyping of complex bioreactors with reduced fabrication times compared to multi-mask photolithography. Microfluidic bioreactors with integrated optical waveguides for diagnostics have been fabricated via ultrashort pulse laser micromachining and digital printing. The microfluidic channels are directly laser machined into poly(dimethylsiloxane) (PDMS) silicone elastomer. Multimode optical waveguides are formed by coating the PDMS with alternating refractive index polymer layers and laser machining to define the waveguide geometry. Tapered alignment grooves are also laser machined to aid in coupling optical fibers to the waveguides. Three-dimensional (3-D) bio-scaffold matrices comprising liquid solutions that can be selectively and rapidly gelled are digitally printed inside the bioreactors and filled with nutrient rich media and cells. This paper will describe the maskless fabrication of complex 3-D bioreactors and discuss their performance characteristics.

CAD/CAM for MEMS and BioMEMS

Novel devices can be relatively simple in theory and modeling, but difficult and many times unfeasible to fabricate in a traditional cleanroom environment. We have developed a CAD/CAM tool capable of integrating multiple materials in the electronic, photonic, and biological regimes for applications in both MEMS and BioMEMS devices. Some materials are known and more fully characterized, such as thick film resistors or conductors, while other materials such as biodegradable scaffolding are new but showing promise to realize heterogenous tissue engineered constructs and drug delivery devices. The tool does not discriminate, but rather places these materials in specified locations with precision volumetric control, gently, conformally, and in 3-D. This paper will describe the enabling aspect of true 3-D maskless fabrication as well as describe multiple device structures and demonstrations.