UV-Photolithography Fabrication of Poly-Ethylene Glycol Hydrogels Encapsulated with Hepatocytes

The development of biomanufacturing technologies particularly, layered manufacturing has advanced cell encapsulation processes in an effort to mimic the cellular microenvironment for invitro studies. This paper illustrates an inexpensive UV-photolithographic method for encapsulation of human hepatocytes in three dimensional structures using poly-ethylene diacrylate (PEGDA) hydrogels as candidate substrates. In order to further develop this technology for layered fabrication, we have quantified the long-term effects of the photo-initiator concentration and UV light exposure on the metabolic rates of encapsulated human hepatocytes under a 21 day study. The photoinitator toxicity was observed immediately after polymerization with no significant cytotoxicity on a long term basis. A cellular viability is examined and reported for the UV photopolymerization process. Cell phenotype maintenance was observed by measuring the amount of urea produced over a 1 week time period. This photo encapsulation process may find use in the fabrication of spatially complex 3D scaffolds for tissue engineering applications, elucidation of the 3D structure-pharmacokinetic response relationship and the fabrication of complex multi-compartment liver tissue analog devices for drug screening applications.Mechanical Engineerin

Biomimetic Design and Fabrication of Interior Architecture of Tissue Scaffolds Using Solid Freeform Fabrication

Modeling, design and fabrication of tissue scaffolds with intricate architecture, porosity and pore size for desired tissue properties presents a challenge in tissue engineering. This paper will present the details of our development in designing and fabrication of the interior architecture of scaffolds using a novel design approach. The Interior Architecture Design (IAD) approach seeks to generate scaffold layered freeform fabrication tool path without forming complicated 3D CAD scaffold models. This involves: applying the principle of layered manufacturing to determine the scaffold individual layered process planes and layered contour; defining the 2D characteristic patterns of the scaffold building blocks (unit cells) to form the Interior Scaffold Pattern; and the generation of process tool path for freeform fabrication of these scaffolds with the specified interior architecture. Feasibility studies applying the IAD algorithm to example models and the generation of fabrication planning instructions will be presented.Mechanical Engineerin

Layered Fabrication of Branched Networks Using Lindenmayer Systems

A current challenge impeding the growth of bone tissue engineering is the lack of functional scaffolds of geometric sizes greater than 10mm due to the inability of cells to survive deep within the scaffold. It is hypothesized that these scaffolds must have an inbuilt nutrient distribution network to sustain the uniform growth of cells. In this paper, we seek to enhance the design and layered fabrication of scaffold internal architecture through the development of Lindenmayer systems, a graphical language based theory to create nutrient delivery networks. The scaffolds are fabricated using the Texas Instruments DLP™ system through UV‐photopolymerization to produce polyethylene glycol hydrogels with internal branch structures. The paper will discuss the Lindenmayer system, process planning algorithms, layered fabrication of samples, challenges and future tasks.Mechanical Engineerin

Freeform Bioprinting of Liver Encapsulated in Alginate Hydrogels Tissue Constructs for Pharmacokinetic Study

An in vitro model that can be realistically and inexpensively used to predict human response to various drug administration and toxic chemical exposure is needed. By fabricating a microscale 3D physiological tissue construct consisting of an array of channels and tissue-embedded chambers, one can selectively develop various biomimicking mammalian tissues for a number of pharmaceutical applications, for example, experimental pharmaceutical screening for drug efficacy and toxicity along with apprehending the disposition and metabolic profile of a candidate drug. This paper addresses issues relating to the development and implementation of a bioprinting process for freeform fabrication of a 3D cell-encapsulated hydrogel-based tissue construct, the direct integration onto a microfluidic device for pharmacokinetic study, and the underlying engineering science for the fabrication of a 3D microscale tissue chamber as well as its application in pharmacokinetic study. To this end, a prototype 3D microfluidic tissue chamber embedded with liver cells encapsulated within a hydrogel matrix construct is bioprinted as a physiological in vitro model for pharmacokinetic study. The developed fabrication processes are further validated and parameters optimized by assessing cell viability and liver cell phenotype, in which metabolic and synthetic liver functions are quantitated.Mechanical Engineerin

Direct Slicing of STEP Based NURBS Models for Solid Freeform Fabrication

Direct slicing of CAD models to generate process planning instructions for solid freeform fabrication may overcome inherent disadvantages of using STL format in terms of the process accuracy, ease of file management, and incorporation of multiple materials. This paper will present the results of our development of a direct slicing algorithm for layered freeform fabrication. The direct slicing algorithm was based on a neutral, international standard (ISO 10303) STEP-formatted NURBS geometric representation and is intended to be independent of any commercial CAD software. The following aspects of the development effort will be presented: 1) Determination of optimal build direction based upon STEP-based NURBS models; 2) Adaptive subdivision of NURBS data for geometric refinement; and 3) Ray-casting slice generation into sets of raster patterns. Feasibility studies applying the direct slicing algorithm to example models and the generation of fabrication planning instructions involving multi-material structures will also be presented.Mechanical Engineerin

Direct slicing of STEP based NURBS models for layered manufacturing

Abstract Direct slicing of CAD models to generate process planning instructions for solid freeform fabrication may overcome inherent disadvantages of using stereolithography format in terms of the process accuracy, ease of file management, and incorporation of multiple materials. This paper will present the results of our development of a direct slicing algorithm for layered freeform fabrication. The direct slicing algorithm was based on a neutral, international standard (ISO 10303) STEP-formatted non-uniform rational B-spline (NURBS) geometric representation and is intended to be independent of any commercial CAD software. The following aspects of the development effort will be presented: (1) determination of optimal build direction based upon STEP-based NURBS models; (2) adaptive subdivision of NURBS data for geometric refinement; and (3) ray-casting slice generation into sets of raster patterns. The development also provides for multi-material slicing and will provide an effective tool in heterogeneous slicing processes.

Computer-aided characterization of effective mechanical properties for porous tissue scaffolds

porous tissue scaffold

Layered Composite Model for Design and Fabrication of Bone Replacement

Biological tissues are inherently heterogeneous. The design of 3D tissue scaffolds for tissue engineering application should, if possible, biomimic the complex hierarchy and structural heterogeneity of the replaced tissues. This is particularly true for design of bone scaffolds with structural properties compatible with the spatial heterogeneity and mechanical properties of the replaced tissue. The paper presents an image-based computer modeling approach for reconstruction, characterization, and biomimetic modeling and design of three-dimensional heterogeneous tissue structure. The presented work will cover: 1) overview of biomimetic modeling and design of bone structures and reverse engineering for CAD-based constructive solid geometry; 2) design of bone scaffold; and 3) slicing and process planning for solid freeform fabricationWe gratefully acknowledge support from NSF CRCD-9980298 and support from Therics, Inc.Mechanical Engineerin

of tissue replacement structures

Internal architecture design and freeform fabricatio

Scalable Linking of Slice Layer Information with Process Monitoring Data in Additive Manufacturing Machines

In smart connected factories, manufacturing machines are capable of generating vast amounts of process data generated internally from within its control systems or from sensors coupled with the process. This streaming data must be stored and queried to perform data analytics or closed loop control to improve manufacturing processes. Currently, structured data schemas are ineffective in handling image and time-series data generated from additive manufacturing machines. In this paper, we propose an unstructured data schema through NoSQL document oriented database systems as an effective and scalable approach to capturing and storing real-time streaming data for process monitoring. In addition, we present an approach to linking in real-time, slice layer information and tag it with process related sensor data for performing fast, scalable queries either in real-time or post-fabrication. We have demonstrated our approach with two classes of additive manufacturing machines – Fused Deposition Modeling and Electron Beam Melting Systems from Makerbot and ARCAM respectively.Mechanical Engineerin