Research Grants in Computer Aided Tissue Engineering

Project Title:         Study of Bio-deposition Induced Effect on Living Cells

Funding Agency:  National Science Foundation: NSF Bio/Nano Division: NSF-0427216;

                               PI: W. Sun, Co-PI: K. Barbee (Drexel) and M. Marcolongo (Drexel)

                               $225,000 from 7/1/2007 - 6/30/2010

Project Title:         Computer-Aided Tissue Engineering

Funding Agency:  National Science Foundation: NSF-ITR  for "National Priorities": NSF-0427216;

                               PI: W. Sun, Co-PI: A. Shokoufandeh (Drexel) and M. Liebschner (Rice)

                               $1,000,000 from 10/1/2004 - 9/30/2008

Project Title:        International Workshop for Biomanufacturing

Funding Agency:  National Science Foundation: NSF-ITR: NSF-0520958

                               PI: W. Sun, $30,000, 6/1/2005 - 5/30/2006

Project Title:         MRI:  Acquisition of a High Resolution X-ray Tomography Unit

Funding Agency:  National Science Foundation: NSF-0521309

                                $349,267, 10/1/2005 - 9/30/2006 (Co-PI)

Project Title:         Representation and Design of Heterogeneous Structures

Funding Agency:  National Science Foundation: NSF-ITR: NSF-0219176

                               PI: W. Sun, Co-PI: A. Shokoufandeh and W. Regli

                               $481,605 from 10/1/2002 - 9/30/2005 

Project Title:         Accuracy and Stability of Computational Representations of Swept Volume Operations

Funding Agency:  NSF/DARPA - 0310619

                               PI: D. Blackmore, Co-PI: M. Leu (Missouri-Rolla), W. Regli and W. Sun (Drexel)

                               $450,000 from 7/1/2003 - 6/30/2006

Project Title:         Biopharmaceutical and Anatomical Tissue Replacement Structures:

                               Process Modeling and Simulation

Funding Agency:  Therics Corporation

                               PI: W. Sun, Co-PI: A. Lau

                               $253,052 from 10/1/2001 - 9/30/2005

Project Title:         Combined Research and Curriculum Development in Tissue Engineering

Funding Agency:  National Science Foundation: NSF-9980298

                               PI: C. Laurencin (Virginia), Co-PI: Ko, Marcolongo and Sun (Drexel)

                               $499,602 from 10/1/1999 - 9/30/2002

Biomechanical design and bio-manufacturing of tissue engineered substitutes:

One of our recent research focuses in computer-aided tissue engineering has been in developing a bio-manufacturing process and a proprietary multi-nozzle biopolymer deposition system* for freeform fabrication of bioactive cell-embedded tissue scaffolds, constructs and tissue precursors. The developed process and system is aiming at providing methods and apparatus for manufacturing complex devices for use in areas including, but not limited to, tissue engineering, 3D cell printing and assembly, tissue scaffold fabrication, tissue cultures, biochips, biosensors, cytotoxicity test samples, and other fields that are currently limited by conventional methods of manufacture.

The developed process and system integrates the  computer-aided design; medical imaging process and 3D reconstruction; heterogeneous material and multi-part assembly; biomimetic and non-biomimetic design; and multiple types of nozzles capable of handling a wide range of materials as well as multiple modes of nozzle operation such as droplet deposition, extrusion, and spraying; and a biologically friendly design capable of direct cell deposition to create a viable and versatile bio-manufacturing process to simultaneously deposit cells with scaffolding materials to form cell-seeded tissue substitutes.  Accordingly, the system also permits construction of complex or smart tissue scaffolds capable of eliciting complex behaviors of cells including, but not limited, to growth, migration, differentiation, and expression.  Tissue engineering scaffolds produced in accordance with the methods and/or using the developed process can also assist with the flow and transport of vital nutrients and oxygen, and the removal of waste products required by cells seeded within the scaffolds.

 *"Methods and Apparatus for Computer-Aided Tissue Engineering for Modeling, Design and Freeform Fabrication of Tissue Scaffolds, Constructs, and Devices", US Provisional Patent #: 60/520,672 (2003), US and International Patent Application #: PCT/US2004/015316 (2004), Sun, Nam, Darling and Khalil.

Modeling and direct fabrication of random heterogeneous tissue structures

This research focuses on image-based multi-scale modeling, direct fabrication and mechanical analysis of bone and scaffold. Based on the digital images, the overall macroscopic geometry of bone can be acquired by traditional reverse engineering technology and the microscopic random trabecular network is described by a two-point correlation function and the function was then used to reconstruct the bone microstructure. It is shown that the reconstructed model is statistically equivalent to the original structure in the microscopic level. Biological tissue engineering design intention can also be integrated in the developed model. A voxel-based direct-fabrication process planning is developed and this makes the manufacture of complex tissue structure possible due to the elimination of CAD modeling and slicing process.

This research is currently being conducted by Zhibin Fang (Ph.D. Candidate)

Hybrid scaffold modeling and fabrication for tissue engineering application

Using multiple materials to freeform fabricate hybrid tissue scaffolds enable us to produce scaffolds with complex architectures to meet many needs of growing tissue.  For instance, poly-caprolactone may be used for structural support while fibrin is used for cell attachment and alginate is used to provide a diffusion network for nutrient transport. The long-term goal of this research is to explore a feasibility of designing and fabricating scaffolds in which multiple tissues will be able grow within a single scaffold, restricted to regions for which they are intended by manipulation of materials and architecture.

This research is currently being conducted by Andrew Darling (Ph.D. Candidate)

Biomimetic design and fabrication of load bearing tissue scaffolds/replacements

The design of 3D tissue scaffolds for tissue engineering application should, if possible, biomimic the complex hierarchy and structural heterogeneity of the replaced tissues. The objective of this research is to develop a computer aided tissue engineering approach for reconstruction, characterization, and the design of load bearing tissue scaffold informatics model. A biomimetic approach for modeling, design and fabrication of tissue scaffolds with intricate architecture, porosity and pore size is proposed. An Interior Architecture Design (IAD) approach which can be applied to generate scaffold layered freeform fabrication tool path without forming complicated 3D CAD scaffold models is developed. This IAD approach 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 scaffolds with the specified interior architectures. 

This research is currently being conducted by Binil Starly (Ph.D. Candidate)

Biopolymer deposition for freeform fabrication of tissue constructs

Polymeric scaffolds have been utilized in tissue engineering as a technique to confide the desired proliferation of seeded cells in vitro and in vivo into its architecturally porous three-dimensional structures. The ideal manufacturing of scaffolds may include cells simultaneously deposited along with the scaffolding materials, growth factor, and other nutritional and biological species. This research is attempted to fabricate biopolymer-based tissue scaffold at a bio-friendly environment, and develop a multi-nozzle biopolymer freeform deposition system. Studies on the biopolymer deposition-ability, 3D scaffold structural formability, and the construction of 3D hydrogel scaffold with living cells under different process parameters, such as nozzle sizes, types, regulating pressure and loading, the property of the biopolymer and the cross-linking agents are currently pursued, along with the study of the process-dependent cellular tissue engineering behavior of 3D tissue constructs.

This research is currently being conducted by Saif Khalil (Ph.D. Candidate)

Topological and transport connectivity for the tissue scaffolds

Scaffold design, porosity characteristics and the scaffold topological connectivity directly affect cell attachment, survival, proliferation, growth and guide new tissue formation.  Cell survival and continued growth depend on delivery of nutrients and removal of waste.  This dependence requires scaffold design to have pathways or connections allowing fluid and mass transport to cells throughout the scaffold.  Collaborating with Computer Science researchers, this study establishes topological connectivity criteria, analyzes optimal transport architectures, and develops 3D skeleton and Earth Mover's Distance based algorithm for topological matching between designed tissue scaffolds to insure suitable connections for scaffold flow, mass transport, properties and fabrication.

This research is currently being conducted by Connie Gomez and Fatih Demirci (Ph.D. Candidate)

Computer-aided tissue engineering approach for advanced tissue scaffold design

By using computer-aided design in conjunction with rapid prototyping and tissue engineering, computer-aided tissue engineering (CATE) has the power to explore many novel ideas that push the envelope of conventional scaffold designs by incorporating biomimetic and non-biomimetic features.  CATE can be used to design and create scaffolds with controlled internal and external architecture; scaffolds with vascular channels of different sizes; modular scaffolds with interconnecting subunits; multi-layered scaffolds with spongy and compact regions; scaffolds with artificial structures such as chambers for drug delivery.

This research is currently being conducted by Jae Nam (Ph.D. student)

Polymer Extrusion using Precision Extrusion Deposition

Successes in scaffold guided tissue engineering require scaffolds to have specific macroscopic geometries and internal architectures in order to provide the needed biological and biophysical functions. Freeform fabrication provides an effective process tool to manufacture many advanced scaffolds with designed properties. Using a novel Precision Extruding Deposition (PED) process technique, Poly-є-Caprolactone (PCL) scaffolds with a controlled pore size of 250 μm and designed structural orientations were fabricated. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using SEM, Micro-Computed Tomography (µ-CT) and the mechanical testing. Preliminary biological study was also conducted to investigate the cell responses to the as-fabricated tissue scaffolds. The results and the characterizations demonstrate the viability of the PED process to the scaffold fabrication as well as a good mechanical property, structural integrity, controlled pore size, pore interconnectivity, and the anticipated biological compatibility of the as-fabricated PCL scaffolds.

This research is currently being conducted by Lauren Shor (Ph.D. student, co-advisor with Dr. Güçeri)

Image Guided Craniofacial Reconstructive Surgery

This is a collaborative research with Dr. Piatt, Chief of Neurosurgery at St Christopher’s Hospital for Children. Critical to the success of craniofacial surgery is the surgeon’s accurate perception of the anatomy of the deformity.  This research is to develop a biomodeling and its application for quantitative control of craniofacial reconstructive procedures. Computed tomographic (CT) images of the patient’s skull are used to construct a 3D model of the deformity. Based on this model, a virtual reconstructive surgery is performed for  both the deformed and reconstructed skulls and the physical medical prototypes are fabricated using a 3D Rapid Prototyping system. The reconstructed skull is then CT scanned.  Employing the proprietary software of the BrainLab® surgical image guidance system, the virtually reconstructed image data set can be superimposed or “fused” with the original data set. The BrainLab® system then enables the surgeon to verify each step of the reconstruction procedure in real time, and discrepancies from the actual and the ideal can be corrected at the region of deviation.

This research is currently being conducted by Binil Starly (Ph.D. Candidate)

Modeling of Cell-Substrate Interaction

This research focuses on modeling cell-substrate interactions and mechanism of durotaxis for hydrogel based tissue scaffolds.

This research is currently being conducted by Kalyani Nair (Ph.D. student)

Biomechanical Design and Analysis of Spinal Implant

This research focuses on full scale computational modeling and biomechanics analysis of vertebral column and implant.

This research is currently being conducted by Peter Evans (M.S. student)

“Methods and Apparatus for Computer-Aided Tissue Engineering for Modeling, Design and Freeform Fabrication of Tissue Scaffolds, Constructs, and Devices”, US Patent #: 60/520,672 (2004), W. Sun, J. Nam, A. Darling and S. Khalil, pending.

“Apparatus, Method and Article for Direct Slicing of Step Based NURBS Models for Solid Freeform Fabrication”, US Patent #: 60/487,463 (2004), Thomas J. Bradbury, Binil Starly, Wing K. Lau, Wei Sun, Alan C. Lau, Adolphe H. Youssef and Christopher M. Gaylo, pending.

“A Functional Electrical Stimulation Micro-Processor Controlled Ankle Orthosis”, Application for the United States Letters Patent, 4/30/2004, S. Siegler, W. Sun, pending.

“Computer-Aided Tissue Engineering of a Biological Body”, Applications for the United States Letters Patent, 11/21/2004, M. A. Liebschner, M. A. Wettergreen, B. S. Bucklen and W. Sun, pending.

“Shear and Bubble-Resistant Macro-Carrier Beads for Anchorage-Dependent Cell Culture and Complementary Bioreactor”, the United States Letters Provisional Patent, D2027/20008, 2005, A. Darling and W. Sun, pending.

“Precision Extrusion Deposition Poly--Caprolactone Structures for Biological Applications”, the United States Letters Provisional Patent, D2027/20009, 2005,, A. Darling, L. Shor, W. Sun and S. Guceri, pending.

“Layered manufacturing utilizing foam as a support and multifunctional material for the creation of “soft” parts and for tissue engineering”, the United States Letters Provisional Patent, D2027/20007, 2005,, J. Nam and W. Sun, pending.

“A method for creating an internal transport system within tissue scaffolds using computer-aided tissue engineering”, the United States Letters Provisional Patent, D2027/20006, 2005,, W. Sun and J. Nam, pending.

“A Process of Using Computer Modeling, Reconstructive Modeling and Simulation Modeling for Image Guided Reconstructive Surgery”, J. Piatt, B. Starly and W. Sun, the United States Letters Provisional Patent, D2027/20010, 2005,, W. Sun and J. Nam, pending.

Dr. Fred Allen, School of Biomedical Sciences and Engineering, Drexel University (cellular biology, tissue engineering)

Dr. Yuehuei An, Medical University of South Carolina (animal testing, in vivo study)

Dr. Dennis Blackmore, NJIT (algebraic algorithm, mathematical modeling)

Dr. Steve Gonda, NASA JSC (bioreactor, microgravity, tissue engineering)

Dr. Selçuk Güçeri, Dept of Mechanical Engineering, Drexel University (Fabrication of ceramic-ceramic composites; Fused deposition rapid prototyping of ceramics, nanotechnology)

Dr. Frank Ko, Dept. of Materials Science and Engineering, Drexel University (biomaterials, tissue engineering)

Dr. Alan Lau, Dept of Mechanical Engineering, Drexel University (computational analysis and simulation, fracture mechanics)

Dr Peter Lelkes, School of Biomedical Sciences and Engineering, Drexel University (Cellular tissue engineering, cellular biology)       

Dr. Ming C Leu, University of Missouri, Rolla (CAD/CAM, virtual reality, manufacturing)

Dr. Michael Liebschner, Dept of Bioengineering, Rice University (bioengineering, biomechanics)

Dr. Feng Lin, Dept of Mechanical Engineering, Tsinghua University (CAD/CAE/CAM)

Dr. Joe Piatt, St. Christopher Children’s Hospital, Philadelphia (neurosurgery, Computer-Assisted Craniofacial Reconstructive Surgery)

Dr. William C. Regli, Dept of Math and Computer Science, Drexel University (Internet computing , artificial intelligence , geometric computation)

Dr. Caroline Schauer, Department of Materials Science and Engineering, Drexel University (biomaterials)

Dr. Ali Shokoufandeh, Dept of Computer Science, Drexel University (mathematic graph theory, pattern recognition, data clustering, gesture recognition)

Dr. Francis Wang, NIST (biopolymers)

Dr. Yongnian Yan, Dept of Mechanical Engineering (CAD/CAM, Tissue Engineering)