Biomimetic design and fabrication of tissue engineered scaffolds using computer aided tissue engineering

The field of tissue engineering brings together the multidisciplinary research of life sciences and engineering to seek man-made substitutes for the regeneration of damaged tissue or organs. A key component in tissue engineering is the use of porous scaffolds to guide cells for attachment, proliferation and differentiation in the tissue regenerative process. Upon satisfactory in-vitro culture, this engineered living scaffold is implanted into the regeneration site of the patient to function as the tissue substitute. Conventional processing techniques for the fabrication of scaffolds often encounter difficulties in the precise control of the internal architecture, interconnectivity and distribution of pores within the scaffold. These challenges, along with the advances in biology, medicine, and information technology for tissue engineering applications, have led to the development of a new field of Computer Aided Tissue Engineering (CATE). CATE enables a systematic application of computer-aided technologies, i.e., computer-aided design (CAD), image processing, computer-aided manufacturing (CAM), and solid freeform fabrication (SFF) for modeling, designing, simulation, and manufacturing of biological tissue and organ substitutes. Through the use of CATE, the design of intricate three dimensional architecture of scaffold can be realized and these scaffolds can be fabricated with reproducible accuracy to assist biologists in studying complex tissue engineering problems. This thesis reports a research addressing some of the challenges in applying the CATE approach for the biomimetic design and freeform fabrication of tissue scaffolds. The major research accomplishments reported in this thesis include: (a) The development of a BioCAD modeling technique for the design and representation of patient specific 3D tissue models based on non-invasive medical image data. (b) The development of a biomimetic design approach for design of load bearing tissue scaffold subject to multiple biophysical, geometrical and manufacturing requirements. This includes the design of the unit cell micro-architecture based on tissue morphologies, unit cell characterization and evaluation of the mechanical and transport properties, and the use of unit cells as building block to design anatomic tissue scaffold replacements. (c) The development of a CAD based path planning procedure through a direct slicing algorithm which can convert a neutral ISO (International Standards Organization) standardized STEP (Standard for the Exchange of Product Data) formatted NURBS (Non-Uniform Rational B-Spline) geometric representation to a tool path instruction set for layered freeform fabrication. (d) The development of a novel Internal Architecture Design (IAD) approach for the mapping of characteristic patterns of the unit cell micro-architectures designed within the 3D scaffold. (Abstract shortened by UMI.)

[1]  James J. Yoo,et al.  Tissue-engineered autologous bladders for patients needing cystoplasty , 2006, The Lancet.

[2]  S. Hollister,et al.  Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. , 2002, Biomaterials.

[3]  James T. Kajiya,et al.  Ray tracing parametric patches , 1982, SIGGRAPH.

[4]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[5]  K. Krishnan,et al.  The Application of Rapid Prototyping Techniques in Cranial Reconstruction and Preoperative Planning in Neurosurgery , 2003, The Journal of craniofacial surgery.

[6]  S Girod,et al.  Three-dimensional simulation and prediction of craniofacial surgery. , 2003, Orthodontics & craniofacial research.

[7]  Linda G Griffith,et al.  Emerging Design Principles in Biomaterials and Scaffolds for Tissue Engineering , 2002, Annals of the New York Academy of Sciences.

[8]  N. M. Aziz,et al.  A model for interfacing geometric modeling data with rapid prototyping systems , 1995 .

[9]  R Kikinis,et al.  Development of a three-dimensional treatment planning system based on computed tomographic data. , 2002, International journal of oral and maxillofacial surgery.

[10]  Jon Owen,et al.  Step - an introduction , 1997, Product data engineering.

[11]  Victor Sholukha,et al.  In vivo registration of both electrogoniometry and medical imaging: development and application on the ankle joint complex , 2006, IEEE Transactions on Biomedical Engineering.

[12]  H R Allcock,et al.  A highly porous 3-dimensional polyphosphazene polymer matrix for skeletal tissue regeneration. , 1996, Journal of biomedical materials research.

[13]  Dietmar W Hutmacher,et al.  Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. , 2004, Trends in biotechnology.

[14]  D H Kohn,et al.  Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds for tissue engineering. , 2000, Biomaterials.

[15]  David Wells,et al.  The Penguin Dictionary of Curious and Interesting Geometry , 1992 .

[16]  T M Barker,et al.  Stereolithographic (SL) biomodelling in craniofacial surgery. , 1998, British journal of plastic surgery.

[17]  Wei Sun,et al.  Reasoning Boolean operation based modeling for heterogeneous objects , 2002, Comput. Aided Des..

[18]  Han Tong Loh,et al.  Fabrication of 3D chitosan–hydroxyapatite scaffolds using a robotic dispensing system , 2002 .

[19]  Shangtian Yang,et al.  Effects of Filtration Seeding on Cell Density, Spatial Distribution, and Proliferation in Nonwoven Fibrous Matrices , 2001, Biotechnology progress.

[20]  Debashish Dutta,et al.  Construction of a Surface Model and Layered Manufacturing Data From 3D Homogenization Output , 1996 .

[21]  Zhiwen Zhao,et al.  Adaptive direct slicing of the solid model for rapid prototyping , 2000 .

[22]  B. Barsky,et al.  An Introduction to Splines for Use in Computer Graphics and Geometric Modeling , 1987 .

[23]  Stephen E. Feinberg,et al.  An image-based approach for designing and manufacturing craniofacial scaffolds. , 2000, International journal of oral and maxillofacial surgery.

[24]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. , 2002, Tissue engineering.

[25]  Eric Keppel,et al.  Approximating Complex Surfaces by Triangulation of Contour Lines , 1975, IBM J. Res. Dev..

[26]  Emanuel M. Sachs,et al.  Solid free-form fabrication of drug delivery devices , 1996 .

[27]  Weiyin Ma,et al.  An adaptive slicing and selective hatching strategy for layered manufacturing , 1999 .

[28]  Wilhelm Barth,et al.  Efficient ray tracing for Bezier and B-spline surfaces , 1993, Comput. Graph..

[29]  W. Eaglstein,et al.  Tissue engineering and the development of Apligraf, a human skin equivalent. , 1997, Cutis.

[30]  Tomoyuki Nishita,et al.  Curve intersection using Bézier clipping , 1990, Comput. Aided Des..

[31]  Wei Sun,et al.  Recent development on computer aided tissue engineering - a review , 2002, Comput. Methods Programs Biomed..

[32]  Debasish Dutta,et al.  An Assessment of Data Requirements and Data Transfer Formats for Layered Manufacturing , 1998 .

[33]  H. Sagan.  Space-filling curves , 1994 .

[34]  André Dolenc,et al.  Slicing procedures for layered manufacturing techniques , 1994, Comput. Aided Des..

[35]  Elaine Cohen,et al.  Practical Ray Tracing of Trimmed NURBS Surfaces , 2000, J. Graphics, GPU, & Game Tools.

[36]  Amit Bandyopadhyay,et al.  Development of controlled porosity polymer-ceramic composite scaffolds via fused deposition modeling , 2003 .

[37]  Ron Jamieson,et al.  Direct slicing of CAD models for rapid prototyping , 1995 .

[38]  L G Griffith,et al.  Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. , 2001, Tissue engineering.

[39]  K. Leong,et al.  Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends. , 2003, Biomaterials.

[40]  H Niederdellmann,et al.  Surgical planning of computer-assisted repositioning osteotomies. , 1999, Plastic and reconstructive surgery.

[41]  Bernd Girod,et al.  Computer-aided 3-D simulation and prediction of craniofacial surgery: a new approach. , 2001, Journal of maxillofacial surgery.

[42]  A. Ahluwalia,et al.  Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition. , 2003, Biomaterials.

[43]  I Zein,et al.  Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. , 2001, Journal of biomedical materials research.

[44]  Richard H. Bartels,et al.  Ray Tracing Free-Form B-Spline Surfaces , 1986, IEEE Computer Graphics and Applications.

[45]  I. Zein,et al.  Fused deposition modeling of novel scaffold architectures for tissue engineering applications. , 2002, Biomaterials.

[46]  Jos Vander Sloten,et al.  On the Assets of CAD Planning for Craniosynostosis Surgery , 2001, The Journal of craniofacial surgery.

[47]  L G Griffith,et al.  Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels. , 1998, Annals of surgery.

[48]  Robert Langer,et al.  Biomaterials and biomedical engineering , 1995 .

[49]  A.C.W. Lau,et al.  Precision extruding deposition and characterization of cellular poly‐ε‐caprolactone tissue scaffolds , 2004 .

[50]  R. Landers,et al.  Rapid prototyping of scaffolds derived from thermoreversible hydrogels and tailored for applications in tissue engineering. , 2002, Biomaterials.

[51]  Uwe Spetzger,et al.  Neuronavigation-assisted Cranial Reconstruction , 2004, Neurosurgery.

[52]  N Samman,et al.  Computer-assisted three-dimensional surgical planning and simulation: 3D virtual osteotomy. , 2000, International journal of oral and maxillofacial surgery.

[53]  Feng Lin,et al.  A decomposition‐accumulation model for layered manufacturing fabrication , 2001 .

[54]  Cato T Laurencin,et al.  Tissue engineered microsphere-based matrices for bone repair: design and evaluation. , 2002, Biomaterials.

[55]  E. Sachlos,et al.  Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds. , 2003, European cells & materials.

[56]  Richard H. Crawford,et al.  A Method to Generate Exact Contour Files for Solid Freeform Fabrication , 1992 .

[57]  M. Vannier,et al.  Three-dimensional imaging, surgical planning, and image-guided therapy. , 1996, Radiologic clinics of North America.

[58]  Wei Sun,et al.  Computer‐aided tissue engineering: overview, scope and challenges , 2004, Biotechnology and applied biochemistry.

[59]  Dietmar W Hutmacher,et al.  Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits. , 2006, Biomaterials.

[60]  A. Mikos,et al.  The Importance of New Processing Techniques in Tissue Engineering , 1996, MRS bulletin.

[61]  Wei Sun,et al.  Application of computer-assisted design in craniofacial reconstructive surgery using a commercial image guidance system. Technical note. , 2006, Journal of neurosurgery.

[62]  Scott J Hollister,et al.  Mechanical and in vivo performance of hydroxyapatite implants with controlled architectures. , 2002, Biomaterials.