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. This design approach is implemented into a process algorithm that converts these 2D patterns to tool path datasets for the 3DP™ (threedimensional printing) and extrusion based freeform fabrication.CATE enables many novel approaches in modeling, design, and fabrication of complex tissue substitutes with enhanced functionality for research in patient specific implant analysis and simulation, image guided surgical planning and scaffold guided tissue engineering. The research will also enable cell biologists and engineers to expand their scope of research and study in the field of tissue engineering and regenerative medicine.Ph.D., Mechanical Engineering -- Drexel University, 200

Transferring Unit Cell Based Tissue Scaffold Design to Solid Freeform Fabrication

Designing for the freeform fabrication of heterogeneous tissue scaffold is always a challenge in Computer Aided Tissue Engineering. The difficulties stem from two major sources: 1) limitations in current CAD systems to assembly unit cells as building blocks to form complex tissue scaffolds, and 2) the inability to generate tool paths for freeform fabrication of unit cell assemblies. To overcome these difficulties, we have developed an abstract model based on skeletal representation and associated computational methods to assemble unit cells into an optimized structure. Additionally we have developed a process planning technique based on internal architecture pattern of unit cells to generate tool paths for freeform fabrication of tissue scaffold. By modifying our optimization process, we are able to transfer an optimized design to our fabrication system via our process planning technique.Mechanical Engineerin

Micro-Organ Devices

Micro-organ devices (MODs) are being developed to satisfy an emerging need for small, lightweight, reproducible, biological-experimentati on apparatuses that are amenable to automated operation and that imp ose minimal demands for resources (principally, power and fluids). I n simplest terms, a MOD is a microfluidic device containing a variety of microstructures and assemblies of cells, all designed to mimic a complex in vivo microenvironment by replicating one or more in vivo micro-organ structures, the architectures and composition of the extr acellular matrices in the organs of interest, and the in vivo fluid flows. In addition to microscopic flow channels, a MOD contains one or more micro-organ wells containing cells residing in microscopic e xtracellular matrices and/or scaffolds, the shapes and compositions o f which enable replication of the corresponding in vivo cell assembl ies and flows

Electrical Cell-Substrate Impedance Spectroscopy Can Monitor Age-Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation

: Human adipose stem cells (hASCs) are an attractive cell source for bone tissue engineering applications. However, a critical issue to be addressed before widespread hASC clinical translation is the dramatic variability in proliferative capacity and osteogenic potential among hASCs isolated from different donors. The goal of this study was to test our hypothesis that electrical cell-substrate impedance spectroscopy (ECIS) could track complex bioimpedance patterns of hASCs throughout proliferation and osteogenic differentiation to better understand and predict variability among hASC populations. Superlots composed of hASCs from young (aged 24-36 years), middle-aged (aged 48-55 years), and elderly (aged 60-81 years) donors were seeded on gold electrode arrays. Complex impedance measurements were taken throughout proliferation and osteogenic differentiation. During osteogenic differentiation, four impedance phases were identified: increase, primary stabilization, drop phase, and secondary stabilization. Matrix deposition was first observed 48-96 hours after the impedance maximum, indicating, for the first time, that ECIS can identify morphological changes that correspond to late-stage osteogenic differentiation. The impedance maximum was observed at day 10.0 in young, day 6.1 in middle-aged, and day 1.3 in elderly hASCs, suggesting that hASCs from younger donors require a longer time to differentiate than do hASCs from older donors, but young hASCs proliferated more and accreted more calcium long-term. This is the first study to use ECIS to predict osteogenic potential of multiple hASC populations and to show that donor age may temporally control onset of osteogenesis. These findings could be critical for development of patient-specific bone tissue engineering and regenerative medicine therapies. SIGNIFICANCE: Human adipose stem cells (hASCs) are an appealing cell source for bone tissue engineering and regenerative medicine applications because they can be obtained in high quantities via liposuction procedures and can differentiate down musculoskeletal lineages. However, a major barrier to clinical translation of hASCs is that cells from different donors have varying capacities to proliferate and differentiate. This study used electrical impedance spectroscopy to noninvasively track osteogenic differentiation of age-grouped donors in real time, showing that age-grouped hASCs have distinct complex impedance patterns. This method could be used to improve understanding of the biology that causes variability among hASC populations and to provide quantitative quality control standards for hASC populations in stem cell manufacturing and bone tissue engineering applications

Preserving Buyer-Privacy in Decentralized Supply Chain Marketplaces

Technology is being used increasingly for lowering the trust barrier in domains where collaboration and cooperation are necessary, but reliability and efficiency are critical due to high stakes. An example is an industrial marketplace where many suppliers must participate in production while ensuring reliable outcomes; hence, partnerships must be pursued with care. Online marketplaces like Xometry facilitate partnership formation by vetting suppliers and mediating the marketplace. However, such an approach requires that all trust be vested in the middleman. This centralizes control, making the system vulnerable to being biased towards specific providers. The use of blockchains is now being explored to bridge the trust gap needed to support decentralizing marketplaces, allowing suppliers and customers to interact more directly by using the information on the blockchain. A typical scenario is the need to preserve privacy in certain interactions initiated by the buyer (e.g., protecting a buyer’s intellectual property during outsourcing negotiations). In this work, we initiate the formal study of matching between suppliers and buyers when buyer-privacy is required for some marketplace interactions and make the following contributions. First, we devise a formal security definition for private interactive matching in the Universally Composable (UC) Model that captures the privacy and correctness properties expected in specific supply chain marketplace interactions. Second, we provide a lean protocol based on any programmable blockchain, anonymous group signatures, and public-key encryption. Finally, we implement the protocol by instantiating some of the blockchain logic by extending the BigChainDB blockchain platform

Micro-Organ Device

A method for fabricating a micro-organ device comprises providing a microscale support having one or more microfluidic channels and one or more micro-chambers for housing a micro-organ and printing a micro-organ on the microscale support using a cell suspension in a syringe controlled by a computer-aided tissue engineering system, wherein the cell suspension comprises cells suspended in a solution containing a material that functions as a three-dimensional scaffold. The printing is performed with the computer-aided tissue engineering system according to a particular pattern. The micro-organ device comprises at least one micro-chamber each housing a micro-organ; and at least one microfluidic channel connected to the micro-chamber, wherein the micro-organ comprises cells arranged in a configuration that includes microscale spacing between portions of the cells to facilitate diffusion exchange between the cells and a medium supplied from the at least one microfluidic channel

The bioprinting roadmap

This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field

FabWave Repository

This dataset, the first of its kind is intended to spur innovations in product design and manufacturing research, including AI based techniques and analytical methods. Over the next 2yrs, we will continuously grow this dataset to make it the largest available feature rich part dataset freely available