Engineering 3D Tissue Test Systems


Book Description

Engineering 3D Tissue Test Systems provides an introduction to, and unique coverage of, a rapidly evolving area in biomaterials engineering. It reveals the current and future research responses, the current and future diagnostic applications, and provides a comprehensive overview to foster innovation. It offers insight into the importance of 3D systems and their use as benchtop models, spanning applications from basic scientific research to clinical diagnostics. Methods and limitations of building 3D tissue structures are evaluated, with attention given to the cellular, polymeric, and fabrication instrumentation components. The book covers the important aspects of polymeric tissue test systems, highlighting the needs and constraints of the industry, and includes a chapter on regulatory and pricing issues.




Biomaterials for 3D Tumor Modeling


Book Description

Biomaterials for 3D Tumor Modeling reviews the fundamentals and most relevant areas of the latest advances of research of 3D cancer models, focusing on biomaterials science, tissue engineering, drug delivery and screening aspects. The book reviews advanced fundamental topics, including the causes of cancer, existing cancer models, angiogenesis and inflammation during cancer progression, and metastasis in 3D biomaterials. Then, the most relevant biomaterials are reviewed, including methods for engineering and fabrication of biomaterials. 3D models for key biological systems and types of cancer are also discussed, including lung, liver, oral, prostate, pancreatic, ovarian, bone and pediatric cancer. This book is suitable for those working in the disciplines of materials science, biochemistry, genetics, molecular biology, drug delivery and regenerative medicine. Reviews key biomaterials topics, including synthetic biomaterials, hydrogels, e-spun materials and nanoparticles Provides a comprehensive overview of 3D cancer models for key biological systems and cancer types Includes an overview of advanced fundamental concepts for an interdisciplinary audience in materials science, biochemistry, regenerative medicine and drug delivery




Biomaterial-Assisted 3D In Vitro Tumor Models


Book Description

This reprint focuses on fundamental and applied research involving the combination of biomaterials and cancer cells to develop a three-dimensional (3D) tumor microenvironment in vitro, in which carcinogenesis mechanisms can be studied and therapies can be screened. Such models are becoming quite popular within the bioengineering community; thus, many technologies are being tested to obtain the best scaffold for each tumor. In any case, only a tight interaction of bioengineers with cancer biologists and oncologists can make such 3D models progress, with them finally reaching a clinical relevance. On the other hand, the medical community is approaching simpler 3D in vitro models not provided with sufficient extracellular matrix biomimicry, such as spheroids and organoids, which may not be self-exhaustive; therefore, cancer researchers could benefit from closer contact with bioengineers. The aim of this reprint is to help generate shared knowledge and promote strong interdisciplinary collaboration with the ultimate goal of contributing to the acceleration of the discovery and validation of more precise therapies to fight cancer.




Biomaterials- and Microfluidics-Based Tissue Engineered 3D Models


Book Description

This contributed volume reviews the latest advances on relevant 3D tissue engineered in vitro models of disease making use of biomaterials and microfluidics. The main focus of this book is on advanced biomaterials and microfluidics technologies that have been used in in vitro mimetic 3D models of human diseases and show great promise in revolutionizing personalized medicine. Readers will discover important topics involving biomaterials and microfluidics design, advanced processing techniques, and development and validation of organ- and body-on-a-chip models for bone, liver, and cancer research. An in depth discussion of microfabrication methods for microfluidics development is also provided. This work is edited by two truly multidisciplinary scientists and includes important contributions from well-known experts in their fields. The work is written for both early stage and experienced researchers, and well-established scientists enrolled in the fields of biomaterials, microfluidics, and tissue engineering, and is especially suited to those who wish to become acquainted with the principles and latest developments of in vitro models of diseases, such as professionals working in pharma, medicine, and engineering.




Biofabrication and 3D Tissue Modeling


Book Description

3D tissue modelling is an emerging field used for the investigation of disease mechanisms and drug development. The two key drivers of this upsurge in research lie in its potential to offer a way to reduce animal testing with respect to biotoxicity analysis, preferably on physiology recapitulated human tissues and, additionally, provides an alternative approach to regenerative medicine. Integrating physics, chemistry, materials science, and stem cell and biomedical engineering, this book provides a complete foundation to this exciting, and interdisciplinary field. Beginning with the basic principles of 3D tissue modelling, the reader will find expert reviews on key fabrication technologies and processes, including microfluidics, microfabrication technology such as 3D bioprinting, and programming approaches to emulating human tissue complexity. The next stage introduces the reader to a range of materials used for 3D tissue modelling, from synthetic to natural materials, as well as the emerging field of tissue derived decellularized extracellular matrix (dECM). A whole host of critical applications are covered, with several chapters dedicated to hard and soft tissues, as well as focused reviews on the respiratory and central nervous system. Finally, the development of in vitro tissue models to screen drugs and study progression and etiologies of diseases, with particular attention paid to cancer, can be found.




Multiscale Biomaterials for Cell and Tissue Engineering


Book Description

Next, a bottom-up approach for fabricating 3D vascularized human breast tumor model with the core-shell microencapsulation technology is developed. Microtumors (i.e., 3D aggregates of cancer cells) are generated in core-shell microcapsules and used together with human endothelial cells and human adipose derived stem cells (hADSCs) as building blocks to self-assemble into vascularized tumor in collagen hydrogel. The utility of the platform in drug screening is further demonstrated. It is shown that vascularization can render increased cancer resistance to chemotherapy. This vascularized tumor system may be valuable for in vitro drug screening to better predict the drug efficacy in cancer patients. Lastly, a multiscale system for efficient co-delivery of cells and proteins/growth factors in vivo is developed to address the issue of low cell survival associated with cell delivery in vivo. The multiscale delivery system is comprised of therapeutic agents-laden nanoparticles encapsulated in microcapsules (nano-in-micro), hADSCs, and collagen hydrogel. The nano-in-micro system enables sustained release of therapeutic proteins to interact with their receptors on the hADSCs in the system which significantly improves the survival and proliferation of the hADSCs after implantation. This is shown to greatly facilitate the tissue regeneration in an ischemic disease model. To conclude, this dissertation work demonstrates how microscale encapsulation of cells via microfluidics provides a powerful suite of tools to engineering the cellular microenvironment at micro and macro scales. The technologies and systems described here could potentially help in building tissue engineering constructs that enable treatment of a myriad of human diseases.




Tumor Organoids


Book Description

Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.




Regenerative Medicine Technology


Book Description

Miniaturization in the fields of chemistry and molecular biology has resulted in the "lab-on-a-chip." Such systems are micro-fabricated devices capable of handling extremely small fluid volumes facilitating the scaling of single or multiple lab processes down to a microchip-sized format. The convergence of lab-on-a-chip technology with the field of cell biology facilitated the development of "organ-on-a-chip" systems. Such systems simulate the function of tissues and organs, having the potential to bypass some cell and animal testing methods. These technologies have generated high interest as applications for disease modeling and drug discovery. This book, edited by Drs. Sean Murphy and Anthony Atala, provides a comprehensive coverage of the technologies that have been used to develop organ-on-a-chip systems. Known leaders cover the basics to the most relevant and novel topics in the field, including micro-fabrication, 3D bio-printing, 3D cell culture techniques, biosensor design and microelectronics, micro-fluidics, data collection, and predictive analysis. The book describes specific tissue types amenable for disease modeling and drug discovery applications. Lung, liver, heart, skin and kidney "on-a-chip" technologies are included as well as a progress report on designing an entire "body-on-a-chip" system. Additionally, the book covers applications of various systems for modeling tissue-specific cancers, metastasis, and tumor microenvironments; and provides an overview of current and potential applications of these systems to disease modeling, toxicity testing, and individualized medicine.




In Vitro Prevascularization of 3D Tissue Constructs


Book Description

There is a need for more effective therapies to combat breast cancer. One reason for the inefficiency of therapeutics is that testing technologies currently employed in drug discovery and development are not reliable when transitioning drugs into human clinical trials. To supplement the currently used in vitro cell culture studies and in vivo animal studies, an in vitro three-dimensional breast tumor system has been suggested with integration of human cells, hydrogel biomaterials, 3D architecture, and endothelialized microchannels. Therefore, the objective of the thesis project, as an initial step in fabrication of the supplemental system for drug testing, is to fabricate and characterize a tissue volume with pre-fabricated EC-lined microchannels representing the vasculature of a breast tumor. It is hypothesized that an in vitro three-dimensional microphysiologic system can be constructed with extracellular matrix and flow-through microchannels that will support a confluent endothelial layer. Results have shown that fabricated threedimensional microenvironments, composed of extracellular matrix components, had a matrix elasticity similar to that of normal mammary tissue. An iterative design process of bioreactor fabrication led to a bioreactor that could contain a three-dimensional scaffold with a mean wall shear stress in the range of 0-5 dyne/cm2 inside the microchannels. In addition, the bioreactor system and endothelialization protocol facilitated the localization and attachment of endothelial cells inside the prefabricated microchannels. Future work will include further characterization of endothelial cell morphology and function and assessment of barrier function and permeability of the engineered endothelium. Continuation of this proof-of-concept project will lead to the formation of a confluent endothelial cell monolayer, which may be used to perfuse the three-dimensional tissue-engineered scaffold, to act as a dissemination route for tumor cells, or to act as a route for therapeutics to the tumor site.