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Hydrogels represent one of the cornerstones in tissue engineering and regenerative medicine, due to their biocompatibility and physiologically relevant properties. These inherent characteristics mean that they can be widely exploited as bioinks in 3D bioprinting for tissue engineering applications as well as injectable gels for cell therapy and drug delivery purposes. The research in these fields is booming and this book provides the reader with a terrific introduction to the burgeoning field of injectable hydrogel design, bioprinting and tissue engineering. Edited by three leaders in the field, users of this book will learn about different classes of hydrogels, properties and synthesis strategies to produce bioinks. A section devoted to the key processing and design challenges at the hydrogel/3D bioprinting/tissue interface is also covered. The final section of the book closes with pertinent clinical applications. Tightly edited, the reader will find this book to be a coherent resource to learn from. It will appeal to those working across biomaterials science, chemical and biomedical engineering, tissue engineering and regenerative medicine.
Hydrogels for Tissue Engineering and Regenerative Medicine: From Fundaments to Applications provides the reader with a comprehensive, concise and thoroughly up-to-date resource on the different types of hydrogels in tissue engineering and regenerative medicine. The book is divided into three main sections that describe biological activities and the structural and physicochemical properties of hydrogels, along with a wide range of applications, including their combination with emerging technologies. Written by a diverse range of international academics for professionals, researchers, undergraduate and graduate students, this groundbreaking publication fills a gap in literature needed in the tissue engineering and regenerative medicine field. Reviews the fundamentals and recent advances of hydrogels in tissue engineering and regenerative medicine applications Presents state-of-the-art methodologies for the synthesis and processing of different types of hydrogels Includes contributions by leading experts in engineering, the life sciences, microbiology and clinical medicine
"Regenerative engineering, with its ability to foster novel therapeutic techniques and strategies, has emerged as the most versatile and innovative technology of the 21st century. The past few years have seen a significant interest in the development of injectable hydrogels as a delivery system to realize the dream of regenerative engineering. The book will explain synthetic approaches towards developing injectable hydrogels, and the clinical implications and applications of injectable hydrogels for engineering various tissues. Injectable Hydrogels for Regenerative Engineering is the first of its kind to bring together the fields of injectable hydrogels and regenerative engineering to give a perspective of the emerging therapeutic strategies for a wide audience."--
Novel injectable materials for non-invasive surgical procedures are becoming increasingly popular. An advantage of these materials include easy deliverability into the body, however the suitability of their mechanical properties must also be carefully considered. Injectable biomaterials covers the materials, properties and biomedical applications of injectable materials, as well as novel developments in the technology.Part one focuses on materials and properties, with chapters covering the design of injectable biomaterials as well as their rheological properties and the mechanical properties of injectable polymers and composites. Part two covers the clinical applications of injectable biomaterials, including chapters on drug delivery, tissue engineering and orthopaedic applications as well as injectable materials for gene delivery systems. In part three, existing and developing technologies are discussed. Chapters in this part cover such topics as environmentally responsive biomaterials, injectable nanotechnology, injectable biodegradable materials and biocompatibility. There are also chapters focusing on troubleshooting and potential future applications of injectable biomaterials.With its distinguished editor and international team of contributors, Injectable biomaterials is a standard reference for materials scientists and researchers working in the biomaterials industry, as well as those with an academic interest in the subject. It will also be beneficial to clinicians. Comprehensively examines the materials, properties and biomedical applications of injectable materials, as well as novel developments in the technology Reviews the design of injectable biomaterials as well as their rheological properties and the mechanical properties of injectable polymers and composites Explores clinical applications of injectable biomaterials, including drug delivery, tissue engineering, orthopaedic applications and injectable materials for gene delivery systems
Essentials of 3D Biofabrication and Translation discusses the techniques that are making bioprinting a viable alternative in regenerative medicine. The book runs the gamut of topics related to the subject, including hydrogels and polymers, nanotechnology, toxicity testing, and drug screening platforms, also introducing current applications in the cardiac, skeletal, and nervous systems, and organ construction. Leaders in clinical medicine and translational science provide a global perspective of the transformative nature of this field, including the use of cells, biomaterials, and macromolecules to create basic building blocks of tissues and organs, all of which are driving the field of biofabrication to transform regenerative medicine. Provides a new and versatile method to fabricating living tissue Discusses future applications for 3D bioprinting technologies, including use in the cardiac, skeletal, and nervous systems, and organ construction Describes current approaches and future challenges for translational science Runs the gamut of topics related to the subject, from hydrogels and polymers to nanotechnology, toxicity testing, and drug screening platforms
"Tissue engineering is a multidisciplinary approach to regenerate tissues by culturing cells inside three dimensional (3D) crosslinked biodegradable polymeric structures known as hydrogels. The hydrogel degrade with time and new tissue is generated. An appropriate gelation time, gel mechanical properties, pore structure, biocompatibility and degradation rate are required to successfully regenerate the tissue. Although many types of hydrogels have been produced, to regenerate a variety of tissues, producing hydrogels containing all the desirable features is still challenging. In this work we first produced in-situ forming biodegradable, injectable hydrogels from two naturally occurring polymers--chitosan (CH) and hyaluronic acid (HA), using [beta]-glycerolphosphate and genipin as two non-toxic crosslinkers. The resulting hydrogels were highly homogenous, thermogelling, possessed excellent mechanical strength (shear strength=3.5 kPa), formed quickly inside the body (within 5 minutes) and did not cause any significant toxicity or inflammation in animals over a period of one week. Next, we developed a highly sensitive platform for real-time monitoring of hydrogel degradation inside living tissues deep inside the body. We used lanthanide-doped NIR-to-NIR upconverting nanoparticles (UCNPs) composed of LiYF4:Yb3+,Tm3+ as photolabels. The UCNPs can upconvert NIR radiation to shorter wavelengths spanning the NIR to UV region, via a sequential multi-photon absorption process. We incorporated these UCNPs inside CH-HA hydrogels, and injected into live intervertebral discs. With time, the hydrogel degraded and the UCNPs diffused out of the injection site whose location and amounts were detected using NIR imaging and PL spectroscopy as deep as 1.2 cm inside the tissues. We developed a correlation between in-vitro and in-vivo hydrogel degradation rate. We found that in-vivo hydrogel degradation was relatively faster than in-vitro degradation most likely because of the higher concentration of enzymes present inside tissues. The addition of UCNPs increased the compression strength of hydrogels and did not cause toxicity to cells up to a concentration of 500 μg/ml. In addition to NIR emission, LiYF4:Yb3+,Tm3+ UCNPs exhibit intense UV emissions, which makes them an excellent in-situ source of UV light. We exploited this to trigger the drug release from photosensitive hydrogels. We first coated UCNPs with CH chains and encapsulated fluorescein isothiocyanate- bovine serum albumin (FITC-BSA) as a model large-protein drug between the polymer chains. We crosslinked CH chains with a photocleavable linker and polyethylene glycol bisazide (PEGBA) to entrap FITC-BSA molecules inside the crosslinked CH shell. Upon NIR irradiation, the upconverted UV emission from the UCNP core was efficiently transferred to the CH shell and the photocleavable crosslinks were broken, resulting in the dissociation of the shell and liberation of FITC-BSA. The drug release was stopped immediately if the laser was turned off without any significant leakage, suggesting a complete control over drug release. Drug release could be achieved efficiently under 2 cm of tissues, using low laser power density (1.8 W/cm2). The UCNPs did not cause toxicity to cells up to 500μg/ml and 9 minutes of laser irradiation. By exploiting the NIR-to-NIR emitted radiation, the UCNPs were detected as deep as 1.5 cm. The possibility of achieving both deep tissue imaging and controlled drug release makes these UCNPs an effective theranostic platform. Combining an injectable hydrogel with UCNPs provides a multifunctional platform for tissue regeneration, bioimaging and on-demand delivery of biomolecular drugs." --
Three-dimensional (3D) cell culture facilitates development of biological relevant assays for drug screening and toxicity testing. Compared to conventional 2D cell culture, cells cultured in 3D can more accurately mimic human tissues and organs and thus provide ex vivo data with potentially better predictive value for cancer research, pharmacology, and toxicology, reducing the need for animal models, improving experimental reproducibility, and reducing time and costs in drug development. The most widely used options for scaffold-based 3D cell culture are, however, based on poorly defined biologically derived extracellular matrix (ECM) with limited possibilities to tailor material properties and that are difficult to combine with state-of-the art biofabrication techniques. The overall aim this thesis was to design and explore modular hyaluronan (HA) based ECM-mimicking hydrogels with tuneable physiochemical properties and biofunctionalities, for development of advanced 3D cell models and biofabrication. The thesis work is presented in five papers. In paper I, we used copper free click chemistry for both hydrogel cross-linking and functionalization with fibronectin derived peptide sequences for culture of human induced pluripotent-derived hepatocytes in a perfused microfluidic system. The tuneable and bioorthogonal cross-linking enabled both retention of high cell viabilities and fabrication of a functional liver-on-chip solution. In paper II, we combined the developed HA-based hydrogel system with homo- and heterodimerizing helix-loop-helix peptides for modulation of both cross-linking density and biofunctionalization. We further demonstrated the possibilities to use these hydrogels as bioinks for 3D bioprinting where both the molecular composition and the physical properties of the printed structures could be dynamically altered, providing new avenues for four-dimensional (4D) bioprinting. In paper III we investigated the possibilities to chemically conjugate full size recombinant human laminin-521 (LN521) in the HA-based hydrogels system using copper-free click chemistry, with the aim to enable 3D culture and 3D bioprinting of neurons. We quantified the impact of using different linkers to tether LN521 and the influence of LN-functionalization on the structural and mechanical properties of the hydrogels. We show that both differentiated and non-differentiated neuroblastoma cells and long-term self-renewing neuroepithelial stem cells (lt-NES) remained viable in the hydrogels. The hydrogels also had a protected effect on lt-NES during syringe ejection and bioprinting. In paper IV, we used HA-based hydrogels modified with peptides sequences derived from fibronectin and laminin for culture of fetal primary astrocytes (FPA). We explored both the interactions between the hydrogels and FPA and possibilities to 3D bioprint FPAs. Finally, in paper V, we developed HA-nanocellulose composite hydrogels with the aim to increase printing fidelity and enable fabrication of multi-layered bioprinted structures without the use of a support bath. In addition to HA, we used wood-fibre derived nanocellulose (NC) to increase the viscosity of the bioink during the printing process. The developed biorthogonal and modular hydrogel systems provide a large degree of flexibility that allows for encapsulation and culture of different cell types and processing using different techniques, which can contribute to further exploration of fabrication of biologically relevant tissue and disease models.