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Hydrogel from wood-based nanofibrillated cellulose (NFC) is used as a matrix for 3D cell culture. As plant based material, it does not contain any human- or animal-derived components.
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Hydrogel from wood-based nanofibrillated cellulose (NFC) is used as a matrix for 3D cell culture. As plant based material, it does not contain any human- or animal-derived components.
As the natural extracellular matrix (ECM) is important in the survival, proliferation, differentiation and migration of the cells, hydrogels mimicking natural ECM structure are considered as potential approaches towards in vivo –like cell culturing. [1] [2] GrowDex is NFC hydrogel for 3D cell culture commercialized by UPM, Finland. [3]
NFC fiber network structure and dimensions in hydrogel resemble human ECM. [4] Stiffness can be tuned to optimize the conditions for each cell type. Shear-thinning property of the material makes the gel ready to use without cross-linking or gelification step. The nanocellulose hydrogel can be completely degraded by cellulase enzyme treatment while retaining the 3D cell structures. [3] [5]
NFC hydrogel in 3D cell culture offers a platform for various biomedical applications. [6] Different cell lines and cell types have been cultured in NFC, including e.g. differentiation of human hepatic cells to functional organotypic cultures, [7] and proliferation of human pluripotent stem cells. [3] Organotypic liver cell cultures can be used e.g. in drug discovery for testing liver toxicity and metabolism of the novel drug candidates. The possibility to use the hydrogel with robotic dispensers enables its use in high throughput screening (HTS) formats. [8]
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals.
In biology, the extracellular matrix (ECM) is a three-dimensional network of extracellular macromolecules, such as collagen, enzymes, and glycoproteins, that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.
Tissue engineering is the use of a combination of cells, engineering, and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological tissues. Tissue engineering involves the use of a tissue scaffold for the formation of new viable tissue for a medical purpose. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance it can be considered as a field in its own.
Ultrastructure is the architecture of cells and biomaterials that is visible at higher magnifications than found on a standard optical light microscope. This traditionally meant the resolution and magnification range of a conventional transmission electron microscope (TEM) when viewing biological specimens such as cells, tissue, or organs. Ultrastructure can also be viewed with scanning electron microscopy and super-resolution microscopy, although TEM is a standard histology technique for viewing ultrastructure. Such cellular structures as organelles, which allow the cell to function properly within its specified environment, can be examined at the ultrastructural level.
Durotaxis is a form of cell migration in which cells are guided by rigidity gradients, which arise from differential structural properties of the extracellular matrix (ECM). Most normal cells migrate up rigidity gradients.
Cell culture is the process by which cells are grown under controlled conditions, generally outside their natural environment. After the cells of interest have been isolated from living tissue, they can subsequently be maintained under carefully controlled conditions. These conditions vary for each cell type, but generally consist of a suitable vessel with a substrate or medium that supplies the essential nutrients (amino acids, carbohydrates, vitamins, minerals), growth factors, hormones, and gases (CO2, O2), and regulates the physio-chemical environment (pH buffer, osmotic pressure, temperature). Most cells require a surface or an artificial substrate (adherent or monolayer culture) whereas others can be grown free floating in culture medium (suspension culture). The lifespan of most cells is genetically determined, but some cell culturing cells have been “transformed” into immortal cells which will reproduce indefinitely if the optimal conditions are provided.
Hyaluronic acid, also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans in that it is nonsulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large: human synovial HA averages about 7 million Da per molecule, or about twenty thousand disaccharide monomers, while other sources mention 3–4 million Da. As one of the chief components of the extracellular matrix, hyaluronan contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors.
A printable organ is an artificially built gadget suitable for organ substitution, created using procedures analogous to 3D printing. The primary use of printable organs is in transplantation. The manufacture of heart, kidney, and liver structures, as well as other major organs are subjects of active research. One may print substructures separately if the entire organ is too complicated to print in place or if only some parts of the original organ need replacement. A few printed organs are close to being suitable for clinical usage.
Cardiomyoplasty is a surgical procedure in which healthy muscle from another part of the body is wrapped around the heart to provide support for the failing heart. Most often the latissimus dorsi muscle is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged myocardium to be treated in other ways, such as remodeling by cellular therapies.
In biology, explant culture is a technique to organotypically culture cells from a piece or pieces of tissue or organ removed from a plant or animal. The term explant can be applied to samples obtained from any part of the organism. The extraction process is extensively sterilized, and the culture can be typically used for two to three weeks.
A nerve guidance conduit is an artificial means of guiding axonal regrowth to facilitate nerve regeneration and is one of several clinical treatments for nerve injuries. When direct suturing of the two stumps of a severed nerve cannot be accomplished without tension, the standard clinical treatment for peripheral nerve injuries is autologous nerve grafting. Due to the limited availability of donor tissue and functional recovery in autologous nerve grafting, neural tissue engineering research has focused on the development of bioartificial nerve guidance conduits as an alternative treatment, especially for large defects. Similar techniques are also being explored for nerve repair in the spinal cord but nerve regeneration in the central nervous system poses a greater challenge because its axons do not regenerate appreciably in their native environment.
Acellular dermis is a type of biomaterial derived from processing human or animal tissues to remove cells and retain portions of the extracellular matrix (ECM). These materials are typically cell-free, distinguishing them from classical allografts and xenografts, can be integrated or incorporated into the body, and have been FDA approved for human use for more than 10 years in a wide range of clinical indications.
Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles, dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers. Furthermore, these dermal fibroblasts produce the protein molecules including laminin and fibronectin which comprise the extracellular matrix. By creating the extracellular matrix between the dermis and epidermis, fibroblasts allow the epithelial cells of the epidermis to affix the matrix, thereby allowing the epidermal cells to effectively join together to form the top layer of the skin.
An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of entire organs and organ systems, a type of artificial organ. It constitutes the subject matter of significant biomedical engineering research, more precisely in bio-MEMS. The convergence of labs-on-chips (LOCs) and cell biology has permitted the study of human physiology in an organ-specific context, introducing a novel model of in vitro multicellular human organisms. One day, they will perhaps abolish the need for animals in drug development and toxin testing.
Decellularization is the process used in biomedical engineering to isolate the extracellular matrix (ECM) of a tissue from its inhabiting cells, leaving an ECM scaffold of the original tissue, which can be used in artificial organ and tissue regeneration. Organ and tissue transplantation treat a variety of medical problems, ranging from end organ failure to cosmetic surgery. One of the greatest limitations to organ transplantation derives from organ rejection caused by antibodies of the transplant recipient reacting to donor antigens on cell surfaces within the donor organ. Because of unfavorable immune responses, transplant patients suffer a lifetime taking immunosuppressing medication. Stephen F. Badylak pioneered the process of decellularization at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. This process creates a natural biomaterial to act as a scaffold for cell growth, differentiation and tissue development. By recellularizing an ECM scaffold with a patient’s own cells, the adverse immune response is eliminated. Nowadays, commercially available ECM scaffolds are available for a wide variety of tissue engineering. Using peracetic acid to decellularize ECM scaffolds have been found to be false and only disinfects the tissue.
Three dimensional (3D) bioprinting is the utilization of 3D printing–like techniques to combine cells, growth factors, and biomaterials to fabricate biomedical parts that maximally imitate natural tissue characteristics. Generally, 3D bioprinting utilizes the layer-by-layer method to deposit materials known as bioinks to create tissue-like structures that are later used in medical and tissue engineering fields. Bioprinting covers a broad range of biomaterials.
A 3D cell culture is an artificially created environment in which biological cells are permitted to grow or interact with their surroundings in all three dimensions. Unlike 2D environments, a 3D cell culture allows cells in vitro to grow in all directions, similar to how they would in vivo. These three-dimensional cultures are usually grown in bioreactors, small capsules in which the cells can grow into spheroids, or 3D cell colonies. Approximately 300 spheroids are usually cultured per bioreactor.
The in vivo bioreactor (IVB) is a regenerative medicine paradigm where bone is grown in vivo. The IVB has basic elements:
Bioinks are substances made of living cells that can be used for 3D printing of complex tissue models. Bioinks are materials that mimic an extracellular matrix environment to support the adhesion, proliferation, and differentiation of living cells. Bioinks distinguish themselves from traditional biomaterials such as hydrogels, polymer networks, and foam scaffolds due to their ability to be deposited as filaments during an additive manufacturing process. Additionally, unlike traditional additive manufacturing materials such as thermoplastic polymers, ceramics, and metals which require the use of harsh solvents, cross-linking modalities and high temperatures to be printed, bioinks are processed under much milder conditions. These mild conditions are necessary to preserve compatibility with living cells, and prevent degradation of bioactive molecules and macroproteins. These bioinks are often adopted from existing hydrogel biomaterials and derived from natural polymers such as gelatins, alginates, fibrin, chitosan, and hyaluronic acids that are sensitive to their processing conditions.
Artificial cartilage is a synthetic material made of hydrogels or polymers that aims to mimic the functional properties of natural cartilage in the human body. Tissue engineering principles are used in order to create a non-degradable and biocompatible material that can replace cartilage. While creating a useful synthetic cartilage material, certain challenges need to be overcome. First, cartilage is an avascular structure in the body and therefore does not repair itself. This creates issues in regeneration of the tissue. Synthetic cartilage also needs to be stably attached to its underlying surface, bone. Lastly, in the case of creating synthetic cartilage to be used in joint spaces, high mechanical strength under compression needs to be an intrinsic property of the material.