Generative Tissue (gTissue) is a living tissue created in a patient (human or non-human) by a surgeon, consisting of an extracellular matrix, cells, and supporting vascular supply with generative properties. The 'g' in gTissue is considered a reference to both generated nature of the living tissue, but also to the generative ability of the tissue to be adapted to the dynamic environmental conditions experienced in the host.
gTissue is a type of living Tissue (biology), hence an ensemble of cells and extracellular matrix that carry out a particular function. However, gTissue is created surgically, grown in a patient, and has a unique cellular and biochemical make-up that make it distinct from other tissues of the body. gTissue was discovered through research in the fields of Tissue Engineering and Regenerative Medicine and first created as a dense connective tissue between the brain and skull during the repair of canine dura mater. [1] It has since been successfully created in humans for a wide range of clinical applications in soft tissue healing and repair. [2] Essentially, the gTissue is created by implanting certain types of non-inflammatory ECM biomaterials that are adopted by the host, including repopulation with host cells and blood vessels, becoming a living tissue. To date, the types of gTissue created can be characterized as variants of soft connective tissues including dermis, tendon, ligament, and fascia.
Initially the cell-free ECM biomaterial is implanted and progressively adopted by the host. Immediately upon surgical implantation, the porous material becomes soaked in blood. This seeds the material with a population of circulating stem cells, and growth factors to support gTissue development. [2] As generation progresses, the growth factors, cytokines, and fibrin provisional matrix signals host cells to repopulate the matrix. To support the metabolic activity of these cells, a vascular network is simultaneously created within the ECM biomaterial. At this stage the material has been adopted and has the characteristics of a living tissue (biology). Under some conditions, following adoption with host cells and vasculature, gTissue can persist indefinitely without any histological evidence of significant change. For example, when created to below the skin of the face in cosmetic procedures intended to add bulk, the gTissue is adopted and stays a living, metabolically active tissue, subdermally. [2]
While gTissue can live indefinitely following adoption without significant change, there are environmental conditions that support the adaption of the tissue. The adaptation of gTissue is one reason it considered a generative tissue. Adaptation includes any change to the gTissue to meet particular environmental demands placed on it, based on the location of implantation. For example, during tendon augmentation procedures, the collagen fiber architecture of the extracellular matrix can transition to an aligned structure similar to native tendon, oriented along the long axis of loading, to meet the mechanical loading requirements. [2] Or when used as an underlay beneath the muscles of the abdominal wall to support the repair of a hernia, gTissue is adapted forming a new mesothelium lining the peritoneal side in order to prevent adhesions to, or abrasion of, the bowel or small intestines.
In order to create gTissue, a surgeon must start by selecting and ECM biomaterial with appropriate characteristics to support the type of healing and repair desired. The ECM biomaterial must be non-inflammatory. Biomaterials that evoke a strong inflammatory response are rapidly remodeled into scar tissue. [3] The ECM biomaterial must also not cause a chronic, low grade inflammatory response, or the material will be steadily degraded and therefore disappear with time. [4] Examples of ECM biomaterials that meet these requirements and have been successfully used to create gTissue include SurgiMend, [5] TissueMend, [6] and Durepair. [7] Additionally, the surgeon must be aware of how the anatomical location and surgical procedure affect host adoption and adaptation in order to grow the desired gTissue. For example, if the gTissue is to persist without change to add bulk, the implanted ECM biomaterial must be placed under low tension.
A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to efficiently transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability to withstand significant amounts of tension.
In biology, the extracellular matrix (ECM) is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite 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 a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose but is not limited to applications involving cells and tissue scaffolds. 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.
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
Hyaluronic acid, also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans as it is non-sulfated, 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 20,000 disaccharide monomers, while other sources mention 3–4 million Da.
Chin augmentation using surgical implants can alter the underlying structure of the face, providing better balance to the facial features. The specific medical terms mentoplasty and genioplasty are used to refer to the reduction and addition of material to a patient's chin. This can take the form of chin height reduction or chin rounding by osteotomy, or chin augmentation using implants. Improving the facial balance is commonly performed by enhancing the Chin using an implant inserted through the mouth. The goal is to provide a suitable projection of the chin as well as the correct height of the chin which is in balance with the other facial features.
Tendinitis/tendonitis is inflammation of a tendon, often involving torn collagen fibers. A bowed tendon is a horseman's term for a tendon after a horse has sustained an injury that causes swelling in one or more tendons creating a "bowed" appearance.
An artificial heart valve is a one-way valve implanted into a person's heart to replace a heart valve that is not functioning properly. Artificial heart valves can be separated into three broad classes: mechanical heart valves, bioprosthetic tissue valves and engineered tissue valves.
A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic or a diagnostic one. As a science, biomaterials is about fifty years old. The study of biomaterials is called biomaterials science or biomaterials engineering. It has experienced steady and strong growth over its history, with many companies investing large amounts of money into the development of new products. Biomaterials science encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.
A foreign body reaction (FBR) is a typical tissue response to a foreign body within biological tissue. It usually includes the formation of a foreign body granuloma. Tissue-encapsulation of an implant is an example, as is inflammation around a splinter. Foreign body granuloma formation consists of protein adsorption, macrophages, multinucleated foreign body giant cells, fibroblasts, and angiogenesis. It has also been proposed that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response.
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.
Biomaterials are materials that are used in contact with biological systems. Biocompatibility and applicability of surface modification with current uses of metallic, polymeric and ceramic biomaterials allow alteration of properties to enhance performance in a biological environment while retaining bulk properties of the desired device.
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.
The Network of Excellence for Functional Biomaterials (NFB) is a multidisciplinary research centre which hosts over sixty biologists, chemists, scientists, engineers and clinicians. It is based at the National University of Ireland, Galway, and is directed by Professor Abhay Pandit.
Decellularization of porcine heart valves is the removal of cells along with antigenic cellular elements by either physical or chemical decellularization of the tissue. This decellularized valve tissue provides a scaffold with the remaining extracellular matrix (ECM) that can then be used for tissue engineering and valve replacement in humans inflicted with valvular disease. Decellularized biological valves have potential benefit over conventional valves through decreased calcification which is thought to be an immuno-inflammatory response initiated by the recipient.
Surgical mesh is a loosely woven sheet which is used as either a permanent or temporary support for organs and other tissues during surgery. Surgical mesh is created from both inorganic and biological materials and is used in a variety of surgeries. Though hernia repair surgery is the most common application, it can also be used for reconstructive work, such as in pelvic organ prolapse.
Nasal chondrocytes (NC) are present in the hyaline cartilage of the nasal septum, and in fact are the only cell type within the tissue. Similar to chondrocytes present in articular cartilage, NC express extracellular matrix proteins such as glycosaminoglycans and collagen.
Tissue engineered heart valves (TEHV) offer a new and advancing proposed treatment of creating a living heart valve for people who are in need of either a full or partial heart valve replacement. Currently, there are over a quarter of a million prosthetic heart valves implanted annually, and the number of patients requiring replacement surgeries is only suspected to rise and even triple over the next fifty years. While current treatments offered such as mechanical valves or biological valves are not deleterious to one's health, they both have their own limitations in that mechanical valves necessitate the lifelong use of anticoagulants while biological valves are susceptible to structural degradation and reoperation. Thus, in situ tissue engineering of heart valves serves as a novel approach that explores the use creating a living heart valve composed of the host's own cells that is capable of growing, adapting, and interacting within the human body's biological system.