Physiological relevance is a scientific concept that refers to the applicability or significance of a particular experimental finding or biological observation in the context of normal bodily functions. This concept is often used in biomedical research, where scientists strive to design experiments that not only yield statistically significant results but also have direct implications for understanding human health and disease.
Physiological relevance is a critical factor in biomedical research because it helps to bridge the gap between basic science and clinical application. Researchers aim to design studies that not only yield statistically significant results but also have direct implications for understanding human health and disease. [1] For example, a study on the effects of a new drug on cancer cells in a lab dish might show promising results. However, these findings would only be considered physiologically relevant if the drug also demonstrated efficacy in animal models or clinical trials, where the complex interplay of various bodily systems and processes are taken into account. [2] [3]
A classic example of physiological relevance is the discovery of insulin. In the early 20th century, scientists found that injecting diabetic dogs with extracts from the pancreas of healthy dogs could normalize their blood sugar levels. This finding was not only statistically significant but also physiologically relevant, as it led to the development of insulin therapy for diabetes in humans.
In tissue engineering, physiological relevance means that living tissue constructs in vitro are morphologically and functionally similar to native tissue. [4] Bioengineering approaches to modify the mechanical properties of scaffolds and functionalize materials with growth factors or gene therapeutics. [5] [6]
One of the main challenges in ensuring physiological relevance is the inherent complexity of biological systems. Many factors can influence the outcome of an experiment, from the genetic makeup of the test subjects to the specific conditions under which the experiment is conducted. Furthermore, what is physiologically relevant in one species may not be in another, making it difficult to extrapolate findings from animal models to humans.
Another challenge is that physiological relevance is not always easy to quantify. Unlike statistical significance, which can be calculated using well-established mathematical formulas, physiological relevance often requires a more subjective, holistic assessment of the data. A limited number of quantitative models have been applied to improve the physiological relevance of biological systems. [5] [7]
Biomechanics is the study of the structure, function and motion of the mechanical aspects of biological systems, at any level from whole organisms to organs, cells and cell organelles, using the methods of mechanics. Biomechanics is a branch of biophysics.
In dynamical systems theory and control theory, a phase space or state space is a space in which all possible "states" of a dynamical system or a control system are represented, with each possible state corresponding to one unique point in the phase space. For mechanical systems, the phase space usually consists of all possible values of position and momentum variables. It is the direct product of direct space and reciprocal space. The concept of phase space was developed in the late 19th century by Ludwig Boltzmann, Henri Poincaré, and Josiah Willard Gibbs.
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 is considered as a field of its own.
Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been isolated from living tissue, they can subsequently be maintained under carefully controlled conditions. They need to be kept at body temperature (37 °C) in an incubator. These conditions vary for each cell type, but generally consist of a suitable vessel with a substrate or rich 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 to form an adherent culture as a monolayer (one single-cell thick), whereas others can be grown free floating in a medium as a suspension culture. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, such as broth or agar. Tissue culture commonly refers to the culture of animal cells and tissues, with the more specific term plant tissue culture being used for plants. 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.
Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-kDa and has 53 amino acid residues and three intramolecular disulfide bonds.
Biological engineering or bioengineering is the application of principles of biology and the tools of engineering to create usable, tangible, economically viable products. Biological engineering employs knowledge and expertise from a number of pure and applied sciences, such as mass and heat transfer, kinetics, biocatalysts, biomechanics, bioinformatics, separation and purification processes, bioreactor design, surface science, fluid mechanics, thermodynamics, and polymer science. It is used in the design of medical devices, diagnostic equipment, biocompatible materials, renewable energy, ecological engineering, agricultural engineering, process engineering and catalysis, and other areas that improve the living standards of societies.
Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the IGFBP3 gene. IGFBP-3 is one of six IGF binding proteins that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes included in this family, shares neither the conserved structural features nor the high IGF affinity. Instead, IGFBP-7 binds IGF1R, which blocks IGF-1 and IGF-2 binding, resulting in apoptosis.
A free gingival graft is a type of gingival grafting performed to correct acquired deficiencies of the gum tissue around teeth or dental implants. Besides autologous tissues, xenogeneic collagen matrices are using for gingival augmentation after dental implantation. Simultaneous injection of stem cells may improve the grafting outcomes due to enhanced vascularization and epithelialization in affected tissues.
Free fatty acid receptor 3 protein is a G protein coupled receptor that in humans is encoded by the FFAR3 gene. GPRs reside on cell surfaces, bind specific signaling molecules, and thereby are activated to trigger certain functional responses in their parent cells. FFAR3 is a member of the free fatty acid receptor group of GPRs that includes FFAR1, FFAR2, and FFAR4. All of these FFARs are activated by fatty acids. FFAR3 and FFAR2 are activated by certain short-chain fatty acids (SC-FAs), i.e., fatty acids consisting of 2 to 6 carbon atoms whereas FFFAR1 and FFAR4 are activated by certain fatty acids that are 6 to more than 21 carbon atoms long. Hydroxycarboxylic acid receptor 2 is also activated by a SC-FA that activate FFAR3, i.e., butyric acid.
Free Fatty acid receptor 4 (FFAR4), also termed G-protein coupled receptor 120 (GPR120), is a protein that in humans is encoded by the FFAR4 gene. This gene is located on the long arm of chromosome 10 at position 23.33. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR4 is a rhodopsin-like GPR in the broad family of GPRs which in humans are encoded by more than 800 different genes. It is also a member of a small family of structurally and functionally related GPRs that include at least three other free fatty acid receptors (FFARs) viz., FFAR1, FFAR2, and FFAR3. These four FFARs bind and thereby are activated by certain fatty acids.
In gene-activated matrix technology (GAM), cytokines and growth factors could be delivered not as recombinant proteins but as plasmid genes. GAM is one of the tissue engineering approaches to wound healing. Following gene delivery, the recombinant cytokine could be expressed in situ by endogenous would healing cells – in small amounts but for a prolonged period of time – leading to reproducible tissue regeneration. The matrix can be modified by incorporating a viral vector, mRNA or DNA bound to a delivery system, or a naked plasmid.
Chromium is claimed to be an essential element involved in the regulation of blood glucose levels within the body. More recent reviews have questioned this, however.
Robert M. Nerem, often referred to as Bob Nerem, a member of the U. S. National Academy of Engineering and the Institute of Medicine, held the Parker H. Petit Distinguished Chair for Engineering in Medicine and Institute Professor Emeritus at the Georgia Institute of Technology where he was an Emeritus Professor until his death.
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.
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 (in its original position or place) 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.
Matthias Lutolf is a bio-engineer and a professor at EPFL where he leads the Laboratory of Stem Cell Bioengineering. He is specialised in biomaterials, and in combining stem cell biology and engineering to develop improved organoid models. In 2021, he became the scientific director for Roche's Institute for Translation Bioengineering in Basel.
Cell engineering is the purposeful process of adding, deleting, or modifying genetic sequences in living cells to achieve biological engineering goals such as altering cell production, changing cell growth and proliferation requirements, adding or removing cell functions, and many more. Cell engineering often makes use of DNA technology to achieve these modifications as well as closely related tissue engineering methods. Cell engineering can be characterized as an intermediary level in the increasingly specific disciplines of biological engineering which includes organ engineering, tissue engineering, protein engineering, and genetic engineering.
Minimally manipulated cells are non-cultured (non-expanded) cells isolated from the biological material by its grinding, homogenization or selective collection of cells, which undergo minimal manipulation. Minimally manipulated cells are usually using for the treatment of skin ulceration, alopecia, and arthritis. Minimally manipulated cells can be used for the intraoperative creation of tissue-engineered grafts in situ.
Microgravity bioprinting is the utilization of 3D bioprinting techniques under microgravity conditions to fabricate highly complex, functional tissue and organ structures. The zero gravity environment circumvents some of the current limitations of bioprinting on Earth including magnetic field disruption and biostructure retention during the printing process. Microgravity bioprinting is one of the initial steps to advancing in space exploration and colonization while furthering the possibilities of regenerative medicine.
Intestines-on-a-chip are microfluidic bioengineered 3D-models of the real organ, which better mimic physiological features than conventional 3D intestinal organoid culture. A variety of different intestine-on-a-chip models systems have been developed and refined, all holding their individual strengths and weaknesses and collectively holding great promise to the ultimate goal of establishing these systems as reliable high-throughput platforms for drug testing and personalised medicine. The intestine is a highly complex organ system performing a diverse set of vital tasks, from nutrient digestion and absorption, hormone secretion, and immunological processes to neuronal activity, which makes it particularly challenging to model in vitro.