physiological relevance
File:Physiological relevance.png (green), ex vivo (red), or in vitro (blue), and arranged in ascending order of physiological relevance, based on the criteria proposed by Klein and Hutmacher (2024){{cite journal|last1=Klein |first1=Leopold |last2=Hutmacher |first2=Dietmar W. |title=Straddling the Line Between In Vitro and Ex Vivo Investigations |journal=Tissue Engineering Part C |date=2024 |volume=30 |issue=10 |pages=443–451 |doi=10.1089/ten.tec.2024.0246 |pmid=39422880 }}{{rp|page=447}}]]
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.
Importance in biomedical research
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.{{Cite journal |last1=King |first1=Oisín |last2=Sunyovszki |first2=Ilona |last3=Terracciano |first3=Cesare M. |date=July 2021 |title=Vascularisation of pluripotent stem cell-derived myocardium: biomechanical insights for physiological relevance in cardiac tissue engineering |journal=Pflügers Archiv: European Journal of Physiology |volume=473 |issue=7 |pages=1117–1136 |doi=10.1007/s00424-021-02557-8 |issn=1432-2013 |pmc=8245389 |pmid=33855631}} 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.{{Cite journal |last1=Bloom |first1=Celia R. |last2=North |first2=Brian J. |date=2021-04-23 |title=Physiological relevance of post-translational regulation of the spindle assembly checkpoint protein BubR1 |journal=Cell & Bioscience |volume=11 |issue=1 |pages=76 |doi=10.1186/s13578-021-00589-2 |issn=2045-3701 |pmc=8066494 |pmid=33892776 |doi-access=free }}{{Cite journal |last1=Kahru |first1=A. |last2=Mortimer |first2=M. |date=2021 |title=Advances in Nanotoxicology: Towards Enhanced Environmental and Physiological Relevance and Molecular Mechanisms |journal=Nanomaterials |volume=11 |issue=4 |pages=919 |doi=10.3390/nano11040919 |issn=2079-4991 |pmc=8066080 |pmid=33916509 |doi-access=free }}
Examples
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.{{Cite journal |last1=Abbott |first1=Rosalyn D. |last2=Kaplan |first2=David L. |date=2015 |title=Strategies for improving the physiological relevance of human engineered tissues |journal=Trends in Biotechnology |volume=33 |issue=7 |pages=401–407 |doi=10.1016/j.tibtech.2015.04.003 |issn=1879-3096 |pmc=4475434 |pmid=25937289}} Bioengineering approaches to modify the mechanical properties of scaffolds and functionalize materials with growth factors or gene therapeutics.{{Cite journal |last1=Klabukov |first1=I. |last2=Tenchurin |first2=T. |last3=Shepelev |first3=A. |last4=Baranovskii |first4=D. |last5=Mamagulashvili |first5=V. |last6=Dyuzheva |first6=T. |last7=Krasilnikova |first7=O. |last8=Balyasin |first8=M. |last9=Lyundup |first9=A. |last10=Krasheninnikov |first10=M. |last11=Sulina |first11=Y. |last12=Gomzyak |first12=V. |last13=Krasheninnikov |first13=S. |last14=Buzin |first14=A. |last15=Zayratyants |first15=G. |date=2023 |title=Biomechanical Behaviors and Degradation Properties of Multilayered Polymer Scaffolds: The Phase Space Method for Bile Duct Design and Bioengineering |journal=Biomedicines |volume=11 |issue=3 |pages=745 |doi=10.3390/biomedicines11030745 |issn=2227-9059 |pmc=10044742 |pmid=36979723 |doi-access=free }}{{Cite journal |last1=Klabukov |first1=I. |last2=Balyasin |first2=M. |last3=Krasilnikova |first3=O. |last4=Tenchurin |first4=T. |last5=Titov |first5=A. |last6=Krasheninnikov |first6=M. |last7=Mudryak |first7=D. |last8=Sulina |first8=Y. |last9=Shepelev |first9=A. |last10=Chvalun |first10=S. |last11=Dyuzheva |first11=T. |last12=Yakimova |first12=A. |last13=Sosin |first13=D. |last14=Lyundup |first14=A. |last15=Baranovskii |first15=D. |date=2023 |title=Angiogenic Modification of Microfibrous Polycaprolactone by pCMV-VEGF165 Plasmid Promotes Local Vascular Growth after Implantation in Rats |journal=International Journal of Molecular Sciences |volume=24 |issue=2 |pages=1399 |doi=10.3390/ijms24021399 |issn=1422-0067 |pmc=9865169 |pmid=36674913 |doi-access=free }}
Challenges
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.{{Cite journal |last1=Tronolone |first1=James J. |last2=Mathur |first2=Tanmay |last3=Chaftari |first3=Christopher P. |last4=Sun |first4=Yuxiang |last5=Jain |first5=Abhishek |date=November 2023 |title=Machine learning chained neural network analysis of oxygen transport amplifies the physiological relevance of vascularized microphysiological systems |journal=Bioengineering & Translational Medicine |volume=8 |issue=6 |pages=e10582 |doi=10.1002/btm2.10582 |issn=2380-6761 |pmc=10658488 |pmid=38023704}}