Insights from Animal Models: Breakthroughs in Tissue Engineering

Drug discovery and the creation of animal models are complex, multi-disciplinary approaches that include many scientific, technical, and regulatory processes. Over the past few years, this particular fish has a popular pet for scientists across the globe and have also been in the limelight #invivo testing.

#zebrafish , or Danio rerio, are small freshwater fish that have gained importance as an animal model for scientific research. Zebrafish are native to South Asian rivers, streams, and rice paddies. They are small, hardy, and have short reproductive cycles, making them an ideal organism for research.

More than 70% of human genes have a zebrafish counterpart, making them a valuable tool for studying human diseases and disorders. Zebrafish is an helpful animal model for studying human diseases due to their suitability for large-scale genetic mutant and therapeutic compound screenings. These efforts are critical for the advancement of #precisionmedicine , leading to the development of new diagnostic and therapeutic solutions.

It is a well known fact that the use of animal models in research has been a subject of ethical debate for many years. There are concerns about the inhumane use of animals as testing models and their validity in whether their physiological responses reflect those of humans.

This article covers the applications of Zebrafish as an animal model, highlighting its importance and some of its drawbacks. It will also highlight how we at BioDimension aim to provide an #alternative method which is safer, accurate and more advanced, making it likely that the use of animals in research will continue to decrease further.?

Why Do Scientists Prefer Zebrafish?

Aside from the genetic similarities to humans, zebrafish are small and active fishes that have a short life-span and reproductive cycle. This short life-span is a very helpful trait, especially for scientific research, as it allows scientists and researchers to create new medicines or learn about? diseases. Using them reduces the time taken to study the effect of a disease or a drug from over six decades to a few years. Their short reproductive cycle also prevents the shortage of the fishes for scientific use.

Zebrafish are organisms that have transparent embryos, with their eggs being almost transparent. This allows scientists to observe their growth and development without having to disturb the maturing embryos. These embryos need short development time, allowing for faster observations. They show well developed eyes, muscles, ears, and a brain all within 24 hours. #segmentation and primary organ system formation is almost completed by the first week of development.

Owing to their small size, these fishes need very little space and have low maintenance. Some of the fields that use Zebrafish as a model organism include:

1. Developmental Biology: to study embryonic development, differential regulation of gene expression in embryos, organ system development, nervous system development, angiogenesis, cellular regeneration (in embryos and adults), etc.
2. Cancer Model System: to understand and study the effects of carcinogens, development of cancers, tumorigenesis, the impact of various type of carcinogens, xenotransplantation, angiogenesis in tumors, and tumor metastasis.
3. Toxicology studies: drug toxicity, #drugdiscovery etc.
4. Human disease studies: to study Alzheimer's disease, Duchenne muscular dystrophy, Huntington's disease, Parkinson's disease, schizophrenia, etc.

Disadvantages of Zebrafish as an Animal Model

One of the main disadvantages of the use of zebrafish models in biomedical research is that their physiology is not identical to that of humans. This model is distant from humans? when compared to other animals like rodents, with 96 million year divergence from humans.

It is also a well-known fact that they need water systems to maintain them. This can affect the way zebrafish metabolize drugs and other substances, making it difficult to extrapolate these findings to humans. Findings from zebrafish studies therefore need to be interpreted with caution and verified through further research in more complex animal models and human clinical trials.

Now, the genetic approach is the most obvious way to develop disease models that involve zebrafish. Thousands of zebrafish gene mutations have already been created and compiled, and 82 percent of the human disease-related genes have a zebrafish ortholog. It is quite a challenging task to find small molecule suppressors for the many genetic disorders that affect humans, but the zebrafish's efficiency in terms of cost and effort makes it possible to envision such a bold try.

Even then, several human disorders are difficult or impossible to model in this species due to a lack of similar organs in the species, such as breast tissue, the prostate, and the lungs. Their skin also lacks certain cellular components found in humans. Some of the diseases that can’t be studied include cardiac septation defects, breast cancer, skin melanomas, lung and prostate cancer, among others.

The earliest zebrafish genetic mutant used for a chemical screen was the gridlock mutant, which harbors a mutation in the hey2 gene. Independent small molecule screens identified compounds that completely and permanently rescued the aortic defect by stimulating arteriogenesis in the heart.

Since then, several other zebrafish genetic models have been used for chemical screening, including models of Long QT syndrome and cardiac arrhythmia. A disadvantage that is noted? when using such disease models is that the small molecules that appear to be improving a disease phenotype might simply be reducing the expression of its transgene.

Furthermore, zebrafish naturally #regenerate most damaged tissues, but any inhibitory pathways identified in zebrafish may not translate to agents that promote regeneration in humans, therefore questioning the full capacity of tissue? regeneration in humans.

It is also difficult to study drug diffusion as zebrafish have 2 copies of many genes in their genome, making it harder to determine their functional roles? as the duplicate genes cause a lot of unnecessary #interference.

#personalizedmedicine and the development of novel cancer treatments are the two main goals of zebrafish-based xenotransplantation models. Only a few cancer cells are required for xenotransplantation in zebrafish. By injecting patient-derived primary cancer cells, patient-derived tumor tissue explants, or human cell lines into various sites or into fish at various developmental stages, a variety of zebrafish xenograft models have been developed. But, this method has some drawbacks, such as the fact that tumor microenvironments differ in both zebrafish and humans and that optimal cell growth occurs at a specific temperature. These methods cause adult immunocompetency problems as well.

Tissue Engineering: An Alternative

#tissueengineering is a field that involves creating functional tissues or organs by combining cells, biomaterials, and biochemical cues. It has the potential to revolutionize #regenerativemedicine and enable the development of new therapies for a wide range of diseases and injuries. Tissue engineering can be used to create tissue models for drug screening and toxicity testing, to repair or replace damaged tissues or organs, and to study disease mechanisms and cellular behavior in a controlled environment.

At Biodimension Technology Private Limited, we provide substitutes to the animal testing. We use 3-D printed human tissues that can be used to replace these animals. Our products, such as BioDSkin, BioDVaginal, and BioDCornea, ensure that the tests are uniform with no variations between the tissues, have a higher shelf-life based on the user's needs, and can be created specific to the user's needs with different markers in the tissues based on the needs of the user.

There are some potential reasons why lab grown tissues may be preferred over zebrafish models:

1. We always have more control over the experimental conditions. With tissue engineering, researchers have complete control over the types of cells used, the physical properties of the tissue scaffold, and the biochemical factors present in the culture medium. This allows for more precise and reproducible experiments, which can be important in drug testing or when studying complex biological processes.
2. Avoidance of ethical concerns is a huge advantage of using lab grown tissues.This process allows researchers to study cells and tissues without the use of animals, which can be beneficial for those who are concerned about animal welfare.

Researchers can also study specific tissues or organs using such reconstructed lab models, as zebrafish models may not always accurately represent the human tissue or organs being studied. The genes of both zebrafish and humans are only 70% similar to each other; therefore, by using tissue engineering, researchers can create more accurate models of specific tissues, such as liver or heart tissue, and study them in vitro.

It also enables cost-effectiveness. While the initial cost of setting up a tissue engineering experiment can be high, once established, it can be a more cost-effective method than using zebrafish models. This is especially true if a researcher needs to perform a large number of experiments or if the experiments require long-term studies.

Zebrafish have emerged as an indispensable animal model in scientific research. Despite its advantages, the use of animal models in research is a subject of ethical debate due to concerns about their validity and animal welfare. To provide an alternative method, BioDimenion aims to develop safer, more accurate, and more advanced technology to further decrease the use of animals in research.

Here at BioDimension, we have devised ways to provide our collaborators and clients with lab-made tissues for various purposes with the help of our highly skilled team of scientists and researchers. Our team is committed to staying up-to-date with the latest advances in the field, allowing us to continually improve and refine our methods. Ultimately, by leveraging the power of lab-based models, we aim to create a more sustainable and humane future for #biomedical research that benefits both humans and animals alike.