ORGAN ON CHIP IN CLINICAL RESEARCH

Organs on chips are micro engineered biomimetic frameworks that imitate key elements of living organs providing accuracy than conventional cell culture for simulating complex cell-cell and cell-matrix interactions. Thus, potentially represent a very interesting tool for preclinical investigations of a drug compound. They likewise permit to read human physiology for a particular organ and subsequently empower the improvement of new in vitro disease models and to study novel drugs. Microfluidics and Microfabrication are the technologies used for organ on chip models to better replicate the functionalities of living organs.

Significance of organ on chip in clinical research:

Pre-Clinical Trials /Investigations always has vital role in examining Pharmacokinetics and dynamics of a drug compound. If the drug cannot exhibit precise adequacy and wellbeing, it ends up huge disappointment entering clinical Trials. Organ on chip is one of ongoing in vitro advancement in pre-clinical trials. The accessibility through organ on chip models gives numerous chances of comprehending pathogenesis of disease or a condition. It assists in better screening of drug in 3d climate like human body. New expansions in organ on chip defines translational exploration of exact medication in human body. In vitro cell culture brought abundant information in Human illness and treatment being significant in drug studies in identifying if a drug could be translated for Clinical trials in people

How Organ on Chip models surpassed 2D and 3D cell cultures:

Cell culture is growing isolated living tissues under artificially controlled microenvironment conditions. It has a vital role in pre-clinical trials for drug discoveries and its action on human body.

2D cultures are isolated cells in monolayers in a cultural flask or a in a flat petri dish. these cultural models do not assist in intercellular and extracellular interactions. Though these have their own benefits, they are do not mimic the natural structures of tissues so are biologically less relevant models.

3D cultures allow cell interactions in all 3 dimensions, exhibiting more like a human body environment. This could enhance improved models in cell migration, differentiation and growth. It shows a better degree of polarization and exhibit gene expression levels. They can mimic acinar (many lobes or clusters) tissues.

Organ on chip take advantages of microfluidics and micro fabrications to enhance inter tissue interfaces which is a limitation for 3D cell culture. They represent dynamic mechanical properties and biochemical functions of living organisms. Organs on chip rely on two core techniques. The first is microfluidics, which empowers controlling limited quantity of fluids, and permits to accurately controlling fluid flows or creating concentration gradients. With microfluidic procedures, supplements and other chemical signals can be conveyed in an exceptionally controlled manner. The subsequent one is microfabrication (photolithography, replica modeling, microcontact printing) that is appropriate to make microstructures permitting to control cell shape and capacity.

Microfluidics: It is the science which contemplates the conduct of liquids through micro channels, and the innovation of assembling microminiaturized gadgets containing chambers and passages through which liquids stream or are confined. Microfluidic frameworks are made of polydimethylsiloxane (PDMS). PDMS has a few properties that make it especially appropriate for the manufacture of microdevices for cell or tissue culture.  PDMS has a rich gas porousness that guarantees oxygen gracefully to the cells inside the micro channels. This takes out the need of an outside oxygenator, ordinarily needed for cell culture in silicon, glass or plastic gadgets. At that point, PDMS empowers live cell imaging because of its optical transparency. PDMS is entirely adaptable, which permits utilizing on chip valves or applying mechanical activities to the cells through PDMS distortions.

Micro fabrications: Miniatured organs in a processor/chip like array which could be manipulated for drug modelling. These are formed by a technique called Soft lithography. These molds are transparent allowing easy representation.

Steps incorporated in formation of organ on chip:

 

The organ on chip also incorporates organoids, bioprinting, inkjet, laser assisted bio printing, micro extrusion and stereolithography processes for formation and reconstruction of cellular structures viable for drug trials or exploration of pathogenesis of diseases.

Advantages:

 Miniaturization, integration and low consumption

 Allow researchers to accurately control the multiple parameters of a system

 Provides Cell patterning, tissue-tissue interface, organ-organ interaction 

Aim at mimicking the complex structure, microenvironment and physiological function of human organs.

Signifies impact on improving the predictability of drug screening models and personalized medicine

Organ-on-a-chip is scalable by combining the other technologies such as semiconductor and molecular biology disciplines.

 Enhances understanding of diseases and drug screening

Implications in clinical Research:

Research advancement of these models are being held on Heart, kidney, Liver, Intestine, lung, placenta, adipose, retina, bone, brain and multiorgan models. Though these techniques contribute to greater insights of physiological aspects of diseases and drug interactions, there are fewer limitations and greater advancements required to study more complex cell and organ interactions and integrities.

Conclusion:

Organ on chip could replace animal models in trials which implies it could be the futuristic in vitro trial models. The biggest challenge in progression is to collect cells from patients, culture and administer diversified treatment options to find the best suited option. Pre-set test banks representing different subpopulations allows huge opportunities for safety and efficacy tests. Through more relevant models it allows unlocking new drugs and drugs that have previously failed. It also benefits personalized medicine with precision in diagnostics, treatment selection and a better overview of similar disease pathogenesis with integration of patient derived cells in devices. 

                                                                                                            Aneesha Chatla BPT, MHM