Sreelipi Sreebhashyam, National Institute of Technology Warangal.
Abstract Background: i The existing animal models have the inability to simulate human body like conditions, for drug-related studies. i To circumvent this, 3D printed organoid-on-chip and human body-onchip systems were developed recently, for in-vitro drug testing [1]. Rationale: i Many articles review the different strategies that could be used to fabricate 3D printed materials for functional organ creation [2]. i Here, we summarize the most effective, existing 3D printing methods to connect these functional organs to form a functional human body model (a conceptual idea). i We intend to extend the scope of existing human body in-vitro models [3] to a 3D-printed functional model suitable for conducting in-vivo personalized clinical studies. i This poster enlists a few conceptual insights that could be employed for achieving such a complicated design (open to improvisations). Conclusion: i A bird’s eye view of the potentials and drawbacks of existing technologies would help realize the intricate complexities involved in designing a functional body.
Introduction i Today, 3D bio-printed tissues emulate human physiology (in human body-on-chip systems) & create better in-vitro working models for drug testing [19]. i Their application in drug development would save the lives of many lab animals, the living systems which we have been exploiting, since ages, for our therapeutic studies. i In light of these advancements, we discuss the potential of 3D bioprinting to replace the clinical studies on humans by personalized working models, in the near future.
Chronological Developments
Conceptual Insights on Design :
internally embedded with 3D printed vascular channels, printed using SWIFT technology (stated in [11]).
P Patient’s adult stem cells (ex: cells are taken from omentum) need to be extracted and cultured to revert them to embryonic state and produce large quantities of iPSCs.
P The organs grow to their live-size by self-
i It is very difficult to obtain the exact density as that of the real organs.
progenitor cells will be mixed with hydrogel to form a personalized hydrogel that acts as bio-ink to print organs.
P The organ system circuit diagram of this 3D
P A controlled environment in which the organs are
i Each organ has a unique ECM (Extracellular Matrix) which may interfere with that of the other organs, so a method should be devised to control the expansion of ECM.
P Every organ is fabricated in 3 layers. Ex: The
PThe iPSCs, differentiated to organ-specific
printed human body is inspired by that of the human on-chip systems [1].
grown could be created by suspending alginate microparticles in xanthan gum- supplemented growth medium, which acts as a support medium (as stated in [10]).
inner layer of the lung is printed with microvasculature endothelial cells, the middle layer with stromal cells & the upper layer with bronchial epithelial cells [3].
P This is the environment, which encompasses
P The vascular interpenetrating networks could be
distinguished architectures (ECMs) of different tissues, formed by organ-specific personalized hydrogels.
P 3D printed organs like heart, lungs, kidneys, blood vessels, etc are printed in their respective positions using specified bio-inks comprising their progenitor cells. P The 3D printed organs are connected and
extended from lungs to heart & from there to other organs (each organ receives oxygen via bio-printed capillaries).
i Most of the challenges involved in fabricating a live sized human body are met by independent labs across the world; hence collaboration is the key to meet the goal.
P The above mentioned SWIFT method proved to
Expert Scientist Comments
have great potential to keep lung, heart, and other laboratory-grown organs alive for longer durations by constantly supplying them with oxygen and other nutrients through vasculature [11].
Heart :
Brain :
N A 3D-printed functional heart was developed with bio-mimetic valves and chambers by a group of scientists from Israel in 2019 [10].
N Three types of brain cells were derived from induced pluripotent cells of the patient, which were grown fully and stacked together in layers by soft tissue 3D bio-printing.
N However, the designed heart could not pump blood. The ECM needs to be remodeled to support massive striation, to get the heart functional [15].
N There are excellent works in the literature that discuss 3D printing a Liver [17].
i Further, 5D (5 axes) bio-printing was developed in 2016 to create stronger, curved implants for orthopedics and dentistry [6].
N Here, we state the first functional liver derived from human induced pluripotent cells, grown in an alginate matrix, proved to have peak level albumin secretions [18].
N A layer of tumor infiltrated cells was allowed to grow at the center of the 3D printed brain and a few chemotherapeutic drugs were tested using the model, as stated in [14].
Lungs : N Functional bio-printed alveolar sacs that enable gas exchange with the red blood cells present in associated vasculature have been discovered, in 2019 [12,13]. N A large number of these alveoli can be synchronized with one another to expand and contract rhythmically (by the aid of an automated machine), forming a functional lung.
The Bright Side
i Recently, a bio-plastic model of a patient was 3D printed using the body scans to optimize radiation dosing for cancer treatments [8].
i The generation of dynamic prints of organs requires advanced tools in Machine learning to extend 3D printing to 4D bioprinting [9].
i The world is currently at a nascent stage where further innovations are required on post-printing culture platforms to assist and maintain large vascularized tissue constructs.
- Dr. Thyageshwar Chandran, Asst. Prof. NIT Warangal
i Then came 4D bioprinting, in 2013, pre-programmed to print the dynamic organs, sensitive to external stimuli, using lately developed smart biomaterials [5].
i 3D printed anatomy models (not-functional) are already being used in surgical training and to demonstrate the surgical issue to the patients [7].
i Different strategies and tools need to be brought under one roof (very expensive for independent labs).
i More sync between medicine, engineering, and biology is required to fully realize the potential of this technology.
Liver
i 3D printed functional human body models have the potential to transform drug development and fasten the pace at which bench-side drugs reach the market.
i Insufficient expansion of iPSCs [induced pluripotent cells]: Huge cell numbers are required for printing a functional organ, imagine the case to print a functional body.
assembly process as the organ-specific progenitor cells differentiate and mature progressively.
i The advent of 3D bio-printing in 2010 had revolutionized the manufacture of bio-mimetic organ implants which could exactly resemble the native tissue [4].
i The development of personalized human models helps us obtain accurate results in clinical studies as the model is a replica of the patient’s body.
Challenges
Blood Vessels :
Kidneys
N A fine channeled vascular system could be developed by using SLATE, an open-source technology [12,13] which is based on blue light-mediated curing.
N Although functional kidneys haven’t been designed till date, Dutch researchers created a kidney organoid in 2018, that induces vascularization, only when transplanted in-vivo.
N A pervasive network of perfusable blood vessels could be embedded within the organ matrix by writing and removing gelatin-based sacrificial bio-ink (this technique called SWIFT, was developed in 2019 [20]).
N It was derived from human pluripotent cells and was functional. It also promotes the progressive maturation of nephrons [16]. [21]
Conclusion i A summary of all the effective strategies to print bio-mimetic organs and some insights on integrating them into a single system would help raise more scientific discussions on improving the current-day technologies to meet the complexities of functional human body design.
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