A printable organ is an artificially
constructed device designed for organ replacement, produced using 3D printing
techniques. The primary purpose of printable organs is in transplantation.
Research is currently being conducted on artificial heart, kidney, and liver
structures, as well as other major organs. For more complicated organs, such as
the heart, smaller constructs such as heart valves have also been the subject
of research. Some printed organs are approaching functionality requirements for
clinical implementation, and primarily include hollow structures such as the
bladder, as well as vascular structures such as urine tubes.
3D printing allows for the layer-by-layer
construction of a particular organ structure to form a cell scaffold. This can
be followed by the process of cell seeding, in which cells of interest are
pipetted directly onto the scaffold structure. Additionally, the process of
integrating cells into the printable material itself, instead of performing
seeding afterwards, has been explored.
Modified inkjet printers have been used to
produce three-dimensional biological tissue. Printer cartridges are filled with
a suspension of living cells and a smart gel, the latter used for providing
structure. Alternating patterns of the smart gel and living cells are printed
using a standard print nozzle, with cells eventually fusing together to form
tissue. When completed, the gel is cooled and washed away, leaving behind only
live cells.
History
3D printing for producing a cellular
construct was first introduced in 2003, when Thomas Boland of Clemson University
Since Boland's initial findings, the 3D
printing of biological structures, also known as bioprinting, has been further
developed to encompass the production of tissue and organ structures, as
opposed to cell matrices. Additionally, more techniques for printing, such as
extrusion bioprinting, have been researched and subsequently introduced as a
means of production.
Organ printing has been approached as a
potential solution for the global shortage of donor organs. Organs that have
been successfully printed and implemented in a clinical setting are either
flat, such as skin, vascular, such as blood vessels, or hollow, such as the
bladder. When artificial organs are prepared for transplantation, they are
often produced with the recipient's own cells.
More complex organs, namely those that
consist of solid cellular structures, are undergoing research; these organs
include the heart, pancreas, and kidneys. Estimates for when such organs can be
introduced as a viable medical treatment vary. In 2013, the company Organovo
produced a human liver using 3D bioprinting, though it is not suitable for
transplantation, and has primarily been used as a medium for drug testing.
Approaches
Researchers have developed different approaches
to producing living synthetic organs. The 3D bio-printing is based on three
main approaches: Biomimicry, autonomous self-assembly and construction of mini
tissue blocks.
Biomimicry
The first approach to bio-printing is
called biomimicry. The main objective of this approach is to create structures
identical to natural structures. Biomimicry requires duplication of the shape,
frame and micro-environment of organs and tissues. Biomimicry application in
bio-printing involves the identical copy of the cellular and extracellular
parts of the organs. For this approach to be successful, tissue replication at
a micron scale is required. This degree of precision involves understanding the
microenvironment, the nature of biological forces, the precise organization of
cells, solubility factors and the composition and structure of the
extracellular matrix.
Self-assembly
The second approach used in bio-printing is
autonomous self-assembly. This approach relies on the natural physical process
of developing embryonic organs. When the cells are in their early development
phase, they create their own extracellular matrix building block, and produce
the proper cell signaling of their own and take the layout and
microarchitecture required to provide the expected biological functions.
Autonomous self-assembly requires knowledge of the processes of development of
tissues and organs in the embryo. Autonomous self-assembly relies on cell
capabilities as the fundamental building block of histogenesis. This technique
therefore requires a very thorough understanding of the mechanisms of embryonic
tissue development as well as the micro-environments in which tissues grow.
Mini-fabric
The third approach to bio-printing is a
combination of both biomimetic and self-assembly approaches. This technique is
referred to as "mini-tissues". Organs and tissues are made from very
small functional components. The mini-fabric approach is to take these small
pieces and arrange them in a larger structure. This approach uses two different
strategies. The first strategy is to use self-assembled cell spheres in large
scale fabrics, using natural patterns as a guide. The second strategy is to
develop accurate reproductions and high quality of fabric and allow them to
mount automatically in large functional fabrics to scale. The mixing of these
strategies is necessary to print a complex three-dimensional biological
structure.
Organ printing has great potential for NBIC
technologies (nano, bio, info and cognitive) to advance medicine and surgical
procedures, to save time, reduce costs and create new opportunities for
patients and patients. health professionals.
3D printing techniques
3D printing for the manufacturing of
artificial organs has been a major topic of study in biological engineering. As
the rapid manufacturing techniques entailed by 3D printing become increasingly
efficient, their applicability in artificial organ synthesis has grown more
evident. Some of the primary benefits of 3D printing lie in its capability of
mass-producing scaffold structures, as well as the high degree of anatomical
precision in scaffold products. This allows for the creation of constructs that
more effectively resemble the microstructure of a natural organ or tissue
structure.
Organ printing using 3D printing can be
conducted using a variety of techniques, each of which confers specific
advantages that can be suited to particular types of organ production. Two of
the most prominent types of organ printing are drop-based bioprinting and
extrusion bioprinting. Numerous other ones do exist, though are not as commonly
used, or are still in development.
Drop-based bioprinting (Inkjet)
Drop-based bioprinting creates cellular
constructs using individual droplets of a designated material, which has
oftentimes been combined with a cell line. Upon contact with the substrate
surface, each droplet begins to polymerize, forming a larger structure as individual
droplets begin to coalesce. Polymerization is instigated by the presence of
calcium ions on the substrate, which diffuse into the liquified bioink and
allow for the formation of a solid gel. Drop-based bioprinting is commonly used
due to its efficient speed, though this aspect makes it less suitable for more
complicated organ structures.
Extrusion bioprinting
Extrusion bioprinting involves the constant
deposition of a particular printing material and cell line from an extruder, a
type of mobile print head. This tends to be a more controlled and gentler
process for material or cell deposition, and allows for greater cell densities
to be used in the construction of 3D tissue or organ structures. However, such
benefits are set back by the slower printing speeds entailed by this technique.
Extrusion bioprinting is often coupled with UV light, which photopolymerizes
the printed material to form a more stable, integrated construct.
Printing materials
Materials for 3D printing usually consist
of alginate or fibrin polymers that have been integrated with cellular adhesion
molecules, which support the physical attachment of cells. Such polymers are
specifically designed to maintain structural stability and be receptive to
cellular integration. The term "bioink" has been used as a broad
classification of materials that are compatible with 3D bioprinting.
Printing materials must fit a broad
spectrum of criteria, one of the foremost being biocompatibility. The resulting
scaffolds formed by 3D printed materials should be physically and chemically
appropriate for cell proliferation. Biodegradability is another important
factor, and insures that the artificially formed structure can be broken down
upon successful transplantation, to be replaced by a completely natural
cellular structure. Due to the nature of 3D printing, materials used must be
customizable and adaptable, being suited to wide array of cell types and
structural conformations.
Hydrogel alginates have emerged as one of
the most commonly used materials in organ printing research, as they are highly
customizable, and can be fine-tuned to simulate certain mechanical and
biological properties characteristic of natural tissue. The ability of
hydrogels to be tailored to specific needs allows them to be used as an
adaptable scaffold material, that are suited for a variety of tissue or organ
structures and physiological conditions. A major challenge in the use of
alginate is its stability and slow degradation, which makes it difficult for
the artificial gel scaffolding to be broken down and replaced with the
implanted cells' own extracellular matrix. Alginate hydrogel that is suitable
for extrusion printing is also often less structurally and mechanically sound;
however, this issue can be mediated by the incorporation of other biopolymers,
such as nanocellulose, to provide greater stability. The properties of the
alginate or mixed-polymer bioink are tunable and can be altered for different
applications and types of organs.
Organ structures
While many of the technical challenges of
organ printing are shared with other applications of 3D bioprinting, there are
some organ-specific structural elements that must be addressed for successful
creation of a transplantable printed organ.
Vascularization
The transfer of nutrients and oxygen to
cells throughout a printed organ is essential for its function. In very small
or thin tissues of less than a millimeter in thickness, cells can receive
nutrients through diffusion. However, larger organs require the transportation
of nutrients to cells deeper inside the tissue, which requires that the tissue
be vascularized, and thus able to receive blood for the exchange of cargo like
oxygen and cell wastes. Early organ printing techniques created solid tissues
that were unable to vascularize, or vascularized only slowly as host blood
vessels entered the transplant, leading to issues like necrosis inside the
tissue that can threaten the health and successful recovery of a transplant
recipient. More recently developed techniques allow printed organs to be
created with a more complex 3D structure, including preexisting internal
vasculature, that permits faster integration of the transplant into the host
circulatory system. There are multiple techniques for creating vascular systems
currently under development. One method is the separate extrusion printing of
vessels that are then incorporated into a larger tissue. Another method is
sacrificial printing, in which the entire tissue is printed at once, and a
dissolvable or otherwise removable bioink is used to form the interior of the
vessels. Once this sacrificial scaffolding is removed, usually by a chemical or
thermal method, the rest of tissue then contains a vascular pattern.
Cell sources
The creation of a complete organ often
requires incorporation of a variety of different cell types, arranged in
distinct and patterned ways. One advantage of 3D-printed organs, compared to
traditional transplants, is the potential to use cells derived from the patient
to make the new organ. This significantly decreases the likelihood of
transplant rejection, and may remove the need for immunosuppressive drugs after
transplant, which would reduce the health risks of transplants. However, since
it may not always be possible to collect all the needed cell types, it may be
necessary to collect adult stem cells or induce pluripotency in collected
tissue. This involves resource-intensive cell growth and differentiation and
comes with its own set of potential health risks, since cell proliferation in a
printed organ occurs outside the body and requires external application of
growth factors. However, the ability of some tissues to self-organize into
differentiated structures may provide a way to simultaneously construct the
tissues and form distinct cell populations, improving the efficacy and
functionality of organ printing.
Source from Wikipedia
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