Page 286 - IJB-9-5

International Journal of Bioprinting Blood components for tissue graft bioprinting

mechanically, piston, or pneumatically driven tools. Once fusion in vitro was guided using a 3D-printed polymer
deposited, their shape is maintained by gelification of the framework .
[9]
ink/bioink by means of induced physicochemical reactions. Ink and bioink formulations are at the core of these
There are two modalities, ink vs. bioink, that differ in the technologies, requiring bioink components to interact
presence of cells in the extruded biomaterial. Primarily, in non-trivial ways. Several (bio)printed tissue grafts,
solvent-based extrusion three-dimensional (3D) printing such as nerve grafts , blood vessels and vascular
[10]
entails the building of scaffolds with tailored geometry but networks , tracheal implants , liver , bone ,
[13]
[14]
[11]
[12]
without cells [3–5] . To create living constructs, 3D printing cartilage , vascular , and parathyroid grafts , have
[16]
[15]
[17]
can be followed by cell seeding. However, depending on been implanted into animals to study their functionality
the geometry of the printout, the access of cells to the (Figure 1). However, the clinical translation of these
core of the construct can be problematic. In contrast, products faces notable challenges for several reasons,
SBE bioprinting uses bioinks (i.e., cell-laden inks), thus mainly related to predictability. First, due to sub-optimal
implementing the concurrent biofabrication of the scaffold experimental models, there is no full understanding of the
and cellular components for the additive manufacturing of physiological complexity involved, including the dynamic
living tissue structures . Composite inks/bioinks can be integration of multiple components (i.e., biomaterials,
[6]
formulated by adding blood-derived products to printable different cell phenotypes, and a large array of signaling
hydrogels. When platelets are added to the solvent, the proteins) and their interactions with the host tissue/organ.
distinction between ink and bioink is blurred, as platelets Many of the critical mechanisms of tissue repair rely on
are considered anucleated cells. Although platelets lack the close interplay between cells and the dynamic tissue
genomic DNA, they contain various RNA biotypes, microenvironment through molecular signaling .
[18]
including coding mRNAs, and the translational machinery
needed to translate them into proteins. Thus, just like cells, Therefore, to fulfill as many requirements as possible
they can react to environmental stimuli granting biological regarding the predictability of bioprinted scaffolds, an
complexity to printable biomaterials . However, platelets utmost need is the correct functionalization of the bioink
[7]
lack other cellular attributes, such as growth and replication with signaling molecules. For example, Sun et al.
[19]
capacities. In the clinical context, regulatory authorities bioprinted functionalized scaffolds with transforming
have classified autologous platelet-rich plasma (PRPs) as growth factor beta 3 (TGF-b3) and connective growth
“non-standardized medicinal products” instead of advanced factor (CTGF) mixed with bone marrow stromal cells
therapies. Therefore, printable biomaterials loaded with (BMSCs) for intervertebral disc (IVD) regeneration.
platelets would have different regulatory considerations In another example, a 3D-printed polycaprolactone
than printable biomaterials loaded with cells. microchamber was coated with platelet-derived growth
factors (PDGFs) and bone morphogenetic protein 2
Bioprinting technologies are used in biomedical (BMP-2), and spheroids containing adipose stromal cells
research for several purposes, such as creating disease (ASCs) were cultured within the microchambers for
models , drug screening, basic cell biology, or the creation dual growth factor delivery in bone regeneration . In
[8]
[20]
of functional implants with structural organization. Due to another example, methacrylated hyaluronic acid (MeHA)
injuries, disease, surgery, and other reasons, a large number combined with collagen bioink was loaded with nerve
of patients with tissue defects need graft implantation. growth factor (NGF), glial cell-derived neurotrophic factor
Both SBE approaches, 3D printing and bioprinting, can be (GDNF), and Schwann cells .
[21]
explored in therapeutic tissue engineering and regenerative However, the functionalization of bioinks with single/
medicine to create mature competent tissue grafts that dual growth factors does not approach the immense
integrate within the host tissue once they are implanted. complexity of cell communication and competent
The medical need for tissue grafts is particularly important tissue biofabrication. Alternatively, biomaterials can be
when tissue defects exceed a critical size. Scalable methods functionalized with tailored blood-derived products
include the development of engineering strategies and to transform inert biomaterials into reactive (stimuli-
[9]
the creation of microtissue building blocks (with fewer response) biomaterials, drawing inspiration from
limitations in nutrient transport) that could fuse to generate physiological repair mechanisms in which hemostasis
a competent implant, either in vitro or with the use of the (blood clot formation, fibrin formation) is the starting
body as a bioreactor. Other challenges involve reproducing point, and platelet degranulation and secretome release
the vasculature and metabolic state of the organ. In one trigger the regenerative cascade .
[18]
instance, microtissue building blocks were bioprinted and
cultured chondrogenically to create a competent tissue This article describes the different types of blood-derived
graft, and the process of microtissue maturation and biomaterials that can be used in solvent-based extrusion

Volume 9 Issue 5 (2023) 278 https://doi.org/10.18063/ijb.762