Page 289 - IJB-9-5

International Journal of Bioprinting Blood components for tissue graft bioprinting

synthesized by megakaryocytes (their parent giant cells the maturation and integration within the host tissue by
located in the bone marrow, spleen, and lungs) before promoting cell trafficking and angiogenesis. These can be
platelet segmentation and release into the blood stream. considered as prerequisites for cross-platform validation,
In addition, these molecules can be captured from the in vitro and in vivo. Adding platelets to the bioink can
peripheral blood by endocytosis through the open influence the immunomodulatory properties of the tissue-
canalicular system. Furthermore, each platelet contains engineered graft as an approach to reduce graft rejection.
5–8 dense granules, which are 200–300 nm in diameter Platelets secrete a broad array of chemotactic proteins with
and contain 5-hydroxytryptamine (5-HT), adenosine the potential to recruit cells from the vasculature to the
diphosphate (ADP), adenosine triphosphate (ATP), Ca , graft and activate them to initiate tissue repair. Chemokines
2+
and pyrophosphates . Several studies have analyzed the are low-molecular-weight proteins (8–10 kDa) that trigger
[33]
proteomes of different blood derivatives and established signaling by binding to CXCR1 and CXCR2 receptors
the link with healing functions . expressed by immune cells, including neutrophils and
[34]
Furthermore, platelet extracellular vesicles (pEVs) have monocytes/macrophages. Moreover, the polarization status
captured recent attention as a sub-platelet therapy [35,36] . of monocytes/macrophages can be shaped toward M2 in
[41]
Essentially, platelets have a propensity to generate the presence of platelets . Furthermore, platelets are key
extracellular vesicles, with a yield of 10–160 pEVs/platelet; regulators of angiogenesis, releasing both promoters of
thus, in typical clinical-grade PC containing 4–7 × 10 vascular development, such as basic fibroblastic growth
11
platelets, approximately 10 –10 pEVs can be found. factor (bFGF), endothelial growth factor (EGF), vascular
14
13
Platelet vesicle heterogeneity is dictated by the activation endothelial growth factor (VEGF), hepatocyte growth
stimulus that triggers their formation: microvesicles (0.1– factor (HGF), and anti-angiogenic proteins, including but
1 µm diameter) shed from the platelet membrane and not limited to thrombospondin (TSP) and platelet factor 4
exosomes [37,38] . (PF-4). These are a few examples of platelet contributions
within a tissue-healing microenvironment.
2.2.2. Functional attributes and biological
mechanisms 2.3. Fresh-frozen plasma
The functionality of a bioink depends on the kinetics of Another blood component frequently used in printing/
cytokine release, which may cause changes in cell behavior bioprinting is FFP. This biomaterial is available in larger
(e.g., differentiation of cells, expression of particular volumes than PCs but contains few signaling proteins.
genes). These changes should be beneficial, and the However, its stability is a major asset, as plasma frozen
fabrication process must be designed such that the changes at -18°C within 8 h of collection can be stored for up
are predictable and the environment of the cell is not to 7 years at -65°C. Plasma is made of 91%–92% water
changed beyond healthy regenerative bounds. Moreover, combined with 8%–9% solid materials, including pro-
the use of blood-derived biomaterials must not sacrifice the coagulant factors, predominantly fibrinogen, which is
structural goals for the bioprinted scaffold. The functional responsible for hemostasis. Additional plasmatic proteins,
priorities during bioink formulation must be determined such as albumin and globulin, help to maintain the
according to the application. For example, the bioprinting colloidal osmotic pressure at approximately 25 mmHg.
of wound dressings does not require research focused on Electrolytes, sodium, potassium, bicarbonate, chloride,
the long-term stability of bioprinted constructs under cell and calcium ions maintain pH; immunoglobulins help
culture conditions . Instead, functional properties such fight infections. The complex formulation of plasma could
[39]
as the ability to recruit defined populations of immune cells contribute exceptionally to the design of bioink, tailoring
(without eliciting an unresolved inflammatory response) its mechanical, biochemical, and immunological properties
and the ability to drive vascular ingrowth and innervation depending on the targeted tissue or biological mechanism.
should be explored . In contrast, the effectiveness Another of the main advantages of plasma products
[40]
of bioprinted cartilage implants relies not only on the is the two physical configurations of the material: liquid
biological properties but also on the mechanical stability. or gel after the addition of exogenous activators. On the
In the context of tissue graft biofabrication, two paramount one hand, liquid plasma facilitates mixture with other
objectives are controlling the immune system to prevent biomaterials; on the other hand, gel-like consistency gives
graft rejection and promote integration.
it a complex fibrillary internal structure, which acts as
Specific evaluation of printouts for tissue grafting its own “smart” support matrix that allows the release of
purposes is focused on several functional attributes: biomolecules into the microenvironment. Calcium ions
maintaining the cell phenotype and function, shaping (Ca ) and thrombin are some of the most commonly used
2+
the immune response to graft implantation, and driving activators to promote the internal network structure of

Volume 9 Issue 5 (2023) 281 https://doi.org/10.18063/ijb.762