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International Journal of Bioprinting 3D bioprinting for nanoparticle evaluation

in oxidative stress environments typical of ischemic essential for the evaluation of new therapeutic approaches
tissues. Lee et al.’s research demonstrates the potential of and materials. 80,81 Three-dimensional bioprinting
3D-bioprinted artificial blood vessels loaded with dual- technology has emerged as a powerful tool in this field,
drug NPs as a promising strategy for vascular regeneration. offering unparalleled precision in creating complex bone
This method not only provides a customizable and efficient tissue constructs. 82–85 These models closely mimic the
means of restoring blood vessel functionality but also offers natural extracellular matrix and mechanical properties of
a novel approach to localized and sustained drug delivery, bone, providing a realistic environment for studying cell
paving the way for advancements in regenerative medicine behavior, disease progression, and the efficacy of various
85
and cardiovascular therapy. 76 treatments. By incorporating different biomaterials and
bioactive molecules, bioprinted bone models can enhance
5.4. Evaluation of gold nanoparticle-coupled cell proliferation, differentiation, and mineralization, which
microRNA therapeutics using a 3D-bioprinted are critical for successful bone regeneration and repair. 86–88
model of calcific aortic valve disease
Van der Ven et al. investigated the use of 3D bioprinting 6.1. Bioprinted SaOS-2 cell model
79
to create a model of calcific aortic valve disease (CAVD) for evaluating nanoparticles via
for evaluating the efficacy of gold NP (AuNP)-coupled bioglass-enhanced biomineralization
92
microRNA (miRNA) therapeutics. 77,78 This research utilizes a The study conducted by Wang et al. delves into the
novel bioprinting technique to develop a realistic human tissue effects of bioglass on the growth and biomineralization of
model that can mimic the complex biological environment SaOS-2 cells encapsulated within a bioprintable hydrogel
of CAVD. The bioprinted constructs were produced using a composed of alginate and gelatin. The bioprinting
hydrogel blend of GelMA and hyaluronic acid methacrylate technology is pivotal for creating complex, 3D tissue
(HAMA), facilitating the precise deposition of cells and ECM models that accurately mimic the ECM of bone tissues,
components to replicate the calcified tissue found in CAVD. thus providing a robust platform for evaluating the
The process involved printing a cylindrical mold using efficacy of NPs in biomedical applications. The bioprinting
Pluronic gel and then infilling it with a pre-polymer hydrogel process involved encapsulating SaOS-2 cells, a type of
solution, which was subsequently crosslinked with ultraviolet osteosarcoma cell line, within an alginate/gelatin hydrogel
light to form stable hydrogel discs. matrix. This matrix was enhanced with various additives,
including polyphosphate (polyP), administered as polyP
The primary innovation in this study lies in the use together with CaCl (polyP·Ca -complex), silica, and
2+
of an injectable, shear-thinning, self-healing hydrogel enzymatically prepared biosilica. These components were
2
system to deliver AuNP-miRNA therapeutics within the chosen for their known biological activities that support
bioprinted CAVD model. The hydrogels were prepared cell growth and mineralization. The bioprinted constructs
from HPMC-C12 and PEG-b-PLA NPs, which provide a were designed using computer-aided techniques to ensure
biocompatible and responsive environment for sustained precise architecture and consistency in scaffold production
miRNA release. The miRNA molecules were conjugated to (Figure 6A).
AuNPs to enhance their stability and delivery efficacy, with
additional functionalization using influenza hemagglutinin One of the key findings was that the inclusion of bioglass
(HA1) peptide to promote endosomal escape and intracellular NPs significantly promoted the mineralization capacity
release. The hydrogel’s shear-thinning properties allow for of the encapsulated SaOS-2 cells. 89–91 Bioglass particles,
minimally invasive injection, making it a practical solution approximately 55 nm in size, were added to the hydrogel,
for in vivo applications. The study demonstrated a linear and their impact on cell proliferation and mineralization
release profile of the AuNP-miRNAs over several days, with was assessed. The study revealed that the bioglass did
the particles maintaining their functional activity in vitro as not adversely affect cell growth; instead, it enhanced the
evidenced by successful transfection and gene knockdown mineralization activity of the cells. When combined
2+
in HEK293 cells. This research highlights the potential of with polyP·Ca -complex, silica, or biosilica, the bioglass
combining advanced bioprinting techniques with smart particles increased the mineral deposition by up to 6.8-fold
hydrogel systems to develop effective and targeted therapies compared to the controls without bioglass (Figure 6B). The
for cardiovascular diseases. 79 primary advantage of using bioprinting in this context
lies in its ability to create a highly controlled environment
6. Three-dimensional bioprinted that mimics the natural ECM, thereby providing a more
bone model accurate assessment of NP efficacy. The bioprinted
hydrogel scaffolds not only supported cell viability but
In the realm of biomedical research and tissue engineering, also facilitated enhanced biomineralization, which is
the development of accurate and functional bone models is crucial for bone tissue engineering. The use of bioglass

Volume 10 Issue 5 (2024) 16 doi: 10.36922/ijb.4273