Page 287 - IJB-9-6

International Journal of Bioprinting Progress in bioprinted ear reconstruction

of the studies used alternative cell sources, such as human a gel or hydrogel matrix, provide a supportive environment
adipose-derived stem cells (ASCs), novel human auricular and allow direct printing of structure that more closely
cartilage progenitor cells (AuCPCs), bovine auricular mimics the natural anatomy of the ear .
[11]
chondrocytes, and tonsil-derived mesenchymal stem cells. A variety of hydrogels were used as scaffolds for
Finally, in 14.9% of the studies, no specific cell type was auricular cartilage tissue engineering in these studies.
mentioned. The most commonly used hydrogel was a combination
Additionally, the nutrient supply the growing cells of gelatin and alginate, which was utilized in several
possess affects the quality of the generated tissue. Despite studies [8,9,27,28,32] . This hydrogel was primarily used for 3D
cartilage typically being largely avascular, additional bioprinting of auricular cartilage, although the specific
strategies have been suggested, such as creating perfusion properties of the hydrogel were not detailed in these studies.
microchannels to allow better nutrient diffusion or Another study by Zopf et al. (2018) used a hyaluronic acid/
[30]
engineering myoglobin complexes on membranes to collagen hydrogel for seeding primary porcine auricular
improve cell survival and tissue development . chondrocytes onto 3D-printed scaffolds . However, the
[29]
[54]
properties of the hydrogel were not explicitly mentioned .
[51]
An additional difficulty identified was achieving a good
distribution of chondrocytes and uniformity of ECM with In a study by Jia et al. (2020), an ACM/gelatin hydrogel
was used. The mechanical properties showed an opposite
conventional cell seeding techniques, leading to insufficient trend to pore size and porosity, and the degradation
mechanical stability and, in turn, macroscopic deformation. rate enhanced with increasing acellular cartilage matrix
For this reason, the printing material chosen must not (ACM) proportion. The hydrogel demonstrated excellent
easily trigger aseptic inflammation so that the formation biocompatibility, with a cell seeding efficiency of more
of ECM is not restricted . The optimum material would than 90% . It should be noted that the specific properties
[11]
[25]
have properties that would stimulate cartilage formation. of the hydrogels were not always detailed in the studies,
For example, materials with low stiffness (<2–10 kPa) were and as such, a comprehensive comparison of the hydrogels
found to promote cartilage formation, whereas scaffolds used is not possible based on the available information.
with high stiffness (>10 kPa) did not and consequently
failed to grow cartilage well . 3.4. Time in vivo and evaluation successful outcomes
[15]
One of the most significant drawbacks of all the in vivo
3.3. Material comparison animal studies in evaluating optimum cell type and
Synthetic polymers, such as PCL, polylactic acid (PLA), material selection was the limited time the scaffolds spent
PEG, and polyurethane (PU), have been the focus of 3D in vivo (see Figure 4). Overall, this was an average of 110
printing material selection for cartilage regeneration due days. The bioink studies were the shortest (mean = 53.25
to their biocompatibility, mechanical properties, and days). Conversely, the longest-running animal study was
degradation characteristics. PCL, the most frequently that by Yin et al. (2020), which lasted 365 days and in
printed material in this review, has been used in the which a composite scaffold composed of polyglycolic acid
biomedical field in implants and sutures for over 70 (PGA)/PLA and a PCL core was seeded and implanted in
years , and is biocompatible with good bioresorbility mice .
[31]
[22]
and mechanical stiffness , making it a good choice for
[9]
surgical reconstruction as it can be safely and gradually The longest-running study in this review is the ongoing
absorbed over 4 years without causing adverse reactions , human pilot trial, which was at the 2.5-year mark at
[20]
while supporting the structure as the cellular components publication. This landmark study had several limitations,
around it mature . PLA is biocompatible, affordable, and such as a small sample size of only five patients. However,
[11]
also degrades slowly, retaining its integrity throughout it showed it is possible to design, print, and integrate
elastic cartilage maturation . PEG is biocompatible and patient-specific auricles in human subjects. Notably, the
[10]
dissolves, without adverse effects on cell viability, within patients underwent 12 weeks of tissue expansion before
40 min of being submerged in an aqueous environment, the reconstruction and subsequently two scar revisions
making it suitable as a sacrificial material for when short- were performed at 6 and 18 months, allowing for tissue
term support is required for printing . PU is strong, biopsies of the scaffold at the same time, which showed
[27]
versatile, and resilient, and while its biodegradability is a good cartilage formation. Good aesthetic results were only
point of contention , Kim et al. (2019) compared porous achieved after 9 months, once postoperative inflammation
[32]
[20]
and non-porous structures printed using PU and found subsided .
that the porous variety encouraged cell proliferation . All studies attempted to evaluate the resulting
[30]
Finally, bioinks, composed of a mixture of cells, growth printed structure’s properties objectively. Histopathology,
factors, and other biocompatible substances suspended in electron microscopy, ultrasound scans, micro-computed
Volume 9 Issue 6 (2023) 279 https://doi.org/10.36922/ijb.0898