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International Journal of Bioprinting Bioprinted cell-laden hydrogel for tracheal application

investigations are warranted to simulate the functionality explored to create a more complete trachea-mimetic cellular
of healthy airway epithelium in future studies. construct with improved cell viability and functionality.
GelMA hydrogel has gained significant attention Secondly, although the anti-bacterial ability of the ICA/
due to its tunable mechanical properties, excellent CS/GelMA hydrogel was initially verified, researchers
biocompatibility, ability to mimic the microenvironment still need to make further efforts to elucidate the specific
of the native ECM, and its potential as a carrier for cells mechanism of anti-bacterial effects on reconstructing
and drug molecules. 16,29 In our current study, we mixed 10 segmental tracheal defects.
μM ICA and 2% w/v CS into 10% w/v GelMA hydrogel
to obtain an effective anti-inflammatory and anti- 5. Conclusion
bacterial property and then 3D-bioprinted the C-shaped In conclusion, our current study developed a novel cell-
chondrocyte-laden hydrogel rings. 16,39,40 The results, laden hydrogel with anti-inflammatory and anti-bacterial
including high expression of inflammatory-related factors activities for tracheal cartilage regeneration and restoration
(TNF-α and IL-6), chondrocyte apoptosis (TUNEL), using a 3D-bioprinting strategy. We confirmed that the
anti-bacterial activity, and gross and histological view ICA/CS/GelMA hydrogel exhibited rheological behavior,
(fibrosis and granulation hyperplasia), consistently photo-triggered gelation, suitable printability, favorable
verified that anti-inflammatory and anti-bacterial biocompatibility, and simulated microenvironments for
effects could contribute to maintaining the cartilaginous chondrogenesis. Moreover, the ICA/CS/GelMA hydrogel
phenotype and promoting tracheal cartilage formation. exerted favorable anti-inflammatory and anti-bacterial
Several contributing factors may explain these results: effects both in vitro and in vivo, resulting in a significant
(i) The 3D-bioprinted C-shaped hydrogel ring exhibited enhancement in tracheal cartilage regeneration and
uniform distribution of chondrocytes and demanded restoration, as well as a significant increase in the survival
less total printing time, which significantly enhanced rate of experimental rabbits after orthotopic transplantation.
cell viability and functionality of the trachea-mimetic Although several limitations still need to be addressed in
cellular construct, including its differentiation capacity future research, this study suggests that 3D-bioprinted cell-
into tracheal cartilage; (ii) our previous study found laden ICA/CS/GelMA hydrogel with anti-inflammatory
17
that C-shaped cartilage has better compliance to increase and anti-bacterial activities is a promising candidate for
airflow velocity and mucous transport, which evidently enhancing tracheal cartilage regeneration and restoration.
contributed to maintenance of lumen patency; (iii) ICA
6,41
has been proven to exert favorable anti-inflammatory and Acknowledgments
chondroprotective effects by modulating autophagy and
apoptosis; 25,26 (iv) ICA also showed chondrogenic effects, None.
including promoting chondrocyte proliferation and
ECM synthesis; (v) CS, which possesses excellent anti- Funding
27
bacterial abilities and has been approved by the FDA for The research was supported by the National Natural
pharmaceutical applications, effectively protected TETC Science Foundation of China (82102348) and the Natural
from infection; (vi) the synergistic effect of ICA and CS was Science Foundation of Shanghai (22YF1437400).
conducive to suppressing inflammation caused by infection,
indirectly enhancing the anti-inflammatory function of Conflict of Interest
ICA; and (vii) the released ICA and CS from the ICA/CS/
GelMA hydrogel can sustainably promote chondrocyte The authors declare no conflict of interest.
proliferation and ECM synthesis, anti-inflammatory and
anti-bacterial effects with the degradation of GelMA. Author contributions
Although our current study successfully demonstrated Conceptualization: Pengli Wang
the potential of 3D-bioprinting technology to fabricate Data curation: Pengli Wang
C-shaped chondrocyte-laden ICA/CS/GelMA hydrogel Formal analysis: Tao Wang
rings for enhancing tracheal cartilage regeneration and Funding acquisitions: Yong Xu, Xue Zhang
restoration, several limitations still need to be addressed Investigation: Pengli Wang
in future research. Firstly, although we found that reducing Methodology: Tao Wang
printing time significantly enhanced cell viability and Project administration: Nan Song
functionality of the trachea-mimetic cellular construct, Resources: Nan Song
including its differentiation capacity into tracheal cartilage, Supervision: Xue Zhang
more advanced 3D bioprinting strategies need to be Visualization: Xue Zhang

Volume 10 Issue 1 (2024) 173 https://doi.org/10.36922/ijb.0146