Page 498 - IJB-9-5

International Journal of Bioprinting CECM-GelMA bioinks of DLP 3D printing for corneal engineering

other important proteins (Figure S5 in Supplementary Funding
File). After culturing for several days, hCFs were in a This work was supported by the National Key R&D
stable state and did not transform into myofibroblasts. Program of China (2021YFC2401400).
However, compared with pure GelMA hydrogel, CECM
has a positive effect on the expression of keratinocyte Conflict of interest
markers and inhibits the transformation of fibroblasts into
myofibroblasts in vitro . The authors declare no conflict of interest.
[57]
In in vivo animal study, suitable bioprinted hydrogel
substitutes were transplanted in rabbits with corneal Author contributions
defect (Figure 8A). After nearly 2 months of follow-up, Conceptualization: Mingshan Zhang, Fang Yang, Qing Ye,
the AS-OCT results demonstrated that the hydrogel Yan Wang
could suitably fill with the defect and maintain the Data curation: Mingshan Zhang, Fang Yang, Yipeng Dong
smooth surface (Figure 8B). During the corneal defect Formal analysis: Mingshan Zhang, Fang Yang
repair process, the experimental group transplanted Funding acquisition: Qing Ye
with CECM-GelMA hydrogel achieved the restoration Investigation: Mingshan Zhang, Fang Yang, Shi-yao Zhang,
of matrix thickness and transparency, which inhibited Methodology: Mingshan Zhang, Fang Yang, Shi-yao Zhang,
the formation of corneal scarring compared with the Daobo Han
corneal defect group (Figure 9). Moreover, collagen fiber Project administration: Mingshan Zhang
structure and protein expression are crucial for preserving Resources: Mingshan Zhang, Fang Yang, Shi-yao Zhang,
the clarity and functionality of the cornea [59,60] . HE and Xinyun Li, Liyun Ling
immunohistochemical stainings revealed that CECM- Software: Daobo Han, Zhichao Deng
GelMA hydrogel had almost acquired the natural corneal Supervision: Qing Ye, Yan Wang, Jianguo Tian, Xuewei Cao
effect after healing. Expression of key proteins such as Visualization: Mingshan Zhang, Fang Yang
α-SMA was downregulated (Figure 10). Writing – original draft: Mingshan Zhang, Fang Yang
Writing – review & editing: Qing Ye, Yan Wang, Mingshan
Essentially, the mechanism of change in fibroblasts is
unclear. Based on our experimental results, it is speculated Zhang
that CECM-based composite corneal structures provide Ethics approval and consent to participate
hCFs with positive microscopic guidance that enables
them to naturally sense, respond to, and provide All animal experiments were approved by the Ethical
critical functionalities to the surrounding biophysical Review Committee on the Welfare of Laboratory Animals
environment. These findings set the foundation for further of Hubei University of Medicine, China (No. 2021-084).
research into artificial corneas with functionalities. All cell lines from human patients were approved by The
Ethics Committee of Tianjin Eye Hospital, China (No.
5. Conclusion 2021-024). Patients agreed to donate lenticules following
the small incision lenticule extraction (SMILE) surgery
In summary, an artificial cornea with double curvature after informed consent was obtained from the patients.
was fabricated by a homemade DLP 3D printing system.
From a practical point of view, the morphology and surface Consent for publication
topography of the corneal substitutes presented a smoother
curvature surface and enable controllable customization. Not applicable.
Notably, CECM-GelMA hydrogel as cornea-specific
alternative exhibits favorable properties including high Availability of data
dynamic strength and compression stress, biocompatibility, Data will be made available on request.
and in vivo recoverability. Collectively, the artificial cornea
manufactured by the DLP 3D system provides an effective References
alternative to ocular tissue and has potential application in
the development of in vitro equivalents. 1. de By T, 2003, Shortage in the face of plenty: Improving the
allocation of corneas for transplantation. Dev Ophthalmol,
Acknowledgments 36: 56–61.

The authors of this work are deeply appreciative of the 2. Gain P, Jullienne R, He Z, et al., 2016, Global survey of
assistance received from professionals and personnel. corneal transplantation and eye banking. JAMA Ophthalmol,
134(2): 167–173.

Volume 9 Issue 5 (2023) 490 https://doi.org/10.18063/ijb.774