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International Journal of Bioprinting 3D bioprinting as a prospective therapeutic strategy for LSCD

Table 3. Advantages of 3D bioprinting for limbal stem cell deficiency
1 Stem–cell–laden bioink could be accurately divided into target positions with 3D printing, thereby greatly reducing the required number of
stem cells and donor tissue. Since the donor tissue required is less than that of conventional tissue engineering, the range of autologous trans-
plantation could be expanded. Therefore, problems such as immune rejection caused by allograft could be avoided.
2 Engineered printers supports mass production of structures in required shape and size in lesser time and lower cost compared with traditional
manual processes.
3 With the integration of a variety of cells, the epithelial layer and the tear film layer with 3D bioprinting, the normal ocular surface could be
restored rapidly, and the acute ocular surface inflammation can be inhibited.
4 The technology of 3D printing multi-layer structures can fulfill the demand for stem cells, which can survive and work properly in complex
structures. Functionalized artificial limbus can benefit from the specific spatial arrangements of different cells and factors in the 3D printing
process for further clinical needs.
5 Personalized artificial limbus together with whole corneal epithelium is available by rapid prototyping. With precise control of the 3D printer
and 3D computer-aided design (CAD) model based on the geometric data of individual eye, it is possible to reconstruct the damaged limbus
and restore optical functions.
6 3D bioprinting allows the integration of multiple materials and print tissue by using multi-bioink within a single process without culturing cells
separately. Such a development can break through the limitations of single materials in conventional tissue engineering.
7 This process is feasible without the artificial processes in tissue engineering, which achieves programmed construction and ensures stable
fabrication quality without being affected by different batches. The biological control of non-toxic, sterile products with a high-quality level and
stability can be ensured with good production management and a mechanized manufacturing system. The potential viral, religious, cultural,
policy, and immune rejection problems associated with allogenic donor corneas can be effectively avoided.

micro/nanoscale as limbal niche? (iii) How to balance the bioprinting in the field of personalized medicine and
degradation of printed structure and the regeneration of the emerging research on tissue and organ implantation
recipients’ tissue? In the actual researches of 3D-printed and regeneration, 3D bioprinting holds great potential
limbus, it is necessary to select ink and other components in the development of artificial limbus. This article
with suitable physical and chemical properties. The summarizes and compares the materials for artificial
corresponding processes based on research needs and the limbus and manufacturing methods, and proposes the
structural characteristics of natural cornea also remain to unique technological advantages and characteristics of 3D
be studied according to properties of ink. bioprinting, which should be taken into consideration in
the construction of key features of limbus. Existing animal
4.3. Future applications and clinical experiments have shown that cultured limbal
High-fidelity corneal models will also play an important stem cells are a safe and effective choice for treating LSCD.
role in clinical treatment and medical education. For 3D-printed limbal substitutes and even fully functional
the curved, thin structure such as cornea, conventional corneal substitutes are the innovations based on the deep
manufacturing processes such as casting for preparing the understanding of alternative stem cells in the human
mold are time-wasting, and it is also difficult to fabricate body. However, in-depth research is still needed in many
the structure with multiple materials. The individual aspects, such as the selection and cultivation of stem cells,
differences between patients are always neglected as well. the improvement of the 3D printing process accuracy, and
3D-printed personalized corneal limbal model can provide the realization of high surface quality of the substitute and
communication tool for doctors, engineers, patients, and growth dynamics of stem cells in the recipient. In summary,
medical students. Mass-produced 3D-printed medical 3D bioprinting has great potential and development
models also play an important role in research planning, prospects in the treatment of LSCD.
prosthesis testing, preoperative diagnosis, and surgery.
Acknowledgments
The main advantages and potential of 3D bioprinting in
the reconstruction of artificial limbus in vitro are presented None.
in Table 3.
Funding
5. Conclusions and future perspectives
The authors would like to thank the support by the National
It is becoming increasingly urgent to develop treatment Key Research and Development Program of China (Grant
for corneal epithelial shedding and LESC deficiency. The No. 2018YFA0703000), the Key Research and Development
development of artificial limbus is an effective solution Projects of Zhejiang Province (Grant No. 2017C01054),
to addressing this issue. With the emergence of 3D the National Natural Science Foundation of China (Grant

Volume 9 Issue 3 (2023) 294 https://doi.org/10.18063/ijb.710