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International Journal of Bioprinting Tunable GelMA-based bioinks for keloid modeling

crosslinking features of GelMA, well-preserved in our tissue integration. While alginate is conventionally used
GxAxMxRx formulation, could support incorporation as an ionically crosslinked matrix, we leveraged it here as
of antifibrotic therapeutics in future applications. a viscoelasticity enhancer, demonstrating its utility even
Additionally, the high batch-to-batch reproducibility and in the absence of calcium. The addition of MC improved
controllability of GelMA production further enhance its mechanical resilience and contributed to the formation
clinical feasibility for biofabrication and drug screening of a cohesive hydrogel network, while laponite-RDS,
platforms. Therefore, while drug delivery was not directly a nanoclay with high surface reactivity, significantly
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addressed in this study, our bioink formulation may offer enhanced the rheological profile by boosting viscosity,
a dual-function system for stiffness-regulated disease shear-thinning behavior, and elastic modulus. This work
modeling and therapeutic testing, warranting further establishes a mechanically tunable and cytocompatible
investigation. Moreover, although degradation rates were bioink capable of supporting 3D bioprinting of keloid-
evaluated and found to differ modestly across formulations like fibrotic tissue constructs. By maintaining constant
(Figure S1C), other potentially influential parameters, bioink composition and modulating stiffness via GelMA
including porosity and mesh size, which may impact both concentration, we demonstrated that matrix mechanics
cellular responses and drug loading or release behavior, alone can significantly influence the activation of patient-
were not quantitatively characterized and should be derived keloid fibroblasts. The platform holds promise for
systematically explored in future work. disease modeling and future applications in drug screening
Despite these promising results, several limitations and regenerative medicine. While this study demonstrates
should be acknowledged. First, the biological effects proof-of-concept for stiffness-regulated fibrosis modeling,
of individual bioink components, including alginate, further work is needed to explore long-term culture
MC, and laponite-RDS, were not independently responses, matrix remodeling, and the independent
assessed under stiffness-matched conditions, and thus biological roles of individual hydrogel components under
compositional influences beyond mechanical cues cannot stiffness-matched conditions. Additionally, the impact
be fully excluded. Second, although the bioink formulation of physiological ions or charged therapeutic molecules
includes electrostatic interactions among charged on bioink stability and drug-release behavior warrants
polymers, its structural stability is primarily governed by investigation in future applications.
GelMA photopolymerization. The impact of physiological
ions or charged biomolecules, especially in the context Acknowledgments
of long-term culture or drug screening, remains to be We thank the Soonchunhyang Biomedical Research Core-
investigated. Lastly, as this study focused on short- Facility of the Korea Basic Science Institute (KBSI) for
term fibrotic responses, future work should investigate providing access to essential instrumentation and technical
long-term ECM remodeling, protein-level signaling support throughout this study.
pathways, and the incorporation of co-culture systems
to more accurately model the complex pathophysiology Funding
of keloid disease. In particular, the current model is This work was supported by the Soonchunhyang University
limited to fibroblast-only constructs, and future studies Research Fund and the National Research Foundation of
incorporating additional skin-resident cell types, such as Korea funded by the Ministry of Science and ICT (MSIT)
keratinocytes, will be essential to more faithfully replicate
the cellular heterogeneity and structural complexity of (grant numbers: RS-2019-NR040068, RS-2023-00284258,
fibrotic skin tissue. and 2017R1D1AB03029770).

4. Conclusion Conflict of interest
The authors declare they have no competing interests.
The 3D bioprinting has emerged as a transformative
technology for fabricating complex, functional, and Author contributions
biomimetic tissue constructs by integrating living cells
with tailored biomaterials and biochemical cues. In this Conceptualization: Laurensia Danis Anggradita, Seung
study, we developed a composite bioink composed of Min Nam, Yongsung Hwang
GelMA, alginate, MC, and laponite-RDS, designed to Formal analysis: Laurensia Danis Anggradita, Sung Sik
achieve tunable mechanical properties, robust printability, Hur, Taekyun Kim, Wonjong Seon,
and high biocompatibility. GelMA served as the primary Mohammed Aboobucker Sithique, Seung Min Nam,
crosslinkable backbone, forming stable networks upon UV Yongsung Hwang
exposure and providing cell-adhesive motifs essential for Funding acquisition: Seung Min Nam, Yongsung Hwang

Volume 11 Issue 4 (2025) 458 doi: 10.36922/IJB025160154