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International Journal of Bioprinting 3D-printed scaffold for biomolecule delivery

tissue engineering. However, further studies are warranted developed porous scaffold, as well as changes in the
2
to elucidate the sequential and spatiotemporal controls thickness of the coating materials to assess their impact
associated with the release of GFs and other biomolecules. on the release kinetics of BMP-2 and bFGF. Such
investigations will provide a deeper understanding
The 3D printing technology has rapidly advanced
and is widely used to develop biomaterials as alternative of how these factors can be optimized for enhanced
implants in dentistry and orthopedics for medical therapeutic outcomes.
therapy. Recently, the development of 3D printing We constructed a GS composite xerogel to reduce
has been further accelerated by the introduction and its brittleness and control the release of GFs from it.
application of various tissue engineering methodologies, The novel GS possibly promoted easy handling when
such as structural changes, surface modification, and the coating was applied to a 3D-structured scaffold. The
biomolecule tethering. The 3D-printed scaffold is often double layers were physically stable and represented
modulated by structural alterations, such as the control a sustained release of GFs. Moreover, the composite
of nano- or micro-sized pores and struts or by adjusting xerogel matrices on 3D-printed PCL scaffolds may
the roughness or morphology of the surface. Our control the spatiotemporal release of GFs and impart
previous study demonstrated that the nanoporous strut bioactivity to the PCL surfaces. GFs, which are included
surface of a 3D-printed scaffold enhanced cell adhesion, separately in a double-layer fashion, can be sequentially
and the increased surface area of the scaffold provided released and may promote biological responses. Previous
an adhesive interface for biomolecules or cells. In this studies have demonstrated that the incorporation of
study, a novel strategy to modify 3D-printed scaffolds gelatin into silica xerogel can reduce the brittleness
was used as a delivery material for biomolecules, such and enhance the flexibility of the composite, thereby
as GFs, cytokines, nucleotides, and drugs. Tethering improving its mechanical properties. While this
biomolecules onto the scaffold modulates cell-cell and modification is expected to increase the resilience of
cell-biomaterial interactions and stimulates cell behaviors, the composite and make it more suitable for bone tissue
such as recruitment, adherence, and proliferation. engineering applications, no specific mechanical testing
Specific cellular modulation facilitates wound healing was conducted in this study, resulting in limited findings
and regenerative processes in damaged tissues. Overall, in this regard. Therefore, a more detailed mechanical
the implementation of the biomimetic interface and evaluation is required to comprehensively assess these
the introduction of exogenous biomolecules into the properties. Future studies will focus on conducting in-
3D-printed scaffold are expected to ultimately contribute depth tests of the GS composite’s mechanical properties,
to the improved biocompatibility and regeneration of such as compressive strength and elasticity, to provide a
the target tissue. Recent studies have also reported that more thorough evaluation of its performance.
surface-modified 3D-printed PCL scaffolds can enhance
cell adhesion and tissue regeneration, particularly when 4. Conclusion
combined with bioactive coatings for controlled GF
delivery. In our results, it was confirmed that 20 GS The matrix for GF delivery should have a large porous
49
released proteins without delamination in a bulk form structure to transport GFs and possess properties to
for 24 days (Figure 2e), even under stirring conditions prevent burst release. In this study, GS controlled the
at 37°C, and sustained the release of GFs for a total of 42 release of GFs, and the hybrid matrix was well-coated on
days without any burst release due to surface delamination 3D synthetic polymer scaffolds. The use of the proposed
after surface erosion (Figure 4f and g). On day 21 of cell coating method and the hybrid-coated 3D-printed
culture, continuous cell proliferation and differentiation scaffolds may contribute to regenerative applications.
were observed, and staining images after differentiation
confirmed that cells were well-distributed on the scaffold Acknowledgments
surface (Figure 5d and e). This indirectly indicates that None.
the GS coating surface remained stable, supporting
continuous cell proliferation and differentiation without Funding
delamination. While our study has demonstrated that the
thickness of both the PCL scaffold and GS gel layers plays This research was supported by National Research
an important role in drug release, further investigation Foundation of Korea (NRF) Grants funded by the Korean
is necessary to fully understand these dynamics. Future government (MEST) (grant nos. NRF-2023R1A2C2004600,
studies will explore variations in PCL scaffold thickness RS-2023-00239273, 2016R1D1A1B03930163) and the
and surface modifications, such as using our previously Korea University Grant.

Volume 10 Issue 6 (2024) 453 doi: 10.36922/ijb.4638