Page 480 - IJB-10-6

International Journal of Bioprinting Nanomaterial-bioinks for DLP bioprinting

Keywords: Hydrogel; Bone implant; Calcium phosphate; Graphene oxide; 3D printing; GelMa, Nanomaterials;
Bioprinting

1. Introduction (CaP), to tailor their properties for bone regeneration. 32,42–55
The use of these nanomaterials has been mainly applied
Bone tissue has a high natural regeneration capacity. to extrusion-based or other printing technologies. 56–59
However, in cases of larger or more complex bone However, for DLP-based bioprinting, the functionalization
defects, as well as certain pathophysiological conditions, of bioinks using nanomaterials has hardly been reported.
surgical intervention is often needed to ensure adequate In addition, data on nanomaterial-modified bioinks are
reconstitution of bone stability and a proper healing often not directly comparable due to different printing
1–6
process. In this context, 3D printing technologies offer a technologies, bioinks, implant designs, and general
tremendous potential to produce patient-specific implants experimental conditions. Nonetheless, these nanomaterials
that vary in size and shape, thus enabling the treatment exhibit highly diverse effects on cellular viability and cell-
of critical-sized bone defects. While 3D printing specific functions, which are not yet fully understood.
7–9
of material-based bone implants has progressed, the
generation of bioprinted constructs containing vital cells is Calcium phosphate (CaP) demonstrates excellent
still a challenging task. bioactivity and provides a mineral component, resembling
the bone matrix. 60,61 Calcium and phosphate ions released
In 3D bioprinting, various printing techniques
exist, including extrusion-based bioprinting. Another from CaP are important inorganic materials known
10
to activate new bone formation.
In the context of
62–64
technical principle for bioprinting is the use of digital nanomaterials applied for 3D printing, we have recently
light processing (DLP). 11–16 A significant advantage of DLP demonstrated that CaP nanoparticles, integrated into
bioprinting lies in its high printing resolution, enabling 3D-printed polycaprolactone bone scaffolds, improve
the creation of complex and biomimetic shapes, along osteoinductive properties. In addition, we have
65
with controlled and precise positioning of pores within demonstrated that GO nanomaterials, particularly
the cell-loaded hydrogel-based constructs. The porous their non-reduced form, can improve cell adhesion of
structure of the constructs, along with the high fluid mesenchymal stem cells and support vascularization by
content in the hydrogel bioinks, facilitates the supply active binding of vascular endothelial growth factor in
of nutrients and oxygen. 17–20 The hydrogels applied as clinically used bone substitute materials. 66
bioinks need to fulfill a broad spectrum of prerequisites,
ranging from rheological properties for the printing In this study, we developed GelMa bioinks that contain
process up to creating an environment for cell survival, the nanomaterials CaP and GO to investigate their
proliferation, migration, and highly cell-type-specific suitability for DLP bioprinting. The impact of the scaffold
bioactivities. 21–24 Collagen type 1, the major constitutional design and the different nanomaterials was assessed in
protein in the bone, is rich in arginine-glycine-aspartic direct comparison but has not yet been reported. The study
acid (RGD) sequences, thus promoting cell adhesion. 25,26 aims to compare the impact of the individual nanomaterials
After hydrolyzation and methacrylation of collagen, on the DLP printing process, the mechanical properties of
the resulting derivate gelatin methacrylamide (GelMa) the constructs, and the cellular viability and osteogenic
enables ultraviolet (UV)-light-mediated formation of a differentiation of human mesenchymal stem cells (hMSCs).
stable hydrogel with tunable mechanical properties, high
biocompatibility, and biodegradability. 15,27–36 Optimization 2. Methods
of basic GelMa bioinks, in terms of the methacrylation 2.1. Design of 3D model with a cancellous bone-
degree and the application of photo-initiators or photo- inspired structure
absorbers, is often a fine-tuning process that needs to A 3D model with a bone-inspired structure was designed
be aligned with the printing technology, the parameters using Shapr3D software (version 5.290). The 3D model
applied in the printing process, and the desired biomedical (Figure 1) provides a cylindrical shape featuring a
goal. 37–41 To fulfill specific biological and mechanical diameter of 7 mm and a height of 3.64 mm. The implant
requirements, additional functionalization of GelMa design includes interconnected pores with a diameter
bioinks is often desirable to enhance their potential for of 500 µm, which are evenly distributed throughout the
bone tissue bioprinting.
model (Figure 1). In addition, larger-sized channels with a
Bioinks used for bone constructs can be modified with diameter of up to 2500 µm with irregular-shaped structures
a series of different nanomaterials, including graphene were integrated into the 3D model, aiming to facilitate the
oxide (GO) or different variants of calcium phosphate ingrowth of vascular structures after the implantation.

Volume 10 Issue 6 (2024) 472 doi: 10.36922/ijb.4015