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International Journal of Bioprinting DIW of concave hydroxyapatite scaffolds

1. Introduction cellular processes. Three-dimensional (3D) structures
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can be obtained by thickening such surfaces, creating
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Additive manufacturing has emerged as a transformative unit cells whose periodic repetition results in scaffolds
technique, enabling the customization of designs and with complex porosity, numerous concave surfaces, and
geometries with a profound impact on the development of high interconnectivity. These scaffolds have reportedly
bone scaffolds. The significant influence of such techniques enhanced cell growth, migration, and vascularization
stems from their ability to create reproducible macroporous through improved body fluid permeability. 16–18
structures and adjust the external shape of the scaffolds to Triply periodic minimal surface (TPMS) structures or their
the specific anatomy and the geometry of the bone defect, negative molds have been created by different additive
allowing for customized implant design. By integrating manufacturing technologies: (i) extrusion-based methods like
these design capabilities with the specific requirements for fused deposition melting (FDM), 16,19 (ii) multijet technology,
optimal bone scaffolds, it becomes possible to enhance, where a piezoelectric printhead deposits either photocurable
guide, and support the natural remodeling process of bone plastic resin or supporting material, 20,21 or (iii) selective laser\light
when compromised by large defects. curing\melting (SL). 14,22–25
1,2
The continuous ingrowth of new bone into a scaffold not The high resolution required for TPMS printing makes
only relies on the compositional properties and mechanical SL the most common method. However, metallic SL is
stability but also pore geometry and distribution. Pores rather expensive, and polymeric SL is restricted to a few
should be open and highly interconnected, which are photo-curable materials, mainly based on resins, which
3
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difficult to achieve by conventional methods, such as lacks the bioactivity and osteoinductive properties often
foaming or sacrificial porogens. Pore size plays a key role achieved with ceramics. Recently, modified hydrogels, such
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in bone extracellular matrix production and organization. as poly(ethylene glycol) diacrylate, have been proposed
Pore dimensions of at least 100 μm are needed for nutrient as biocompatible alternatives. For bioceramic TPMS
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transport and waste removal. Enhanced bone formation scaffolds, SL technology has been used in two ways: (i)
and vascularization have been reported for scaffolds with generating sacrificial molds that can be easily impregnated
pore sizes larger than 200–300 μm. 3,5,6 Though initial fast with calcium phosphate (CaP) slurry, or (ii) loading a
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woven bone ingrowth can happen with pores as small photo-curable resin with CaP 28–32 or other bioceramic
as 1–10 µm. Additionally, an in vitro study reported particles. 13,31,32 Both pathways require a sintering process
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that pore geometry is also crucial, with concave surfaces to harden the green bodies and simultaneously eliminate
accelerating and enhancing osteogenic differentiation. The the organic resin. The resulting TPMS CaP structures
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presence of concavities has been associated with favorable have displayed greater new bone formation in vivo
microenvironments capable of confining relevant ions and in comparison to CaP granules or inorganic bovine
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8
biological molecules that foster cell membrane contacts. xenograft blocks. Moreover, Montazerian et al. and
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16
Notably, the presence of concavities in biomimetic apatite Deng et al. incorporated porosity gradients in these
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scaffolds was demonstrated to outperform the same geometries, more closely mimicking the highly anisotropic
scaffolds with convexities in vivo. Foamed apatite scaffolds, and heterogeneous structure of trabecular bone.
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with interconnected concave pores, induced a significantly
Direct-ink writing (DIW) is another additive
higher amount of new bone in a canine model compared manufacturing technique, based on extruding a flowable
to scaffolds with interconnected convex pores, and new paste through a nozzle and building a 3D part by stacking
bone formed preferentially in the concavities of the foamed filaments. One main advantage of DIW is its diversity
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apatite scaffold. However, controlling the foaming
9,10
process is challenging and has poor reproducibility in of printable materials, including highly loaded ceramic
pastes. It has been successfully applied for the fabrication
terms of pore interconnectivity, distribution, and size, and of customized synthetic bone grafts. Among the wide
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foams have lower mechanical strengths.
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variety of materials that can be used, the development of
Additive manufacturing techniques open up new reactive inks based on CaP bone cement that hardens at
possibilities for the fabrication of pore structures with body temperature through a dissolution-precipitation
controlled geometries, including designs inspired by reaction represents a breakthrough in the field. 36,37 A widely
nature. For instance, triply periodic minimal surfaces used and simple formulation consists of α-tricalcium
(TPMSs) have attracted great interest in bone regeneration phosphate particles (α-Ca (PO ) α-TCP) suspended in
4 2,
3
due to the periodical nature-inspired models that a Pluronic F127 hydrogel. This formulation transforms
resemble the trabecular bone structure with a mean into calcium-deficient hydroxyapatite (CDHA) after
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curvature close to zero. In nature, these surfaces play hardening. 37–39 These inks have a shear-thinning behavior
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an essential role in guiding chemical, biochemical, and and adequate rheological properties for DIW, ensuring
Volume 10 Issue 6 (2024) 225 doi: 10.36922/ijb.3805