Strategic advances in Vat Photopolymerization for 3D printing of calcium phosphate-based bone scaffolds: A review

Abstract

3D-printing has emerged as a leading technology for fabricating personalized scaffolds for bone regeneration. Among the 3D-printing technologies, vat photopolymerization (VP) stands out for its high precision and versatility. It enables the creation of complex, patient-specific scaffolds with advanced pore architectures that enhance mechanical stability and promote cell growth, key factors for effective bone regeneration. This review provides an overview of the advances made in vat photopolymerization printing of calcium phosphates, covering both the fabrication of full ceramic bodies and polymer-calcium phosphate composites. The review examines key aspects of the fabrication process, including slurry composition, architectural design, and printing accuracy, highlighting their impact on the mechanical and biological performance of 3D-printed scaffolds. The need to tailor porosity, pore size, and geometric design to achieve both mechanical integrity and biological functionality is emphasized by a review of data published in the recent literature. This review demonstrates that advanced geometries like Triply Periodic Minimal Surfaces and nature-inspired designs, achievable with exceptional precision by this technology, enhance mechanical and osteogenic performance. In summary, VP's versatility, driven by the diversity of material options, consolidation methods, and precision opens new horizons for scaffold-based bone regeneration.

Keywords: 3D printing; Additive manufacturing; Bone regeneration; Hydroxyapatite; Scaffold; Vat polymerization.

Graphical abstract

Fig. 1

Schematic representation of Vat Photopolymerization techniques, categorized as: (A) laser-based techniques, such as Stereolithography (SLA) and Two-photon Polymerization (2PP); and (B) projection-based techniques, such as Digital Light Processing (DLP), Liquid Crystal Display-based masking projection (LCD-DLP), or masked stereolithography apparatus (mSLA), and Continuous Liquid Interface Production (CLIP).

Fig. 2

(A) Schematic representation of post-printing processes resulting in composite or full ceramic parts. Composite scaffolds, consist of a continuous polymeric matrix containing dispersed ceramic particles. Full ceramic scaffolds are obtained through a high-temperature treatment consisting in debinding and sintering. The resulting microstructure consists of ceramic particles bound together. (B) Schematic representation of different calcium phosphate ceramics and other inorganic components used on both the full-ceramic route (in red) and composite route (in blue), following Table 2, Table 3 (Abbreviations: α-CS: α-Calcium silicate, AK: akermanite, BCP: biphasic calcium phosphate, BG: bioglass, BR: bregidite, BT: barium titanate, CPP: calcium pyrophosphate, HA: hydroxyapatite, MAEP: monoalcohol ethoxylate phosphate, MCPM: mono-calcium phosphate monohydrate, OCP: octacalcium phosphate, Si-CaP: silicon-calcium phosphate, SWCNT: single-walled carbon nanotube, TCP: tricalcium phosphate).

Fig. 3

Effect of the selected printing parameters on mechanical properties; strategies proposed in the literature to improve the mechanical properties of calcium phosphate scaffolds obtained by VP. (A) the “stair-stepping” effect typically visualized in VP printing causes shear driven delamination/cracks when loaded perpendicularly to the printing plane. Photography of printed specimens at three different printing orientations, namely 0-, 45- and 90-degree angle. Figures taken from Ref. [117]. (B) In agreement with the later, β-TCP full ceramic scaffolds performed better when tested in the parallel configuration compared to the perpendicular one [156]. (C) Sintering method effects: conventional and advanced sintering methods such as Rapid Sintering in Air (RSA), and pressure-less Spark Plasma sintering (pl-SPS) have different effects on the microstructure and final compressive performance of β-TCP full ceramic scaffolds [160], red arrows pointing at microcracks.

Fig. 4

Mechanical properties of calcium phosphate ceramic and composite VP-printed scaffolds. (A) Compressive strength, elastic modulus, and compressive strain at failure as a function of the porosity of the scaffold. Each dot represents one condition. The dashed grey areas represent the values of natural bone (cortical and trabecular) obtained from Ref. [207]. (B) Box plots of all the data from the above graphs, grouped by processing strategies. Polymer-ceramic composites show improved strain at failure while maintaining adequate compressive properties. A normality test was performed, resulting in a non-parametric distribution; therefore, a Mann-Whitney test was conducted, revealing no significant differences in compressive strength (p > 0.05) and significant differences in elastic modulus and compressive strain at failure (∗∗∗p < 0.01).

Fig. 5

Effect of the scaffold's composition on mechanical properties; strategies proposed in the literature to improve the mechanical properties of calcium phosphate scaffolds obtained by VP. (A) when infiltrating a polymer (PCL) through the hollow internal canals/pores of a β-TCP full ceramic scaffold, creating a hybrid structure, its strain energy density further increases [157]. (B) Multicomponent printing, by the addition of other components (MgO) to the β-TCP initial powder. After sintering, whitlockite forms and further influences the mechanical properties [169]. (C) Fracture mode modification by incorporating ZnO as doping agent to HA ceramic scaffolds by dispersion of particles, piezoelectric properties, and residual stress toughening [147].

Fig. 6

Pore geometry and mechanical properties of VP-printed calcium phosphate scaffolds. A) Different pore geometries, classified as strut-based, TPMS, and nature-inspired. Figures were taken from Refs. [122,157,210,211]; B) Compressive strength as a function of porosity classified as different pore geometries for full ceramic and composite scaffolds. The original data are reported in the Supplementary information. The values for natural bone (dashed grey areas) were taken from Ref. [207].

Fig. 7

Effect of the scaffold's architecture on mechanical properties; strategies proposed in the literature to improve the mechanical properties of calcium phosphate scaffolds obtained by VP. Pore geometry plays an important role, (A) improving mechanical properties from convex-self intersecting orthogonal pattern to smooth Schwarz-TPMS of β-TCP full ceramic scaffolds [121], (B) Schwarz geometry outperforms gyroid and diamond counterparts for CDHA-epoxy composite scaffolds with similar porosities [189]. (C) Geometry modification, by elongating a BCP full ceramic gyroid structure yielded better compressive performance [113]. Blue arrows point the loading direction. (D) Porosity gradient can enhance its strength, as recorded in HA-AK full ceramic scaffolds [56].

Fig. 8

Effect of the scaffold's composition on biological performance; strategies proposed in the literature to improve the biological performance of calcium phosphate scaffolds obtained by VP. (A) Multicomponent printing, by the addition of other components (MgO) to the β-TCP initial powder, Mg-doped scaffolds performed better bone regeneration at orthotopic implantation for both 6 and 12 weeks compared to undoped full ceramic β-TCP counterpart [171]. (B) BMP-2-coated BCP ceramic scaffold performed better bone formation at ectopic and orthotopic implantation for both 2 and 3 month after implantation compared to uncoated BCP scaffolds [184]. (C) The addition of biological elements such as platelet lysates (PL) containing growth factors to a GelMA coating on BCP full ceramic scaffolds enhance the scaffold's vascularization properties in terms of vessel area/total area formation percentage [111].

Fig. 9

Effect of the scaffold's architecture on biological performance; strategies proposed in the literature to improve the biological performance of calcium phosphate scaffolds obtained by VP. (A) β-TCP full ceramic scaffolds with similar porosity for gyroid and grid-like geometries show different proliferation results of mouse bone marrow stem cells (mBMSCs) at day five. Gyroid-TPMS geometry showed a higher proliferation compared to common grid-like counterpart [167]. (B) flow-channel designs promote bone ingrowth and vascularization in ectopic implantation by facilitating a rapid infiltration of the HA full ceramic scaffold's inner struts and the smooth transportation of substances, forming a richer metabolic microenvironment [107]. (C) Hexagonal close-packed (HCP) BCP full ceramic structures promoted osteoinductivity, with enhanced new bone formation after 10 weeks in vivo ectopic implantation, and slightly promoted bone formation in orthotopic implantation after 8 weeks [215].