Three-Dimensional Printed Hydroxyapatite Bone Substitutes Designed by a Novel Periodic Minimal Surface Algorithm Are Highly Osteoconductive

Abstract

Autologous bone remains the gold standard bone substitute in clinical practice. Therefore, the microarchitecture of newly developed synthetic bone substitutes, which reflects the spatial distribution of materials in the scaffold, aims to recapitulate the natural bone microarchitecture. However, the natural bone microarchitecture is optimized to obtain a mechanically stable, lightweight structure adapted to the biomechanical loading situation. In the context of synthetic bone substitutes, the application of a Triply Periodic Minimum Surface (TPMS) algorithm can yield stable lightweight microarchitectures that, despite their demanding architectural complexity, can be produced by additive manufacturing. In this study, we applied the TPMS derivative Adaptive Density Minimal Surfaces (ADMS) algorithm to produce scaffolds from hydroxyapatite (HA) using a lithography-based layer-by-layer methodology and compared them with an established highly osteoconductive lattice microarchitecture. We characterized them for compression strength, osteoconductivity, and bone regeneration. The in vivo results, based on a rabbit calvaria defect model, showed that bony ingrowth into ADMS constructs as a measure of osteoconduction depended on minimal constriction as it limited the maximum apparent pore diameter in these scaffolds to 1.53 mm. Osteoconduction decreased significantly at a diameter of 1.76 mm. The most suitable ADMS microarchitecture was as osteoconductive as a highly osteoconductive orthogonal lattice microarchitecture in noncritical- and critical-size calvarial defects. However, the compression strength and microarchitectural integrity in vivo were significantly higher for scaffolds with their microarchitecture based on the ADMS algorithm when compared with high-connectivity lattice microarchitectures. Therefore, bone substitutes with high osteoconductivity can be designed with the advantages of the ADMS-based microarchitectures. As TPMS and ADMS microarchitectures are true lightweight structures optimized for high mechanical stability with a minimal amount of material, such microarchitectures appear most suitable for bone substitutes used in clinical settings to treat bone defects in weight-bearing and non-weight-bearing sites.

Triply Periodic Minimal Surface-Based Scaffolds for Bone Tissue Engineering: A Mechanical, In Vitro and In Vivo Study

“… 19 Moreover, the low bone ingrowth in Primitive scaffolds could be related to the lowest porosity and surface-to-volume ratio of this microarchitecture among the studied designs. 33 …”

“…The images obtained after μCT scanning were used to calculate the maximal sphere diameter by ImageJ (NIH) as the diameter of the largest circle that fits into the pore structure of the scaffold, as previously described. 33 The transparency defined as a percentage of material-free area in the projection of the scaffold in the different spatial directions 34 was calculated in three projections of the scaffolds (view from the top, the front, and the edge between the front and its side to the right; Table 4 ).…”

“…The goal of this study was to compare Diamond, Gyroid, and Primitive TPMS microarchitectures realized by the same methodology and material and to test them in terms of mechanics, in vitro cell seeding with human bone marrow stromal cells (hBMSCs), and in vivo implantation in the calvarial bone of rabbits in comparison with a standard Lattice structure. 33 …”

Designing a Novel Porous Fixation Plate with a Gyroid Lattice Structure for Humerus Fractures Using a Probabilistic Approach

“…[1] To minimize these complications, porous implants with stiffness closely matching that of bone have been developed. [2,3] An implant designed with 5-10% porosity for cortical bone and 50-90% porosity for trabecular bone is known to increase stiffness compliance and reduce the stress shielding effect. [4] The literature suggests that an implant's pore size should range between 100 and 700 μm to enhance bone compatibility, allowing for the development of new cells and implant integration.…”

“…[ 1 ] To minimize these complications, porous implants with stiffness closely matching that of bone have been developed. [ 2,3 ]…”