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

Ekaterina Maevskaia; Nupur Khera; Chafik Ghayor; Indranil Bhattacharya; Julien Guerrero; Flora Nicholls; Christian Waldvogel; Ralph Bärtschi; Lea Fritschi; Dániel Salamon; Mutlu Özcan; Patrick Malgaroli; Daniel Seiler; Michael de Wild; Franz E Weber

doi:10.1089/3dp.2022.0134

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

3D Print Addit Manuf. 2023 Oct 1;10(5):905-916. doi: 10.1089/3dp.2022.0134. Epub 2023 Oct 10.

Authors

Affiliations

¹ Oral Biotechnology & Bioengineering, Center of Dental Medicine, University of Zurich, Zurich, Switzerland.
² Central Biological Laboratory, University Hospital Zurich, Zurich, Switzerland.
³ Spherene, Zurich, Switzerland.
⁴ Center of Dental Medicine, Division of Dental Biomaterials, Clinic for Reconstructive Dentistry, University of Zurich, Zurich, Switzerland.
⁵ Institute for Medical Engineering and Medical Informatics IM2, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, FHNW, Muttenz, Switzerland.
⁶ CABMM, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.

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.

Keywords: 3D printing; ADMS; TPMS; adaptive density minimal surfaces; additive manufacturing; bone substitute; ceramics; hydroxyapatite; microarchitecture; osteoconduction; titanium; triply periodic minimal surface.