Introduction: In the last decades, advances in bone tissue engineering mainly based on osteoinduction and on stem cell research. Only recently, new efforts focused on the micro- and nanoarchitecture of bone substitutes to improve and accelerate bone regeneration. By the use of additive manufacturing, diverse microarchitectures were tested to identify the ideal pore size [1], the ideal filament distance and diameter [2], or light-weight microarchitecture [3], for osteoconduction to minimize the chance for the development of non-unions. Overall, the optimal microarchitecture doubled the efficiency of scaffold-based bone regeneration without the need for growth factors or cells. Another focus is on bone augmentation, a procedure mainly used in the dental field.
Methods: For the production of scaffolds, we applied the CeraFab 7500 from Lithoz, a lithographybased additive manufacturing machine. Hydroxyapatite-based and tri-calcium-phosphate-based scaffolds were produced with Lithoz TCP 300 or HA 400 slurries.
Results: The histomorphometric analysis revealed that bone ingrowth was significantly increased with pores between 0.7-1.2 mm in diameter. Best pore-size for bone augmentation was 1.7 mm in diameter. Therefore, pore-based microarchitectures for osteoconduction and bone augmentation are different. Moreover, microporosity appeared to be a strong driver of osteoconduction and influenced osteoclastic degradation for tri-calcium phosphate-based scaffolds. For hydroxyapatitebased scaffolds, however, microporosity appears to influence osteoconductivity to a lesser extent. Osteoclasts were able to degrade hydroxyapatite-based scaffolds irrespective of nanoarchitecture but tri-calcium phosphate-based scaffolds only at high and moderate levels of microporosity. The evaluation of the gene expression profiles at early bone healing leading to osteoconduction revealed that a reduction of the filament size from 1.25 mm to 0.5 mm yielded in differentiation of mesenchymal stem cells towards osteoclasts, enhanced angiogenesis and increased osteoconduction.
Discussion: Micro- and nanoarchitectures are key driving forces for osteoconduction and bone augmentation. A variety of microarchitectures can be realized by additive manufacturing. We identified optimized lattice, pore, filament and adjusted density minimal surface architectures for bony bridging and bone augmentation purposes. Based on these new results additive manufacturing appears as the tool of choice to produce personalized bone tissue engineering scaffolds to be used in cranio-maxillofacial surgery, dentistry, and orthopedics.
References:
- Ghayor et al Weber FE (2021) The optimal microarchitecture of 3D-printed β-TCP bone substitutes for vertical bone augmentation differs from that for osteoconduction. Materials and Design 204 (2021) 109650
- Guerrero J, et al Weber FE, (2023) Influence of Scaffold’s Microarchitecture on Angiogenesis and Regulation of Cell Differentiation During the Early Phase of Bone Healing: a Transcriptomics and Histological Analysis. Int J Bioprint, 9(1): 0093.
- Maevskaia et al Weber FE (2022) 3D-printed hydroxyapatite bone substitutes designed by a novel periodic minimal surface algorithm are highly osteoconductive.