High‐Strength Hydroxyapatite Scaffolds with Minimal Surface Macrostructures for Load‐Bearing Bone Regeneration

Abstract

Triply periodic minimum surfaces (TPMS), which outperform other structures in terms of bulk moduli and relative density, have been widely used to dramatically improve the mechanical strength of natural echinoderm skeletons and engineered scaffolds. Herein, TPMS‐structure‐based 3D‐printed hydroxyapatite (HAp) scaffolds to highly improve their limited mechanical strength and evaluate the underlying mechanism in terms of mechanical match and biological bone repair process as a bone regeneration scaffold are constructed. The results show that TPMS‐structure‐based HAp scaffolds have a greater compressive strength range that is sufficient to meet the strength requirements for human cortical and trabecular bone, and outperform traditional HAp scaffolds with Cross‐hatch structures in terms of compressive strength, cell density, and osteogenic differentiation. The reduction of stress concentration and open‐cell permeable structure of Split‐P scaffolds can benefit the generation and ingrowth of new bone after the in vivo implantation in the rabbit femur bone. Furthermore, RNA‐seq and immunochemistry staining results of in vivo samples unravel the bone repair mechanism in a time sequence. The optimized scaffolds with TPMS macrostructures and an in‐depth understanding of repair mechanisms will contribute to the development of bone regeneration materials that perform on par with load‐bearing bone.

Material–Structure–Function Integrated Additive Manufacturing of Degradable Metallic Bone Implants for Load‐Bearing Applications

“…As evidenced by EDS mappings, the interconnective structure can stimulate bone ingrowth and induction, which is beneficial for transporting nutrients and metabolic products simultaneously. [ 41 ] At the micro‐scale, gyroid scaffolds are constructed by a sequential surface structure (TPMS) with high relative surface areas and improved permeability, leading to admirable cell adherence and retention. [ 42 ] As disclosed by Werner et al, cells are capable of sensing the surface curvature of spiral struts.…”

Macropore Regulation of Hydroxyapatite Osteoinduction via Microfluidic Pathway

“…Other studies have reported that the bone formation of porous ceramic scaffolds mainly occurred in the pore’s inner wall, near the opening of the pore after an ectopic implantation in vivo [ 38 , 39 , 40 ]. Recently, Zhang et al has investigated the osteogenic properties of triply periodic minimum surfaces structure-based HA scaffolds, and also found that the amount of new bone formation and the distribution area above the scaffolds were significantly different from those of the HA scaffolds with cross-hatch structures [ 41 ]. Those results have indicated the influence of the shape of the macro-pores on the osteoinduction of materials [ 37 , 42 ].…”

Bone Tissue Engineering Scaffolds: Function of Multi‐Material Hierarchically Structured Scaffolds

“…Split‐P structure showed the highest compression across all pore size ranges (300, 600, and 900 µm) while the cross‐hatch and gyroid structure showed the lowest compression strengths at all pore sizes Reproduced with permission. [ 101 ] Copyright 2022, Wiley‐VCH GmbH. IV) The interconnected nature of TPMS structures allowed for increased cell migration throughout the porous volume which is reflected in its higher cell density compared to the cross‐hatch structure.…”

“…For example, a HAp scaffold with a split‐P architecture was shown to be more favorable in the formation of new bone compared to HAp scaffolds with the cross‐hatch architecture when implanted into rabbit joints. [ 101 ] Bone growth was shown to begin at the outer surfaces of the scaffold and continue inward and the interconnected architecture of the split‐P scaffold enabled the complete recovery of the rabbit femur within 12 weeks. [ 101 ] The architecture of these structures (pore size, porosity, and geometry) will influence mechanical strength, permeability, and cellular growth.…”

“…[ 101 ] Bone growth was shown to begin at the outer surfaces of the scaffold and continue inward and the interconnected architecture of the split‐P scaffold enabled the complete recovery of the rabbit femur within 12 weeks. [ 101 ] The architecture of these structures (pore size, porosity, and geometry) will influence mechanical strength, permeability, and cellular growth. Similar to natural bone structures, there is a hierarchical distribution of structural features as shown previously.…”