Mechanobiologically optimized 3D titanium-mesh scaffolds enhance bone regeneration in critical segmental defects in sheep

Abstract

Three-dimensional (3D) titanium-mesh scaffolds offer many advantages over autologous bone grafting for the regeneration of challenging large segmental bone defects. Our study supports the hypothesis that endogenous bone defect regeneration can be promoted by mechanobiologically optimized Ti-mesh scaffolds. Using finite element techniques, two mechanically distinct Ti-mesh scaffolds were designed in a honeycomb-like configuration to minimize stress shielding while ensuring resistance against mechanical failure. Scaffold stiffness was altered through small changes in the strut diameter only. Honeycombs were aligned to form three differently oriented channels (axial, perpendicular, and tilted) to guide the bone regeneration process. The soft scaffold (0.84 GPa stiffness) and a 3.5-fold stiffer scaffold (2.88 GPa) were tested in a critical size bone defect model in vivo in sheep. To verify that local scaffold stiffness could enhance healing, defects were stabilized with either a common locking compression plate that allowed dynamic loading of the 4-cm defect or a rigid custom-made plate that mechanically shielded the defect. Lower stress shielding led to earlier defect bridging, increased endochondral bone formation, and advanced bony regeneration of the critical size defect. This study demonstrates that mechanobiological optimization of 3D additive manufactured Ti-mesh scaffolds can enhance bone regeneration in a translational large animal study.

A Novel Bone Substitute with High Bioactivity, Strength, and Porosity for Repairing Large and Load‐Bearing Bone Defects

“…It is long known that mechanical strains generated from loads placed on a scaffold are intimately linked to cellular responses and tissue regeneration, and mechanical loading can act as an independent stimulator in bone healing . The choice of fixation device can affect stress shielding in the implant, thereby altering the patterns of strain distribution and having a direct impact on the outcomes of bone regeneration in clinically relevant defects . As observed in this study, the rigidity of the fixation system and the quality of the bone–implant interface had profound effects on subsequent implant loading.…”

Bone Tissue Engineering via Carbon‐Based Nanomaterials

“…First, most metals possess much higher elastic modulus than bone that could lead to stress shielding. Thus, it is necessary to construct scaffolds with porous metals to reduce the chance of stress shielding as well as to increase the possibility of vascularization in the scaffold . Second, due to the lack of integration with host tissues, metallic scaffolds generally could not integrate biomolecules around.…”

Real-time monitoring of mechanical cues in the regenerative niche reveal dynamic strain magnitudes that enhance bone repair

“…Indeed, there is substantial clinical need to enhance bone regeneration for the millions of patients undergoing these procedures each year, as a significant sub-set are afflicted with prolonged disability or multiple revision surgeries due to non-union or poor osseointegration ( 9 ). Mechanical stimulation strategies have spanned a range of approaches and garnered significant scientific and clinical interest including external or percutaneous fixators and actuators ( 10 ), and stabilization hardware or scaffolds with reduced stiffness to permit load sharing ( 11 – 13 ). Additionally, more functionally relevant, non-invasive methods such as physical rehabilitation and exercise may be implemented to enhance load transfer while simultaneously inhibiting adjacent tissue atrophy and accelerating functional recovery of daily activities ( 14 – 16 ).…”