Mechano-driven intervertebral bone bridging via oriented mechanical stimulus in a twist metamaterial cage: An in silico study.

Stiffer cages provide sufficient mechanical support but fail to promote bone ingrowth due to stress shielding. It remains challenging for fusion cage to satisfy both bone bridging and mechanical stability. Here we designed a fusion cage based on twist metamaterial for improved bone ingrowth, and proved its superiority to the conventional diagonal-based cage in silico. The fusion process was numerically reproduced via an injury-induced osteogenesis model and the mechano-driven bone remodeling algorithm, and the outcomes fusion effects were evaluated by the morphological features of the newly-formed bone and the biomechanical behaviors of the bone-cage composite. The twist-based cages exhibited oriented bone formation in the depth direction, in comparison to the diagonal-based cages. The axial stiffness of the bone-cage composites with twist-based cages was notably higher than that with diagonal-based cages; meanwhile, the ranges of motion of the twist-based fusion segment were lower. It was concluded that the twist metamaterial cages led to oriented bone ingrowth, superior mechanical stability of the bone-cage composite, and less detrimental impacts on the adjacent bones. More generally, metamaterials with a tunable displacement mode of struts might provide more design freedom in implant designs to offer customized mechanical stimulus for osseointegration.

Effect of Internal Mechanical Environment of Porous Scaffolds on Mechano-driven Bone Ingrowth: A Numerical Study.

Porous cages with lower global stiffness induce more bone ingrowth and enhance bone-implant anchorage. However, it's dangerous for spinal fusion cages, which usually act as stabilizers, to sacrifice global stiffness for bone ingrowth. Intentional design on internal mechanical environment might be a promising approach to promote osseointegration without undermining global stiffness excessively. In this study, three porous cages with different architectures were designed to provide distinct internal mechanical environments for bone remodeling during spinal fusion process. A design space optimization-topology optimization based algorithm was utilized to numerically reproduce the mechano-driven bone ingrowth process under three daily load cases, and the fusion outcomes were analyzed in terms of bone morphological parameters and bone-cage stability. Simulation results show that the uniform cage with higher compliance induces deeper bone ingrowth than the optimized graded cage. Whereas, the optimized graded cage with the lowest compliance exhibits the lowest stress at the bone-cage interface and better mechanical stability. Combining the advantages of both, the strain-enhanced cage with locally weakened struts offers extra mechanical stimulus while keeping relatively low compliance, leading to more bone formation and the best mechanical stability. Thus, the internal mechanical environment can be well-designed via tailoring architectures to promote bone ingrowth and achieve a long-term bone-scaffold stability.

Simulation on bone remodeling with stochastic nature of adult and elderly using topology optimization algorithm.

Reliable and accurate predictions of bone remodeling provide essential assistance for personalized implant design and orthopedic diagnosis. However, the bone remodeling simulations fail to accurately mimic the sophisticated architecture of trabecular bone so far, due to the neglection of the stochastic behaviors of bone remodeling. In this study, we coupled the Physiological Stochasticity in Bone Remodeling into the conventional Topology Optimization algorithm (named PSBR-TO method) to predict the cancellous structure of human femur. The sensitivity function of topology optimization was amended according to the bone remodeling rules from in vivo study (Razi et al., 2015) to reflect the stochastic process of bone remodeling in various physiological conditions. To demonstrate the algorithm, the bone structures of adults and the elderly were simulated by adopting the corresponding remodeling rules. The results showed that PSBR-TO gives rise to highly similar morphological features with the natural femur bone, in terms of the trabecular orientations and bone content distribution. The predicted femurs for adults and the elderly showed that the region-dependent variations in trabecular structural parameters during aging, including BV/TV, Tb.Th, and Tb.Sp, were consistent with the natural bone. Additionally, a loading collection of thirteen activities was employed in the algorithm and succeeded in driving the femur model to reproduce cancellous structure without extra constraint of structure perimeter or local density. By means of PSBR-TO, the trabecular structure in diverse physiological conditions can be accurately predicted, showing the valuable contribution on the clinical diagnosis and patient-specific design of bone implants.

Soft, Bistable Actuators for Reconfigurable 3D Electronics.

Existing strategies for reconfigurable three-dimensional (3D) electronics are greatly constrained by either the complicated driven mechanisms or harsh demands for conductive materials. Developing a simple and robust strategy for 3D electronics reconstruction and function extension remains a challenge. Here, we propose a solvent-driven bistable actuator, which acts as a substrate to reconstruct the combined 3D electronic device. Extraction of silicon oil from a hybrid poly(dimethylsiloxane) (PDMS) circle sheet buckles the dish to a bistable structure. The ultraviolet (UV)/ozone treatment on one surface of the PDMS structure introduces an oxidized layer, yielding a bilayered, solvent-driven bistable smart actuator. The snap-back stimulus to the oxidized layer differs from the snap-through stimulus. Experimental and numerical studies reveal the fundamental regulations for buckling configurations and the bistable behavior of the actuator. The prepared bistable actuator drives the bonded kirigami polyimide (PI) sheets to diverse 3D structures from the original bending configuration, reversibly. A frequency-reconfigurable electrically small monopole antenna is presented as a demonstration, which paves a way for the applications of this actuator in the field of reconfigurable 3D electronics.

Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors.

Spaced training is robustly superior to massed training, which is a well-documented phenomenon in humans and animals. However, the mechanisms underlying the spacing effect still remain unclear. We have reported previously that spacing training exerts memory-enhancing effects by inhibiting forgetting via decreasing hippocampal Rac1 activity. Here, using contextual fear conditioning in rat, we found that spaced but not massed training increased hippocampal 5-HT2A receptors' expression. Furthermore, hippocampal administration of 5-HT2A receptor antagonist MDL11939 before spaced training blocked the enhanced memory, while hippocampal administration of 5-HT2A receptor agonist TCB-2 before massed training promoted the memory. Moreover, MDL11939 activated hippocampal Rac1, while TCB-2 decreased hippocampal Rac1 activity in naïve rats. These results indicated the possibility of interaction between 5-HT2A receptors and Rac1, which was demonstrated by co-immunoprecipitation experiments. Our study first demonstrates that activation of hippocampal 5-HT2A is a mechanism underlying the spacing effect, and forgetting related molecular Rac1 is engaged in this process through interacting with 5-HT2A receptors, which suggest a promising strategy to modulate abnormal learning in cognitive disorders.