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There has been a tremendous amount of research in the past decade to optimize the mechanical properties and degradation behavior of the biodegradable Mg alloy for orthopedic implant. Despite the feasibility of degrading implant, the lack of fundamental understanding about biocompatibility and underlying bone formation mechanism is currently limiting the use in clinical applications. Herein, we report the result of long-term clinical study and systematic investigation of bone formation mechanism of the biodegradable Mg-5wt%Ca-1wt%Zn alloy implant through simultaneous observation of changes in element composition and crystallinity within degrading interface at hierarchical levels. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study.biodegradable implant | bone formation | clinical application T he century-old concept of the fixation device that holds the fractured bones in place to allow repair through the natural bone remodeling process is still being practiced today without alteration (1-5). The recent rapid growth of the elderly demographic of physically active adults has tremendously intensified the occurrence of bone trauma cases, highlighting once again the major drawbacks of current surgical approaches and osteosynthesis systems, such as inevitable secondary surgery to remove the inert fixation devices after complete bone healing and inflammatory response due to the release of metal ions. In the past decade, countless studies have been performed to control and optimize the mechanical and corrosion properties of magnesium-based alloys (6-9), which, thanks to their degradation in the physiological environment, could overcome the limitations of inert implant materials and shift the paradigm of conventional bone fixation devices toward new horizons. Driven by these new possibilities, important findings regarding, among others, the degradation mechanism of Mg-based alloys (10, 11), the formation of corrosion protective layers by degradation products (12, 13), and the osteogenetic properties of Mg ions (14, 15) have been reported in the literature. However, such findings are based on the observation of degradation products and of bone healing at the macroscale level. Due to lack of fundamental understanding on biocompatibility and underlying bone formation mechanism of the degradation product, there is so far only one known case of statistically insignificant clinical study result (16) with a short-term follow-up. In our previous study, we reported successful development and long-term in vivo study of uniformly slowly degrading Mg-5wt%Ca-1wt%Zn alloy system (SI Appendix, Figs. S1 and S2) featuring adequate mechanical strength [ultimate tensile strength (UTS) ∼250 MPa] (17) a...

Osteopetrotic bone shows dissociation between bone mineral density (BMD) and bone strength. In this study, volumetric BMD; preferential orientation of the extracellular matrix (ECM), which is composed of collagen fibers and apatite crystals as bone material quality; and mechanical properties of the src osteopetrotic and normal mouse femoral cortical bone were analyzed and compared with each other at a bone tissue level. The degree of preferential orientation of ECM along the femoral long axis was significantly decreased in the src mice femur, suggesting deteriorated bone quality. Young's modulus, as a tissue-level mechanical property analyzed by nano-indentation technique along the long bone direction, also was decreased in the src mice cortical femur, in spite of the similar volumetric cortical BMD. To the best of our knowledge, this is the first report to demonstrate the synchronous deterioration of Young's modulus and anisotropic ECM organization in the src osteopetrotic mouse bone. These results indicate that the deterioration of the preferential ECM orientation is one major cause of the impaired mechanical property in the src mouse bone.

The size-dependent wettability of sessile water droplets is an important matter in wetting science. Although extensive studies have explored this problem, it has been difficult to obtain empirical data for microscale sessile droplets at a wide range of diameters because of the flaws resulting from evaporation and insufficient imaging resolution. Herein, we present the size-dependent quantitative change of wettability by directly visualizing the three phase interfaces of droplets using a cryogenic-focused ion beam milling and SEM-imaging technique. With the fundamental understanding of the formation pathway, evaporation, freezing, and contact angle hysteresis for sessile droplets, microdroplets with diameters spanning more than three orders of magnitude on various metal substrates were examined. Wetting nature can gradually change from hydrophobic at the hundreds-of-microns scale to super-hydrophobic at the sub-μm scale, and a nonlinear relationship between the cosine of the contact angle and contact line curvature in microscale water droplets was demonstrated. We also showed that the wettability could be further tuned in a size-dependent manner by introducing regular heterogeneities to the substrate.

Osteoclasts are nearly non-existent in mutant osteopetrotic (op/op) mice due to defects in the expression of the macrophage colonystimulating factor (M-CSF). Thus, areal distribution of the biological apatite (BAp) c-axis in a femoral cross-section of an op/op mouse was investigated using a microbeam X-ray diffraction system to understand the role of osteoclasts on formation of BAp preferential alignment.The incident X-ray beam is focused to 20 mm in diameter. The diffraction analysis is performed at 20 mm displacement intervals from the periosteal surface along the radial axis of the anterior portion at a cross-section of the femoral diaphysis. The osteopetrotic (op/op) mouse and its normal littermate used as a control were 12 weeks old.The lack of osteoclasts induces both abnormality of the skeletal system and calcification of the medullary cavity, which are typical features of osteopetrosis. Preferential alignment of the BAp c-axis in the osteopetrotic (op/op) mouse always shows a lower degree than that in the control mouse, regardless of the distance from the periosteum. Moreover, areal distributions of preferential alignment of the BAp c-axis on the femoral cross-section show quite different tendencies between the op/op and control mice. The preferential alignment of BAp gradually increases towards the periosteal surface in the op/op mouse due to the intramembranous ossification, while that in the control mouse is the lowest near the cortical envelope on the cross-section. This is because the decrease in the number of osteoclasts suppresses the normal modeling or remodeling, resulting in degradation of preferential alignment of the BAp c-axis as a bone quality parameter in the op/op mouse.