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...

Electrospinning has been used for the fabrication of extracellular matrix (ECM)-mimicking fibrous scaffolds for several decades. Electrospun fibrous scaffolds provide nanoscale/microscale fibrous structures with interconnecting pores, resembling natural ECM in tissues, and showing a high potential to facilitate the formation of artificial functional tissues. In this review, we summarize the fundamental principles of electrospinning processes for generating complex fibrous scaffold geometries that are similar in structural complexity to the ECM of living tissues. Moreover, several approaches for the formation of three-dimensional fibrous scaffolds arranged in hierarchical structures for tissue engineering are also presented.

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