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The delayed transition of macrophages (MΦs) from pro-inflammatory M1 to the pro-healing M2 state on implant surfaces is one of the most important reasons for poor osseointegration. This work reports the construction of closely packed nanopores with a small diameter on the micropitted titanium (Ti) surface by two-step acid etching to promote the M1-to-M2 transition of MΦs and pays special attention to the potential mechanisms by which the nanopores decorating the micropits exert immunomodulatory effects. The results show that the structure composed of hybrid nanopores (10-25 nm) and micropits (5-15 μm) can be produced on the Ti surface by a two-step acid etching process. Compared with the unitary micropits, the micropit/nanopore surface could facilitate the switch of MΦs from the pro-inflammatory M1 to the pro-healing M2 phenotype. RNA sequencing reveals that the MAPK, PI3K-AKT and C-type lectin signaling pathways play key roles in the micro/nano-structure-mediated transition. In addition, the micro/nano-structured surface down-regulated CYP1A2 expression, reducing the generation of mitochondrial ROS, in turn restraining the oxidative stress and further attenuating inflammation. This work provides novel insights into the underlying mechanisms of immunomodulation by the nano-structure-decorated micro-structures on the Ti surface, which is significant for designing the surface of orthopedic implants from the perspective of immunomodulation.

Bone repair materials with excellent mechanical properties are highly desirable, especially in load-bearing sits. However, the currently used ceramic- and polymer-based ones mainly show poor mechanical properties. Recently, biodegradable metals have attracted extensive attention due to their reliable mechanical strength and degradability. As biodegradable metals, zinc-based materials are promising due to their suitable degradation rate and good biocompatibility. Here, we fabricated biodegradable porous Zn scaffolds with relatively high mechanical properties by vacuum heating-press sintering using NaCl particles as space holders. The microstructure, actual porosity, compressive mechanical properties, in vitro degradation behavior and the vitality of osteoblasts of porous Zn scaffolds were tested and investigated. The results show the porosities of the prepared porous Zn scaffolds are ranging from 11.3 % to 63.3 %, and the pore sizes are similar to the size range of the screened NaCl particles (200-500 μm). Compressive yield strength of 14.2-73.7 MPa and compressive elastic modulus of 1.9-6.7 GPa are shown on porous Zn scaffolds, some of which approach to that of cancellous bone (2-12 MPa and 0.1-5 GPa). Compared to bulk Zn, although the porous structures cause a partial loss of strength, the reliable mechanical properties are still retained. In addition, the porous structures not only greatly increase the degradation rate, but also promote the proliferation of osteoblasts. Based on these results, biodegradable porous Zn scaffolds (porosity in the 40 %-50 %) fabricated by vacuum heating-press sintering method show high application potential for clinical bone repair.

Osseointegration of implants is a complex physiological process that requires temporal and spatial regulation of immune responses, angiogenesis, and osteogenesis. To achieve efficient and long-term osseointegration, type I collagen (COL1) decorated nanoporous network was developed on titanium substrates via alkali treatment, polydopamine coating, and layer-by-layer (LBL) self-assembly. It was noted that the simple physisorbed COL1 could be easily desorbed from the nanostructured surface, however, multilayer COL1 constructed by polydopamine and LBL self-assembly obscured the nanoporous network of the alkali-treated titanium surfaces. Interestingly, the nanostructured surface covalently immobilized with COL1 (T-ADC) could timely convert macrophages (MΦs) from pro-inflammatory M1 to pro-healing M2 phenotype, generating a beneficial osteoimmune microenvironment and promoting angio/osteo-genesis. RNA sequencing revealed that the nanostructure and COL1 could synergistically activate RhoA/ROCK, PI3K-AKT, and classical MAPK signaling pathways in MΦs to sustain the cell cycle, and trigger autocrine feedback-mediated JAK-STAT and FoxO signaling pathways, which in turn motivated autophagy and oxidative stress resistance and attenuated lipopolysaccharide-induced Toll-like receptor signaling pathway and its downstream NF-κB and JNK/p38 MAPK signaling cascades, leading to the inhibition of inflammation and osteoclastic-related gene expression of MΦs. Simultaneously, T-ADC prominently facilitated angiogenesis of endothelial cells and osteogenesis of osteoblasts as well as their cross-talks, further highlighting synergistically positive effects of the nanostructure and COL1 on osseointegration. In vivo experiments revealed that T-ADC could induce abundant new bone mass and ameliorative osseointegration, corroborating the in vitro results. The study elucidated that the COL1 decorated nanoporous network on titanium surfaces could significantly regulate early inflammatory reaction and subsequent angio/osteo-genesis processes, resulting in favorable osseointegration.

In this study, crossed Nitinol wires were joined by laser welding, and the microstructures of the joint in various zones were revealed by transmission electron microscopy. A series of nanoindentation experiments were performed across the joint, and the size changes of indentations after heating were used to evaluate the shape memory effects. Compared to BM, HAZ retained about the 95% shape recovery, higher than FZ, which retained about the 75% recovery rate.

Angiogenesis, an essential prerequisite to osteogenesis in bone repair and regeneration, can be mediated by immunoregulation of macrophages. Magnesium and its alloys are promising biodegradable bone implant materials and can affect immunoregulation of macrophages by the degradation products (magnesium ions). Nevertheless, the mechanism of macrophage-derived exosomes stimulated by Mg ions in immunoregulation is still not well understood. Herein, 10–50 mM magnesium ions are shown to inhibit the macrophage viability and proliferation in a dose-dependent manner, but a high concentration results in macrophage apoptosis. The exosomes secreted by macrophages from magnesium ion stimulation inhibit angiogenesis of endothelial cells, as manifested by the suppressed cell viability, proliferation, migration, and tube formation, which arise at least partially from exosome-mediated downregulation of endothelial nitric oxide and the vascular endothelial growth factor. The findings reported in this paper suggest that the bio-functionality of biodegradable magnesium alloys must be considered from the perspective of immunoregulation of macrophage-derived exosomes. Our results also suggest potential cancer therapy by inhibiting tumor-associated angiogenesis.

Laser welding has been considered to be one of the most promising joining processes for Nitinol medical device manufacturing. Presently, there is still a limited understanding about how laser welding affects the microstructure and the resultant corrosion behaviors. This work aimed to reveal the microstructural factors that influence the corrosion resistance of laser-welded crossed Nitinol joints. The microstructures within various zones of the joints were characterized by using transmission electron microscopy (TEM), and the corrosion behaviors of the joints in 0.9% NaCl and Hank’s solutions were studied. The base metal exhibits a single austenite (B2) phase and the highest corrosion resistance. The phase constituent of the fusion zone is the coexistence of the B2 matrix and some precipitates (T2Ni, TiNi3, and Ti3Ni4 particles), resulting in a slight decrease in corrosion resistance. The heat affected zone (HAZ) shows the austenite matrix but with the precipitation of R-phase, which considerably reduces the corrosion potential, making it the weakest zone.