Bio-Functional Design, Application and Trends in Metallic Biomaterials.

Introduction of metals as biomaterials has been known for a long time. In the early development, sufficient strength and suitable mechanical properties were the main considerations for metal implants. With the development of new generations of biomaterials, the concepts of bioactive and biodegradable materials were proposed. Biological function design is very import for metal implants in biomedical applications. Three crucial design criteria are summarized for developing metal implants: (1) mechanical properties that mimic the host tissues; (2) sufficient bioactivities to form bio-bonding between implants and surrounding tissues; and (3) a degradation rate that matches tissue regeneration and biodegradability. This article reviews the development of metal implants and their applications in biomedical engineering. Development trends and future perspectives of metallic biomaterials are also discussed.

Prognostic factors for squamous cervical carcinoma identified by competing-risks analysis: A study based on the SEER database.

Cervical cancer has a high incidence of malignant tumors and a high mortality rate, with squamous cervical carcinoma (SCC) accounting for 80% of cases. A competing-risks model is recommended as being more feasible for evaluating the prognosis and guiding clinical practice in the future compared to Cox regression. Data originating from the Surveillance, epidemiology, and end results (SEER) database during 2004 to 2013 were analyzed. Univariate analysis with the cumulative incidence function was performed to assess the potential risk of each covariate. Significant covariates (P < .05) were extracted for inclusion in a Cox regression analysis and a competing-risks model that included a cause-specific (CS) hazard function model and a sub-distribution (SD) hazard function model. A total of 5591 SCC patients met the inclusion criteria. The three methods (Cox regression analysis, CS analysis, and SD analysis) showed that age, metastasis, American Joint Committee on Cancer stage, surgery, chemotherapy, radiation sequence with surgery, lymph node dissection, tumor size, and tumor grade were prognostic factors affecting survival in patients with SCC. In contrast, race and radiation status were prognostic factors affecting survival in the Cox regression and CS analysis, but the results were different in the SD analysis. Being separated, divorced, or widowed was an independent prognostic factor in the Cox regression analysis, but the results were different in the CS and SD analyses. A competing-risks model was used as a new statistical method to more accurately identify prognostic factors than conventional Cox regression analysis leading to bias in the results. This study found that the SD model may be better suited to estimate the clinical prognosis of a patient, and that the results of an SD model analysis were close to those of a CS analysis.

Customized additive manufacturing of porous Ti6Al4V scaffold with micro-topological structures to regulate cell behavior in bone tissue engineering.

Scaffold micro-topological structure plays an important role in the regulation of cell behavior in bone tissue engineering. This paper investigated the effect of 3D printing parameters on the scaffold micro-topological structure and its subsequent cell behaviors. By setting of different 3D printing parameters, i.e., the 3D printing laser power, the scanning interval and the thickness of sliced layers, the highest resolution up to 20 µm can be precisely fabricated. Scaffolds' characterization results indicated that the laser power affected the forming quality of melt tracks, the scanning interval distance determined the size of regularly arranged pores, and the thickness of sliced layers affected the morphological and structural characteristics. By regulating of these printing parameters, customized porous Ti6Al4V scaffold with varied hierarchical micro-topological structure can be obtained. In vitro cell culturing results showed that the regular porous micro-topological structure of scaffolds with the aperture close to cell size was more suitable for cell proliferation and adhesion. The overall distribution of cells on regular porous scaffolds was similar to the orderly arrangement of cultivated crops in the field. The findings suggested that customization of the scaffold provided an effective way to regulate cellular behavior and biological properties.

Fabrication of customized Ti6AI4V heterogeneous scaffolds with selective laser melting: Optimization of the architecture for orthopedic implant applications.

Orthopedic implants with heterogeneous porous structures were known as ideal bone osteointegration. This research introduced the selective laser melting (SLM), finite element analysis (FEA), and a hydrothermal process (HT) for manufacturing a three-level heterogeneous porous structure. The macroporous structure was designed via CAD and micropores were tuned via laser power regulation. A nano-size layer of hydroxyapatite crystals was coated by an HT process. The mechanical properties were reinforced via a core-shell structure with core reinforcement. The existence of micropores and nano-hydroxyapatite coating enhanced the in vitro proliferation of preosteoblasts and osteogenic cellular behaviors of rBMSCs. Thus, the three-level heterogeneous porous titanium implants could inspire researchers with potential clue of cyto-implant interaction mechanism, therefore building ideal orthopedic implants with accelerated osteointegration. STATEMENT OF SIGNIFICANCE: Porous structures of titanium implants play an important role in bone tissue regeneration; The geometrical environment influence cell behaviour and bone tissue ingrowth in all macro-/micro-/nanoscale. In this study, a novel method to fabricate heterogeneous scaffolds and its macro-/micro-/nanoscopic structures were studied. A CAD model was used to obtain the macroscopic structure and the insufficient laser power was introduced for porous microstructure. Therefore, a layer of nano hydroxyapatite was coated via hydrothermal process. Cytoproliferation and cytodifferentiation results indicated that a integrity of regular/irregular, macro-/micro-/nanoscale porous structure had advance in recruiting stem cells and promoting differentiation. This research is beneficial to the development of bone implants with better bone regeneration ability.

Direct 3-D printing of Ti-6Al-4V/HA composite porous scaffolds for customized mechanical properties and biological functions.

Customized scaffold plays an important role in bone tissue regeneration. Precise control of the mechanical properties and biological functions of scaffolds still remains a challenge. In this study, metal and ceramic biomaterials are composited by direct 3-D printing. Hydroxyapatite (HA) powders with diameter of about 25 µm and Ti-6Al-4V powders with diameter of 15-53 µm were mixed and modulated for preparing 3-D printing inks formulation. Three different proportions of 8, 10, and 25 wt.% HA specimens were printed with same porosity of 72.1%. The green bodies of the printed porous scaffolds were sintered at 1,150°C in the atmosphere of argon furnace and conventional muffle furnace. The porosities of the final 3-D-printed specimens were 64.3 ± 0.8% after linear shrinkage of 6.5 ± 0.8%. The maximum compressive strength of the 3-D-printed scaffolds can be flexibly customized in a wide range. The maximum compressive strength of these scaffolds in this study ranged from 3.07 to 60.4 MPa, depending on their different preparation process. The phase composition analysis and microstructure characterization indicated that the Ti-6Al-4V and HA were uniformly composited in the scaffolds. The cytocompatibility and osteogenic properties were evaluated in vitro with rabbit bone marrow stromal cells (rBMSCs). Differentiation and proliferation of rBMSCs indicated good biocompatibility of the 3-D-printed scaffolds. The proposed 3-D printing of Ti-6Al-4V/HA composite porous scaffolds with tunable mechanical and biological properties in this study is a promising candidate for bone tissue engineering.

3D printed titanium scaffolds with homogeneous diamond-like structures mimicking that of the osteocyte microenvironment and its bone regeneration study.

Biofabrication of personalized titanium scaffold mimicking that of the osteocyte microenvironment is challenging due to its complex geometrical cues. The effect of scaffolds geometrical cues and implantation sites on osteogenesis is still not clear. In this study, personalized titanium scaffolds with homogeneous diamond-like structures mimicking that of the osteocyte microenvironment were precisely designed and fabricated by selected laser melting method. The effects of different geometric cues, including porosity, pore sizes and interconnection properties, on cellular behavior were investigated. Biomimetic mechanical properties of porous titanium alloy scaffold were predesigned and simulated by finite element analysis.In vitroexperiment revealed that homogeneous diamond-like structures mimicking that of the osteocyte microenvironment triggered osteocyte adhesion and migration behavior. Typical implantation sites, including rabbit femur, beagle femur, and beagle skull, were used to study the implantation sites effects on bone regeneration.In vivoexperimental results indicated that different implantation sites showed significant differences. This study helps to understand the scaffolds geometrical microenvironment and implantation sites effects on osteogenesis mechanism. And it is beneficial to the development of bone implants with better bone regeneration ability.

Dual modulation of crystallinity and macro-/microstructures of 3D printed porous titanium implants to enhance stability and osseointegration.

The macro architecture and micro surface topological morphology of implants play essential roles in bone tissue regeneration. 3D printing technology provides enormous advantages for the rapid fabrication of personalized bone tissue repair implants. This study presents a demonstration of dual-modulation (DM) 3D printed porous titanium implants to enhance stability and osseointegration. Titanium implants with the first level of modulation of macro porous architecture and mechanical properties are obtained using macro architecture design and 3D printing fabrication. The first level of modulation achieved scaffolds with a wide range of compressive strengths (36.76-139.97 MPa) when varying the scaffold macro architectures. In the second level of modulation of surface topological morphology, alkali treatment, heat treatments and electrochemical deposition of hydroxyapatite coating were conducted for further regulating the biological function of implants. DM 3D printed scaffolds significantly promoted bone marrow mesenchyme stem cell adhesion and proliferation, indicating good cytocompatibility. In addition, in vivo osseointegration experiments indicated that the DM scaffolds formed better tissue-materials interfaces. New bone formation rates in DM scaffolds are higher than those in conventional 3D printed scaffolds after 6 months of implantation (58.1% versus 36.1%). These results demonstrate that DM scaffolds could enhance early stability and osseointegration. This study may provide new insights into the design, fabrication and post-processing of 3D printed porous titanium implants for various applications in personalized bone tissue regeneration.

Scaffold Structural Microenvironmental Cues to Guide Tissue Regeneration in Bone Tissue Applications.

In the process of bone regeneration, new bone formation is largely affected by physico-chemical cues in the surrounding microenvironment. Tissue cells reside in a complex scaffold physiological microenvironment. The scaffold should provide certain circumstance full of structural cues to enhance multipotent mesenchymal stem cell (MSC) differentiation, osteoblast growth, extracellular matrix (ECM) deposition, and subsequent new bone formation. This article reviewed advances in fabrication technology that enable the creation of biomaterials with well-defined pore structure and surface topography, which can be sensed by host tissue cells (esp., stem cells) and subsequently determine cell fates during differentiation. Three important cues, including scaffold pore structure (i.e., porosity and pore size), grain size, and surface topography were studied. These findings improve our understanding of how the mechanism scaffold microenvironmental cues guide bone tissue regeneration.