Exploring fibroblast interactions on nanocrystalline surfaces in physiological environments through a phenomenological lens.

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, particularly accounting for the percentage and nature of crystal boundaries. Recognising and understanding these physical and chemical characteristics establish the groundwork for formulating precise guidelines crucial in the development of the forthcoming generation of biomedical devices.

The significance of nanoscale surface in favourably modulating the cellular functionality is described with the aim to provide the solution to the current day challenges in the biomedical arena. Furthermore, the perspective presented advances the nano-bio science forward by implying that the nanoscale structure induces chemical and physical changes that can be considered responsible for favourable modulation of cellular activity in the living organism.

Process-structure-biofunctional paradigm in cellular structured implants: an overview and perspective on the synergy between additive manufacturing, bio-mechanical behaviour and biological functions.

The overview describes the synergy between biological sciences and cellular structures processed by additive manufacturing to elucidate the significance of cellular structured implants in eliminating stress shielding and in meeting the bio-mechanical property requirements of elastic modulus, impact resistance, and fatigue strength in conjunction with the biological functionality. The convergence of additive manufacturing, computer-aided design, and structure-property relationships is envisaged to provide the solution to the current day challenges in the biomedical arena. The traditional methods of fabrication of biomedical devices including casting and mechanical forming have limitations because of the mismatch in micro/microstructure, mechanical, and physical properties with the host site. Additive manufacturing of cellular structured alloys via electron beam melting and laser powder bed fusion has benefits of fabricating patient-specific design that is obtained from the computed tomography scan of the defect site. The discussion in the overview consists of two aspects - the first one describes the underlying reason that motivated 3D printing of implants from the perspective of minimising stress shielding together with the mechanical property requirements, where the mechanical properties of cellular structured implants depend on the cellular architecture and percentage cellular porosity. The second aspect focuses on the biological response of cellular structured devices.

Improving Biological Functions of Three-Dimensional Printed Ti2448 Scaffolds by Decoration with Polydopamine and Extracellular Matrices.

Extracellular matrices (ECMs) provide important cues for cell proliferation and differentiation in the complex environment, which show a significant influence on cell functions. Herein, cell-derived ECMs were deposited on the polydopamine (PDA)-decorated porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds fabricated by the electron beam melting method in order to improve biological functions. The influence of PDA-ECM coatings on cell functions was further investigated. The results demonstrated that the PDA-ECM coating facilitated adhesion, proliferation, and migration of MC3T3-E1 cells on Ti2448 scaffolds. Moreover, Ti2448-PDA-ECM scaffolds promoted osteogenesis differentiation of cells indicated by greater alkaline phosphatase activity and further mineralization, compared to the plain Ti2448 group. Meanwhile, Ti2448-PDA-ECM scaffolds enhanced bone growth after implantation for one month in rabbit femoral bone defects. Our findings suggest that the bioinspired PDA-ECM coating can be implemented on the porous Ti2448 scaffolds, which significantly improve the biological functions of orthopedic implants.

The significance of thermomechanical processing on the cellular response of biomedical Co-Cr-Mo alloys.

Strengthening of biomedical Co-Cr-Mo alloys has been explored via thermomechanical processing for enhancing the durability of their biomedical applications. However, the effects of cold and hot deformation on the cellular activity continue to be unclear. In this study, we prepared Co-Cr-Mo alloy rods via cold swaging and hot-caliber rolling and studied the relationship between the microstructure and cellular response of pre-osteoblasts. The cold-swaged rod experienced strain-induced martensitic transformation, which increased the volume fraction of the hexagonal close-packed (hcp) ε-martensite to ∼60 vol.% with an increase in area reduction (r) to 30%. The 111γ fiber texture of the face-centered cubic (fcc) γ-matrix followed the Shoji-Nishiyama orientation relationship with ε-martensite. Cell culture results revealed beneficial effects of cold swaging on the cell response, in terms of adhesion, proliferation and morphology of cells, although increasing r did not significantly affect cellular metabolism levels. The addition of small content of Zr (0.04 wt.%) led to enhanced focal adhesion of cells, which became more significant at higher r. The microstructural evolution during hot-caliber rolling, namely, grain refinement without any phase transformation and strong texture development, did not appreciably affect the cellular activity. These findings are envisaged to facilitate alloy design and microstructural optimization for favorable tuning the osseointegration of biomedical Co-Cr-Mo alloys.

Effects of integrated bioceramic and uniaxial drawing on mechanically-enhanced fibrogenesis for bionic periosteum engineering.

Periosteum is clinically required for the management of large bone defects. Attempts to exploit the periosteum's participation in bone healing, however, have rarely featured biological and mechanical complexity for the scaffolds relevant to translational medicine. In this regard, we report engineering of bioinspired periosteum with co-delivery of ionic and geometry cues. The scaffold demonstrated microsheet-like fibre morphology and was developed based on bioresorbable poly(-caprolactone) and bioactive copper-doped tricalcium phosphate (Cu-TCP). A coordinated interaction was found between the effects of Cu-TCP addition and uniaxial drawing, leading to tunable fibrogenesis for different fibre morphologies, organisation, and surface wettability. The coordination resulted in significant enhancements in Young's Modulus, yield stress and ultimate stress along fibrous alignment, without causing reductions across fibres. This demonstrated mechanical anisotropy of the scaffold similar to natural periosteum, and seeding with mouse calvarial preosteoblasts, the scaffold supported cell alignment with deposition of CaP-like nodules and extracellular matrix. This work provides new insights on periosteum engineering with osteo-related composite fibres. The artificial periosteum can be used in clinical settings to facilitate repair of large bone defects.

Utility of a real-time fluorescence imaging device in guiding antibiotic treatment in superficial skin infections.

The prescription of antibiotics empirically without confirmation of an infective etiology is on the rise. Administration of appropriate antibiotics can be guided by real-time fluorescence imaging using a point-of-care device. These composite images show the presence, type and the burden of infection. The time saved by this method over microbiological testing, especially in resource-poor settings, can lead to a paradigm shift in treatment by facilitating prompt and adequate antimicrobial therapy, surgical debridement as well as follow-up. Thumbnail sketches of a series of four cases highlighting different scenarios in which a fluorescent imaging device utilizing artificial intelligence and machine learning was found useful is presented in this report.

Fully endoscopic cervical spine surgery: What does the future hold?

Fully endoscopic cervical spine surgery is an emerging novel approach to address cervical spinal pathology. Techniques, both anterior and posterior have been adapted to address various cervical pathologies. The primary goal of these procedures like other open techniques is to surgically decompress the canal centrally and/or along the foramen. The narrative review aims to provide the reader an overview of the rapidly advancing field of endoscopic cervical spinal surgery and evaluate whether these newer approaches could potentially reduce the cost and the risk associated with instrumented cervical fusion.

Fully endoscopic lumbar spinal surgery: Is it time to change?

Spinal surgery is becoming safer and progressively less invasive with advances in optical and instrument technology. The amount of decompression achievable with endoscopic approaches is now comparable to open approaches with the advantage of much less tissue trauma. This review aims at examining the status of endoscopic approaches in lumbar decompressive surgery.

Recent Advances on Development of Hydroxyapatite Coating on Biodegradable Magnesium Alloys: A Review.

The wide application of magnesium alloys as biodegradable implant materials is limited because of their fast degradation rate. Hydroxyapatite (HA) coating can reduce the degradation rate of Mg alloys and improve the biological activity of Mg alloys, and has the ability of bone induction and bone conduction. The preparation of HA coating on the surface of degradable Mg alloys can improve the existing problems, to a certain extent. This paper reviewed different preparation methods of HA coatings on biodegradable Mg alloys, and their effects on magnesium alloys' degradation, biocompatibility, and osteogenic properties. However, no coating prepared can meet the above requirements. There was a lack of systematic research on the degradation of coating samples in vivo, and the osteogenic performance. Therefore, future research can focus on combining existing coating preparation technology and complementary advantages to develop new coating preparation techniques, to obtain more balanced coatings. Second, further study on the metabolic mechanism of HA-coated Mg alloys in vivo can help to predict its degradation behavior, and finally achieve controllable degradation, and further promote the study of the osteogenic effect of HA-coated Mg alloys in vivo.

The significance of phase reversion-induced nanograined/ultrafine-grained (NG/UFG) structure on the strain hardening behavior and deformation mechanism in copper-bearing antimicrobial austenitic stainless steel.

The unique concept of phase reversion involving severe deformation of parent austenite into martensite, followed by annealing for a short duration, whereby the strain-induced martensite reverts to austenite, was adopted to obtain nano-grained/ultrafine-grained (NG/UFG) structure in a Cu-bearing biomedical austenitic stainless steel resulting in high strength-high ductility combination. Work hardening and accompanying deformation mechanism are two important aspects that govern the mechanical behavior of biomedical devices. Thus, post-mortem electron microscopy of the strained region was carried out to explore the differences in the deformation mechanisms induced by grain refinement, while the strain hardening behavior was analyzed by Crussard-Jaoul (C-J) analysis of the tensile stress-strain data. The strain hardening behavior consisted of four stages and was strongly affected by grain structure. Twinning-induced plasticity (TWIP) was the governing deformation mechanism in the NG/UFG structure and contributed to good ductility. In striking contrast, transformation-induced plasticity (TRIP) contributed to high ductility in the coarse-grained (CG) counterpart and was the governing strain hardening mechanism. When the grain size is less than ~1 µm, the increase in the strain energy and the austenite stability significantly reduce the possibility of strain-induced martensite transformation such that there is a distinct transition in deformation mechanism from nanoscale twinning in the NG/UFG structure to strain-induced martensite in CG structure. The differences in the deformation mechanisms are explained in terms of austenite stability - strain energy relationship.

The synergistic effect of grain boundary and grain orientation on micro-mechanical properties of austenitic stainless steel.

Micro/nano-scale deformation behavior including hardness, elastic modulus, and pop-ins, was studied in a medical austenitic stainless steel followed by post-mortem EBSD characterization. Relatively higher hardness and modulus was observed near {101} and more pop-ins occurred in this orientation at high loading rate. The activation volume (v) obtained from nanoindentation had weak dependence on grain orientation and was ~10-20 b3, indicating that neither diffusional creep processes nor conventional dislocation segments passing through dislocation forests controls plastic deformation in our study. The plastic zone radius (c) and the distance of the indent from the grain boundary (d) were used to describe the effect of grain boundary on the pop-in effect. The ratio of c/d meets amplitude version of Gaussian peak function distribution for a given orientation, whose peak value remains nearly constant for all the orientations.

The effect of different coatings on bone response and degradation behavior of porous magnesium-strontium devices in segmental defect regeneration.

Regeneration of long-bone segmental defects remains a challenge for orthopedic surgery. Current treatment options often require several revision procedures to maintain acceptable alignment and achieve osseous healing. A novel hollow tubular system utilizing magnesium-strontium (Mg-Sr) alloy with autogenous morselized bone filled inside to repair segmental defects was developed. To improve the corrosion and biocompatible properties, two coatings, Ca-P and Sr-P coatings, were prepared on surface of the implants. Feasibility of applying these coated implants was systematically evaluated in vitro and in vivo, and simultaneously to have a better understanding on the relationship of degradation and bone regeneration on the healing process. According to the in vitro corrosion study by electrochemical measurements, greater corrosion resistance was obtained for Ca-P coated sample, and attributed to the double-layer protective structure. The cytotoxicity and alkaline phosphatase (ALP) assays demonstrated enhanced bioactivity for Sr-P coated group because of the long-lasting release of beneficial Sr2+. At 12 weeks post-implantation with Mg-Sr alloy porous device, the segmental defects were effectively repaired with respect to both integrity and continuity. In addition, compared with the Ca-P coated implant, the Sr-P coated implant was more proficient at promoting bone formation and mineralization. In summary, the Sr-P coated implants have bioactive properties and exceptional durability, and promote bone healing that is close to the natural rate, implying their potential application for the regeneration of segmental defects.

The Significance of Coherent Transformation on Grain Refinement and Consequent Enhancement in Toughness.

Coherent transformation is considered to be an effective approach to refine the microstructure and enhance toughness of structural steels. However, there are gaps in the knowledge on the key aspects of microstructure that govern toughness. In this regard, a low alloyed experimental steel with lean chemistry was subjected to a simple heat treatment involving austenitization at different temperatures, followed by quenching and tempering to obtain bainitic microstructures with different boundary composition. The microstructure of the four experimental steels was characterized by electron backscattered diffraction and mechanical properties were determined. The study indicated that the density of high angle grain boundaries does not adequately reflect the change of ductile-to-brittle transition temperatures (DBTT) of the experimental steels. Thus, we propose here a new mechanism on reducing DBTT from the perspective of misorientation of boundary, which takes into consideration these aspects in defining DBTT. One is inhibition effect on cleavage fracture by boundaries with high {100}-plane misorientation angles, and the other is ductility improvement by boundaries with high {110}-plane misorientation angles. Furthermore, the contribution of prior austenite grain boundary, packet boundary, block boundary, and sub-block boundary on toughness is also analyzed.

The significant impact of mechanically-induced phase transformation on cellular functionality of biomedical austenitic stainless steel.

The implant surface and tissue experience strain when micro-motion occurs at the bone-implant interface under physiological loading. Moreover, strain is also introduced on the surface during mechanical processing of biomedical devices. Both these situations can induce phase transformation depending on the degree of stability of the microstructural constituents. In this regard, we elucidate here the interplay between mechanically-induced phase transformation (strain-induced martensite) in austenitic stainless steel on osteoblast functions. Strain-induced martensite significantly impacted cellular functions, notably, cell attachment, cell-surface interactions, proliferation, and synthesis of prominent proteins (fibronectin, actin, and vinculin). Strain-induced martensite favorably modulated cellular activity and contributed to small differences in hydrophilicity in relation to the non-strained austenitic stainless steel surface. The study provides a pathway for tuning biological functionality via microstructural control facilitated by mechanical strain.

Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease.

BACKGROUND AND AIMS: Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease. METHODS: Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. RESULTS: Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease. CONCLUSIONS: This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

The significance of phase reversion-induced nanograined/ultrafine-grained structure on the load-controlled deformation response and related mechanism in copper-bearing austenitic stainless steel.

The ingenious concept of phase reversion annealing involving cold deformation of parent austenite to strain-induced martensite, followed by annealing was used to obtain nano-grained/ultrafine-grained (NG/UFG) structure in a Cu-bearing biomedical austenitic stainless steel resulting in high strength-high ductility combination. Having employed the concept effectively, the primary objective of this study is to critically analyze the interplay between the load-controlled deformation response, strain-rate sensitivity and deformation mechanism of NG/UFG austenitic stainless steel via nanoscale deformation experiments and compare with its coarse-grained (CG) counterpart. The study demonstrated that the strain-rate sensitivity of NG/UFG was ~1.5 times that of the CG structure. Post-mortem electron microscopy of plastic zone surrounding the indents indicated that the active deformation mechanism was nanoscale twinning with typical characteristics of a network of intersecting twins in the NG/UFG structure, while strain-induced martensite transformation was the effective deformation mechanism for the CG structure. The fracture morphology was also different for the two steels, essentially ductile in nature, and was characterized by striations marking the line-up of voids in NG/UFG steel and microvoid coalescence in CG counterpart. The differences in deformation mechanisms between the NG/UFG and CG structure are attributed to the austenite stability - strain energy relationship. Furthermore, the presence of ~3 wt % Cu in austenitic stainless steel had somewhat moderate effect on strain-rate sensitivity and activation volume at similar level of grain size in its Cu-free counterpart. Specifically, in the NG/UFG structure, the nanoscale twin density was noticeably higher in Cu-bearing austenitic stainless steel as compared to Cu-free counterpart, as Cu is known to increase the stacking fault energy.

Mechanistic understanding of compression-compression fatigue behavior of functionally graded Ti-6Al-4V mesh structure fabricated by electron beam melting.

In recent years, mesh structures have attracted significant interest for structural and functional applications. However, the mechanical strength and energy absorption ability of uniform mesh structured materials degrade with density. To address this challenge, we propose the concept of functionally graded mesh structures. The objective of the proposed research is to fundamentally understand the compressive behavior of graded mesh structures. The compression-compression fatigue behavior of functionally graded Ti-6Al-4V mesh structure under identical bulk stress condition is studied here. During cyclic deformation, it was observed that the local stress distribution in the struts was not uniform because of inhomogeneous mechanical properties of the constituents. Fatigue cracks first initiated in the lowest strength constituent, and then propagated until structural failure occurred. However, no obvious damage was observed in other constituents during the entire process. In contrast with iso-strain state, the fatigue life of graded structure is mainly determined by the constituent with the lowest strength.

The Impact of Isothermal Treatment on the Microstructural Evolution and the Precipitation Behavior in High Strength Linepipe Steel.

Isothermal treatment affects the microstructural evolution and the precipitation behavior of high-strength low alloy (HSLA) steels. In this regard, thermal simulation of different isothermal treatment temperatures was adopted by using a thermomechanical simulator. The results showed that hardness reached the maximum value at 600 °C holding temperature, which was related to a finer grain structure and granular bainite. The strengthening effect of precipitates was remarkable due to the combination of small particle size and small interparticle spacing. It is presumed that the precipitation started after 600 s at 600 °C. Precipitation strengthening continued to exist, even though coarsening of ferrite grains led to softening phenomena when the specimen was isothermally held at 750 °C, which led to relatively high hardness. The precipitates were fcc (Ti, Nb) (N, C) particles, and belonged to MX-type precipitates. Average size of precipitates increased from 3.14 to 4.83 nm when the specimens were isothermally held between 600 °C and 800 °C. Interparticle spacing of precipitates also increased with increasing isothermal treatment temperatures. These led to a reduction in precipitation strengthening. At the same time the polygonal ferrite content increased and ferrite grain size got larger, such that the hardness decreased continuously.

In-situ monitoring of the electrochemical behavior of cellular structured biomedical Ti-6Al-4V alloy fabricated by electron beam melting in simulated physiological fluid.

Ti-6Al-4V alloys with cellular structure fabricated by additive manufacturing are currently of significant interest because their modulus is comparable to bone and the cellular structure allows the cells to penetrate and exchange nutrients, promoting osseointegration. We describe here a unique simulation device that replaces the traditional steady electrochemistry approach, enabling in-situ study of variation of ion concentration and surface potential with pore depth for cellular structured Ti-6Al-4V alloys fabricated by electron beam melting (EBM) in phosphate buffered saline (PBS). This approach addresses the scientific gap on the electrochemical behavior of cellular structured titanium alloys. The study indicated that concentration of H+ and Cl- increased with the increase of pore depth, while the surface potential decreased. The exposed surface of inner cellular structure was not corroded but passivated after immersing in PBS at 37 °C for 14 days, which was independent of pore depth. Furthermore, X-ray photoelectron spectroscopy (XPS) and Mott-Schottky (M-S) studies suggested that a thinner passive film containing a greater donor density was formed on the surface of cellular structured Ti-6Al-4V alloy at the deepest pore depth. This is attributed to insufficient oxygen supply and Cl-adsorption on the surface inside the pores. STATEMENT OF SIGNIFICANCE: Porous titanium alloys are promising implants in biomedical applications. However, it is a challenge to accurately characterize the corrosion behavior of porous titanium alloys with complex pore structure using traditional electrochemical methods. In this study, we have adopted a special device to simulate the environment within the pore structure. The variation in ion concentration and surface potential of Ti-6Al-4V fabricated by EBM with pore depth was in-situ monitored. After immersing in PBS for 14 days, Ti-6Al-4V exhibited good corrosion properties and the samples with less than 60 mm pore depth were not corroded but passivated. Also, we analyzed the difference in corrosion property at different pore depth. This type of in-situ corrosion performance monitoring in EBM-produced Ti-6Al-4V has not been previously studied.

On the mechanical behavior of austenitic stainless steel with nano/ultrafine grains and comparison with micrometer austenitic grains counterpart and their biological functions.

Conventional coarse-grained (CG) biomedical austenitic stainless steel with grain size in the micrometer range was subjected to a novel phase reversion concept involving severe cold deformation, followed by annealing, when the cold deformed martensite reverts to austenite with grain size in the nanometer/ultrafine (NG/UFG) regime (~200-400 nm). The mechanical behavior of CG and NG/UFG steels was studied via load-controlled and displacement-controlled experiments using a nanoindentation technique with the aim to simulate micromotion. The plastic zone associated with the indentation-induced deformed region was characterized by post-mortem electron microscopy of the deformed region to elucidate the deformation mechanism. Nanoscale twinning was the deformation mechanism in steel with grain size in the NG/UFG regime, and contributed to the ductility of high strength steel. In contrast, strain-induced martensite contributed to the ductility of low strength CG steel with micrometer grain size. Interestingly, besides the differences in the mechanical behavior, the biological functions of the two steels were remarkably different. Higher cell attachment, proliferation and higher expression level of prominent proteins, fibronection, actin and vinculin were favored by a surface with grain size in the nanometer regime and was in striking contrast with the surface with micrometer grain size. This behavior is attributed to the differences in the fraction of grain boundaries that are high energy two-dimensional defects. The study advances our understanding of the mechanical behavior of biomaterials and their cellular functions.