The cancer microenvironment influences tumor progression and metastasis and is pivotal to consider when designing in vivo-like cancer models. Current preclinical testing platforms for cancer drug development are mainly limited to 2D cell culture systems that poorly mimic physiological environments and traditional, low throughput animal models. The aim of this work was to produce a tunable testing platform based on 3D printed scaffolds (3DPS) with a simple geometry that, by extracellular components and response of breast cancer reporter cells, mimics patient-derived scaffolds (PDS) of breast cancer. Here, the biocompatible polysaccharide alginate was used as base material to generate scaffolds consisting of a 3D grid containing periostin and hydroxyapatite. Breast cancer cell lines (MCF7 and MDA-MB-231) produced similar phenotypes and gene expression levels of cancer stem cell, epithelial-mesenchymal transition, differentiation and proliferation markers when cultured on 3DPS and PDS, contrasting conventional 2D cultures. Importantly, cells cultured on 3DPS and PDS showed scaffold-specific responses to cytotoxic drugs (doxorubicin and 5-fluorouracil) that were different from 2D cultured cells. In conclusion, the data presented support the use of a tunable alginate-based 3DPS as a tumor model in breast cancer drug discovery. © 2021 The Author(s).

In the present study, a model for simulations of removal torque experiments was developed using finite element method. The interfacial retention and fracturing of the surrounding material caused by the surface features during torque was analyzed. It was hypothesized that the progression of removal torque and the phases identified in the torque response plot represents sequential fractures at the interface. The 3-dimensional finite element model fairly accurately predicts the torque required to break the fixation of acid-etched implants, and also provides insight to how sequential fractures progress downwards along the implant side.

Osseointegrated transfemoral amputation prostheses have proven successful as an alternative method to the conventional socket-type prostheses. The method improves prosthetic use and thus increases the demands imposed on the bone-implant system. The hypothesis of the present study was that the loads applied to the bone-anchored implant system of amputees would result in locations of high stress and strain transfer to the bone tissue and thus contribute to complications such as unfavourable bone remodeling and/or elevated inflammatory response and/or compromised sealing function at the tissue-abutment interface. In the study, site-specific loading measurements were made on amputees and used as input data in finite element analyses to predict the stress and strain distribution in the bone tissue. Furthermore, a tissue sample retrieved from a patient undergoing implant revision was characterized in order to evaluate the long-term tissue response around the abutment. Within the limit of the evaluated bone properties in the present experiments, it is concluded that the loads applied to the implant system may compromise the sealing function between the bone and the abutment, contributing to resorption of the bone in direct contact with the abutment at the most distal end. This was supported by observations in the retrieved clinical sample of bone resorption and the formation of a soft tissue lining along the abutment interface. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1113–1122, 2017.

In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26 week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39 ± 4%) than CoCr (27 ± 4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications. Statement of Significance Although cobalt chromium (CoCr) based alloys are used extensively in orthopaedic surgery, stress shielding due to the high stiffness of CoCr is of concern. To reduce the stiffness mismatch between CoCr and bone, CoCr and Ti6Al4V implants having an interconnected open-pore architecture were prepared by electron beam melting (EBM). After six months of submerged healing in sheep, both alloys showed similar patterns of bone formation, with densification around the implant and gradual ingrowth into the porous network. The molecular and elemental composition of the interfacial tissue was similar for both alloys. Osteocytes made direct contact with both alloys, with similar overall osteocyte density and distribution. The work attests to the potential for achieving osseointegration of EBM manufactured porous CoCr implants.

During the past two decades, a plethora of fossil micro-organisms have been described from various Triassic to Miocene ambers. However, in addition to entrapped microbes, ambers commonly contain microscopic inclusions that sometimes resemble amoebae, ciliates, microfungi, and unicellular algae in size and shape, but do not provide further diagnostic features thereof. For a better assessment of the actual fossil record of unicellular eukaryotes in amber, we studied equivalent inclusions in modern resin of the Araucariaceae; this conifer family comprises important amber-producers in Earth history. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS), we investigated the chemical nature of the inclusion matter and the resin matrix. Whereas the matrix, as expected, showed a more hydrocarbon/aromatic-dominated composition, the inclusions contain abundant salt ions and polar organics. However, the absence of signals characteristic for cellular biomass, namely distinctive proteinaceous amino acids and lipid moieties, indicates that the inclusions do not contain microbial cellular matter but salts and hydrophilic organic substances that probably derived from the plant itself. Rather than representing protists or their remains, these microbe-like inclusions, for which we propose the term 'pseudoinclusions', consist of compounds that are immiscible with the terpenoid resin matrix and were probably secreted in small amounts together with the actual resin by the plant tissue. Consequently, reports of protists from amber that are only based on the similarity of the overall shape and size to extant taxa, but do not provide relevant features at light-microscopical and ultrastructural level, cannot be accepted as unambiguous fossil evidence for these particular groups.

Metal powder bed additive manufacturing technologies, such as the Electron Beam Melting process, facilitate a high degree of geometric flexibility and have been demonstrated as useful production techniques for metallic parts.However, the EBM process is typically associated with lower resolutions and higher surface roughness compared to similar laser-based powder bed metal processes. In part, this difference is related to the larger powder size distribution and thicker layers normally used. As part of an effort to improve the resolution and surface roughness of EBM fabricated components, this study investigates the feasibility of fabricating components with a smaller powder size fraction and layer thickness (similar to laser based processes). The surface morphology, microstructure and tensile properties of the produced samples were evaluated. The findings indicate that microstructure is dependent on wall-thickness and that, for thin walled structures, tensile properties can become dominated by variations in surface roughness.

Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo leading to insights into host defence mechanisms in biomaterial-associated infections.

Conditioning films and biofilms forming on surfaces of solid materials exposed to aqueous media play a key role in in the interaction between the geo- and biospheres. In this study, time-of-flight secondary ion mass spectrometry and scanning electron microscopy were used to investigate the time scale, mode of formation, and chemistry of conditioning films and biofilms that formed on Si substrates exposed to aquifer water in the subsurface Äspö Hard Rock Laboratory, SE-Sweden. The detection of fragment ions of amino acids, carbohydrates, and carboxylic acids revealed that different types of organic compounds had adhered to the Si surface already after 10 min of exposure to the aquifer fluids, whereas the attachment of microbial cells was first observed after 1000 min. The organic compounds first formed isolated μm-sized accumulations and subsequently started to distribute on the wafer surface more homogenously. Simultaneously further microorganisms attached to the surface and formed biofilm-like cell accumulations after 3 months of exposure to aquifer water.

The aim of this work was to study the feasibility to use a biomimetic method to prepare biomimetic hydroxyapatite (HA) coatings on CoCr substrates with short soaking times and to characterize the properties of such coatings. A second objective was to investigate if the coatings could be applied to porous CoCr implants manufactured by electron beam melting (EBM). The coating was prepared by immersing the pretreated CoCr substrates and EBM implants into the phosphate-buffered solution with Ca2+ in sealed plastic bottles, kept at 60 °C for 3 days. The formed coating was partially crystalline, slightly calcium deficient and composed of plate-like crystallites forming roundish flowers in the size range of 300-500 nm. Cross-section imaging showed a thickness of 300-500 nm. In addition, dissolution tests in Tris-HCl up to 28 days showed that a substantial amount of the coating had dissolved, however, undergoing only minor morphological changes. A uniform coating was formed within the porous network of the additive manufactured implants having similar thickness and morphology as for the flat samples. In conclusion, the present coating procedure allows coatings to be formed on CoCr and could be used for complex shaped, porous implants made by additive manufacturing.

Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti–6Al–4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti–Ta–Nb–Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti–Ta–Nb–Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti–Ta–Nb–Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti–Ta–Nb–Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti–Ta–Nb–Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.